MBR 2019 - Pathology Handouts

CELL ADAPT, INJURY, HEMODYNAMICS,
INFLAM, NEOPLASIA
ALITA B. SANTOS, M.D.
PATHOLOGY NOTES: CELLULAR RESPONSES TO INJURY

The Cell Cycle -Acute Cell Injury
G0 Phase – Terminally differentiated cells =Reversible Injury(Sublethal cell injury)
G1 – Gap Phase 1 =Cell Death
G2 – Gap Phase 2 :Necrosis necoptosis
M – Mitotic Phase :Apoptosis necoptosis
S – Synthesis Phase -Subcellular Alterations and Cell Inclusions
-Intracellular Accumulations
Labile cells – Continuously Cycling Cells -Pathologic calcifications
Stable cells – Facultative Dividers
Permanent cells – Terminally Differentiated CAUSES OF CELL INJURY
Cells -Hypoxia
-Physical Agents
-Chemical Agents and Drugs
-Infectious Agents
-Immunologic Reactions
-Genetic Derangement
-Nutritional Imbalances
CELLULAR ADAPTATION and INJURY
*Adaptive change reverts back to normal once

the stimulus is removed
MECHANISMS OF ADAPTATION
1. Increasing cellular activity
- size (hypertrophy)
- number (hyperplasia)
2. Decreasing cellular activity (atrophy)
3. Altering cellular structure
(metaplasia)
*Pure hypertrophy without hyperplasia

occurs only in heart and skeletal muscle
(permanent cells). There is increased RNA &
DNA in nucleus and increased amount of
cytoplasm.
Pathologic stimuli causing ATROPHY:
-reduced functional demand (disuse)
-Inadequate supply of oxygen
Necrosis Apoptosis
-Lack of trophic hormones
Stimuli Hypoxia, toxins Physiologic and
-Malnutrition pathologic
-Denervation of skeletal muscle Histology Cellular swelling Single cells
Coagulation Chromatin con-
METAPLASIA - Conversion of one necrosis densation
differentiated (mature) cell type into another Disruption of Apoptotic
-Change of columnar bronchial epithelium organelles bodies
into squamous epithelium in smokers DNA Random, diffuse Internucleosom
(squamous metaplasia) breakdown ATP depletion al
Mechanisms Membrane injury Gene activation
-Chronic infection in cervix – squamous
Free radical Endonuclease
damage
metaplasia of endocervical glandular Tissue Inflammation No inflammation
epithelium reaction Phagocytosis of
- Intestinal metaplasia (Barret’s esophagus) apoptotic bodies
of stratified squamous epithelial lining of the
distal esophagus in GERD
USTFMS MEDICAL BOARD REVIEW 2019 1 | PATHOLOGY

INFLAM, NEOPLASIA
NECROSIS -Definition: Spectrum of =Alcoholic liver disease
morphologic changes that follow cell death in =Nutritional deficiencies
living tissue; differentiate from autolysis and =Mitochondrial myopathies
apoptosis. -Cytoskeletal abnormalities
-Morphologic patterns: =Chediak-Higashi syndrome, Immotile Cilia
=Coagulative necrosis Syndrome
=Liquefative necrosis =Mallory bodies, Neurofibrillary tangles in Alheimer’s
=Caseous necrosis disease
=Enzymatic fat necrosis
=Hemorrhagic necrosis HEMODYNAMIC DISORDERS
=Fibrinoid necrosis
- Edema - Embolism
INCLUSIONS - Congestion - Infarction
-Pigments - Hyperemia - DIC
- Carbon - Hemorrhage - Shock
- Hemosiderin - Thrombosis
- Bilirubin
- Lipofuscin 1. MECHANISMS OF EDEMA
- Melanin 1. Increased hydrostatic pressure
-Proteins 2. Decreased colloid osmotic pressure
-Carbohydrates 3. Increased vascular permeability
-Lipids 4. Lymphatic obstruction/obliteration
INTRACELLULAR ACCUMULATIONS CLINICALLY IMPORTANT FORMS OF EDEMA

-Fatty Change/Steatosis Cerebral – infections, tumor, trauma, hypertension
N.B. Differentiate from stromal infiltration of Facial – allergy, nephritic syndrome, sunbathing
fat/fatty ingrowth Laryngeal – infection, allergy
-Proteins Hydrothorax – heart failure, pneumonia, tumors
=Reabsorption droplets in proximal renal Pulmonary – heart failure, toxic inhalation, infection,
tubules ARDS
=Russell bodies – immunoglobulin in plasma Hydropericardium – Infection, myocardial infarct
cells Arm – infection, lymphatic obstruction (post-
=Alpha1-antitrypsin in liver cells mastectomy edema)
-Glycogen- e.g. D. mellitus Ascites – liver disease, heart failure, peritoneal tumor
-Pigments seeding, tumors
=Exogenous: carbon(coal dust) – Scrotal – infection, lymphatic obstruction (in filariasis)
anthracosis Pedal – heart failure, pregnancy, lymphatic obstruction
=Endogenous: lipofuscin, melanin, Anasarca (generalized edema) – renal diseases,
hemoglobin derivatives (hemosiderin – diff. tumors
between hemosiderosis and
hemochromatosis) *Meig’s syndrome – hydrothorax in the presence of
ovarian fibroma
PATHOLOGIC CALCIFICATIONS *Filariasis – leg and scrotal edema due to lymphatic
-Dystrophic Calcification obstruction
=Alterations in areas of necrosis;
intracellular or extracellular or both 2. CONGESTION
=Psammoma bodies, in atherosclerosis, -Seen together with edema
aging, damaged heart valves -With 2 types:
-Metastatic Calcification A. Active congestion or Hyperemia – due to
=In normal tissues whenever there is increased blood flow from arterial/arteriole circulation;
hypercalcemia seen in acute inflammation; blood vessels are dilated
=Associated with hyperparathyroidism, Vit. and engorged with blood; seen with tissue edema due
D intoxication, systemic sarcoidosis, milk-alkali to increased vascular permeability
syndrome, hyperthyroidism, Addison’s disease,
increased bone catabolism(tumors), B. Passive congestion or Congestion - due to
immobilization obstruction to venous outflow; systemic (RV failure);
localized (pulmonary congestion in LV failure); e.g.
SUBCELLULAR ALTERATIONS “Nutmeg” liver
-Lysosomes: Heterophagy and Autophagy
=Lipofuscin pigments: residual bodies, 3. HEMORRHAGE
“wear and tear” pigments -Extravasation of blood into the surrounding tissues
=Hereditary lysosomal storage disorders usually due to ruptured blood vessels
=Acquired/iatorgenic storage disease
-Induction (Hypertrophy) of SER
-Mitochondrial alterations

INFLAM, NEOPLASIA
MAJOR CLINICAL FORMS OF HEMORRHAGE COMMON SITES OF SYSTEMIC INFARCTION FROM

Intracerebral hemorrhage - apoplexy ARTERIAL EMBOLI
Hematocephalus – intraventricular -Brain, retina, heart, spleen, kidney, small intestine,
Hematemesis – vomiting lower leg
Hemoptysis – expectoration
Hemopericardium SOURCES OF VENOUS EMBOLI
Hemothorax -Infected venous catheter
Melena – rectal discharge caused by UGIB -Pulmonary embolus without infarction
Hematochezia -Pulmonary embolus with infarct
Hematuria -Thromboembolus of main pulmonary artery, shock
Hemoperitonium -Injection of air or foreign material
Menorrhagia and metrorrhagia -Amniotic fluid embolism
Petechia, Ecchymosis, Purpura, Hematoma -Tumor emboli
-Fat embolism in fracture
4. THROMBOSIS - Thrombophlebitis – *Deep leg vein thrombosis is the
-Pathologic process resulting to formation of no.1 source of embolism
a solid blood clot within a vessel
PREDISPOSITION TO THROMBOSIS *Venous emboli usually lodges in the lungs causing
(VIRCHOW’S TRIAD) hemorrhagic infarcts
-hypercoagulability of blood
-damage to endothelium 7. SHOCK
-slow flow/stasis/turbulence -inadequate perfusion of the different tissues of the
COMPOSITION OF THROMBUS body with oxygen and nutrients, and removal of
-platelets waste products, thus causing generalized tissue injury
-fibrin and/or death.
-entrapped red cells
FATE OF THROMBUS CAUSES OF SHOCK
-lysis -Cardiogenic
-organization =MI, myocarditis, cardiac tamponade
-propagation -Hypovolemic
-recanalization =External fluid loss
-embolization :hemorrhage, diarrhea, dehydration
MOST IMPORTANT COMPLICATIONS =Internal fluid loss
-vessel occlusion :endotoxemia, burns, trauma, anaphylaxis
-embolization
ESSENTIAL COMPONENTS OF SHOCK
“Lines of Zahn” – seen in a true thrombus but -↓Cardiac output or ↓Venous return
not in post-mortem blood clots -Sudden drop of BP
-Sudden ↓↓↓ of oxygen and nutrients to vital organs
5. INFARCTION -Kidney malfunction resulting to retention of wastes
-Process of tissue necrosis resulting from
interference of blood supply COMPLICATIONS OF SHOCK
- 2 TYPES OF INFARCTS
=White Infarct - Solid organs; Arterial
supply occlusion; coagulation necrosis
=Red/Hemorrhagic Infarct – Hollow
organs; Organs with double blood supply;
Venous outflow occlusion; hemorrhagic and
fibrinoid necrosis
6. EMBOLISM
-Process by which an intravascular mass in
the vessel is carried by the circulation to a site
distant from its point of origin
8. DISSEMINATED INTRAVASCULAR
COAGULOPATHY
SOURCES OF ARTERIAL EMBOLI
-an acquired syndrome characterized by systemic
Carotid artery (atherosclerosis)
activation of blood coagulation, which results in the
Mural thrombus, LA (atrial fibrillation)
formation of intravascular fibrin thrombi and multiple
Endocarditis, Mitral valve
organ failure due to impaired perfusion
Endocarditis, aortic valve
• manifests clinically as coagulation problems
Mural thrombus, LV (myocardial infarction)
• common seen are shock, acute renal failure,
Aortic athrosclerosis
and acute respiratory failure
Mural thrombus, aorta
• vascular thrombi and focal tissue infarction
Mural thrombus, iliac artery aneurysm
common
INFLAM, NEOPLASIA
NEOPLASIA DYSPLASIA
-Abnormal growth and differentiation
Normal cells, if subjected to certain =Variations in size and shape of cells
pathologic stimuli, may have genetic =Enlargement, irregularity, and hyperchromasia of
alteration to the cells. Most gene alterations nuclei
involve growth factors, growth factor =Disorderly arrangement of cells within the
receptors, signal transduction and epithelium
transcription regulation. The transformed -A preneoplastic lesion (a stage in the cellular
cell proliferates with poor regulation of evolution to cancer)
growth as a result of genetic changes and this
mass of transformed cells is called a TUMOR NOMENCLATURE
NEOPLASM. *Prefix alludes to tissue of origin
BENIGN MALIGNANT *Suffix depends on:
Well-defined margins Poorly defined 1. BENIGN - “OMA”
2. MALIGNANT
2.1. Epithelial - CARCINOMA
Local growth only Invasive
2.2. Mesenchymal - SARCOMA
May metastasize*
POPULAR EXCEPTIONS: hepatoma, melanoma,
seminoma, lymphoma
Resembles cell of origin Failure to achieve
cellular differentiation TUMOR GRADING
-Grading of cancer is an attempt to establish some
estimate of its aggressiveness
Few Mitoses Many mitoses, some
abnormal of level of malignancy based on the cytologic
differentiation of tumor.
Grade I – Well-differentiated – when there is a close
Uniform cells Cellular and nuclear resemblance to tissue of origin
pleomorphism Grade III – Poorly-differentiated – when there is
more anaplasia
Grade II – Moderately differentiated – features in
Normal of slightly ↑ N:C ↑↑N:C
between the two grades
*BENIGN TUMORS THAT CAN

METASTASIZE: Giant Cell Tumor of the
Bone; Pleomorphic adenoma (salivary glands)

Tissue of Origin Benign Malignant
Composed of One Parenchymal Cell type Fibroma Fibrosarcoma

Tumors of mesenchymal origin Lipoma Liposarcoma
Connective tissue and derivatives Chondroma Chondrosarcoma
Osteoma Osteogenic sarcoma
Endothelial and related tissues

Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Synovium Synovial sarcoma
Mesothelium Mesothelioma
Brain coverings Meningioma Invasive meningioma
Blood cells and related cells
Hematopoietic cells Leukemias
Lymphoid tissue Hodgkin’s Lymphoma
Muscle
Smooth Leiomyoma Leiomyosarcoma
Straited Rhabdomyoma Rhabdomyosarcoma
Tumors of epithelial origin Squamous cell papilloma Squamous cell or epidermoid

Stratified squamous carcinoma
Basal cells of skin or adnexa Basal cell carcinoma
Papilloma Papillary carcinomas
Epithelial lining of glands or ducts Adenoma Adenocarcinoma
Cystadenoma Cystadenocarcinoma
Respiratory passages Bronchial adenoma Bronchogenic carcinoma

INFLAM, NEOPLASIA
Renal epithelium Renal tubular adenoma Renal cell carcinoma
Liver cells Liver cell adenoma Hepatocellular carcinoma
Transitional cell carcinoma
Urinary epithelium Transitional cell papilloma Choriocarcinoma
Hydatidiform mole
Placenta epithelium Seminoma
Embryonal carcinoma
Testicular epithelium (Germ cells) Malignant melanoma
Nevus
Tumors of melanocytes
More than one Neoplastic Cell Type-Mixed

Tumors, Usually Derived from One Germ-
Cell Layer
Salivary glands Pleomorphic adenoma (mixed Malignant mixed tumor of
tumor of salivary origin) salivary gland origin
Renal anlage
More than one Neoplastic Cell Type Mature teratoma, dermoid Wilms tumor
derived from more than One Germ-Cell cyst Immature teratoma,
Layer- Teratogenous Teratocarcinoma,
Totipotential cells in gonads or in Teratosarcoma
embryonic rests
MAIN ROUTES OF METASTASIS 5. Healing. Restoration of injured tissue to its

-Local invasion – most common normal structure and function. This is limited by the
-Lymphatic spread – commonly used by carcinomas extent of tissue destruction and by the regenerative
-Vascular spread – commonly used by sarcomas capacity of the specific tissue.
-Transcoelomic spread
Cardinal Signs
TUMOR STAGING o Celsus, a Roman writer of the first century
-Assesses the tumor spread; Better than grading in ad: first listed the four cardinal signs of
gauging prognosis inflammation: rubor (redness), tumor
T (Tumor) – tumor size; assesses local invasion (swelling), calor (heat), and dolor (pain).
N (Nodes) – regional lymph node involvement; o Rudolf Virchow,19th century: fifth clinical
assesses lymphatic spread sign, loss of function (functio laesa), was
M (Metastasis) – presence of distant metastasis; added
assesses hematologic/vascular spread
1. ACUTE INFLAMMATION – Rapid in onset
IMMUNOLOGICAL STAINS THAT CAN POINT (typically minutes) and is of short duration, lasting
TO THE TISSUE OF ORIGIN for hours or a few days;
Cytokeratin – epithelial origin o Main characteristics are the exudation of fluid
Vimentin – mesenchymal origin and plasma proteins (edema) and the
Leukocyte Common Antigen (LCA) – emigration of leukocytes, predominantly
lymphocytes neutrophils (also called polymorphonuclear
Smooth muscle actin (SMA) – smooth muscles leukocytes).
Desmin – muscles o rapid host response that serves to deliver
MyoD1 – skeletal muscles leukocytes and plasma proteins, such as
Glial Fibrillary Acidic Protein (GFAP) – glial cells antibodies, to sites of infection or tissue injury.
Neuron Specific Enolase (NSE) – neurons
o three major components:
● alterations in vascular caliber that lead
INFLAMMATION AND REPAIR to an increase in blood flow,
● structural changes in the
Inflammation - May be acute or chronic, microvasculature that permit plasma
depending on the nature of the stimulus and the proteins and leukocytes to leave the
effectiveness of the initial reaction in eliminating the circulation, and
stimulus or the damaged tissues. ● emigration of the leukocytes from the
microcirculation, their accumulation in
Processes the focus of injury, and their activation
1. Exudation of fluid from vessels to eliminate the offending agent
2. Attraction of leukocytes to the injury.
Phagocytosis – Leukocyte engulf and destroy 1.1. Stimuli for Acute Inflammation
bacteria, tissue debris and other particulate matter Acute inflammatory reactions may be
3. Activation of chemical mediators triggered by a variety of stimuli:
4. Proteolytic degradation of cellular debris
INFLAM, NEOPLASIA
1. Infections concentration of red cells in small

2. Tissue necrosis vessels, and increased viscosity of the
3. Foreign bodies blood. This is called stasis which
4. Immune reactions (also called mainly explains the cardinal signs of
hypersensitivity reactions): rubor and calor.
5. Chemical injury
6. Trauma 1.3. Reactions of Leukocytes
7. Physical injury from thermal extremes 1.3.1. Recruitment of Leukocytes to
or from ionizing radiation Sites of Infection and Injury
1.2. Reactions of Blood Vessels ● called extravasation
1.2.1. Blood vessels undergo a series of ● As stasis develops, blood
changes that are designed to maximize the leukocytes, principally neutrophils,
movement of plasma proteins and accumulate along the vascular
circulating cells out of the circulation and endothelium. At the same time
into the site of infection or injury. endothelial cells are activated by
1.2.1.1. Exudation: The escape of mediators produced at sites of
fluid, proteins, and blood cells from the infection and tissue damage, and
vascular system into the interstitial tissue express increased levels of adhesion
or body cavities Edema: denotes an molecules. Leukocytes then adhere
excess of fluid in the interstitial tissue or to the endothelium, and soon
serous cavities; it can be either an afterward they migrate through
exudate or a transudate. the vascular wall into the
● Exudate interstitial tissue.
o extravascular fluid that has a high ● can be divided into the following
protein concentration, contains steps:
cellular debris, and has a high 1.3.1.1. Leukocyte Adhesion to
specific gravity. Endothelium
o increase in the normal permeability Stasis → hemodynamic conditions
of small blood vessels in an area of change (wall shear stress decreases) →
injury and, therefore, an white cells assume a peripheral position
inflammatory reaction along the endothelial surface. These
o Pus: a purulent exudate, is an processes are collectively called
inflammatory exudate rich in emigration including:
leukocytes (mostly neutrophils), the
debris of dead cells and, in many *Margination- process of leukocyte
cases, microbes. redistribution (peripheral).
● Transudate: *Pavementing- occurs as leukocytes
o fluid with low protein content (most line the endothelial surface
of which is albumin), little or no *Rolling- individual and then rows of
cellular material, and low specific leukocytes adhere transiently to the
gravity. endothelium, detach and bind again on
o ultrafiltrate of blood plasma that the vessel wall.
results from osmotic or hydrostatic *Adhesion- cells finally come to rest
imbalance across the channels vessel at some point where and adhere firmly
wall without an increase in vascular (resembling pebbles over which a
permeability stream runs without disturbing them).
*Transmigration or diapedesis-
1.2.2. Changes in Vascular Flow and Migration across the endothelium and
Caliber vessel wall in the tissues toward a
1.2.2.1. Vasodilation chemotactic stimulus is called. This
1.2.2.2. Increased Vascular occurs mainly in post-capillary venules.
Permeability of the microvasculature 1.3.1.2. Chemotaxis of
● hallmark of acute inflammation
▪ leads to edema;explains the cardinal Leukocytes – process by which
sign of tumor leukocytes are attracted to and move toward
▪ Several mechanisms: 1) am injury; chemotactic factors for neutrophils,
Contraction of endothelial cells produced at the site of injury, include:
resulting in increased products from bacteria, complement
interendothelial spaces; 2) components especially C5a, arachidonic
Endothelial injury, resulting in acid metabolites especially leukotriene (LT)
endothelial cell necrosis and B4 (LTB4), hydroxyeicosa-tetraeonic acid
detachment; 3) Transcytosis: (HETE), and kallikrein
▪ The loss of fluid and increased vessel
diameter lead to slower blood flow,

INFLAM, NEOPLASIA
1.3.2. Recognition of Microbes and secretions of mesothelial cells lining the

Dead Tissues peritoneal, pleural, and pericardial
● G protein–coupled receptors found cavities.
on neutrophils, macrophages, and ● Accumulation of fluid in these cavities is
most other types of leukocytes called an effusion.
recognize short bacterial peptides ● Eg. The skin blister resulting from a burn
containing N-formylmethionyl residues. or viral infection represents a large
Because all bacterial proteins and few accumulation of serous fluid, either
mammalian proteins (only those within or immediately beneath the
synthesized within mitochondria) are epidermis of the skin.
initiated by N-formylmethionine, this
receptor enables neutrophils to detect 1.4.2. Fibrinous Inflammation
and respond to bacterial proteins. ● increase in vascular permeability →
● Receptors for opsonins: Leukocytes large molecules such as fibrinogen
express receptors for proteins that coat pass the vascular barrier → fibrin is
microbes. formed and deposited in the
● Receptors for cytokines: Leukocytes extracellular space.
express receptors for cytokines that ● fibrinous exudate
are produced in response to microbes. ● develops when the vascular leaks
One of the most important of these are large or there is a local
cytokines is interferon-γ (IFN-γ), which procoagulant stimulus (e.g., cancer
is secreted by natural killer cells cells)
reacting to microbes and by antigen- ● characteristic of inflammation in the
activated T lymphocytes during lining of body cavities, such as the
adaptive immune responses. IFN-γ is meninges, pericardium and pleura.
the major macrophage-activating ● may be removed by fibrinolysis and
cytokine. clearing of other debris by
macrophages
1.3.3. Removal of Offending Agents ● Histologically, fibrin appears as an
Recognition of microbes or dead cells eosinophilic meshwork of threads or
by the receptors described above sometimes as an amorphous
induces several responses in leukocytes coagulum
that are referred to under the rubric of
leukocyte activation 1.4.3. Pseudomembranous
Phagocytosis involves three ● With superficial grayish exudates
sequential steps: (1) recognition and consisting of necrotic, loosely
attachment of the particle to be adherent mucosal debris
ingested by the leukocyte; (2) its (pseudomembrane)
engulfment, with subsequent formation ● E.g. Pseudomembranous colitis-
of a phagocytic vacuole; and (3) killing the cause most often is overgrowth
or degradation of the ingested material. of exotoxin-producing Clostridium
Killing and Degradation – The final difficile (fibrinous necrosis of the
step in the elimination of infectious superficial mucosa is caused by the
agents and necrotic cells is their killing exotoxin , not by bacterial infection)
and degradation within neutrophils and
macrophages. 1.4.4. Suppurative and Purulent
Inflammation; Abscess
1.4. Morphologic Patterns of Acute ● Large amounts of pus or purulent
Inflammation exudate consisting of neutrophils,
● morphologic hallmarks of all acute liquefactive necrosis, and edema
inflammatory reactions are fluid.
o dilation of small blood vessels, ● Certain bacteria (e.g.,
o slowing of blood flow, and Staphylococcus spp.) produce this
o accumulation of leukocytes and fluid in localized suppuration and are
the extravascular tissue therefore referred to as pyogenic
● The importance of recognizing the gross and (pus-producing) bacteria.
microscopic patterns is that they often ● Eg. acute appendicitis.
provide valuable clues about the underlying
cause. 1.4.5. Ulcers
● a local defect, or excavation, of the
surface of an organ or tissue that is
1.4.1. Serous Inflammation produced by the sloughing
● outpouring of a thin fluid that may be (shedding) of inflamed necrotic
derived from the plasma or from the tissue

INFLAM, NEOPLASIA
● can occur only when tissue necrosis ▪ In time the abscess may become walled
and resultant inflammation exist on off and ultimately replaced by connective
or near a surface. tissue.
● It is most commonly encountered in
▪ the mucosa of the mouth, stomach, 1.5.4. Progression of the response to Chronic
intestines, or genitourinary tract; inflammation – may follow acute inflammation or
and be insidious in onset; simultaneous process of tissue
▪ the skin and subcutaneous tissue of injury and healing
the lower extremities in older o longer duration and is associated with the
persons who have circulatory presence of lymphocytes and macrophages, the
disturbances that predispose to proliferation of blood vessels, fibrosis, and tissue
extensive ischemic necrosis. destruction.
● Eg. peptic ulcer of the stomach or o Terminated when the offending agent is
duodenum, in which acute and eliminated.
chronic inflammation coexist. o The inflammatory response is closely intertwined
with the process of repair.
1.5. Outcomes of Acute Inflammation o Inflammation may be harmful in some
1.5.1. Complete resolution: Injury to situations.
epithelial tissue, since all are labile cells and can o May contribute to a variety of diseases that are
readily proliferate to replace the injured and dead not thought to be primarily due to abnormal
cells, usually heal by complete resolution. Complete host responses. For instance, chronic
resolution can also be achieved in proper healing of inflammation may play a role in atherosclerosis,
bones, although this tissue is of mesenchymal origin. type 2 diabetes, degenerative disorders like
1.5.2. Healing by connective tissue Alzheimer disease, and cancer.
replacement (Fibrosis). – This usually happens in
tissues wherein the connective tissues is fibroblastic 2. CHRONIC INFLAMMATION
in nature. Collagen fiber deposition of activated o inflammation of prolonged duration (weeks or
stable cells lead to fibrosis. months) in which inflammation, tissue injury,
and attempts at repair coexist, in varying
Type of Healing Primary Secondary combinations.
Intention intention o may follow acute inflammation, as described
earlier, or
Type of wound Small, Linear Large, Jagged o may begin insidiously, as a low-grade,
and edges and smoldering response without any manifestations
anastomose irregular; of an acute reaction.
d; Dirty/Infected
Clean 2.1. Causes of Chronicity of Inflammation
Time of healing 3-7 days Prolonged 2.1.1. Persistent infections by

microorganisms that are difficult to
Amt. of + ++++ eradicate
granulation ● Eg. mycobacteria, and certain
tissue viruses, fungi, and parasites
Contracture +/- ++ to ++++ ● delayed-type hypersensitivity
● may cause granulomatous
reaction
1.5.3. Abscess formation: Usually ensuing
from Suppurative or Purulent Morphologic 2.1.2. Immune-mediated inflammatory
Pattern of Inflammation, Abscesses are diseases.
localized collections of purulent 2.1.3. Prolonged exposure to
inflammatory tissue caused by suppuration potentially toxic agents, either
buried in a tissue, an organ, or a confined exogenous or endogenous.
space. Eg. exogenous agent: particulate
▪ produced by deep seeding of pyogenic silica, a nondegradable inanimate
bacteria into a tissue. material that, when inhaled for
▪ have a central region that appears as a prolonged periods, results in an
mass of necrotic leukocytes and tissue inflammatory lung disease called
cells. silicosis
▪ There is usually a zone of preserved Endogenous: endogenous toxic
neutrophils around this necrotic focus, and plasma lipid components causing
outside this region vascular dilation and Atherosclerosis
parenchymal and fibroblastic proliferation
occur, indicating chronic inflammation and
repair.

INFLAM, NEOPLASIA
2.2. Morphologic Features ● Platelet-Activating Factor

● Infiltration with mononuclear cells, which ● Reactive Oxygen Species
include macrophages, lymphocytes, and ● Nitric Oxide
plasma cells ● Cytokines and Chemokines
● Tissue destruction, induced by the persistent ● Lysosomal Constituents of Leukocytes
offending agent or by the inflammatory cells ● Neuropeptides
● Healing by connective tissue replacement of a. Plasma Protein-Deived Mediators
damaged tissue, accomplished by i. Complement
proliferation of small blood vessels ii. Coagulation and Kinin
(angiogenesis) and fibrosis Systems
2.3. Role of Macrophages* in Chronic
Inflammation 4. SYSTEMIC EFFECTS OF INFLAMMATION
● The macrophage ● acute-phase response- systemic changes
o dominant cellular player in chronic associated with acute inflammation, also
inflammation; known as the systemic inflammatory
o one component of the mononuclear response syndrome
phagocyte system (sometimes called ● These changes are reactions to cytokines
reticuloendothelial system). whose production is stimulated by bacterial
o Diffusely scattered products such as LPS and by other
- liver (Kupffer cells), inflammatory stimuli.
- spleen and lymph nodes (sinus histiocytes), ● The acute-phase response consists of
- lungs (alveolar macrophages), and several clinical and pathologic changes:
- central nervous system (microglia). ➢ Fever characterized by an elevation of body
● Bone marrow Mononuclear phagocytes → temperature, usually by 1° to 4°C,
blood monocytes → tissue macrophages. is one of the most prominent manifestations
● The half-life of blood monocytes is about 1 of the acute-phase response, especially
day, whereas the life span of tissue when inflammation is associated with
macrophages is several months or years. infection.
● Other Cells Involved ➢ produced in response to pyrogens that act
1. Macrophages by stimulating prostaglandin synthesis in the
2. Plasma cells vascular and perivascular cells of the
3. Eosinophils hypothalamus.
4. Mast cells ➢ Bacterial products, such as LPS (called
exogenous pyrogens), stimulate leukocytes
2.4. Granulomatous Inflammation to release cytokines such as IL-1 and TNF
is a distinctive pattern of chronic inflammation that (called endogenous pyrogens) that increase
is encountered in a limited number of infectious and the enzymes (cyclooxygenases) that convert
some noninfectious conditions. AA into prostaglandins.
● Immune reactions are usually involved in ➢ In the hypothalamus, the prostaglandins,
the development of granulomas Granuloma especially PGE2, stimulate the production of
● is a cellular attempt to contain an offending neurotransmitters which function to reset
agent that is difficult to eradicate. the temperature set point at a higher level.
● there is often strong activation of T ➢ NSAIDs, including aspirin, reduce fever by
lymphocytes leading to macrophage inhibiting prostaglandin synthesis
activation, which can cause injury to normal ➢ Acute-phase proteins are plasma
tissues. proteins, mostly synthesized in the liver,
2.4.1. Two types of granulomas (which differ whose plasma concentrations may increase
in their pathogenesis) several hundred-fold as part of the response
o Foreign body granulomas are incited to inflammatory stimuli.
by relatively inert foreign bodies. ➢ Three of the best-known of these proteins
o Immune granulomas are caused by a are C-reactive protein (CRP), fibrinogen, and
variety of agents that are capable of serum amyloid A (SAA) protein.
inducing a cell-mediated immune ➢ Elevated serum levels of CRP have been
response. The prototype of the immune proposed as a marker for increased risk of
granuloma is that caused by infection myocardial infarction in patients with
with Mycobacterium tuberculosis. rare in coronary artery disease. It is postulated that
other granulomatous diseases. inflammation involving atherosclerotic
plaques in the coronary arteries may
3. MEDIATORS OF INFLAMMATION predispose to thrombosis and subsequent
● Vasoactive Amines: Histamine and infarction, and CRP is produced during
Serotonin inflammation.
● Arachidonic Acid Metabolites: ➢ hepcidin - is the iron-regulating peptide
Prostaglandins, Leukotrienes and whose production is increased in the acute-
Lipoxins phase response

INFLAM, NEOPLASIA
o Leukocytosis o Eg. Allergies and autoimmune

➢ is common feature of inflammatory diseases.
reactions, especially those induced by o Prolonged inflammation and the
bacterial infections. fibrosis that accompanies it are also
➢ The leukocyte count usually climbs to responsible for much of the
15,000 or 20,000 cells/μL, pathology in many infectious,
o Leukemoid reactions: count reach metabolic, and other diseases.
extraordinarily high levels of 40,000 to
100,000 cells/μL; they are similar to the MUSCULOSKELETAL PATHOLOGY
white cell counts observed in leukemia and Vocabulary:
have to be distinguished from leukemia. Eburnation – thinning out of articular cartilage
➢ occurs initially because of accelerated seen in osteoarthritis
release of cells from the bone marrow Involucrum – hard callus (new bone) forming a
postmitotic reserve pool (caused by sleeve of living tissue around the segment of
cytokines, including TNF and IL-1) and is devitalized infected bone
therefore associated with a rise in the Osteopetrosis – Marble Bone disease –
number of more immature neutrophils in the thickened dense bones
blood (shift to the left). Osteogenesis imperfecta (Brittle Bone
➢ Most bacterial infections induce an increase disease) – autosomal dominant disorder with
in the blood neutrophil count, called defects in the extracelllular structural protein leading
neutrophilia. to deficiency in the synthesis of type I
➢ Viral infections, such as infectious collagen; extreme skeletal fragility due to too little
mononucleosis, mumps, and German bone resulting in a type of osteoporosis with marked
measles, cause an absolute increase in the cortical thinning and attenuation of trabeculae; asso
number of lymphocytes (lymphocytosis). with blue sclerae
➢ In bronchial asthma, allergy, and parasitic Pannus formation – destruction of cartilage and
infestations, there is an increase in the bone; seen in RA and septic arthritis
absolute number of eosinophils, creating an Sequestrum – necrotic bone seen in osteomyelitis
eosinophilia.
➢ Certain infections (typhoid fever and 1. THE NORMAL BONE
infections caused by some viruses, Bone as an “organ” is composed of bone
rickettsiae, and certain protozoa) are tissues, cartilage, fat, marrow elements,
associated with a decreased number of vessels, nerves and fibrous tissue. Bone as
circulating white cells (leukopenia). “tissue” is defined by the relationship
Leukopenia is also encountered in infections between the collagen and mineral structure
that overwhelm patients debilitated by and the bone cells.
disseminated cancer, rampant tuberculosis, The functions of bone are classified as
or severe alcoholism. mechanical, mineral storage and
➢ Other manifestations of the acute-phase hemopoietic. Since the latter has been
response include increased pulse and blood discussed in the Hematopathology Module,
pressure; decreased sweating, mainly this will focus on the pathology involving its
because of redirection of blood flow from mechanical and mineral storage functions.
cutaneous to deep vascular beds, to
minimize heat loss through the skin; rigors 1.1. Bone Marrow
(shivering), chills (search for warmth), 1.2. Blood supply – The long tubular bones get blood
anorexia, somnolence, and malaise, supply from nutrient and perforating arteries and
probably because of the actions of cytokines contain Haversian and Volkmann’s canals. Each
on brain cells. artery is paired with a vein and probably, some free
➢ In severe bacterial infections (sepsis) the nerve endings. Drainage of the veins proceeds
large amounts of organisms and LPS in the either from the cortex outwards to the periosteal
blood stimulate the production of enormous veins or inward into the marrow spaces and out the
quantities of several cytokines, notably TNF nutrient veins.
and IL-1.
1.3. Periosteum – Composed of an internal cambium
5. CONSEQUENCES OF DEFECTIVE OR layer and the outer fibrous layer, the periosteum is
EXCESSIVE INFLAMMATION a specialized connective tissue that covers all bones
● Defective inflammation of the body and is capable of forming bone.
o typically results in increased
susceptibility to infections, 1.4. The Bone Matrix
o associated with delayed wound 1.4.1. Mineralized Matrix – represents 60% of
healing, the total tissue and is capable of
● Excessive inflammation neutralizing substantial amounts of acid.
o is the basis of many types of human 1.4.2. Organic Matrix – represents 30% of the
disease. total tissue. Further broken down to 88%

INFLAM, NEOPLASIA
Type I collagen, 10% osteocalcin, 2.2. Delayed Maturation of Bone

osteopontin, sialoprotein and other 2.2.1. Osteogenesis Imperfecta (Brittle Bone
proteins and 1-2% lipids and Disease) – an autosomal dominant disorder
glycosaminoglycans causing defects in the extracellular structural
1.4.3. The Cells of Bone – represents 10% of protein leading to deficiency in the synthesis of
the total tissue. It has specific functions type 1 collagen. This results to too little bone
related to the formation, resorption and resulting in a type of osteoporosis with marked
remodeling of the bone. cortical thinning and attenuation of trabeculae.
There is extreme skeletal fragility
1.4.3.1. Osteoprogenitor cells – derived from
primitive stem cells. It is found in the 2.3. Osteoporosis – disorder associated with devreased
marrow, periosteum, and all the bone mass in which there is increased porosity of the
supporting structures within the marrow skeleton resulting from reduced bone mass and
cavity. It ultimately differentiates into predisposing the bone to fracture.
osteoclasts and osteocytes. 2.4. Paget’s Disease of the Bone (Osteitis Deformans) –
1.4.3.2. Osteoblasts – protein synthesizing cells that a disease caused by osteoclast dysfunction resulting in
produce and mineralize bone tissue. a gain of bone mass; the newly formed bone is
1.4.3.3. Osteocytes – osteoblasts that are disordered and architecturally unsound; flask -shaped
completely embedded in bone matix and appearance of bone on xray; mosaic cement lines;
isolated in a lacuna. there are three phases: osteolytic, mixed and
1.4.3.4. Osteoclasts – exclusive bone-resorptive osteosclerotic.
cells that are multinucleated and contain
many lysosomes rich in hydrolytic enzymes. 3. DISEASES ASSOCIATED WITH ABNORMAL
MINERAL HOMEOSTASIS
1.5. Bone Formation and Growth – Bone 3.1. Renal Osteodystrophy – describes
formation starts with primary ossification, all the skeletal changes of chronic renal disease
secondary ossification, formation of including
metaphysic and obliteration of the growth – increased osteoclastic bone
plate. resorption
– delayed matrix mineralization
1.6. Microscopic Organization of Bone. The – osteosclerosis
organization of bone can be classified into – growth retardation
lamellar and woven bone with the following – osteoporosis
differences: 3.2. Osteomalacia and Rickets – Most
often related to lack of Vit. D or some disturbance in
LAMELLAR WOVEN its metabolism, rickets (disorder in children) and
Arrangement of Parallel Irregular osteomalacia (disorder in adults) are characterized
Type I collagen by matrix demineralization
Osteocytes in Few Numerous 3.3. Brown tumor (Osteitis Fibrosa
matrix Cystica) – seen in association with
Osteocyte Uniform Pleomorphic Hyperparathyroidism
morphology 4. BONE INFECTIONS (OSTEOMYELITIS)
Deposition/ Slow Rapid
Production 4.1. Staphylococcus spp – most common pathogen;
Tensile strength Strong Low causes Acute Osteomyelitis which can later become
Present in adult Normal Abnormal chronic
skeleton
Found in bone Rare Usual 4.2. Mycobacterium tuberculosis - Tuberculosis of
forming tumor the bone is caused by a primary focus elsewhere in
Pathologic Reaction to Reaction to the body, usually the lungs or lymph nodes
formation persistent rapidly
stress and growing 4.2.1. Pott’s Disease (Tuberculous Spondylitis)
slowly tumor or – Tuberculosis affecting the bodies of the
growing virulent vertebrae, sparing the lamina spines and
tumors infection the adjacent vertebrae.
– there is little or no reactive bone formation,
2. DEVELOPMENTAL ABNORMALITIES IN collapse of the affected vertebra is usual,
afterwhich kyphosis and scoliosis ensue
BONE CELLS, MATRIX AND STRUCTURE
2.1. Disorders of the Growth Plate
2.1.1. Achondroplasia – an autosomal dominant 4.2.2. Tuberculous Osteomyelitis of the Long
Bones – least common bone manifestation of
disorder, the main pathology is on the reduction in
the proliferation of the chondrocytes in the growth tuberculosis; occurs near the joint; the greater
trochanter of the femur is a common site.
plate; major cause of dwarfism

INFLAM, NEOPLASIA
4.2.3. Skeletal Syphilis – – Osteoid Osteoma – benign, asso with a

Congenital Syphilis – osteochondritis and “nidus” on x-ray
periostitis – Osteoblastoma – has both osteoma and
Acquired Syphilis – begins in the tertiary stage osteosarcoma features
Characteristic findings: – Osteosarcoma – most common primary
-frequently involves the nose(saddle nose matrix producing malignant bone tumor
deformity due to destruction of the vomer), palate, bimodal age distribution - 70% occurs in
skull and extremities; patients younger than 20 y/o; second peak
-saber shin – massive periosteal bone deposition in the elderly associated with history of
on the medial and anterior surface of the tibia bone infarcts, irradiation and Paget’s
causing anterior bowing; disease;
-characterized by edematous granulation tissue associated with mutations of the RB gene;
containing numerous plasma cells and necrotic about 60% occur about the knee (distal
bone; femur and proximal humerus;
-gummas – centers of coagulated, necrotic material radiologic signs: permeative growth
and margins composed of plump, palisading pattern; Codman’s triangle (due to
macrophages and fibroblasts surrounded by large periosteal upliftment); soft tissue
numbers of mononuclear leukocytes component (due to rapid growth-
doubling time is only about 3-4 weeks);
4.2.4. Morphologic variants of osteomyelitis: sunburst appearance (due to osteophyte
Brodie abscess – morphologic variant of formation in the soft tissue component);
osteomyelitis characterized by small intraosseous may have 4-fold increase in serum alk
abscess that frequently involves the cortex and is phos levels (due to ↑↑↑↑bone matrix
walled off by reactive bone production)
Sclerosing Osteomyelitis of Garre – morphologic *Most common subtype arises in the metaphysis of
variant of osteomyelitis that is associated with long bones, is primary, solitary, intramedullary,
extensive new bone formation and typically develops poorly differentiated, osteoblastic
in the jaw
7.2.2. Chondoid (Cartilage) forming tumors
– Osteochondroma – most common
5. OSTEONECROSIS (Avascular Necrosis / Aseptic benign bone tumor; bone polyp;
Necrosis) – refers to the death of bone and marrow bony stalk and a cartilaginous cap
in the absence of infection – Chondroma or Enchondroma -
benign
6. NON-NEOPLASTIC TUMOROUS – Chondroblastoma – benign;
CONDITIONS OF THE BONE young adults; chickenwire
6.1. Simple Bone Cyst – most common at the appearance
proximal metadiaphysis of humerus; fallen fragment – Chondrosarcoma - Second most
sign; contains white chylous material common malignant matrix-
producing bone tumor;
6.2. Aneurysmal Bone Cyst – contains bloody usually seen in ≥ 40y/o;
material; differentiated from hemangioma and 2 Male : 1 Female;
arterio-venous malformation because of absence of associated with pre-existing
endothelial lining enchondroma;
central portions of the
6.3. Eosinophilic Granuloma – aka skeleton;rarely involves the distal
Histiocytosis X; may present as punchhole lesions in extremities;
the skull like Multiple Myeloma; not a tumor because popcorn appearance on xray;
it is form of chronic inflammation; Histiocytes and prognosticating factors: grade
mixed leukocytes with slight predominance of (usually low grade), size
eosinophils on histology
7. BONE TUMORS 7.2.3. Fibrous and Fibro-osseous Lesions of the
Bone-
7.1. Metastatic (Secondary) Bone Tumors - the - Nonossifying Fibroma
most common form of skeletal malignancy; 75% - Fibrous Dysplasia – Chinese
originates from CA of the prostate(characterized by characters on histopath
blastic NOT lytic lesions), breast, kidney, thyroid - Fibroblastic collagen-producing bone
(mostly from Follicular CA or Papillary CA Follicular sarcomas
Variant) and lungs; pathways of spread include 1) Fibrosarcoma – see soft tissue
direct extension, 2) lymphatic or hematogenous tumor notes
dissemination and 3) intraspinal seeding Malignant Fibrous Histiocytoma
– see No. 7.
7.2. Primary Matrix Producing Bone Tumors –
7.2.1. Osteoid (Bone) matrix producing

INFLAM, NEOPLASIA
7.2.4. Giant cell tumor of the bone body granulomas surrounding urate crystals in the
(Osteoclastoma) affected joint
– benign locally aggressive
neoplasm; 8.4. Infectious arthritis – kissing bones on
– arises in patients with fused bone xray due to narrowing of the joint space; pannus
plates; formation; Staphylococcus sp. is the most common
– believed to have a monocyte- pathogen; synovial fluid can become purulent; most
macrophage lineage; commonly affected: knee followed by hip
– majority arise around the knee
(distal femur and prox tibia); 8.5. Tumors and Tumor-like Lesions of Joints –
– high recurrence rate (40-60%) True neoplasms of the joints are rare. Ganglion
– can metastasize to the lungs cysts, Baker cyst, Synovial Chondromatosis
– malignant dedifferentiation may and Pigmented Villonodular Synovitis, and
occur Nodular Tenosynovitis (aka Giant cell tumor of
– soap-bubble appearance on x- the tendon sheath) are amongst the tumor and
ray tumor-like lesions seen in the joints.
– sheets of mononuclear cells
punctuated by osteoclast-like giant 9. SOFT TISSUE TUMORS – mesenchymal
cells proliferations that arise in the extraskeletal , non-
– can be seen in multiple sites epithelial tissue of the body
(instead of brown tumor) in pxs
with hyperparathyroidism 9.1. LIPOSARCOMA – tissue of origin: fat;
benign counterpart: LIPOMA
7.2.5. Small Round Cell Tumors of the Bone H&E - immature fat cells or lipoblasts
– Malignant Lymphoma and Special Stains - Oil Red O
Multiple Myeloma – most common Immunohistochemistry - Vimentin
primary malignant bone tumor Cytogenetics – in myxoid and round cell
- Ewing’s Tumor and Primitive variant of liposarcoma: t(12;16) (q13;p11)
Neuroectodermal Tumor (PNET) Cytogenetics – in conventional LIPOMA:
- second most common group of rearrangements of 12q14-q15, 6p, 13q
sarcomas in children; – in pleomorphic LIPOMA:
youngest average age of rearrangements of 16q and 13q
presentation of all bone tumors;
boys > girls; 9.2. FIBROSARCOMA – tissue of origin:
fusion of EWS gene on 22q12 to a fibroblasts; benign counterpart: FIBROMA
member of the ETS family of H&E - pleomorphic spindle-shaped cells in a
transcription factor, mainly FLT 1; herringbone pattern (45° angle insertion) with
CD-99 (+), LCA (-); Onion skin mitotic figures present
appearance on xray due to Special Stains - Trichrome-Masson (green)
alternating lytic and blastic processes Immunohistochemistry - Vimentin
Cytogenetics - trisomies in Chromosomes 8,
11 and 17
8. DISEASES OF THE JOINT
8.1. Osteoarthritis – The single most common 9.3. MALIGNANT FIBROUS HISTIOCYTOMA
form of joint disease; a slowly progressive – tissue of origin: fibroblast+histiocytes; benign
destruction of the articular cartilage (eburnation) counterpart: FIBROUS HISTIOCYTOMA
that is manifested in the weight bearing joints H&E - spindled fibroblast-like cells in a
and fingers of older persons or the joint of younger storiform/cartwheel pattern with
persons subjected to trauma rounded histiocyte-like cells
Special Stains - Trichrome-Masson (green)
8.2. Rheumatoid arthritis – a systemic, Immunohistochemistry - Vimentin
chronic inflammatory disease in which chronic
polyarthritis involves diarthrodial joints 9.4. RHABDOMYOSARCOMA – tissue of origin:
bilaterally; rice bodies (due to hyperplasia of the skeletal muscles; benign counterpart:
synovial tissues); asso with Rheumatoid factor RHABDOMYOMA
(presence of lots of lymphocytes in hyperplastic H&E – tadpole-shaped/racket-shaped
synovium); joint effusion is a prominent sign rhabdomyoblasts characterized by abundant
eosinophilic cytoplasm
8.3. Gouty arthritis – caused by deposition of Special Stains - phosphotungstic acid-
urate crystals in the joints; most commonly affected: hematoxylene, Trichrome-Masson (red)
big toe ff by knees; The clinical course of gout Immunohistochemistry - Vimentin, actin,
maybe divided into 1) asymptomatic hyperuricemia ( desmin, MYOD1, myogenin
↑BUA), 2) acute gouty arthritis, 3) intercritical gout, Electron Microscopy - Z-line
and 4) chronic tophaceous gout. *Tophi are foreign Cytogenetics -

INFLAM, NEOPLASIA
*SARCOMA BOTRYOIDES (seen as
bunch of grapes in young children) is another
name for EMBRYONAL RHABDOMYOSARCOMA
9.5. LEIOMYOSARCOMA – tissue of origin:
smooth muscles; benign counterpart: LEIOMYOMA
(most commonly grows in the myometrium)
H&E - spindle cells with blunt-ended cigar

shaped nuclei intersecting at right (90°) angles
Immunohistochemistry - vimentin, smooth

muscle actin, desmin
Cytogenetics - Translocation t (12;14) is often
present in leiomyomas. Hereditary leiomyomatosis
associated with renal cell carcinoma is transmitted
as an autosomal dominant trait involving 1q42.3. It
has been found out, however, that t(12,14) is not
the genetic abnormality seen in most cases of
Leiomyosarcoma and thus, at present,
Leiomyosarcomas are not believed to be a
malignant degeneration originating from
9.6. SYNOVIAL SARCOMA – tissue of origin:

synovial tissues; benign counterpart: None
H&E - biphasic pattern showing 1) spindle
cells resembling fibrosarcoma and 2)
epithelial cells
Immunohistochemistry - 1) (+) Vimentin 2) (+)

Cytokeratin and EMA
ABS/leli

REVIEW TEST
ALITA B. SANTOS, MD
CELL ADAPT, INJURY AND DEATH, C. Glomerular capillary hydrostatic pressure

HEMODYNAMICS, INFLAMMATION AND is increased
REPAIR, NEOPLASIA D. Glomerular capillary oncotic pressure is
REVIEW TEST deceased
(These questions were all taken from the September 2017
Board Examinations) _____7. A 4 y/o child presents with temperature of
40C which she has had for four days. On physical
_____1. The tissue that is most resistant to invasion examination, she is noted to have conjunctivitis, an
of cancer cells: erythematous rash, cervical lymphadenopathy and
A. Bone B. Heart swollen hands and feet. Laboratory findings include
C. Cartilage D. Spleen an absolute neutrophilic leukocytosis, left shift,
normal platelets and elevated erythrocyte
_____2. Which of the following is LEAST likely sedimentation rate (ESR). Which of the following is
related to malignancy? the most likely diagnosis?
A. Hepatoma B. Sarcoma A. Scarlet fever
C. Myoma D. Seminoma B. Kawasaki syndrome
C. Acute rheumatic fever
_____3. Combined hypertrophy and hyperplasia are D. Disseminated lupus erythematosus
most likely to occur on:
A. Post-menstruation endometrium _____8. The most frequent finding in the adrenal
B. Skeletal muscle of an athlete who “pumps gland of patients with Addison disease is:
iron” A. Atrophy
C. Left ventricular myocardium in a patient B. Infarction
with aortic stenosis C. Metastatic Carcinoma
D. Enlarged prostate gland D. Tuberculosis
_____4. A 60 y/o man comes to your clinic with a 2 _____9. A 35 y/o woman complains of nausea,
month history of coughing up blood. You suspect fatigue and loss of appetite of about 1 month
tuberculosis and take a sample to identify the duration. Her liver enzymes are slightly elevated. A
microorganism and to determine the antibiotic needle biopsy of her liver is taken and you diagnose
sensitivity. You place your patient on standard chronic active hepatitis. What is the inflammatory
antibiotic treatment for tuberculosis while awaiting cell type in this liver section?
the laboratory results. However, the man died 7 A. Monocytes
days after the first clinic visit. Histopathologic C. Polymorphonuclear leukocytes
findings show multinucleated giant cells with nuclei B. Cytotoxic T-lymphocytes
arranged like a horseshoe (Langhans giant cells) and D. Mast cells
foreign body giant cells. How would you diagnose
these lesions? _____10. A 36 y/o morbidly obese primigravida
A. Acute inflammation presented at the ER at 17 weeks gestational age
B. Chronic inflammation complaining of abdominal pain. At clinical
C. Granulomatous inflammation examination, the uterus appeared to be of higher
D. Metaplasia volume compared to the gestational age. The
abdomen was painful but treatable and the
_____5. At the time carcinoma of the esophagus is obstetrical exam was normal. The patient was then
discovered in most patients, the tumor cells have referred to the Obstetrics Department for further
spread beyond its local confines. The early spread is evaluation. The sonographic assessment shows
most likely ascribed to: three subserous uterine myomas located on the
A. Histological type of the tumor anterior wall, the right wall and the left wall of the
B. Rich esophageal submucosal lymphatics uterus, respectively. All myomas were vacuolated
C. History of alcoholism inside as for suspected necrosis. The scan also
D. History of chronic tobacco abuse showed other multiple myomas greater than 3 cm in
size. Vital signs were monitored BP 140/90mmHg.
_____6. A 7 y/o boy presents to the physician with Maternal heart rate 124 bpm, SO2 94%, apyretic).
acute onset edema and facial swelling. Dipstick Amniotic fluid was normal and fetal well-being was
urinalysis revealed proteinuria. Renal biopsy showed preserved. Endometrial biopsy showed uterine
no appreciative changes under light and fibroids with whorled (fascicular) pattern of smooth
immunofluorescence microscopy but electron muscle bundles separated by well-vascularized
microscopy demonstrates glomerular epithelial cell connective tissue. The most likely cellular adaptation
process effacement. A diagnosis of minimal change for the case is:
disease is made. How does sthe disease affect the A. Hypertrophy
pressures governing the flow of fluid across the B. Atrophy
glomerulus? C. Metaplasia
A. Bowman’s space hydrostatic pressure is D. Dysplasia
increased
B. Bowman’s space oncotic pressure is
decreased
UST FMS MEDICAL BOARD REVIEW 2019 | PATHOLOGY

REVIEW TEST
ALITA B. SANTOS, MD
_____11. A 26 y/o man developed recurrent _____15. A 55 y/o woman with hypercalcemia
episodes of Neisseria gonorrhea. His 25 y/o brother discovered as an incidental finding during a normal
also suffered gonorrheal infections. A genetic work- routine physical examination (Including pelvic and
up revealed a deficiency in the C3b component of breast examination) most likely has which of the
complement of both areas. What functions of the following?
inflammatory response would be affected in these A. Sarcoidosis
individuals? C. Metastatic breast cancer
A. Chemotaxis B. A history of taking thiazide diuretics
B. Anaphylaxis D. A benign parathyroid adenoma
C. Vascular permeability
D. Phagocytosis _____16. The principal cause of multi-organ
dysfuction syndrome associated with septic shock is
_____12. A 65 y/o man with a 40 pack-year history the following?
of smoking presents with a 7 kg weight Loss over A. Direct invasion multiple organs during
the last 3 months and recent onset of streak of gram-negative bacteremia
blood in the sputum. Physical examination reveals a B. The release of cytotoxic exotoxins by
thin, afebrile mas with clubbing of the fingers, an gram-negative bacteremia
increased anteropostero diameter, scattered coarse C. Induction of pro-inflammatory cytokines
ronchi and wheezes over both lung fields and distant (TNF, IL-1 and IL-6)
heart sounds. A chest x-ray exhibit left hilar D. Drug-induced toxicity during therapy for
adenopathy, dilated tubular markings and flattened gram-negative bacteremia
diaphragms. A sputum cytology using Papanicolaou’s
stain shows numerous cells with deeply eosinophilic _____17. The most common primary malignant
staining cytoplasm and irregular, hyperchromic tumor of the ovary:
nuclei intermixed with inflammatory cells. Which of A. Endometrioid carcinoma
the following is the most likely diagnosis? C. Serous cystadenocarcinoma
A. Tuberculosis B. Mucinous cystadenocarcinoma
C. Bronchiectasis D. Yolk-sac tumor
B. Pulmonary embolism and infarction
D. Squamous cell carcinoma of the lungs _____18. Routine gynecological cytologyrevealed a
CIN Grade 3 (Severe dysplasia, carcinoma-in-situ) in
_____13. A malnourished child was brought to lying- a 27 y/o woman. Salient features of the biopsy
in clinic because of breathing difficulties. He was the shows carcinoma-in-situ extend downwards into
seventh child born to a couple in Tondo, Manila. The glandular structures. The lumen of the cervical canal
father delivered the baby at home, which the is at the top. The epitheliuim has migrated into an
parents did not weigh at birth. Initially the mother undelying branching gland of the cervix displacing
breast-fed the baby until nipple bleeding forced her the columnar epithelium and practically filling the
to stop at 2 ½ months thes shifted to formula milk. lumen of the glands. The basement membrane is
In the course of feeding, the patient’s parents intact. Question: Significant risk factors for
believed their child had a milk allergy and developing this lesion include all of the following,
consequently restricted his daily intake. Dietary EXCEPT:
history revealed a prolonged, inadvertent A. History of prostitution
administration of a restricted diet, deficient in B. Lack of circumcision of male sex partners
protein and several other nutrients. Consequently, C. Early age of first sexual intercourse
the child with his life-threatening condition died 5 D. History of penile condyloma in male sex
hours later and ruled out as child neglect by the partners
DSWD representative. In the autopsy, the
pathologist found no evidence of dehydration on the _____19. Which lobe of the prostate is cancer most
ocular chemistries and ruled that ”malnutrition” was commonly found?
the immediate and underlying cause of death. A. Anterior lobe
Question: what is the wear and tear pigment that B. Posterior lobe
has been inculpated in cases of malnutrition? C. Lateral lobe
A. Lipofuscin D. Median lobe
B. Ceroid
C. Hemosiderin _____20. Sputum cytology is most likely to be
D. Melanin positive for cancer cells in a patient with:
A. Left upper lobe atelectasis
_____14. The presence of elevated alpha feto- B. Solitary pulmonary nodules
protein in the serum strongly suggests the following C. Adenocarcinoma
conditions, EXCEPT: D. Lymphoma
A. Neural tube defect
C. Yolk sac tumor _____21. A 35 y/o woman visits her physician after
B. Neuroendocrine tumor feeling ahard lump in her neck. Her physician notes
D. Hepatocellular carcinoma that she has a single, hard, non-tender nodule in the
left lobe of the thyroid that moves when she
swallows. There is no cervical lymphadenopathy.
REVIEW TEST
ALITA B. SANTOS, MD
The patient denies any changes in her health. The _____29. “Blushing” is a localized hemodynamic
patient does not have tremor, restlessness, heat dysfunction of:
intolerance or an increased level of anxiety. Blood A. Active hyperemia
test show normal thyroid hormone and calcitonin B. Acute passive hyperemia
levels. A scintiscan shows a cold nodule in the left C. Chronic passive congestion
lobe of her thyroid. Tissue is obtained and a D. Hypovolemia
histological section shows branching papillae with a
fribovascular stalk. These papillae are lined by _____30. A 35 y/o man who works at a facility
epithelial cells with empty-looking, ground glass processing highly radioactive substance accidentally
nuclei often called “Orphan Annie eye” receives a high whole body dose of ionizing radiation
nuclei.Concentrically calcified psamomma bodies are estimated to be 1, 500 rads. He dies 1 week later. At
also seen. Which of the following types of tumors autopsy, histologic examination of the skin shows
would most likely result in these findings? scattteered, individual epidermal cells with shrunken
A. Follicular carcinoma markedly acidophilic cytoplasm and pyknotic
B. Medullary carcinoma fragmented nuclei. These morphologic changes most
C. Multinodular goiter likely indicate which of the following processes?
D. Papillary carcinoma A. Apoptosis
B. Coagulation necrosis
_____22. Dysplastic nevus is to melanoma as actinic C. Liquefaction necroisis
keratosis is to: D. Tumor initiation
A. Basal cell carcinoma
B. Kaposi’s sarcoma _____31. Edema due to the following pathologic
C. Squamous cell carcinoma mechanisms is correctly matched with each clinical
D. Lentigo maligna setting, EXCEPT:
A. Increased capillary hydrostatic pressure –
_____23. The pleural effusion associated with the Malignancy
following is an exudate, EXCEPT: B. Decreased plasma oncotic pressure
A. Congestive heart failure Nephrogenic syndrome
B. Pulmonary tuberculosis C. Increase vascular permeability – Trauma
C. Metastatic carcinoma and inflammation
D. Mesothelioma D. Lymphatic blockage – Elephantiasis
_____24. Lesions mistaken clinically as malignant _____32. A predominant factor in the formation of
are the following, EXCEPT: ascites in cirrhosis is:
A. Acral lentiginous C. Papilloma A. Peripheral vasoconstriction
B. Ameloblastoma D. Hemangioma B. High serum oncotic pressure
C. Peritoneal inflammation
_____25. A hamartomatous polyp associated with a D. Renal sodium avidity
syndrome that increase risk of developing cancer in
the pancreas, breast or lung: _____33. High power photomicrograph
A. Hyperplastic polyp demonstrates shadowy outlines of dead fat cells.
B. Peutz-Jeghers polyp There is a bluish cast from the calcium deposists
C. Tubular adenoma which are basophilic. Gross pathology shows chalky,
D. Juvenile polyp white areas from the combination of the newly
formed free fatty acids with calcium (saponification).
_____26. Which lesion is mostly to be associated This pancreas shows sign of:
with breast malignancy? A. Coagulation necrosis
A. Phylloides tumor B. Liquefaction necrosis
B. Paget’s Disease of the Breast C. Caseation necrosis
C. Mammary Duct Ectasia D. Enzymatic fat necrosis
D. Intraductal Papilloma
_____34. A 78 y/o man with disseminated
_____27. Which of the following primary carcinoma treated with chemotherapy died of
malignancies does not commonly metastasize to pulmonary complications. Gross examination of the
bone? lungs showed areas of consolidation. The final
A. Thyroid C. Lung diagnosis of Aspergillosis was made at autopsy.
B. Prostate D. Colon Question: Which of the following lesions LEAST likely
in the lungs infected by the fungus?
_____28. Which of the following types of A. Proliferation with preexisting pulmonary
hepatocellular injury is commonly seen after cavities
acetaminophen overdose? B. Granulomatous inflammation
A. Acute hepatitis C. Necrotizing pneumonia
B. Centrilobular necrosis D. Focal hemorrhagic necrosis
C. Granuloma formation
D. Microvascular fatty change

REVIEW TEST
ALITA B. SANTOS, MD
_____35. A 19 y/o man comes to the emergency

Department because of blood in his sputum. On
history, the patient mentions he has had weight loss
and night sweats. On examination, the patient has a
fever and bronchial breath sounds with crepitant
rales.Laboratory tests show lymphocytosis and an
increased erythrocyte sedimentation rate. X-ray film
of the chest showed a calcified lung lesion and hilar
lymphadenopathy. Which of the following is the
stain used to identify the most likely infectious
organism?
A. Congo red
B. Giemsa Stain
C. Periodic acid-Schiff
D. Ziehl-Nielsen
_____36. A patient who has had an aortic valve

replacement is on therapeutic doses of Warfarin
(Coumadin). She is most likely to have a normal
level of which factor?
A. Factor VII
B. Protein C
C. Factor V
D. Factor X
_____37. What is the main cause of Acute Tubular

Necrosis other than ischemic injury?
A. Medication
B. Vasculitis
C. Hypertension
D. Systemic lupus erythematosus

NEOPLASTIC HEMATOPATHOLOGY
ALEJANDRO E. AREVALO, MD
I. Neoplastic Hematopathology Malignant Lymphomas

♣ 2/3 NHL and virtually all cases of HL
Bone marrow nontender nodal enlargement (often >2
- Pleuripotent stem cells in the bone marrow cm)
give rise to two types of multipotent stem cells: ♣ 1/3 NHL – extranodal sites (skin, stomach,
1. Non-lymphoid stem cells brain)
Differentiate in the bone marrow ♣ Leukemic forms – suppression of normal
Form circulating erythrocytes, granulocytes, hematopoiesis; infiltrate and enlarge the
monocytes and platelets spleen and liver
2. Lymphoid stem cells ♣ Plasma cell neoplasm – local “lytic” bony
Differentiate in the bone marrow and then destruction
migrate to the lymphoid tissues
Undergo differentiation to form B and T- Non-Hodgkin’s Lymphoma (NHL)
lymphocytes of the immune system ♣ Vast majority of lymphoid neoplasms (80
85%) are of B-cell origin, with most of the
White blood cells remainder being T-cell tumors
♣ Lymphoid neoplasms (lymph nodes) ♣ Only rarely are tumors of NK or histiocytic
origin non-Hodgkin’s lymphoma
♣ Myeloid neoplasms (bone marrow)
1. Acute myelogenous leukemias
Clinical features:
immature progenitor cells
♣ Four entities constitute the majority of
2. Myelodysplastic syndromes
Lymphoid lymphomas and leukemias in
ineffective hematopoiesis and peripheral
adults:
blood cytopenias
1. Follicular lymphoma
3. Chronic myeloproliferative diseases
2. Diffuse large B-cell lymphoma
increased production of one of more
3. Chronic lymphocytic
terminal differentiated myeloid elements
eukemia/small lymphocytic
leading to elevation of peripheral blood
leukemia
counts
4. Multiple myeloma
♣ Two groups are most common in children
AML
and young adolescents:
 Myeloproliferative Disorders
1. Acute lymphoblastic
 Chronic Myelogenous Leukemia
leukemia/lymphoma
 Polycythemia Vera
2. Burkitt lymphoma
 Essential Thrombocythemia
 Primary Myelofibrosis
Hodgkin Lymphoma (WHO Classification)
Lymphoid neoplasms
Spleen
♣ Lymphoma – proliferation arising as discrete
♣ Hypersplenism – triad of splenomegaly,
tissue masses
Reduction of one or more of the cellular
1 Hodgkin lymphoma
elements of the blood and correction by
2. non-Hodgkin’s lymphoma
splenectomy
3. Plasma cell neoplasms (terminally
♣ Congestive splenomegaly – persistent or
differentiated B-cells arising in the bone
Chronic venous congestion;
marrow)
- cirrhosis of the liver is the only
common cause of striking
♣ Leukemia – widespread involvement of the
congestive splenomegaly;
bone marrow accompanied by presence of
large numbers of tumor cells in the peripheral
Other causes: obstruction of the extrahepatic portal
blood. (ex: acute lymphoblastic leukemia)
vein or splenic vein.
Classification of Lymphomas
♣ Splenic infacts – occlusion of the major
2001 World Health Organization (WHO)
splenic artery; almost always due to
Classification(Hemato-lymphoid tumors)
emboli that arise in the heart
♣ Neoplasms –
Represent the FIRST TRUE international consensus
1. Benign: lymphangiomas,
on lymphoma classification (2001)
hemangiomas, fibromas, osteomas,
chondromas
The classification includes all lymphoid neoplasms
2. Splenic involvement by leukemias and
Hodgkin Lymphoma
lymphomas
Non-Hodgkin’s Lymphoma
♣ Splenic rupture – caused by a crushing
Lymphoid leukemias –circulating phases
injury or
Plasma cell neoplasms
severe blow; in the absence of trauma, it
is designated as spontaneous rupture
♣ Spontaneous rupture – infectious
mononucleosis,
UST FMS MEDICAL BOARD REVIEW 2019 1 | PATHOLOGY
malaria, typhoid fever, leukemia and acute Other causes:

splenitis 3. Anemia of chronic disease
4. Marrow stem cell failure (aplastic anemia,
Thymus pure cell cell aplasia and anemia of renal
♣ Thymic hypoplasia or aplasia – seen in failure)
DiGeorge syndrome (total absence or
severe lack of cell mediated immunity and Hypochromic anemia
hypoparathyroidism). IRON DEFICIENCY ANEMIA
♣ Thymic Hyperplasia – appearance of ♣ Commonest nutritional deficiency disorder
Lymphoid follicles within the thymus present throughout the world
(thymic follicular hyperplasia) ♣ Pathogenesis:
1. When the supply of iron is inadequate for
1. Most frequently encountered in myasthenia the equirement of hemoglobin synthesis
gravis 2. Development depends upon one or more of
2. Grave’s disease, Systemic lupus
erythematosus, Scleroderma, Rheumatoid The following factors:
arthritis Increased blood loss
♣ Thymomas – tumors of thymic epithelial cells Increased requirements
(anterosuperior mediastinum) Inadequate dietary intake
Decreased intestinal absorption
Divided into:
 Benign or encapsulated thymoma Development of anemia progresses in 3 stages:
(cytologically and biologically benign) Storage iron depletion
 Malignant thymoma  Iron-deficient erythropoiesis
 Type 1 (invasive thymoma) – cytologically  Frank iron deficiency anemia
benign, but biologically aggressive and
capable of local invasion Bone marrow findings:
 Type II (thymic carcinoma) – cytologically Not essential in such cases
malignant with all of the features of cancer Marrow cellularity is increased (erythroid
and comparable behavior hyperplasia – M:E ratio is decreased)
Erythropoiesis is normoblastic with
II. Non-neoplastic Hematopathology predominance of micronormoblasts (small
polychromatic normoblasts) –cytoplasmic
Anemia maturation lags behind causing late
♣ Hemoglobin concentration in blood below the normoblasts to have pyknotic nucleus but
lower limit of the normal range for age and sex persisting polychromatic cytoplasm.
of the individual Myeloid, lymphoid and megakaryocytic cells
♣ 13 g/dL for males; 11.5 g/dL for females; are normal in number and morphology
newborn infants 15 g/dL at birth; 9.5 g/dL at 3 Marrow iron: deficient reticuloendothelial
months iron stores and absence of siderotic iron
♣ Other parameters: granules from developing normoblasts.
1. Red cell count
2. Hematocrit (PCV) Peripheral blood: microcytic and hypochromic
3. Absolute values (MCV, MCH, MCHC) erythrocytes
Classification of Anemia Biochemical:

♣ Two widely accepted classifications are based of  Serum iron level is low (often under 50ug/dL
pathophysiology and morphology: (NV:80-180 ug/dL)
 Total iron binding capacity (TIBC) is high;
Pathophysiologic classification, 3 groups: reduced in anemia of chronic disease
Anemia due to impaired red cell production  Serum ferritin – very low indicating poor
Anemia due to increased red cell destruction tissue iron stores (High in iron overload and
(hemolytic anemias) normal in anemia of chronic disorders)
Anemia due to increased blood loss  Red cell protoporphyrin is very low due to its
accumulation within red cells as a result of
ANEMIAS OF DIMINISHED ERYTHROPOIESIS insufficient iron supply to form heme
♣ Results from a deficiency of some vital
Substances for red blood cell formation Megaloblastic anemia
1. Vit B12 and folate – characterized by ♣ Two principal types:
defective DNA synthesis (megaloblastic 1. Pernicious anemia – major form of Vitamin
anemia) B12 deficiency anemia
2. Iron deficiency anemia – heme synthesis is 2. Folate deficiency anemia
impaired ♣ Impaired DNA synthesis
♣ Erythroid precursor cells and erythrocytes are
abnormally large

♣ Neutrophils are larger than normal ♣ Results from failure or suppression of

(macropolymorphonuclear) and are multipotent myeloid stem cells, with inadequate
hypersegmented (5-6 or more nuclear lobes) production or release of differentiated cells
♣ Most cases (known etiology) follow exposure to
Pernicious anemia chemicals and drugs
♣ Cause: atrophic gastritis with failure of production ♣ Myelotoxins: benzene, chloramphenicol,
of intrinsic factor alkylating agents, antimetabolites (6
♣ Diagnostic features: mercaptopurine, vincristine and busulfan).
1. Moderate to severe megaloblastic anemia ♣ Whole-body irradiation
2. Leukopenia with hypersegmented ♣ Infections (HIV-1, viral hepatitis –non-A, non-B,
granulocytes non-C and non-G types),
3. Mild to moderate thrombocytopenia
4. Neurologic changes Fanconi’s anemia – autosomal recessive disorder
5. Achlorydia even after histamine release characterized by defects in DNA repair; accompanied
6. Inability to absorb an oral dose of cobalamin by multiple congenital anomalies (hypoplastic kidney
7. Low serum levels of vitamin B12 and spleen, hypoplastic anomalies of bone,
8. Excretion of methylmalonic acid in the urine particularly involving the thumbs and radii)
9. Striking reticulocyte response and ♣ Reticulocytosis is not present
improvement in hematocrit levels after ♣ Absent splenomegaly
parenteral administration of vitamin B12
Pure red cell aplasia
Anemia of Folate Deficiency ♣ Specific aplasia of the erythroid elements
♣ Deficiency of folic acid (pteroylmonoglutamic acid) ♣ Can be primary or secondary (thymoma or large
♣ Three major causes of folic acid deficiency: granular lymphocyte leukemia)
1. Decreased dietary intake
2. Increased requirements Other forms of marrow failure:
3. Impaired use ♣ Space occupying lesions that destroy significant
♣ No neurologic changes amounts of bone marrow or perhaps disturb
♣ Recognition: the marrow architecture depress its productive
1. Decreased folate levels in the serum or red capacity (myelophthisic anemia)
cells
2. Increased excretion of FIGlu after an HEMOLYTIC ANEMIAS
administered dose of histidine ♣ Premature destruction of the red cells
1. Extravascular (mononuclear phagocyte
Anemia of chronic disease system)
♣ Most common cause of anemia in hospitalized Hereditary spherocytosis and sickle cell
patients anemia
♣ Associated with reduced erythroid proliferation 2. Intravascular
and impaired iron ultilization; mimic iron Hemoglobinemia, hemoglobinuria,
deficiency. methemalbuminemia, jaundice and
♣ Bone marrow failure due to systemic diseases hemosiderinemia
(anemia of chronic disorders) ♣ Accumulation of hemoglobin catabolic products
1. Anemia of inflammation/infections, ♣ Marked increase in erythropoiesis within the
disseminated malignancy Bone marrow
2. Anemia in renal disease Hemolysis, anemia and jaundice, Hemoglobinuria
3. Anemia due to endocrine and nutritional from intravascular hemolysis
deficiencies (hypometabolic states)
4. Anemia in liver disease Hereditary spherocytosis
♣ Inherited disorder (autosomal dominant –
♣ Chronic illnesses associated with this form of 75%); intrinsic defect in the red cell membrane
anemia can be grouped into three categories: ♣ Spheroidal shape of the erythrocyte – defect in
1. Chronic microbial infections the skeleton of the red cell membrane
(osteomyelitis, bacterial endocarditis, ♣ Deficiency of spectrin – most common
and lung abscess) Biochemical abnormality in patients with all
2. Chronic immune disorders (rheumatoid forms of HS,
arthritis and regional enteritis)
3. Neoplasms (Hodgkin lymphoma, Associated with reduced membrane stability and
carcinomas of the lung and breast) loss of membrane fragments
♣ Splenectomy – beneficial effect
♣ Features: low serum iron and reduced iron-binding
capacity associated with abundant stored iron G6PD deficiency
(defect in the reuse of iron). ♣ Reduced ability of the red cells to protect
themselves against oxidative injuries
Aplastic anemia ♣ Reduced glutathione catalyzes the breakdown
♣ Pancytopenia (anemia, neutropenia and of oxidative compounds (H2O2)
thrombocytopenia)
♣ Several variants alpha chain synthesis; precipitated as Heinz

o G6PD B – most common normal form bodies)
o G6PD A - and mediterranean ♣ Two alpha-gene deletion – alpha thalassemia
trait (asymptomatic; suspected in a patient of
♣ Protective against malaria refractory microcytic hypochromic anemia in
♣ Stimulus for hemolysis whom iron deficient anemia and beta
o Drugs (antimalarials, sulfonamides, thalassemia minor have been excluded)
nitrofurantoins) ♣ One alpha gene deletion – alpha thalassemia
o Infections (hepatitis, pneumonia and Trait (silent carrier state)
typhoid)
♣ Hemolysis is both intravascular and PATHOPHYSIOLOGY:
extravascular ♣ Alpha thalassemia major – inability to
♣ Denaturation of hemoglobin and formation of synthesize adult hemoglobin
precipitates (Heinz bodies) ♣ Alpha thalassemia trait – reduced production of
normal adult hemoglobin
Sickle cell disease
♣ Production of abnormal hemoglobin Beta- Thalassemia
♣ Normal adult hemoglobin: HbA (96%) HbA2 ♣ Arise from different types of mutations of Beta
(3%) HbF (1%) globin gene resulting from single base changes.
♣ Point mutation leading to substitution of valine ♣ Decreased rate of Beta-chain synthesis resulting
For glutamic acid at the sixth position of the in reduced formation of HbA in the red cells
Beta globin chain (HbS) ♣ B0 – complete absence of synthesis
♣ Deoxygenation, HbS molecules undergo ♣ B+ - partial synthesis of the beta globin chains
aggregation and polymerization.
♣ Slight protection against falciparum malaria Three types:
♣ Beta-thalassemia major (Homozygous form) –
Factors that affect the rate of sickling: most severe; Mediterranean or Cooley’s anemia
♣ Amount of HbS and interaction with the other 1. B0-thalassemia major
hemoglobin chain in the cell 2. B+-thalassemia major
1. Heterozygote – sickle cell trait ♣ Beta-thalassemia intermedia – intermediate
2. Homozygote – sickle cell anemia degree of severity; does not require regular
♣ Rate of HbS polymerization is affected by the blood transfusions
hemoglobin concentration per cell ♣ Beta-thalassemia minor or trait (Heterozygous
♣ Acidosis (fall in pH) form) – mild asymptomatic condition
♣ Major consequences: ♣ PATHOPHYSIOLOGY:
o Chronic hemolytic anemia ♣ Beta thalassemia major – premature red cell
o Occlusion of small blood vessels destruction brought about by erythrocyte
membrane damage caused by the precipitated
Thalassemia alpha globin chains. Other factors: shortened
♣ Reduced rate of synthesis of one or more of the red cell life-span, ineffective erythropoiesis and
globin polypeptide chains (quantitative hemodilution due to increased plasma volume
abnormalities of polypeptide globin chain ♣ Beta-thalassemia minor – very mild ineffective
synthesis) erythropoiesis, hemolysis and shortening of red
♣ First described in people of Mediterranean cell life span
countries where it derives it name
“Mediterranean anemia” Paroxysmal Noctural Hemoglobinuria
♣ Thalassa in greek means “the sea” – region ♣ Results from a mutation in the
around the Mediterreanean basin phosphatidylinositol glycan A or PIGA (gene
♣ Normal adult hemoglobin (HgA): alpha 2 beta 2 that is essential for the synthesis of the GPI
♣ Classified into alpha and beta thalassemias anchor)
♣ May occur as heterozygous (alpha or beta ♣ Absence of GPI-linked proteins makes the red
thalassemia minor or trait – generally blood cells sensitive to lysis (GPI-linked proteins
asymptomatic) or a homozygous (alpha and inactivate complement)
beta thalassemia major-severe congenital ♣ Three GPI linked proteins that regulate
hemolytic anemia) complement activity
Alpha- Thalassemia 1. CD55 – decay accelerating factor (DAF)
♣ Deletion of one or more of the alpha chain 2. CD59 – membrane inhibitor of reactive
genes (short arm of chromosome 16) lysis (MIRL); most important
(limits spontaneous in vivo
Four types: activation of the alternative
♣ Four alpha gene deletion – Hb Bart’s Hydrops complement pathway by rapid
fetalis (gamma globulin chain tetramer which inactivation of C3 convertase)
has high oxygen affinity leading to severe 3. C8 – binding protein
tissue hypoxia)
♣ Three alpha gene deletion – HgH disease (Beta
globin chain tetramer and markedly impaired
Immunohemolytic anemia microangiopathic hemolytic anemia and

♣ Autoimmune hemolytic anemia thrombocytopenia (absence of neurologic
♣ Major diagnostic criterion: Coombs deficits)
2. Dominance of renal failure
antiglobulin test (capacity of the antibodies prepared Bleeding disorders related to defective
from animals against human globulins to agglutinate platelet functions
red cells if these are present on red cell surfaces) ♣ Congenital
1. Defective adhesion of platelets to the
♣ Classification: subendothelial collagen (Bernard-Soulier
1. Warm antibody type – IgG; does not usually syndrome)
fix complement; active at 37C Inherited deficiency of platelet
2. Cold agglutinin type – IgM; fixes membrane glycoprotein(Ib-IX) –
complement; most active at 0-4C receptor for von Willebrand
3. Cold hemolysins (Paroxysmal cold factor(vWF)
4. hemoglobinuria) – IgG antibodies bind to 2. Defective platelet aggregation
red blood cells at low temperature, fix
complement, cause hemolysis when the glycoprotein (IIb-IIIa).
temperature is raised to 30C 3. Disorders of platelet secretion
Storage pool diseases
Hemolytic anemia resulting from trauma to
red blood cells ♣ Acquired defects of platelet function
♣ Associated with cardiac value prosthesis, 1. Ingestion of aspirin and other NSAIDS
narrowing or obstruction of the vasculature 2. Uremia
♣ Microangiopathic hemolytic anemia –
characterized by mechanical damage to the red Hemorrhagic Diatheses related to
cells as they squeeze through abnormally Abnormalities in clotting factors
narrow vessels ♣ Development of large ecchymoses or
♣ DIC, malignant hypertension, SLE, TTP, HUS hematomas after an injury, or as prolonged
♣ Red cell fragments (schistocytes), burr cells, bleeding after a laceration or any form of
helmet cells and triangle cells. surgical procedures
♣ Acquired disorders (multiple clotting
Anemia due to blood loss abnormalities)
♣ Acute post-hemorrhagic anemia 1. Vitamin K deficiency (depressed synthesis
♣ Anemia of chronic blood loss of factors II,VII, IX and X and protein C)
2. Parenchymal liver diseases
Bleeding disorders 3. DIC
♣ Results from: ♣ Hereditary deficiencies (single clotting factor)
1. Increased fragility of the vessels (bleeding 1. Deficiency of factor VIII (hemophilia A)
caused by vessel wall abnormalities) 2. Deficiency of factor IX (Christmas disease
2. Platelet deficiency/dysfunction (bleeding or hemophilia B)
related to reduced platelet number)
3. Derangements in the coagulation Disseminated Intravascular Coagulation (DIC)
mechanism (bleeding due to coagulation ♣ Acute, subacute or chronic
abnormalities) thrombohemorrhagic disorder occuring as a
secondary complication in a variety of diseases
Idiopathic thrombocytopenic purpura (ITP) ♣ Consumption of platelets, fibrin and
♣ Autoimmune disorder: acute or chronic. coagulation factors and, secondarily, activation
♣ Formation of autoantibodies (IgG) against of fibrinolytic mechanisms.
platelet membrane glycoproteins (IIb-IIIa or ♣ Two major mechanisms that trigger DIC:
Ib-IX) 1. Release of tissue factor or thromboplastic
♣ Opsonized platelets are rendered susceptible to substances into the circulation
phagocytosis. 2. Widespread injury to the endothelial cells
♣ Spleen is the major site of removal for the
sensitized platelets.
♣ Bone marrow: increased number of
megakaryocytes (accelerated thrombopoiesis)
Thrombotic Microangiopathies:TTP/HUS
♣ TTP (thrombotic thrombocytopenic purpura)
1. Adult women and the pentad (fever,
thrombocytopenia, microangiopathic
hemolytic anemia, transient neurologic
deficits and renal failure)
♣ HUS (hemolytic uremic syndrome)
1. onset in childhood and characterized by
REVIEW TEST
ALEJANDRO E. AREVALO, M.D.
CHOOSE THE BEST ANSWER:
________1. A patient with severe anemia showed a _________ 9. The acronym CRAB is associated with
reticulocyte count of 20%. This indicates that the what lesion/neoplasm?
bone marrow demonstrates a/an_______________ A. Diffuse large B-cell lymphoma
state. B. Hodgkin lymphoma
A. Aplastic C. Tuberculosis
B. Hypoproliferative D. Kahler’s disease
C. Hyperproliferative
D. Normal/non-reactive ________ 10. The blast percentage in the WHO
classification for a diagnosis of acute leukemia is
_______ 2. In iron deficiency anemia, which of the A. 10%
following cell/s is/are increased? B. 20%
A. Erythroid islands C. 30%
B. Granulocytic component D. 40%
C. Lymphocyte subsets
D. Megakaryocytes
_______ 3. Which of the following is increased or

present in beta thalassemia?
A. alpha 2 beta 2
B. Beta tetramers
C. Alpha 2 delta 2
D. Alpha tetramers
_______ 4. Hemoglobin Bart is composed of 4

chains of
A. Alpha
B. Beta
C. Delta
D. Gamma
________ 5. The beta globulin gene is located in

A. Chromosome 10
B. Chromosome 11
C. Chromosome 12
D. Chromosome 13
________6. All of the following globulin gene locus

is located in one chromosome, EXCEPT
A. Alpha
B. Beta
C. Delta
D. Gamma
________ 7. Which of the following cell normally

returns to the bone marrow during the maturation
process?
A. B-lymphocyte
B. T-lymphocyte
C. hematogone
D. plasma cell
________ 8. The most common type of non-

Hodgkin’s lymphoma, according to the WHO
classification
A. Follicular lymphoma
B. Diffuse large B cell lymphoma
C. MALToma
D. Peripheral T-cell lymphoma

GENETICS
I. Human Genetic Architecture  less than 2% of the human genome encodes

II. Genes and Human Diseases proteins, whereas more than one half
A. Mutations represents blocks of repetitive DNA
III. Mendelian Disorders sequences whose functions remain
A. Transmission Patterns of Single Gene mysterious.
Disorders  humans have a mere 20,000 to 25,000 genes
1. Autosomal Dominant that code for proteins rather than the
2. Autosomal Recessive 100,000 predicted.
3. X-Linked
B. Biochemichal and Molecular Basis of On average, any two individuals share greater than
Single Gene (Mendelian) Disorders 99.5% of their DNA sequences.
C. Disorders Associated With Defects in  this 0.5% represents about 15 million base
Structural Proteins pairs.
1. Marfan Syndrome  two most common forms of DNA variations:
2. Ehler-Denlos Syndrome o single-nucleotide polymorphisms (SNPs) -
D. Disorders Associated With Defects in represent variation at single isolated nucleotide
Receptor Proteins positions and are almost always biallelic (i.e., one of
1. Familial Hypercholesterolemia only two choices exist at a given site within the
E. Disorders Associated with Defects in population, such as A or T).
Enzymes  less than 1% of SNPs occur in coding
1. Lysosomal Storage Disease regions
2. Glycogen Storage Disease  SNP is just a marker that is co-inherited with
3. Alkaptonuria a disease-associated gene as a result of
F. Disorder Associated with Defects In physical proximity
Proteins That Regulate Cell Growth  SNPs could serve as reliable markers of risk
IV. Complex Multigenic Disorders for multigenic complex diseases such as
V. Chromosomal Disorders type II diabetes and hypertension.
A. Normal Karyotype o copy number variations (CNVs)- consisting of
B. Structural Abnormalities of chromosomes different numbers of large contiguous stretches of
C. Cytogenic Disorders Involving autosomes DNA from 1000 base pairs to millions of base pairs.
1. Trisomy 21  responsible for between 5 and 24 million
2. Other Trisomies base pairs of sequence difference between
3. Chromosome 22q11.2 Deletion s any two individuals.
syndrome  approximately 50% of CNVs involve gene-
D. Cytogenic Disorders Involving Sex coding sequences; thus, CNVs may underlie
chromosomes a large portion of human phenotypic
1. Kleinfelter Syndrome diversity.
2. Turner Syndrome  significant over-representation of certain
3. Hermaphroditism and gene families in regions affected by CNVs;
pseudohermaphroditism these include genes involved in the immune
VI. Single Gene Disorders With Nonclassic Inheritance system and in the nervous system.
A. Diseases Caused By Trinucleotide –  subject to strong evolutionary selection, since
Repeat Mutations they would enhance human adaptation to
1. Fragle X Syndrome changing environmental factors.
B. Mutations in Mitochondrial Genes
C. Genomic Imprinting Epigenetics- heritable changes in gene expression
1. Prader-Wili Syndrome and that are not caused by alterations in DNA sequence;
angelman Syndrome changes are involved in tissue-specific expression of
D. Gonadal Mosaicism genes and genomic imprinting.
VII. Molecular Diagnosis of Genetic Diseases
A. Indications for Analysis of germ Line Genetic Proteomics - the measurement of all proteins
Alterations expressed in a cell or tissue.
B. Indications for Analysis of Acquired Genetic
Alterations microRNAs (miRNAs)- do not encode proteins but
C. PCR and Detection of bDNA Sequence instead inhibit gene expression
Alterations  fundamental mechanism of gene regulation
 approximately 1000 genes in humans that
Genetic Disorders encode miRNAs, accounting for about 5% of
the human genome
I. Human Genetic Architecture
 a given miRNA can silence many target
Human Genome
genes. The precise mechanism by which the
 Genetics- the study of single or a few genes
target specificity of miRNA is determined
and their phenotypic effects,
remains to be fully elucidated.
 genomics -the study of all the genes in the
genome and their interactions.

GENETICS
Another species of gene-silencing RNA, called small a. Mutations

interfering RNAs (siRNAs), works in a manner quite  mutation - permanent change in the DNA
similar to that of miRNA.  in germ cells, are transmitted to the
progeny and can give rise to inherited
II. Genes and Human Diseases diseases
 lifetime frequency of genetic diseases is  in somatic cells, do not cause hereditary
estimated to be 670 per 1000. diseases but are important in the genesis
 50% of spontaneous abortuses during the of cancers and some congenital
early months of gestation have a malformations
demonstrable chromosomal abnormality  may result in partial or complete deletion of
 about 1% of all newborn infants possess a a gene or, more often, affect a single base
gross chromosomal abnormality,  point mutation - a single nucleotide base
 approximately 5% of individuals under age may be substituted by a different base
25 develop a serious disease with a  frameshift mutations - one or two base
significant genetic component. pairs may be inserted into or deleted from
the DNA, leading to alterations in the
Classification of Genetic Disorders: reading frame of the DNA strand
Disorders related to mutations in single genes with General principles relating to the effects of gene
large effects. mutations:
 mutations cause the disease or predispose Point mutations within coding sequences:
to the disease and are typically not present  may alter the code in a triplet of bases and
in normal population. lead to the replacement of one amino acid by
 highly penetrant, meaning that the presence another in the gene product
of the mutation is associated with the  alter the meaning of the sequence of the
disease in a large proportion of individuals encoded protein
 follow the classic Mendelian pattern of  are often termed missense mutations.
inheritance  “conservative” missense mutation -
 also referred to as Mendelian disorders substituted amino acid causes little change in
 disorders are generally rare unless they are the function of the protein
maintained in a population by strong  “nonconservative” missense mutation-
selective forces (e.g., sickle cell anemia in replaces the normal amino acid with a very
areas where malaria is endemic) different one; eg. sickle mutation affecting
the β-globin chain of hemoglobin; triplet CTC
Chromosomal disorders. (or GAG in mRNA), glutamic acid  CAC (or
 arise from structural or numerical alteration GUG in mRNA), valine.
in the autosomes and sex chromosomes  stop codon (nonsense mutation)- change
 like monogenic disease they are uncommon an amino acid codon to a chain terminator;
but associated with high penetrance. eg. glutamine (CAG)  stop codon (UAG) if
U is substituted for C; leads to premature
Complex multigenic disorders. termination of β-globin gene translation, and
 far more common than the previous two the short peptide that is produced is rapidly
categories degraded, resulting in deficiency of β-globin
 caused by interactions between multiple chains  β0-thalassemia
variant forms of genes and environmental
factors Mutations within noncoding sequences:
 variations are common within the  mutations that do not involve the exons
population and are also called  lead to a marked reduction in or total lack of
polymorphisms transcription
 only when several such polymorphisms are  eg. certain forms of hereditary anemias
present in an individual that disease occurs,  point mutations within introns may lead to
hence the term multigenic or polygenic defective splicing of intervening sequences.
 each polymorphism has a small effect and is This, in turn, interferes with normal
of low penetrance processing of the initial mRNA transcripts and
 called multifactorial disorders since results in a failure to form mature mRNA.
environment is an important factor Therefore, translation cannot take place, and
 eg. atherosclerosis, diabetes mellitus, the gene product is not synthesized.
hypertension, and autoimmune diseases;
even normal traits such as height and Deletions and insertions:
weight  small deletions or insertions involving
 have been very difficult to discern the coding sequence leading to
 recent progress has made possible alterations in the reading frame of the
genome wide association studies (GWAS), a DNA strand; frameshift mutations.
systematic method of identifying disease-associated  if the number of base pairs involved is
polymorphisms that is beginning to unravel the three or a multiple of three, frameshift
molecular basis of complex disorders does not occur; instead an abnormal
GENETICS
protein lacking or gaining one or more are congenital; individuals with Huntington disease,
amino acids is synthesized. for example, begin to manifest their condition only
after their 20s or 30s.
Trinucleotide-repeat mutations:
 belong to a special category of genetic III. Mendelian Disorders
anomaly. a. Transmission Patterns of Single Gene Disorders
 characterized by amplification of a sequence  Autosomal Dominant
of three nucleotides  Autosomal Recessive
 almost all affected sequences share the  X-Linked
nucleotides guanine (G) and cytosine (C). b. Biochemichal and Molecular Basis of Single
 eg. in fragile-X syndrome, prototypical of this Gene (Mendelian) Disorders
category of disorders, there are 250 to 4000 c. Disorders Associated With Defects in
tandem repeats of the sequence CGG within Structural Proteins
a gene called familial mental retardation 1  Marfan Syndrome
(FMR1); normal number of repeats:  Ehler-Denlos Syndrome
averaging 29. d. Disorders Associated With Defects in Receptor
 prevent normal expression of the FMR1 gene, Proteins
thus giving rise to mental retardation.  Familial Hypercholesterolemia
 distinguishing feature of trinucleotide-repeat e. Disorders Associated with Defects in Enzymes
mutations is that they are dynamic (i.e., the  Lysosomal Storage Disease
degree of amplification increases during  Glycogen Storage Disease
gametogenesis). These features, discussed in  Alkaptonuria
greater detail later, influence the pattern of f. Disorder Associated with Defects In Proteins That
inheritance and the phenotypic Regulate Cell Growth
manifestations of the diseases caused by this
class of mutation. IV. Complex Multigenic Disorders
 To summarize, mutations can interfere with
protein synthesis at various levels. V. Chromosomal Disorders
 Transcription may be suppressed with gene a. Normal Karyotype
deletions and point mutations involving b. Structural Abnormalities of
promoter sequences. Chromosomes
 Abnormal mRNA processing may result c. Cytogenic Disorders Involving
from mutations affecting introns or splice Autosomes
junctions or both.  Trisomy 21
 Translation is affected if a stop codon  Other Trisomies
(chain termination mutation) is created  Chromosome 22q11.2 Deletion Syndrome
within an exon. d. Cytogenic Disorders Involving Sex
 Some point mutations may lead to the Chromosomes
formation of an abnormal protein without  Kleinfelter Syndrome
impairing any step in protein synthesis.  Turner Syndrome
 Three major categories of genetic  Hermaphroditism and
disorders: Pseudohermaphroditism
1. disorders related to mutant genes of large
effect VI. Single Gene Disorders With Nonclassic
2. diseases with multifactorial inheritance Inheritance
3. chromosomal disorders. a. Diseases Caused By Trinucleotide – Repeat
4. single-gene disorders with nonclassic Mutations
patterns of inheritance  Fragle X Syndrome
 includes disorders resulting from triplet- b. Mutations in Mitochondrial Genes
repeat mutations, c. Genomic Imprinting
 those arising from mutations in  Prader-Wili Syndrome and Angelman
mitochondrial DNA (mtDNA), and Syndrome
 those in which the transmission is d. Gonadal Mosaicism
influenced by genomic imprinting or
gonadal mosaicism VII. Molecular Diagnosis of Genetic Diseases
 caused by mutations in single genes, but a. Indications for Analysis of germ Line
they do not follow the mendelian pattern of Genetic Alterations
inheritance. b. Indications for Analysis of Acquired Genetic
Alterations
Hereditary vs, Congenital
c. PCR and Detection of bDNA Sequence
hereditary disorders- are derived from
Alterations
one's parents and are transmitted in the germ line
through the generations and therefore are familial
congenital - “born with.”
Some congenital diseases are not genetic; for
example, congenital syphilis. Not all genetic diseases

REVIEW TEST
ALEJANDRO E. AREVALO, M.D.
GENETICS
REVIEW TEST
A. Matching type:
______ 1. Inversion A. Formation of “der” chromosome
______ 2. Trisome 21 B. Mirror image
______ 3. Ring chromosome C. Numerical
______ 4. Translocation D. 180 degrees rotation
__ ____5. i(X)(q10)chromosome E. Deletion
B. Multiple choice
_________ 6. Sickle cell anemia is an example of a single base substitution. Which DNA is exchanged
for what DNA and the corresponding mRNA in sickle cell?
A. T to C to G mRNA
B. T to A to U mRNA
C. T to G to C mRNA
D. C to T to A mRNA
_________ 7. Sickle cell anemia is a point mutation that causes a change in the amino acid from
A. Valine to glutamic acid
B. glutamic acid to valine
C. Glutamic acid to lysine
D. Lysine to glutamic acid
_________ 8. The RBC produced with sickle cell anemia during deoxygenated state has this particular
shape abnormalitiy
A. Mexican hat cell
B. Holly leaf cell
C. Thorny cell
D. Cup shaped cell
_________ 9. TP53 is located in which chromosome?

A. Chromome 17
B. Chromosome 18
C. Chromosome 19
D. Chromsome 20
________ 10. The two hit hypothesis was proposed by

A. Lyon
B. Knudson
C. Muller
D. Fallona

PATHOLOGY OF THE HEAD AND NECK
HERBERT Z. MANAOIS, M.D.
PATHOLOGY OF THE HEAD AND NECK B. Pyogenic granuloma

- common in pregnant women (pregnancy
I. Oral Cavity tumor)
II. Upper Airways Nose, Sinuses and - organizing granulation tissue
Nasopharynx Larynx
III. Ears IV. Odontogenic cysts and tumors
IV. Neck - remnants of odontogenic epithelium
V. Salivary Glands
___________________________________ A. Dentigerous cyst
- around the crown of the unerupted tooth
Oral Cavity - fluid accumulation between developing
tooth and dental follicle
I. Infections/Inflammatory and Reactive B. Odontogenic keratocyst

Lesions - aggressive behavior
A. Herpes Simplex Virus C. Periapical cyst

- most are caused by HSV-1 but HSV-2 (genital - around the apex of the tooth
herpes) may occur - Inflammatory in origin – longstanding
- children between 2 to 4 years of age pulpitis; unlike the first two
- often asymptomatic
- may cause acute herpetic gingivostomatitis D. Ameloblastoma
- latent infection in adults with reactivation - 80% occur in the mandible
(recurrent herpetic stomatitis) - cystic, indolent, locally invasive
- vesicles and bullae that rupture and painful - stellate reticulum
ulcers
- Tzanck test of vesicle fluid: intranuclear viral E. Odontoma
inclusions and multinucleated giant cells - most common type of odontogenic tumor
(polykaryons) (Robbins and Cotran, 9th ed, pp 735)
B. Candidiasis (Thrush) V. Premalignant Lesions

- most common fungal infection - 2:1 male predominance
- Candida albicans : normal oral flora - tobacco smoking
- Risk Factors:
1. Immune status – diabetes, A. (Nonhairy) Leukoplakia
chemotherapy, AIDS, bone - white patch/plaque that cannot be scraped off
marrow AND cannot be chraracterized clinically or
transplant recipients pathologically as any OTHER disease
2. C. albicans strain - buccal mucosa, floor of the mouth, ventral
3. Normal flora present surface of tongue, palate and gingiva
- hyperkeratosis & acanthosis --- dysplasia---
- Pseudomembranous: most common clinical carcinoma-in-situ
form
- superficial curdy gray to white membrane B. Erythroplakia
- easily scraped off - less common, more ominous
- red velvety possibly eroded area
II. Oral Manifestations of Systemic Disease - severe dysplasia---carcinoma-in-situ---
minimally invasive carcinoma
A. Hairy leukoplakia
- EBV is accepted as the cause VI. Malignant tumors
- immunocompromised patients
- HIV patients A. Squamous cell carcinoma
- almost always on the lateral border of the - most common malignant head and neck
tongue tumor
- white fluffy (“hairy”) patches that cannot be - smoking, alcohol, sunlight (actinic
scraped off (unlike oral thrush) radiation), betel chewing
- hyperkeratosis, acanthosis and balloon cells - HPV (especially 16)
- HPV-associated do better
III. Fibrous proliferative lesions - “field cancerization” – second primary
tumors
A. Irritation fibroma - ulcerated/protruding masses
- repeated trauma - Dysplasia – Carcinoma-in-situ- Invasive
- fibrous tumor covered by squamous Squamous Cell Carcinoma
epithelium - atypical squamous cells in nests and sheets
with keratin pearl formation

Upper Airways - Nose,

Upper Airways - Larynx
Sinuses, Nasopharynx
I. Inflammation
I. Infections and inflammatory lesions - most common
- allergic
A. Pharyngitis and tonsillitis - viral : respiratory syncytial virus
- viral : rhinoviruses, echoviruses, adenovirus - bacterial : H. influenza and B-hemolytic
- bacterial : B-hemolytic streptococci - streptococci
rheumatic fever - chemical : smoking
B. Allergic rhinitis (hay fever) II. Benign Tumors

- hypersensitivity reaction
- IgE-mediated immuno response A. Reactive nodules (vocal cord nodules and
polyps)
II. Benign Tumors - heavy smokers and vocal cord strain (singer’s
nodules)
A. Nasal polyps - singer’s nodules : bilateral
- recurrent attacks of rhinitis causing mucosal - polyps : unilateral
protrusion - voice change and progressive hoarseness
- loose stroma with inflammatory cells with - loose myxoid connective tissue covered with
overlying mucosa squamous epithelium
- most are not atopic - virtually never become cancerous
B. Angiofibroma B. Squamous papilloma and papillomatosis

- benign, vascular tumor - true vocal cords
- almost exclusively in in adolescent males - multiple fingerlike or raspberry-like
- locally aggressive with intracranial extension projections
- fatal due to hemorrhage and intracranial - HPV 6 and 11
Extension - adults: single
- children: multiple
C. Sinonasal (Schneiderian) papilloma - fibrovascular core covered by stratified
- benign but locally aggressive and recurrent squamous epithelium
- nasal cavity and parasinuses
- exophytic type: most common II. Malignant Tumor
- inverted/endophytic: most important
biologically A. Squamous cell carcinoman (95%)
- HPV 6 and 11 - male chronic smokers
- hyperplasia --- dysplasia --- carcinoma-in-situ
III. Malignant Tumors --- invasive carcinoma
- hoarseness, dysphagia, dysphonia
A. Olfactory Neuroblastoma - smoking, alcohol, HPV infection, asbestos,
(Esthesioneuroblastoma) radiation, nutrition
- from neuroectodermal olfactory cells - usually vocal cords
- bimodal age distribution - intrinsic or extrinsic
- small round blue cells
- (+) neuron specific enolase, synaptophsin,
chromogranin, CD56 Ears
B. NUT midline carcinoma I. Inflammatory lesions

- extremely aggressive and resistant to therapy
A. Otitis media
C. Nasopharyngeal Carcinoma - most common
- associated with EBV infection - involves the middle ear and mastoid
- Africa - children; southern China – adult - infants and children
- Three types: 1. Acute
1. Squamous cell carcinoma, keratinizing – - viral but may have superimposed
least radiosensitive bacterial infection (S. pneumoniae, H.
2. Squamous cell carcinoma, nonkeratinziing Influenza, Moraxella catarrhalis)
3. Undifferentiated carcinoma – 2. Chronic
most radiosensitive - Pseudomonas, S. aureus, fungus, or
mixed
- temporal cerebritis or abscess

B. Cholesteatoma D. Ranula
- not a neoplasm, does not always have - sublingual gland duct damage
cholesterol - epithelial cyst
- cystic, lined by squamous/mucus-secreting
epithelium II. Benign and malignant neoplasms
- associated with chronic otitis media - most common benign: pleomorphic adenoma
- most common malignant: mucoepidermoid
C. Otosclerosis carcinoma
- abnormal bone deposition in the middle ear - most commonly involved: parotid
- bilateral - the likelihood of malignancy is inversely
- autosomal dominant proportional to the size of the gland
- hearing loss - female predominance; but for Warthin tumor, male
greater than female
Neck III. Benign Tumors
I. Tumors A. Pleomorphic adenoma (Benign mixed

tumors)
A. Branchial Cyst (Lymphoepithelial Cyst) - mixed: ductal (epithelial) and myoepithelial
- remnants of 2nd branchial arch cells = epithelial and mesenchymal
- young adults (20-40 years old) differentiation
- lateral neck along sternocleidomastoid - remarkable histologic diversity
- cystic, lined by squamous or columnar - parotid - 60% of tumors
- encapsulated but may have protrusions into
B. Thyroglossal Duct Cyst the gland, thus the recurrence
- remnant of the thyroid anlage - epithelial - ductal cells
- anywhere along the developmental tract - mesenchymal – myxoid, chondroid, hyaline,
- cystic, lined by squamous or columnar osseous stroma
epithelium + thyroid tissue - painless, slow-growing, discrete
C. Paraganglioma (Carotid body tumor) B. Warthin's tumor (Papillary Cystadenoma

- rare tumors; most common location is adrenal Lymphomatosum)
medulla - second most common salivary gland neoplasm
- 70% of extra-adrenal are in the head and neck - exclusive in the parotid gland
- develop in two locations: - benign
- male predominance
1. Paravertebral - smokers have 8X the risk
2. Related to the great vessels of the head and - lining of oncocytic columnar cells with a
neck; most common: lymphoid stroma
- carotid body tumor
- microscopic: nests of round to oval cells IV. Malignant Tumors
(Zellballen)
A. Carcinoma ex pleomorphic adenoma
(malignant mixed tumor)
Salivary glands - malignant transformation of a pleomorphic
adenoma
I. Benign and inflammatory lesions - adenocarcinoma or undifferentiatedcarcinoma
B. Mucoepidermoid carcinoma
A. Xerostomia ("dry mouth") - most common malignant tumor of the salivary
- decreased saliva production glands
- autoimmune Sjogren's Disease - squamous, mucin-secreting and intermediate cells
- radiation therapy - mainly in the parotid
- medications: antihypertensive, diuretics,
sedatives, antipsychotics, antidepressants C. Adenoid cystic carcinoma
- 50% occur in the minor salivary gland
B. Sialadenitis - cribriform "lacelike" pattern
- trauma, viral, bacterial, or autoimmune - perineural invasion, recur, metastasize
- most common viral sialadenitis : mumps D. Acinic cell carcinoma
- bacterial sialadenitis: submandibular gland; - resemble normal serous glands
S.aureus and S. viridans - most arise in the parotid
C. Mucocele --Fin--
- most common lesion of the salivary glands “Move swift as the Wind and closely-formed as the Wood.
- duct blockage or rupture Attack like the Fire and be still as the Mountain.”
- most common on lower lip due to trauma ― Sun Tzu, The Art of War

REVIEW TEST

_____7. What virus is associated with
_____1. Which of the following is TRUE of nasopharyngeal carcinoma?
leukoplakia? A. Epstein-Barr virus
A. It is a red patch or plaque B. Human papilloma virus 16 and 18
B. It can be scraped off C. Hepatitis B virus
C. May be due to lichen planus or Candida D. Cytomegalovirus
infection
D. Considered precancerous _____8. A 22-year-old male complained of a mass in
the upper lateral aspect of the neck. Histologic
_____2. What is the most common head and neck examination shows a cyst lined by squamous
malignancy? epithelium with lymphoid tissue. What is the most
A. Squamous cell carcinoma likely diagnosis?
B. Adenocarcinoma A. Thyroglossal duct cyst
C. Mucoepidermoid carcinoma B. Branchial cyst
D. Lymphoma C. Cystic colloid goiter
D. Tuberculous lymphadenitis
_____3. TRUE of squamous cell carcinoma of the
head and neck, EXCEPT: _____9. What is the most common lesion of the
A. Associated with tobacco and alcohol salivary glands?
abuse A. Pleomorphic adenoma
B. Harbor oncogenic variants of HPV B. Sialadenitis
C. Multiple primary tumors may develop C. Sialolithiasis
D. Composed of dysplastic glands invading D. Mucocele
the stroma
_____10. TRUE of neoplasms of the salivary glands:
_____4. A 15-year-old Caucasian boy with A. Submandibular gland is most commonly
adenomatous polyposis developed nasopharyngeal involved
mass which bled profusely during the operation. B. Likelihood of being malignant is inversely
What is the most likely diagnosis? proportional to the size of the gland
A. Undifferentiated carcinoma C. Slight male predominance
B. Angiofibroma D. Adenoid cystic carcinoma is the most
C. Angiosarcoma common malignant neoplasm
D. Inflammatory nasal polyp
_____11. What is the most common type of
_____5. A 65-year-old male smoker came in odontogenic tumor?
because of hoarseness of voice. Biopsy of his A. Ameloblastoma
laryngeal mass showed sheets of atypical epithelial B. Odontoma
cells with keratin pearl formation. What is the most C. Dentigerous cyst
likely diagnosis? D. Odontogenic keratocyst
A. Adenocarcinoma
B. Squamous cell carcinoma _____12. What is most common histologic subtype
C. Melanoma of laryngeal carcinomas?
D. Lymphoma A. Squamous cell carcinoma
B. Adenocarcinoma
_____6. A three-year-old boy complained of fever, C. Sarcoma
lymphadenopathy, and multiple vesicles and D. Lymphoma
erosions on the gingiva. Tzanck smear showed
multinucleated giant cells and intranuclear inclusion. _____13. Squamous papillomas in adults differ from
What is the most common etiologic agent of the papillomas in children because:
lesion? A. Usually single
A. HSV 1 B. Associated with HPV 6 and 11
B. HSV 2 C. Do not recur
C. EBV D. Frequently become malignant
D. HPV

REVIEW TEST
_____14. Which of the following salivary gland

tumor is common among smokers?
A. Warthin tumor
B. Pleomorphic adenoma
C. Mucoepidermoid carcinoma
D. Acinic cell carcinoma
_____15. This ear lesion is caused by abnormal

bone deposition in the middle ear?
A. Cholesteatoma
B. Odontoma
C. Otosclerosis
D. Otitis media
_____16. A 22-year-old female complained of a

lateral neck mass. The pathologists described the
tumor as having cells arranged in “zelballen”
pattern. What is the most likely diagnosis?
A. Mucoepidermoid carcinoma
B. Papillary thyroid carcinoma
C. Pleomorphic adenoma
D. Paraganglioma
_____17. What autoimmune disease is associated

with xerostomia?
A. SLE
B. Rheumatoid arthritis
C. Sjogren syndrome
D. Fatal midline syndrome
_____18. TRUE of nasopharyngeal carcinoma:

A. HPV-associated
B. EBV-associated
C. Keratinizing type is most radiosensitive
D. Undifferentiated type is least
radiosensitive
_____19. Which of the following has the highest risk

of recurrence and progression to carcinoma?
A. Leukoplakia
B. Hairy leukoplakia
C. Erythroplakia
D. None of the above
_____20. This is known as the pregnancy tumor of

the oral cavity?
A. Irritation fibroma
B. Pyogenic granuloma
C. Odontogenic keratocyst
D. Odontoma

GASTROINTESTINAL PATHOLOGY
ROWEN T. YOLO, MD
I. Pathology of the Oesophagus: 4. Osophageal varices:

4.1. Dilated submucosal oesophageal
1. Tracheoesophageal fistula veins secondary to portal hypertension
1.1. Congenital diosorder suggested in a 4.2. May result in upper GI haemorrhage
newborn due to copious salivation associated (after bleeding peptic ulcer and\
with choking, coughing, and cyanosis on Mallory Weiss syndrome)
attempted food/ water intake
1.2 Variants: 5. Oesophagitis and related disorders of
1.2.1. - Upper oesophagus ends in a the oesophagus
blind pouch (oesophageal 5.1. Reflux oesophagitis
atresia) 5.1.1. Reflux of gastric acid into the
- Lower portion of the oesophagus
oesophagus communicates 5.1.2. SSx: odynophagia, substernal
with the trachea near the pain (heartburn), burning pain
tracheal bifurcation relieved by anatacids
- Most common variant (90%) 5.1.3. Most commonly asso. With
1.2.2. - Fistulous connection between hiatal hernia and incompetent
the upper oesophagus and the LES, heavy alcohol and tobacco
trachea use, increased gastric volume,
- Lower oesophageal segment pregnancy, scleroderma
is not connected to the upper 5.1.4. Assuming recumbent position
oesophagus often precipitates GE reflux
- 2nd most common variant 5.1.5. Associated clinical condition is
1.2.3 - Fistulous connection between termed GERD.
the trachea and a completely 5.1.6. May cause oesophagitis,
patent oesophagus stricture, ulceration, or columnar
- 3rd variant metaplasia (Barret esophagus)
2. Oesophageal diverticula 5.2. Barret esophagitis

2.1. False (pulsion) diverticula – Most 5.2.1. Columnar metaplasia (intestinal
common type with prominent goblet cells)
- results from herniation of the of osophageal squamous
mucosa through a defect s in the epithelium
muscular layer 5.2.2. Complication of long standing
2.2. True (traction) diverticula GERD
- consists of a diverticula composed 5.2.3. Precursor of dysplasia and
of mucosal, muscular, and serosal esophageal adenocarcinoma
layers 5.2.4. Infectious: Candida esophagitis
- results from periesohageal asso. With antibiotic use, DM,
inflammation and scarring malignancy, AIDS,
2.3. Diverticula occurs 3 characteristic locations: immunosuppressive drugs
2.3.1. Immediately above the HSV-1 asso with
oesophageal sphincter (Zenker) immunosuppressed patients
2.3.2. Near the midpoint of the
oesophagus 5.3. Carcinoma of the esophagus
2.3.3. Immediately above the lower 5.3.1. AdenoCA > SCC
oesophageal sphincter 5.3.2. AdenoCA arises most ofen from
(Epiphrenic) aberrant gastric mucosa,
submucosal glands,
3. Achalasia or Barret esophagus
3.1. Persistent contraction of the lower 5.3.3. SCC arises most frequently in
oesophageal sphincter (incomplete the upper and middle thirds
LES relaxation) + 5.3.4. Pathologic manifestation includes
Increase LES tone + absence of luminal obstruction, spread by
oesophageal peristalsis = dilatation of local extension into adjacent
the oesophagus stuctures such as trachea,
3.2. Loss of ganglion cells in the myenteric bronchi, aorta, or diffuse
plexus which leads to progressive infiltration into the
dilatation of the oesophagus (primary oesophageal wall.
achalasia); Trypanosoma cruzi (Chaga
disease) in South America (secondary II. Pathology of the Stomach:
achalasia)
3.3. Clin correlation: Dysphagia, asso with 1. Congenital pyloric stenosis
squamous cell carcinoma (approx. 1.1. Results on gastric outlet – episodes of
5%) projectile vomiting, commonly manifest
bet. 3-6 weeks of life, common in boys
ROWEN T. YOLO, MD
1.2. Caused by hypertrophy of the circular 2.2.3.3. Increased risk of

muscular layer of the pylorus (often gastric cancer
-asso. with a palpable mass)
3. Peptic Ulcer of the Stomach
2. Gastropathy and Gastritis 3.1. Most often, ulcer occurs at or near -
2.1. Acute (erosive) gastritis the lesser curvature, antral and
2.1.1. Aetiologies: prepyloric regions
2.1.1.1. NSAIDs 3.2. Ulcer is NOT a precursor lesion of
2.1.1.2. Heavy cigarette carcinoma of the stomach
smoking and alcohol 3.3. Unlike peptic ulcer that occurs
intake elsewhere, peptic ulcer of the
2.1.1.3. Ingestion of acids and stomach is NOT dependent on
alkali (accidental or increased gastric acid secretion;
suicidal) however, acid and pepsin are
2.2.1.4. Asso. with burn injury believed to play a role because
(Curling ulcer); Brain gastric, because gastric peptic
injury (Cushing ulcer) ulcers rarely occur in association
2.1.2. Pathology: focal damage to with absolute achlorhydia
gastric mucosa, acute 3.4. Postulated aetiopathogenic
inflammation, necrosis mechanism of gastric peptic ulcer
and haemorrhage. formation:
2.1.3. If rare or absent inflammatory 3.4.1. H-pylori mediated processes –
cells the term gastropathy is bacterial ureases and
applied proteases break +down
glycoprotein in gastric mucus,
2.2. Chronic gastritis thus, interfering with epithelial
2.2.1. Autoimmune gastritis protection
2.2.1.1. Asso. with presence of 3.4.2. Increased permeability of
antibodies to parietal gastric mucosa to H+,
cells (and/or intrinsic resulting in back diffusion of
factor), achlorydia, H+ with injury to the gastric
pernicious anemia, and mucosa
other autoimmune 3.4.3. Bile-induced gastritis leading
disease such as to gastric ulceration
chronic thyroiditis,
Addison disease; aging 4. Malignant tumours of the stomach
partial gastrectomy, and 4.1. Carcinoma of the stomach
gastric carcinoma 4.1.1. Most common after 50 years of
age, increased incidence in
2.2.2. Helicobacter pylori associated men, more freq in blood type A
gastritis suggesting a genetic
2.2.2.1. NO asso. With predisposition.
pernicious anemia, 4.1.2. Incidence higher in Japan,
antibodies to parietal Finland, and Iceland
cells, or Reduced 4.2. Aetiologies
gastric acid secretion 4.2.1. H. pylori
2.2.2.2. Often increased gastric 4.2.2. Nitrosamine from dietary
acid secretion occurs amines, nitrates used as food
2.2.2.3. H. pylori is strongly preservatives
asso. with gastric and 4.2.3. Excessive salt intake, diet low in
duodenal peptic ulcers fresh fruits and vegetables
and its role in the 4.2.4. Achlorhydria
development of gastric 4.2.5. Chronic gastritis with or without
adenocarcinoma and pernicious anemia
gastric lymphoma of 4.2.6. Germline defect- mutation in the
the mucosa-associated E-cadherin gene (CDH1). These
lymphoid tissue (MALT) Are comprised of signet ring
type. cells with diffuse infiltration.
Patients with these
2.2.3. Meńetrier disease (giant mutations are predisposed to
hypertrophic gastritis) developing lobular carcinoma of
2.2.3.1. Extreme prominence the breast Hereditary non-
and enlargement of polyposis colorectal cancer
the gastric rugae (HNPCC or Lynch syndrome)
2.2.3.2. Severe loss of plasma are increased risk for gastric
proteins from the altered mucosa carcinoma.
ROWEN T. YOLO, MD
4.3. Pathology 5.1.2. Except for peptic ulcer of the

4.3.1. Almost all are adenocarcinoma stomach, peptic ulcer is always
4.3.2. Commonly involves the distal associated with hypersecretion
stomach, along the lesser of gastric acid and pepsin.
curvature of the antrum, - Ulceration is closely related to -
or pre-pyloric region. Rarely H. pylori infection which affects
involves the fundus essentially all patients with
4.3.3. Aggressive spread to to duodenal ulcer and the majority
adjacent organs, peritoneum, of patients with gastric ulcer.
and early lymphatic metastasis 5.1.3. H. pylori increases gastric acid
to regional lymph nodes and secretion and apparently
liver impairs both gastric and
4.3.4. Metastasis to the duodenal mucosal defences.
supraclavicular lymph nodes is 5.1.4. Increased frequency in subjects
called Virchow node in blood group O, suggesting
4.3.5. Bilateral metastatic involvement genetics may play a role
to the ovaries- Krukenberg 5.1.5. Peptic ulcer is NOT a precursor
tumours (Poorly differentiated of malignancy
carcinoma or signet ring 5.1.6. Complications- haemorrhage
carcinoma) with melena, obstruction and
4.3.6. Intestinal type – polypoid perforation
(fungating), ulcerating 5.1.7. Peptic ulcer is sometimes
carcinoma. High asso. with associated with aspirin, or other
H.pylori NSAIDS, smoking,
4.3.7. Infiltrating or diffuse carcinoma Zollinger-Ellison syndrome,
(linitis plastic). Not asso. with primary hyperparathyroidism,
H. pylori MEN type I (Werme syndrome).
4.3.8. Lymphoma – approx. 4% of
malignant gastric tumours 5.2. Crohn disease vs. Ulcerative colitis
(MALT type). High asso. with
H. pylori Crohn Disease Ulcerative Colitis
infection. Prognosis is better
than adenocarcinoma,
May involve any portion of Affects only colon
may regress with antibiotic
the GIT, usually the
treatment
ieocaecal region,small
4.3.9. Gastrointestinal stromal tumours
intestine, or colon
(GIST) - derived from
mesenchymal pacemaker Chronic inflammatory Inflammation and
cells of Cajal. Most common in reaction extends through ulceration limited to
the submucosa of the stomach. the entire thickness of the the mucosa and
Most cases are indolent, some intestinal wall submucosa
are aggressive and may Lymphocytic infiltrates, Crypt abscesses,
metastasize. Mitotic count, size non-caseating granulomas, pseudopolyps
and location predict behavior.
fibrosis, thickening of the
- Tumours express c-kit intestinal wall with
oncogene (CD117) which narrowing of the lumen;
encodes for tyrosine kinase fistulous tract between
involved in cell cycle loops of intestines or
proliferation. 10% also has between the intestine and
activating mutations in other sites; mucosal
Platelet derived growth factor
cobblestone appearance;
receptor-α (PDGFRα) skip lesions
- Treatment involves surgical
Incidence of secondary Greatly increased
resection and treatment with
malignancy much lower incidence of colon
imatinib which inhibits the
than in UC cancer in long-
tyrosine kinase activity of c-kit
standing cases
and PDGFRα
5. Pathology of the Small Intestine 5.3. Meckel diverticulum

5.1. Peptic ulcer 5.3.1. Most common congenital anomaly
5.1.1. Occurrence most frequent in the of the small intestine.
first portion of the duodenum,
5.3.2. Represents the remnant of the
the stomach, or the lower end of
the oesophagus, all of which embryonic vitteline duct located in
are exposed to acid and the distal small intestine.
pepsin 5.3.3. May contain ectopic gastric,
ROWEN T. YOLO, MD
duodenal, colonic, or pancreatic most frequently in the

tissue appendix, localized in the
5.3.4. Asymptomatic but complications – small intestine in about 30%
peptic ulcerations in ectopic gastric 5.5.1.2. Slow growing, low-grade
mucosa with bleeding or malignancy, but may
perforation may occur. Other metastasize. Metastasis
complications include: very uncommon for
- Intussusception – often in young appendiceal primaries, but
infants and children is seen with some
- Volvulus – causing bowel frequency in
Obstruction small bowel tumours.
5.5.1.3. Metastatic to liver- leads
Disorder Morphologic Comments to carcinoid syndrome
features caused by elaboration of
Celiac Flat mucosal Gluten vasoactive peptides and
disease surface with sensitivity amines, esp. serotonin
marked villous
- Cutaneous flushing
atrophy; increased
lymphocytes and - Watery diarrhea and
plasma cells in the abdominal cramps
lamina propia - Bronchospasm
Tropical Histology varies Tropical disease - Valvular lesion of the
sprue from no changes of probable right side of the heart
to abnormalities infectious origin; 5.5.2. Lymphoma – presents with
similar to celiac often responds
malabsorption when diffusely
disease to antibiotics
Whipple No characteristic Deficiency of involved
disease histologic change disaccharidases 5.5.3. Adenocarcinoma – rare, usually
sited in brush arise in periampullary / ampullary
border of region
mucosal cells of 5.5.4. GIST – more likely to behave
small intestine; malignantly when originates from
lactase
small intestine as
deficiency which
leads to milk opposed to stomach
intolerance is 5.5.5. Metastasis – the most common
most frequent small bowel malignancy
Abetalipopro No characteristic Β-lipoprotein
-teinemia features in the deficiency is 6. Pathology of the Large Intestine
intestine; caused by 6.1. Hirshsprung disease (congenital
circulating hereditary
megacolon) – dilataion of the colon
acanthocytes (RBC deficiency of
with spiny apoprotein β due to the absence ganglion cells of
projection) the submucosa and myenteric neural
suggest the plexuses; dilatation is
diagnosis proximal to the aganglionic
Intestinal Generalized Marked segment
lymphangiec dilatation of the gastrointestinal 6.2. Diverticula
-tasia small intestinal protein loss with
6.2.1. Are pulsions (false) diverticula
lymphatics resultant
hypoproteinemia (pockets of mucosa and
and generalized submucosa herniated
oedema through the muscularis layer).
6.2.2. Most frequently involve the
5.5. Tumour of the small Intestine sigmoid colon
5.5.1. Most common malignant 6.2.3. Almost always multiple. Common
tumours include in the elderly
neuroendocrine (carcinoid) 6.2.4. Diverticulosis – multiple
tumours, lymphoma, adenocarcinoma diverticula without inflammation,
and GISTs. seen in population who
5.5.1.1. Neuroendocrine consumes low fiber diet
(carcinoid) tumour occur 6.2.5. Diverticulitis – diverticula with

ROWEN T. YOLO, MD
inflammation 6.4.2. Pseudomembranous colitis

6.2.5.1. Affects older individuals 6.4.2.1. Distinguished by
6.2.5.2. Complications – superficial grayish
perforation, bleeding, mucosal exudates
peritonitis, abscess consisting of necrotic
formation, bowel loosely, adherent
stenosis. Presents with mucosal debris
bright red rectal bleeding (pseudomembrane)
6.2.5.3. SSx: lower abdominal
pain and tenderness, 6.4.2.2. Often caused is overgrowth of
fever, leukocytosis, and exotoxin-producing Clostridium
other signs of acute difficile. Fibrinous necrosis of the
inflammation superficial mucosa is caused by the
the exotoxin not by the bacterial
6.3. Vascular lesions of the colon invasion.
6.3.1. Ischaemic bowel disease 6.4.2.3. SSx: fever, toxicity, and diarrhea most
6.3.1.1. Caused by often secondary to broad spectrum antibiotic
atherosclerotic occlusion therapy
of at least two (2) of the
major mesenteric arterial 6.4.3. Amoebic colitis
vessels 6.4.3.1. Caused by Entamoeba
6.3.1.2. Most often affects the histolytica
splenic flexure and the 6.4.3.2. Characteristic flask-
rectosigmoid junction shape ulcer
(so- called “watershed
areas” due to poor 6.4.5. Cholera
vascular supply 6.4.5.1. Caused by Vibrio
6.3.1.3. Result in mucosal, cholerae, a non-invasive
mural, or transmural toxin-producing
infarction involving the bacterium
wall of the intestine 6.4.5.2. Characterized by toxin-
mediated loss of fluid
6.3.2. Angiodysplasia and electrolytes with the
6.3.2.1. Tortuous dilatation of mucosa of the small
small vessels spanning bowel and colon
the intestinal mucosa or remaining normal in
submucosa appearance
6.3.2.2. Multiple lesions,
involving the caecum 6.5. Tumours of the Colon
and ascending colon 6.5.1. Benign Intestinal polyps
6.3.2.3. Common case of
Non-neoplastic polyp
otherwise unexplained
Hyperplastic polyp No clinical significance
lower bowel bleeding
6.3.3. Haemorrhoids Inflammatory polyps

6.3.3.1. Dilated internal and Lymphoid polyp Most common site is the
external venous rectal mucosa. May be
reaction to local irritation
plexuses in the anal
Inflammatory Asso. with UC and other
canal.
pseudopolyp inflammatory diseases of
6.3.3.2. Predisposed by low fiber the colon; consists of
diet granulation tissue and
regenerating mucosa
6.4. Inflammatory lesions of the colon
6.4.1. Ulcerative colitis Hamartomatous polyps
6.4.1.1. Unknown aetiology Juvenile polyp Occurs most frequently in
children
6.4.1.2. (See tabulation)
Peutz-Jegher polyp Asso. with Peutz-Jegher
syndrome

ROWEN T. YOLO, MD
Neoplastic polyps 6.5.2.6. Pathology

Tubular adenoma Benign but may undergo - Carcinoma of the rectosigmoid presents
malignant change; hereditary as an annular constricting mass
multiple polyposis syndromes - Carcinoma of the right colon does not
asso. with greatly increased risk obstruct early, presents often with iron
of malignancy deficiency secondary to chronic blood
loss
Tubulovillous Morphologically resembles
adenoma tubular adenoma wit additional
features similar to those of
villous adenoma; greater
malignant potential than tubular
adenoma
Villous adenoma Large sessile tumour with

velvety surface composed of
finger-like villi; high potential for
malignant change
Sessile serrated Resemble hyperplastic polyps
adenoma but are neoppastic and may
progress to malignancy;
predilection for the right colon;
demonstrates microsatellite
instability
6.5.2. Colorectal Adenocarcinoma

6.5.2.1. One of the mostcommon neoplasm
of the western world
6.5.2.2. Associated withincreased
serumconcentration of CEA which is
used as a marker to monitor disease
rather than its diagnostic value
6.5.2.3. Cancer develops through a set in
anatomic changes progressing from
normal mucosa to adenomatous
polyp to carcinoma to metastatic
tumour,with parallel set of
molecular changes in oncogenes
and tumour suppressor genes, most
commonly in the APC pathway
6.5.2.4. - A subset in cases develop NOT
through the APC pathway but
through defects in the mismatch
repair genes (chiefly MLH1, MSH2,
MSH6, and PMS2). Mismatched
repair gene mutation are seen in
patients with HNPCC or Lynch
syndrome.
- Px with this syndrome are at
risk for a variety of other
neoplasms including
gynecologic, urothelial, gastric,
and skin tumours.
- Sporadic mismatch repair
defects may also occur and are
usually related to abnormal
methylation resulting in
microsatellite instability
6.5.2.5. Predisposing factors – adenomatous
polyps, inherited multiple polyposis
syndrome, long-standing ulcerative
colitis, genetic factors, low fiber
high animal fat diet

REVIEW TEST
ROWEN T. YOLO, MD
CHOOSE THE BEST ANSWER: ____10. This occurs when a segment of the
intestine, constricted by a wave of peristalsis,
____1. Rotavirus selectively infects and destroys telescopes into the immediately distal segment:
mature enterocytes in the small intestine causing A. Volvulus
this type of diarrhea: B. Intussusceptions
A. Dysentery C. Diverticulosis
B. Osmotic D. Hernia
C. Exudative
D. Inflammatory MATCHING TYPE:
A. Ulcerative colitis
____2. What is the most important characteristic of B. Crohn disease
adenomas that correlates with risk of malignancy?
A. Degree of dysplasia ____11. Limited to colon and rectum
B. Type of adenoma ____12. Granulomas
C. Size of the adenoma ____13. Perianal fistula
D. Number of adenomas ____14. Toxic megacolon
____15. Fat/vitamin malabsorption
____3. This tumor suppressor gene is mutated in
70% to 80% of colon cancers: ____16. Colonization of this organ with Salmonella
A. p53 typhi or Salmonella paratyphi may be associated
B. WNT with gallstones and the chronic carrier state:
C. APC A. Small intestine
D. KRAS B. Gallbladder
C. Large intestine
____4. What is the most common malignancy of the D. Liver
gastrointestinal tract?
A. Gastrointestinal stromal tumor ____17. This type of gastric polyp has been
B. Squamous cell carcinoma prevalent recently as a result of proton pump
C. Adenocarcinoma inhibitor therapy?
D. Carcinoid tumor A. Inflammatory polyp
B. Hyperplastic polyp
____5. Pseudomyxoma peritoneii develops as a C. Fundic gland polyp
complication to what type of carcinoma: D. Gastric adenoma
A. Appendiceal mucinous carcinomas
B. Desmoplastic small round cell tumor ____18. What is the most common location of
C. Ovarian adenocarcinomas colonic diverticula?
D. Pancreatic adenocarcinomas A. Sigmoid
B. Transverse
____6. What is the most common site of metastatic C. Ascending
lesions in colorectal carcinomas? D. Descending
A. Bone
B. Lung ____19. Loss of function of this protein serves as a
C. Brain key step in the development of diffuse gastric
D. Liver cancer, creating a signet-ring cell morphology:
A. Estrogen receptor
____7. Colorectal adenomas are characterized by B. Progesterone receptor
the presence of which epithelial change? C. Her-2-Neu
A. Dysplasia D. E-cadherin
B. Metaplasia
C. Hyperplasia ____20. What type of malignancy is associated with
D. Atrophy Barrett esophagus?
A. Squamous cell carcinoma
____8. Most common location of polyps in the B. Adenocarcinoma
gastrointestinal tract: C. Carcinoid tumor
A. Esophagus D. Gastrointestinal stromal tumor
B. Stomach
C. Colon
D. Small intestine ____21. Hirschprung disease results from:
A. Outpouching of the ileum
____9. What is the most common intestinal B. Faulty migration of precursors of
neoplastic polyp? intestinal ganglionic cells
A. Adenoma C. Increased pressure in the large intestine
B. Inflammatory related to straining during defecation
C. Hamartomatous D. Destruction of tissue by pus that breaks
D. Hyperplastic through the wall

REVIEW TEST
ROWEN T. YOLO, MD
____22. This is a functional disorder characterized

by a loss of normal esophageal peristalsis and
incomplete or abnormal relaxation of the lower
esophageal sphincter:
A. Atresia
B. Zenker diverticula
C. Achalasia
D. Schatzki ring
____23. Possible outcomes of hemorrhoids once

exposed, EXCEPT:
A. Inflamed
B. Thrombosed
C. Recanalized
D. Organized
____24. What is the most common location of H.

pylori within the stomach causing gastritis?
A. Cardia
B. Antrum
C. Fundus
D. Pyloric sphincter
____25. Most common cause of acute appendicitis?

A. Gallstones
B. Tumors
C. Fecalith
D. Mass of worms
____26. Most common location of carcinoid tumors?

A. Colon
B. Appendix
C. Ileum
D. Stomach
____27. Extra-intestinal manifestations of Crohn

disease include: (pp 811)
A. Uveitis
B. Migratory polyarthritis
C. Sacroiliitis
D. All of the above

ENDOCRINE PATHOLOGY
ROWEN T. YOLO, MD
Anatomy and Physiology: • Acidophilic adenoma

• entire gland rests in the sella turcica, a diffuse growth composed solely of
depression in the sphenoid bone. acidophilic cells, which produce either
• weighs about 0.5 grams and is less than 15 growth hormone or prolactin
mm in diameter. • Pituitary Microadenoma
• releasing and inhibiting factors synthesized • Basophilic Adenoma - composed of
in the hypothalamus are delivered to the corticotrophs and produces Cushing’s
anterior lobe via a portal system, which disease.
supplies 80 to 90% of the blood flow to the • Chromophobe adenoma – 25 % of pituitary
pituitary. Short portal vessels allow blood adenomas present as space occupying
exchange between the two lobes. lesions (causing pressure atrophy of normal
• composed of two tissue types, each with a tissue) or a trophic hormone insufficiency;
separate embryologic origin. The anterior 25% produce prolactin.
lobe, also called the adenohypophysis, is • Prolactinoma – most common functioning
made up of secretory cells derived from pituitary tumor; patient presented with
Rathke's pouch, an embrologic extension of amenorrhaea, galactorrhea, infertility,
the primitive oral cavity. increased intracranial pressure and visual
• the posterior lobe, the neurohypophysis, is problems.
composed of neural tissue; it is a direct
extension of the brain and is attached to the HYPOPITUITARISM
hypothalamus by the pituitary stalk. 1. Sheehan’s Syndrome
2. Simmond’s disease
Normal Anterior Pituitary Gland 3. Empty Sella Syndrome
• pars distalis, is composed of round to 4. Dwarfism
polygonal epithelial cells arranged in cords 5. Diabetes Insipidus
and nests, amid a rich fibrovascular
network. These cells release their granules Neurohypophysis
in response to releasing factors elaborated • principal targets of oxytocin is the pregnant
in the hypothalamus. uterus at parturition and the lactating
• histologically, cells of the anterior pituitary breasts
are classified on the basis of staining • principal targets of vasopressin are the
characteristics on H & E: acidophils, kidneys’ collecting ducts and the peripheral
basophils & chromophobes. arterioles.
• immunoperoxidase techniques can be used • head trauma, extension of local tumors,
to classify the cells by their hormone surgery or radiation may disrupt the
contents as seen in next slide. pituitary stalk and cause diabetes insipidus.
• Pathology of the Pituitary Gland
- Histology:
1. Adenohypophysis PITUITARY TUMOURS:
2. Somatotrophs (GH cells) (diffuse, sinusoidal and papillary patterns)
3. Lactotrophs (Prl cells) 1. Pituitary Adenoma
4. Mammosomatotrophs (GH & Prl) 2. Pituitary Carcinoma
5. Gonadotrophs (FSH- LH cells)  Pressure Effects
6. Thyrotrophs (TSH cells)  Hormonal Effects
7. Corticotrophs (ACTH- MSH, β-lipoprotein
β-endorphin) Hyperpituitarism
• term used to denote secretion of one or
- Histology: more of the tropic hormones of the anterior
- Neurohypophysis: lobe.
- Nerve fibers with specialized Glial cells called • due to:
Pituicytes that secrete octapeptides: 1) loss of feedback inhibition by target
1. ADH (vasopressin) organ hormones (low levels) to the
2. Oxytocin hypothalamus.
2) most often, an adenoma of the
Pathology of the Pituitary Gland adenohypophysis; 70% elaborate a
single tropic hormone: prolactin, GH, or
HYPERPITUITARISM ACTH. Neoplasms secreting TSH, LH,
1. Gigantism and FSH are very rare.
2. Acromegaly
3. Hyperprolactinaemia • more common in men between 20 and 50
- amenorrhea - galactorhea syndrome years but may be seen in women as well.
- impotence / reduced libido in males
Adenomas classified as to size
• Pituitary Macroadenoma • Adenomas <10 mm in diameter are referred
• Prolactinoma to as microadenomas and may be present
• Functioning Pituitary Adenoma as incidental findings in 25% of adult
ENDOCRINE PATHOLOGY
ROWEN T. YOLO, MD
autopsies. Most are apparently - Adrenal cortical (functioning) carcinoma

nonfunctioning but may produce symptoms - Bilateral Adrenal hyperplasia
if secretory.
• Adenomas >10mm are referred to as - Cushing’s Syndrome
macroadenomas. These extend beyond the - central (truncal) obesity
sella & press on nearby sensitive structures, - buffalo hump
such as cranial nerves III, IV, and VI, the - wasting / skeletal muscle atrophy
cavernous sinus, the hypothalamus, and the - atrophy of skin and subcutaneous tissue
optic chiasm producing various symptoms. - osteoporosis
- systemic hypertension (80%)
Differential Diagnosis: - diabetes mellitus (20%)
• Rathke’s Cysts – remnant of pars intermedia - amenorrhea, hirsutism and infertility in
may produce colloid-filled cysts and cause women
compression atrophy of pituitary gland - insomnia
• Sheehan’s Syndrome – postpartum pituitary - depression
necrosis, which leads to selective or total - confusion
hypopituitarism gland enlarges in pregnancy - psychosis
due to hyperplasia of prolactin cells making
it vulnerable to ischemic necrosis in obstetric 1. Conn’s Syndrome
emergencies that result in hypotension or - causing Primary Hyperaldosteronism
shock - Adrenal cortical adenoma (aldosteronoma)
• Empty Sella Syndrome – arachnoid herniates - Adrenal cortical (functioning) carcinoma
through a defect in the diaphragm a sella - Bilateral Adrenal hyperplasia (congenital
resulting in pressure atrophy of pituitary; hyperaldosteronism)
hypoituitarism usually not seen - hypertension, mild to moderate
• Craniopharyngioma – embryologic remnant - hypokalemia with asso. muscular
of Rathke’s pouch grossly seen as cysts weakness
containing oily fluid - peripheral neuropathy and arrhythmias
• Craniopharyngioma (Ameloblastoma) - retention of sodium and water
recapitulates dental enamel organ; cysts - polyuria
lined by stratified squamous or columnar - polydipsia
epithelium embedded in loose fibrous
connective tissue stroma. 2. Adrenogenital Syndrome
- causing Adrenal Virilism
ADRENAL GLANDS - Adrenal cortical adenoma
- Adrenal cortical (functioning) carcinoma
ANATOMY AND PHYSIOLOGY: - Congenital Adrenal hyperplasia (21
 Supra-renal Glands Hydroxylase deficiency)
 Approximately 5 gms each
 Adrenal Cortex - Adrenogenital Syndrome
o Zona glomerulosa o Children:
(mineralocortocoids)  distortion of external
o Zona Fasciculata genitalia in girls
(glucocorticoids)  precocious puberty in boys
o Zona Reticularis (glucocorticoids o Adults:
/androgen)  hirsutism, oligomenorrhea,
 Adrenal Medulla (catecholamines) deepening of voice,
hypertrophy of clitoris
Pathology of the Adrenal Glands  increased urinary excretion
of 17 - ketosteroids
 ADRENOCORTICAL HYPERFUNCTION
o (HYPERADRENALISM) HYPOADRENALISM:
 ADRENOCORTICAL INSUFFICIENCY 1. Primary acute adrenocortical insufficiency
o (HYPOADRENALISM) 2. Primary chronic adrenocortical insufficiency
 TUMOURS OF THE ADRENAL GLAND (Addison’s disease)
3. Secondary adrenocortical insufficiency
HYPERADRENALISM:
1. Cushing’s Syndrome Primary acute adrenocortical insufficiency
2. Conn’s Syndrome  Bilateral adrenalectomy
(primary aldosteronism)  Septicemia, endotoxic shock, adrenal
3. Adrenogenital Syndrome apoplexy (Waterhouse- Frederichsen
(adrenal virilism) Syndrome)
 Rapid steroid withdrawal
Pathology of the Adrenal Glands
1. Cushing’s Syndrome Primary chronic adrenocortical insufficiency
- Adrenal cortical (functioning) adenoma - causing Addison’s disease
ENDOCRINE PATHOLOGY
ROWEN T. YOLO, MD
- tuberculosis SECONDARY HYPERPARATHYROIDISM:

- autoimmune or idiopathic adrenalitis - occurs due to increased PTH elaboration
- histoplasmosis secondary to a disease elsewhere. The -
- amyloidosis hypocalcaemia stimulates compensatory
- metastatic disease to the adrenal glands hyperplasia of the parathyroid glands.
- sarcoidosis 1. Chronic renal insufficiency
- haemochromatosis 2. Vitamin D Deficiency
3. Intestinal malabsorption syndrome
Secondary adrenocortical insufficiency –
resulting from deficiency of ACTH TERTIARY HYPERPARATHYROIDISM:
1. selective ACTH deficiency - is a complication of secondary
2. panhypopituitarism hyperparathyroidism, in which hyperfunction
persists in spite of the removal of the cause
TUMOURS OF THE ADRENAL GLAND of the secondary hyperparathyroidism.
1. Adrenocortical Adenoma Possibly, an autonomous hyperplastic
2. Adrenocortical Carcinoma nodule of the parathyroid gland develops,
3. Phaeochromocytoma (chromaffin tumour) which continuously secrete large quantities
of PTH without regard to the need of the
PARATHYROID GLANDS body
ANATOMY AND PHYSIOLOGY: HYPOPARATHYROIDISM:

• Normally (4) in number, embedded in the 1. Surgically- induced
posterior aspect of the thyroid substance. 2. Congenital absence of the glands
However, anatomic variation in numbers 3. Familial hypoparathyroidism (autoimmune
may occur polyendocrine syndrome type 1)
• Yellowish- brown, flattened nodules, each 4. Idiopathic hypoparathyroidism
weighing approx. 35 – 45 mg.
• Parenchymal cells and stromal cells HYPOPARATHYROIDISM:

• Chief cells, oxyphil cells and clear cells - tetany char. by neuromuscular irritability
• Secrete parathyroid hormone (PTH), major (+ Chvostek sign and Trousseau sign)
source is the chief cells - mental status change
- ocular disease (cataracts)
Pathology of the Parathyroid Glands - intracranial manifestations
• HYPERPARATHYROIDISM - cardiovascular manifestations
• HYPOPARATHYROIDISM - dental abnormalities
• TUMOURS OF THE PARATHYROID GLANDS
HYPERPARATHYROIDISM: TUMOURS OF THE PARATHYROID GLANDS

1. Primary Hyperparathyroidism 1. PARATHYROID ADENOMA
2. Secondary Hyperparathyroidism 2. PARATHYROID CARCINOMA
3. Tertiary Hyperparathyroidism
PRIMARY HYPERPARATHYROIDISM:
1. Parathyroid adenomas (80%)
2. Parathyroid Carcinoma (2- 3 %)
3. Primary parathyroid (chief cell) hyperplasia
seen in 15% of cases
4. Component of MEN syndrome
PRIMARY HYPERPARATHYROIDISM:
- elevated PTH
- hypercalcaemia
- hypophosphataemia
- hypercalciuria
- nephrolithiasis / nephrocalcinosis
- metastatic calcification
- generalized osteitis fibrosa cystica
- depression, anxiety, coma, psychosis, coma
- hypertension (in about 50%)

REVIEW TEST
ROWEN T. YOLO, M.D
CHOOSE THE BEST ANSWER: the scalp. Her thyroid is palpably enlarged. Her
serum TSH is 11.7 mU/L with thyroxine of 2.1
____01. A 40-year-old woman notes increasing micrograms/dL. A year ago, serum anti-thyroglobulin
enlargement and discomfort in her neck over the and anti-microsomal autoantibodies were positive at
past week. The nurse practitioner palpates diffuse, high titers. Which of the following thyroid diseases is
symmetrical enlargement with tenderness in the she most likely to have?
region of the thyroid gland. Thyroid function tests A. DeQuervain disease
show serum TSH of 0.8 mU/L (0.4 to 4.0 mU/L) and B. Hashimoto thyroiditis
thyroxine of 11.9 micrograms/dL (4.6-12 ug/dL). C. Multinodular goiter
She is referred to an endocrinologist, but the next D. Subacute lymphocytic thyroiditis
available appointment is in 8 weeks. When
examined by the endocrinologist her thyroid is no _____05. A 45-year-old woman has had multiple
longer palpable and there is no pain. Repeat thyroid episodes of lower abdominal pain for the past year.
function tests reveal a serum TSH of 3.8 mU/L and She passed a urinary tract stone during following an
thyroxine of 5.7 micrograms/dL. Which of the episode of excruciating pain. During the past month
following thyroid diseases is most likely to produce she also has pain in her right middle finger. On
these findings? physical examination there is pain on palpation of
A. DeQuervain thyroiditis her right 3rd proximal phalanx. Laboratory studies
B. Hashimoto thyroiditis show a serum calcium of 13.7 mg/dL (8.5-
C. Graves disease 10.2 mg/dL), phosphorus of 1.9 mg/dL (2.5 to
D. Riedel thyroiditis 4.5 mg/dL), creatinine 1.1 mg/dL (0.6–1.1 mg/dL),
and albumin 4.8 g/dL (3.5 to 5.5 g/dL). Which of the
____02. A 24-year-old medical student has difficulty following bone lesions is she most likely to have?
concentrating on her studies for the past months. A. Osteitis fibrosa cystica
She is constantly gets up early and barely gets a B. Osteoid osteoma
good night’s rest. She always complains that the C. Osteomyelitis
pathology laboratory is too hot. She seems nervous D. Osteosarcoma
and often spills her coffee. She has been eating
more but has lost 6 kg in the past 2 months. On ____06. A clinical study in USTH is performed with
physical examination her temperature is 37.5°C, subjects who were diagnosed with transient or
pulse 105/minute, respiratory rate 24/minute, and sustained hyperthyroidism, compared with a control
blood pressure 140/80 mm Hg. Which of the group of subjects who were euthryoid. The
following laboratory findings is diagnostic of this pathologic findings in the thyroid glands of these
woman’s disease? subjects are analyzed to determine the spectrum of
A. Decreased catecholamines disease processes present. Which of the following
B. Decreased radioactive iodine uptake pathologic processes is most likely to be found with
C. Decreased TSH equal frequency in both the study and the control
D. Increased serum calcium subjects?
A. Subacute granulomatous thyroiditis
_____03. A 43-year-old female has noted B. Multinodular goiter
enlargement of her anterior neck region over the C. Hashimoto thyroiditis
past 8 months. On physical examination her vital D. Medullary carcinoma
signs include T-36.8°C, Pulse rate- 64/minute, RR-
17/minute, and BP- 130/80 mm Hg. There is _____07. A 50-year-old woman feels a 'lump' in her
nodular, symmetrical thyroid enlargement without neck that she barely notices 6 months before. Her
tenderness. A chest radiograph is normal. Fine physician palpates a firm 2.0 cm nodule to the left of
needle aspiration of the thyroid yields cells midline in the region of the thyroid gland. By
consistent with a neoplasm. Laboratory studies show scintigraphic scanning this nodule appears “cold”
that she is euthyroid, but her serum ionized calcium with normal activity in the surrounding normally
is elevated. She is taken to surgery and frozen sized thyroid gland. Which of the following is the
sections of nodular masses show a malignant most likely diagnosis?
neoplasm composed of polygonal cells in nests. A A. Follicular adenoma
thyroidectomy is performed. Immunostaining for B. Thyroglossal duct cyst
calcitonin of the permanent sections is positive, and C. Toxic nodular goiter
the neoplasm has amyloid stroma with Congo red D. Papillary carcinoma
staining. Which of the following neoplasm is she
most likely to have? _____08. A 21-year-old medical student felt a
A. Anaplastic carcinoma “lump” in her neck for the past 5 months. On
B. Medullary thyroid carcinoma physical examination there is a firm nodule in the
C. Papillary thyroid carcinoma. right lobe of her thyroid. Following fine needle
D. Parathyroid carcinoma aspiration and cytologic diagnosis of a neoplasm, a
thyroidectomy is performed. Grossly, there is a 3.0
_____04. A 52-year-old woman has increasing cold cm mass in the right lower pole that on sectioning is
intolerance, associated with weight gain of 5 kg, and cystic and has fine excrescences. Which of the
sluggishness over the past two years. A physical following microscopic pathologic finding is most
examination reveals dry, coarse skin and alopecia of associated with this lesion?
REVIEW TEST
ROWEN T. YOLO, M.D
A. Atrophic thyroid follicles 8.8 microU/mL in association with a serum total

B. Amyloid stroma thyroxine of 15.1 microgram/dL. Which of the
C. Clear nuclear chromatin following is the most likely explains the clinical
D. Giant cells manifestations?
A. Diffuse thyroid hyperplasia
_____09. A 47-year-old man with SLE progressed to B. Pituitary TSH adenoma
chronic renal failure and was placed on chronic C. Chronic thyroiditis
hemodialysis. He developed severe hypertension. He D. Multinodular goiter
had difficulty accepting the reality of his disease, he
often missed dialysis appointments and did not take _____13. A 30-year-old previously healthy
his antihypertensive medication regularly. basketball champion complaints of lateral visual field
Laboratory studies now show serum ionized calcium deficits. His facial features have changed over the
is 4.9 mg/dL with phosphorus 7.5 mg/dL and past year. His shoe size has increased. A head CT
albumin 3.6 g/dL. The prominent clinical and scan reveals enlargement of the sella turcica. Which
laboratory manifestations of his illness is a reflection of the following hormones is most likely being
of which endocrine abnormality? secreted in excessive amounts in this man?
A. Hyperparathyroidism A. ACTH
B. Hypothyroidism B. Antidiuretic hormone
C. Hyperthyroidism C. Growth hormone
D. Hypopituitarism D. Luteinizing hormone
____10. A 35-year old mother, who has two healthy _____14. A 12-year-old boy has had worsening
children, notes that she has had no menstrual headaches for 2 months. On eye examination show
periods for the past year, but she is not pregnant diminished peripheral vision, but no loss of visual
and takes no medications. Within the past week, she acuity. A head CT scan reveals a 2.0 cm mass
has noted some milk production from both of her expanding the sella turcica and eroding the sphenoid
breasts. She has been bothered by intermittent bone. The mass is cystic with scattered
headaches for the past 3 months. After nearly calcifications. Which of the following is the most
hitting a jeepney while changing lanes whilst driving likely diagnosis?
her vehicle, she is concerned with her poor vision. A. Craniopharyngioma
An ophthalmologist finds her lateral vision to be B. Empty sella syndrome
reduced. On physical examination she is afebrile and C. Hypothalamic a
normotensive. Which of the following is most likely D. Pituitary adenoma
to be present in this patient?
A. Craniopharyngioma _____15. The mother of a 1-year-old infant noted
B. Pituitary adenoma enlargement of her baby's abdomen within the past
C. Rathke’s cyst 3 months. This is confirmed by the pediatrician, who
D. Sheehan syndrome notes that the baby is otherwise normally
developed. An abdominal CT scan reveals a 5.0 cm
____11. A 25-year-old primigravida who received no retroperitoneal mass, with some scattered
prenatal care presents with profuse vaginal bleeding calcifications, superior to the right kidney.
after the onset of labor at 38 weeks gestation. Laboratory studies show an elevated urinary
Emergency caesarean section is performed due to vanillylmandelic acid (VMA), while the urinary
abruption placenta. She remains hypotensive for 6 homovanillic acid (HVA) is only slightly increased.
hours and requires transfusion of 10 packed RBC The mass is removed and microscopically is
units. Postpartum, she becomes unable to breast- composed of sheets of small blue cells. What is the
feed the infant. She does not have a resumption of most likely diagnosis?
normal menstrual cycle after 6 months. She A. Congenital adrenal hyperplasia
becomes more sluggish and tired. Laboratory B. Neuroblastoma
findings include hyponatremia, hyperkalemia, and C. Non-Hodgkin lymphoma
hypoglycemia. Which of the following pathology D. Pheochromocytoma
most likely explains her postpartum clinical
presentations? ____16. A 15-year-old previously healthy grade VIII
A. Bilateral adrenal haemorrhage student has had a mild pharyngitis followed by a
B. Pituitary necrosis high fever over the past 48 hours. When seen in the
C. Post-partum goiter -emergency room, where his skin now shows
D. Pregnancy-induced Insulitis extensive areas of purpura. Vital signs include
temperature of 40°C, pulse rate of 110/minute,
_____12. A 35-year-old woman has had insomnia respiratory rate 22/minute, and blood pressure
for the past 4 months, as well as episodes of 70/50 mm Hg deteriorating to palpatory. Laboratory
diarrhea with up to 4 loose stools per day. On studies show a serum sodium-120mmol/L,
physical examination, she exhibits bilateral potassium- 5.3 mmol/L, chloride- 92 mmol/L, CO2 22
proptosis. Her outstretched hands have a fine mmol/L, glucose- 30 mg/dL (70 to 100 mg/dL)., and
tremor. On palpation of her neck, the thyroid gland creatinine- 1.1 mg/dL. He died after 2 hours.
does not appear to be enlarged but a solitary nodule Autopsy will reveal which of the following expected
is palpable. Laboratory studies show a serum TSH of pathologic change in the adrenal glands?
REVIEW TEST
ROWEN T. YOLO, M.D
A. Adrenal cortical carcinoma _____20. A 52-year-old woman complaints of

B. Bilateral Adrenal apoplexy diffuse, dull, constant abdominal pain for the past 2
C. Bilateral adrenal macronodular months. On physical examination no abnormal
hyperplasia findings are noted. An abdominal CT scan shows a 3
D. Phaechromocytoma cm right adrenal mass. The right adrenal is excised
and on microscopic examination the mass is
_____17. A 39-year old male financial analyst notes composed of cells resembling normal adrenal cortex.
moon facie and buffalo hump changes, and Which of the following features is the most reliable
complaints of gradual increase in abdominal girth indicator that this mass is malignant?
and constant back pain exacerbated by movement A. Cellular atypia
and increasing weakness over the past 3 months. B. Necrosis
On physical examination his blood pressure is C. High mitosis
170/110 mm Hg. He is overweight, with a BMI of D. Invasion
28. A radiograph of the spine reveals a compressed
fracture at T10-T11. MRI scan of the whole body _____21. A 69-year-old woman with severe
reveals a 10.0 cm retroperitoneal mass in the right rheumatoid arthritis has been on chronic NSAID and
with cannon ball lesions in both lungs suggestive of corticosteroid therapy for the past 20 years. She is
metastatic disease. Laboratory findings include a admitted for an orthopedic procedure to correct a
serum glucose of 155 mg/dL. Which of the following joint deformity from her disease. She continues to
pathologic lesion most likely explains his findings? receive her regular dosage of 5 mg of prednisone
A. Adrenal cortical carcinoma per day. Four days postoperatively, she develops an
B. Anaplastic thyroid carcinoma aspiration pneumonia with Pseudomonas aeroginosa
C. Extra adrenal phaeochromocytoma cultured from sputum. Five days following the
D. Pancreatic insulinoma surgery, she becomes obtunded. Laboratory findings
at that time include: sodium 100 mmol/L, potassium
_____18. A 33-year-old woman has noted a weight 5.5 mmol/L, glucose 30 mg/dL, and creatinine 1.1
gain of 7 kg over the past year. She has normal mg/dL. Which of the following complications is most
menstrual periods. On physical examination her likely to have occurred in this patient?
blood pressure is 170/100 mm Hg. Her skin shows A. Anterior pituitary necrosis
marked plethora. Abdominal striae are present. A B. Acute Addisonian crisis
serum electrolyte panel shows sodium 145 mmol/L C. Conn syndrome
(135-147 mEq/L), potassium 4.5 mmol/L (3.5-5.0 D. Waterhouse-Friderichsen syndrome
mEq/L)., glucose 170 mg/dL, and creatinine 0.9
mg/dL. Which of the following imaging findings _____22. A 15-year old boy presents with
would be most expected to be present in this mucocutaneous neuromas and marfanoid features.
patient? His older brother has had a total thyroidectomy for
A. 2 cm solitary adrenal nodule with medullary thyroid carcinoma and later has been
abdominal CT scan diagnosed with bilateral tumours of the adrenal
B. 4 cm mass at aortic bifurcation with MRI medulla. It is likely that investigation of both
imaging brothers will demonstrate an abnormality of which of
C. 2 cm “hot” solitary thyroid nodule with the ff gene/gene products?
Tc99 scintigraphic scan A. BRAF
D. Multiple pulmonary nodules on chest B. KRAS
radiograph C. N-myc
D. RET
_____19. A 50-year-old physician has episodic
headaches for the past 3 months. On physical _____23. An 80-year old grandfather is found
examination his blood pressure reaches up to comatose in his house. On physical examination he
190/110 mm Hg on occasions, with no other has decreased skin turgor. Laboratory studies show
remarkable findings. Laboratory studies show blood glucose of 800 mg/dL. Urinalysis reveals no
sodium 144 mmol/L, potassium 4.2 mmol/L, glucose ketosis or proteinuria, and 4+ glucosuria. Which of
90 mg/dL, and creatinine 1.3 mg/dL. An abdominal the following is the most likely diagnosis?
CT scan shows an 3.0 cm left adrenal mass. During A. Type I diabetes mellitus
surgery, as the left adrenal gland is removed, there B. Type II diabetes mellitus
was a marked rise in blood pressure that caused - C. Cushing syndrome
apprehension with the OR team. Which of the D. Neuroendocrine tumor secreting
following laboratory test findings most likely explains glucagon
his findings?
A. Decreased serum cortisol
B. Increased urinary 17-ketosteroids
C. Increased plasma ACTH
D. Increased urinary VMA

REVIEW TEST
ROWEN T. YOLO, M.D
_____24. 10. A 65-year-old professor retiree from a

hypertensive haemorrhage in the brain. At autopsy,
the pancreas is found to have amyloid deposits in
the islets of Langerhans. Which of the following
metabolic complications was he most likely to have
experienced?
A. Hypoglycemic shock
B. Ketoacidosis
C. Pancreatitis
D. Hyperosmolar coma
_____ 25. A 20-year old student dies of

overwhelming sepsis due to pneumonia. He is a
known diabetic since birth. Examination of the
pancreas will most likely show which striking
diagnostic feature?
A. Amyloid deposition
B. Compensatory islet cell hyperplasia
C. Leukocytic infiltration of the islets
D. Hyaline arteriosclerosis
_____26. The morbidity associated with long-

standing diabetes types I and II is due to damaged
induced macrovascular and microvascular disease.
The hallmark of diabetic macrovascular disease is:
A. Accelerated atherosclerosis involving
large and medium-sized arteries
B. Endothelial basement membrane
thickening of the glomerular capillaries
C. Hyaline atherosclerosis of the wall of
arterioles and capillary-type vessels
D. Monckeber’s medial arterial sclerosis of
medium-sized arteries and arterioles

CARDIOVASCULAR PATHOLOGY
JOCELYN MYRA R. CAJA, MD
Heart Disease - Intrinsic disease of the lungs or pulmonary

40% of all deaths vasculature
80% due to IHD - Functional RV outflow obstruction (cor
5-10% Hypertensive HD, Congenital HD, pulmonale) or tricuspid or pulmonary valvular
Common Valvular Disease disease
Abnormal circulatory function with the

• Manifestations:
1. portal, systemic and dependent
following:
peripheral congestion and edema
1. Disruption of continuity of circulation – permits 2. hepatomegaly
blood to escape e.g. gunshot wound through the
- centrilobular congestion and atrophy –
thoracic aorta
“nutmeg appearance”
2. Disorder of cardiac conduction
- centrilobular necrosis
(e.g. heart block) or other arrhythmia
- centrilobular hemorrhagic necrosis
(e.g.ventricular fibrillation) – uncoordinated - centrilobular sclerosis
contractions of muscular wall
3. congestive splenomegaly
2. Lesions preventing valve opening or narrowing 4. renal congestion, hypoxic injury and ATN (more
the lumen of a vessel (e.g. AS or coarctation) –
marked in right than left sided CHF)
obstructs blood flow and overworks the pump
3. Regurgitation flow – (e.g. MR or AR) – causes Ischemic Heart Disease
output from each contraction to be directed
backward • Group of closely related syndromes resulting from
5. Failure of the pump itself (e.g. CHF) – potential ischemia
common end point of many forms of serious HD • Ischemia – insufficient O2 (hypoxia/anoxia)
- reduced available nutrient substrates
Congestive Heart Failure - inadequate removal of metabolites
• From impaired cardiac function rendering the Causes:
heart to maintain an output sufficient for 1. reduced coronary blood flow (>90%)
metabolic requirements of the tissues & organ of - coronary atherosclerosis with vasospasm,
the body. thrombosis or both
2. increased myocardial demand (tachycardia,
• Characterized by: diminished CO “forward failure” hypertrophy)
or damming back of blood in the venous system
- exceeding vascular supply
“backward failure” or both 3. Hypoxia due to diminished oxygen transport
• Compensatory changes: - severe anemia, advanced lung disease,
1. pressure and volume stress induces cyanotic congenital HD, CO poisoning,
hypertrophy cigarette smoking
- hypertrophy initially adaptive but can make
myocytes vulnerable to injury Four General Ischemic Syndromes:
2. ventricular dilatation
I. Angina Pectoris
to improve contraction by stretching of
myofibers • Paroxysmal substernal / precordial pain /
3. blood volume expansion by salt and water discomfort due to ischemia without frank
retention infarction
4. tachycardia • >75% stenoses in major coronary arteries,
vasospasm, plaque disruption or fissures
Left-Sided Heart Failure
• Stab le, Prinzmetal, Unstable
• Major causes are IHD, hypertension, aortic and
mitral valve disease, myocardial disease II. Myocardial Infarction (MI)
• Manifested as: pulmonary congestion and edema • Death of cardiac muscle cells
• ↓ CO causes ↓ renal perfusion leading to: • AMI means necrosis of myocytes as a result of a
1. further salt and water retention reduction or cessation in coronary flow
2. ischemic ATN
3. impairment of waste excretion – prerenal • at least 6 hours survival needed for recognizable
azotemia structural changes to develop in tissue
• CNS perfusion reduced, resulting in hypoxic • infarcted tissue is grossly redder than normal at
encephalopathy 12 hrs, becomes paler and yellow in 3 days
• may be regional or diffuse
Right-Sided Heart Failure
• may be subendocardial or transmural
• Typically, consequence of left-sided failure
• Pure right-sided causes: Current protocol: myoglobin, troponin I or T, CK
mass & activity
• Interference: hemolysis, lipemia, icterus

• Creatine kinase (CPK): cytoplasmic & Hypertensive Heart Disease

mitochondrial enzyme for creatine in striated -Excluded: RV enlargement due to congenital
muscle needed for contraction; higher in skeletal heart disease
than in cardiac muscle injury Systemic (left-sided) Hypertensive Heart Disease
• CK-MB mass: “gold standard” biochemical Criteria:

marker for early diagnosis of AMI a. LV hypertrophy (concentric)
• CK-MB activity: used for rapid screening, but b. History of HPN
cannot distinguish between BB & MB c. Absence of other lesion that might induce cardiac
• Myoglobin: earliest, sensitive, but nonspecific hypertrophy
marker for early diagnosis of AMI; must rule out
skeletal muscle trauma or renal failure; highly Pulmonary (Right-sided) Heart Disease (Cor
suggestive when level doubles in 1 to 2 hrs even if pulmonale)
still within normal limits
Criteria:
• Troponin I & T: highly specific for myocardial RV hypertrophy or dilatation 2 to pulmonary
injury; useful when assessment is delayed hypertension or LV pathology
Typical diagnostic windows: Valvular Heart Disease
• Myoglobin: rise 2-4 hr; peak 6-12 hr, nil >24 hr
• Degenerative Calcific Aortic Valve Stenosis
• CK-MB mass: rise 4-6 hr, peak 12-24 hr, nil >48 • Mitral Annular Calcification
hr • Mitral Valve Prolapse
• Troponin I: rise 4-8 hr, peak 12-14 hr, nil >5 - enlarged, myxomatous, floppy, balloon back
days into the LA during systole
• Troponin T: rise 4-8 hr, peak 14-18 hr, nil >14
Rheumatic Fever & Rheumatic Heart Disease
days
Rheumatic Fever
• CK total: rise 6-8 hr, peak 24-36 hr, nil >3 days
• Acute, recurrent inflammatory disease of children
(5-15 y/o) occurring 1-5 weeks after a group A
• LDH: rise 8-12 hr, peak 24-48 hr, nil >7 days Streptococcal infection (sore throat)
• Secondary to host anti-Streptococcal Ab cross
III. Chronic Ischemic Heart Disease reacts with cardiac Ag
• In elderly with moderate to severe multivessel
coronary atherosclerosis → insidiously develop Five Major Jones Criteria
CHF • Erythema margination
• May result from post-infarction cardiac • Sydenham’s chorea
decompensation or slow ischemic myocyte
degeneration • Carditis
• Diagnosis by exclusion of other causes of CHF • Subcutaneous nodules
• Death – due to AMI; arrhythmic event; 2 to • Migratory large joint polyarthritis
unrelated causes
Minor Criteria:
IV. Sudden Cardiac Death Fever, arthralgia
• Unexpected cardiac death within 1 hour of
Typically, myocarditis and arthritis
symptom onset
resolve into complication but valvular
involvement may lead to deformation
Causes:
and scarring (Chronic RHD) and
1. marked atherosclerotic stenosis - 75-95%
subsequent CHF
2. MI - 25%
3. aortic valvular stenosis
Acute RF: Aschoff bodies
4. hereditary / acquired conduction system
abnormalities • Pathognomonic focal inflammatory nodules
5. electrolyte derangements • Foci of fibrinoid necrosis, initially surrounded by
6. MVP lymphocytes, macrophages, few plasma cells
7. dilated or hypertrophic cardiomyopathy then replaced by fibrous scar
8. myocarditis • In pericardium induces fibrinous pericarditis
• Ultimate mechanism: fatal arrhythmia • Inflammatory valvulitis – beady fibrinous
vegetations “verrucae”

Chronic RHD or healed valve: Contributory factors: genetic defect, alcohol toxicity,
1. fibrous thickening of leaflet peripartum CMP, postviral myocarditis
2. bridging fibrous across commissures
“commissural fusion”
• Cardiomegaly (up to 900 gm)
3. thick, fused, shortened MV chordae
2. Hypertrophic CMP
Infective Endocarditis (IE) • Idiopathic Hypertrophic Subaortic Stenosis
(IHSS), HOCM
• Colonization of heart valves by microorganisms –
friable, bulky vegetations • Heavy, contractile, poorly compliant heart
• Young adults, familial (autosomal dominant)
Acute IE
• LVH > RVH, atrial dilatation
• Highly virulent organism: Staph. aurues
• concentric / symmetric hypertrophy
• Previously normal valve – necrotizing, ulcerative
infection 3. Restrictive CMP
• Rapidly develop fever, rigors, malaise • Rare entity with diverse causes → restriction of
• Death in 50-60% of patients ventricular filling
Subacute IE
• Interstitial myocardial fibrosis
• Moderate to low virulence organism: Strep.

• Endomyocardial fibrosis
faecalis, bovis • Loeffer’s endocarditis
• Seeding an abnormal or previously injured valve • Endocardial fibroelastosis
• Insidious onset of fever, nonspecific malaise II. Specific Heart Muscle Disease
• Less fatal than acute IE Myocarditis
Clinical Consequences of IE:

• Myocardial inflammation
1. direct injury to valves (regurgitation/ • Broad, entirely asymptomatic
stenosis with CHF) or myocardium (ring
abscess, perforation) • Arrhythmia, CHF, sudden death
2. emboli to spleen, kidneys, brain (mets
infection) Congenital Heart Disease
3. renal injury (embolic infarction/ infection),
nephritic syndrome, renal failure 1. Left to Right Shunts/ Acyanotic or Late
Diagnosis – confirmed by blood cultures Cyanosis:
 Ventricular Septal Defect (VSD)
Nonbacterial Thrombotic Endocarditis (NBTE) - hole within the membranous or muscular portions
of the intraventricular septum
• Marantic endocarditis - produces a left-to-right shunt
• Small, sterile, bland fibrin and platelet thrombi - more severe with larger defects
(vegetations) loosely adherent to valve leaflets
• Setting: in cancer, prolonged debilitating illness  Atrial Septal Defect (ASD)
- hole from septum secundum or septum primum
• DIC or hypercoagulable state defect interatrial septum
- produces modest left-to-right shunt
Endocarditis associated with SLE (Libmans-
Sack’s Endocarditis)  Patent Ductus Arteriosus (PDA)
• Valvulitis of uncertain pathology - normally closes soon after birth
- remains open
• M and T valves with fibrinoid necrosis, mucoid - left-to-right shunt develops
degeneration → small, fibrinous sterile
vegetations 2. Right to Left Shunts/ Cyanotic or Early
Cyanosis:
Myocardial Disease  Tetralogy of Fallot - pulmonic stenosis results in
right ventricular hypertrophy and a right-to-left
I. Cardiomyopathy shunt across a VSD, which also has an overriding
• Heart muscle disease of unknown cause aorta
 Transposition of Great Vessels
1. Dilated Cardiomyopathy (CMP) - aorta arises from the right ventricle, pulmonic
trunk from the left ventricle
• Gradual four-chamber hypertrophy & dilatation
- VSD, or ASD with PDA, is needed for
• Any age, slow/progressive CHF extrauterine survival
• Cause: unknown - right-to-left shunting.

 Truncus Arteriosus 4. Neurologic: psychogenic, inc ICP, sleep

- incomplete separation of the aortic and apnea, acute stress
pulmonary outflows, with VSD
- allows mixing of oxygenated and deoxygenated Vascular pathology in HPN:
blood 1. Hyaline arteriosclerosis – increased protein
- right-to-left shunting deposition  pink hyaline, lumen markedly
 Hypoplastic Left Heart Syndrome - - varying narrowed
degrees of hypoplasia or atresia of the aortic and 2. Hyperplastic arteriosclerosis – onion-skinning,
mitral valves lumenal obliteration, occurs in severe (malignant)
- small to absent left ventricular chamber HPN, may be accompanied by fibrinoid deposits/
 Coarctation of Aorta – vessel wall necrosis (necrotizing arteriolitis)
- proximal (infantile form) or just distal (adult
form) to the ductus Arteriosclerosis
- narrowing of the aortic lumen leading to -“hardening of the arteries” arterial wall thickening &
outflow obstruction loss of elasticity
 Total Anomalous Pulmonary Venous Return 3 patterns:
(TAPVR) --- 1. arteriolosclerosis – affects small arteries and
- pulmonary veins do not directly connect to the arterioles, may cause downstream ischemic injury
left atrium 2. Monkeberg medial sclerosis – calcific depostis in
- drain into left innominate vein, coronary sinus, muscular arteries, >50y/o, do not encroach on
or some other site - lead possible mixing of lumen, not clinically significant
blood and right-sided overload 3. atherosclerosis – “gruel” or “hardening”, most
frequent and clinically important
Tumors of the Heart Atherosclerosis

Primary tumors of the heart – rare - characterized by intimal lesions –atheroma
Most common primary cardiac tumors: (atheromatous plaques)
1. myxomas Major Risks:
2. fibromas Nonmodifiable Modifiable
3. lipomas Inc age Hyperlipidemia
4. papillary fibroelastomas Male gender Hypertension
5. rhabdomyomas Family history Cigarette smoking
6. angiosarcomas and other sarcomas Genetic abn Diabetes
1st Five most common tumors - benign Additional risk factors:
- account for 80% to 90% of primary tumors Inflammation (C-reactive protein)
of the heart Pathogenesis:
 Endothelial injury
Metastatic tumors to the heart occur in about 5% of  Accumulation of lipoproteinsin the vessel
persons dying of cancer wall
 Monocyte adhesion to the
Vascular Diseases endotheliummacrophage and foam cells
Congenital Anomalies  Platelet adhesion
- development of berry aneurysms  Factor release from activated platelets,
- AV fistulas macrophage & vascular wall  smooth
- fibromuscular dysplasia muscle recruitment
 Smooth muscle cell proliferatiom& ECM
Hypertensive Vascular Disease production
sustained diastolic press > 89 mm Hg, or sustained  Lipid accumulation
systolic press > 139 mm Hg, increased risk of
atherosclerosis, clinically significant hypertension Morphology:
Causes: Fatty streaks – earliest lesion
Essential HPN 90-95% cases Atherosclerotic plaque
Secondary HPN: Susceptible to:
1. Renal: AGN, Chronic renal disease, - Rupture, ulceration, erosion, thrombosis
polycystic disease, renal artery stenosis, - Hemorrhage into a plaque
renal vasculitis, renin-producing tumors - Atheroembolism
2. Endocrine: adrenocortical hyperfunction, - Aneurysm formation
exogenous hormones, pheochromocytoma, Consequences:
acromegaly, hypothyroidism, Large elastic arteries, large & medium-sized
hyperthyroidism, pregnancy-induced muscular arteries – major targets
3. Cardiovascular: coarctation of aorta, *arteries supplying the heart, brain, kidneys, and
polyarteritis nodosa, increased intravascular lower extremitiesmyocardial infarction, cerebral
volume, increased cardiac output, rigidity of infarction (stroke), aortic aneurysms, and peripheral
aorta vascular disease
- Atherosclerotic stenosis
- Acute plaque change
- Thrombosis Vasculitis
- Vasoconstriction Type Examples Description
Aneurysm & Dissection can be involved

Aneurysm - Localized abnormal dilatation of blood with aneurysm
vessel or heart; congenital or acquired formation and/or
1. True aneurysm – involves intact attenuated thrombosis.
arterial wall or thinned out ventricular wall SMALL- Wegener Granulomatous
(heart) e.g. atherosclerotic, syphilitic, congenital VESSEL granulomatosis inflammation
vascular aneurysm, ventricular aneurysm after VASCULITIS involving the
transmural MI respiratory tract
2. False aneurysm – defect in vascular wall leading and necrotizing
to extravascular hematoma e.g. ventricular vasculitis affecting
rupture after MI contained by pericardial small vessels,
adhesion including
glomerular vessels.
Dissection – blood enters the arterial wall itself as Associated with
hematoma dissecting between layers PR3-ANCAs.
Abdominal Aortic Aneurysm (AAA)
- common in abdominal aorta, atherosclerotic Arterioles, Churg-Strauss Eosinophil-rich
plaque compresses underlying media; risk: venules, syndrome granulomatous
men & smokers usually >50y/o capillaries, inflammation
Thoracic aortic aneurysm and involving the
- commonly associated with HPN occasionally respiratory tract
Aortic Dissection small arteries and necrotizing
- two groups: vasculitis affecting
1. men aged 40-60 w/ antecedent HPN small vessels.
2. younger patients w/ systemic or localized Associated with
abnormalities of connective tissue asthma and blood
(Marfan syndrome) eosinophilia.
Associated with
Vasculitis MPO-ANCAs.
Vasculitis Microscopic Necrotizing small-

Type Examples Description polyangiitis vessel vasculitis
with few or no
LARGE- Giant-cell Granulomatous
immune deposits;
VESSEL (temporal) inflammation;
necrotizing arteritis
VASCULITIS arteritis frequently involves
of small and
the temporal artery.
medium-sized
Usually occurs in
arteries can occur.
patients older than
Necrotizing
age 50 and is
glomerulonephritis
associated with
and pulmonary
polymyalgia
capillaritis are
rheumatica
common.
Aorta and Takayasu Granulomatous Associated with
large arteritis inflammation MPO-ANCAs.
branches to usually occurring in
extremities, patients younger Non-Infectious causes usually immunologic
head, and than age 50 Infectious causes
neck
MEDIUM- Polyarteritis Necrotizing Raynaud’s Phenomenon
VESSEL nodosa inflammation - from exaggerated vasoconstriction of digital
VASCULITIS typically involving arteries and arterioles
renal arteries but - paroxysmal pallor & cyanosis of digits of hands or
sparing pulmonary feet
vessels
Veins and Lymphatics
Main visceral Kawasaki Arteritis with Varicose Veins
arteries and disease mucocutaneous Thrombophlebitis and Phlebothrombosis
their branches lymph node Superior Vena Caval Sydromes
syndrome; usually Lymphagitis and Lymphedema
occurs in children.
Coronary arteries

Tumors
BENIGN NEOPLASMS, DEVELOPMENTAL AND

ACQUIRED CONDITIONS
Hemangioma
Capillary hemangioma
Cavernous hemangioma
Pyogenic granuloma
Lymphangioma
Simple (capillary) lymphangioma
Cavernous lymphangioma
(cystic hygroma)
Glomus tumor
Vascular ectasias
Nevus flammeus
Spider telangiectasia (arterial
spider)
Hereditary hemorrhagic
telangiectasis (Osler-Weber-
Rendu disease)
Reactive vascular proliferations

Bacillary angiomatosis
INTERMEDIATE-GRADE NEOPLASMS
Kaposi sarcoma
Hemangioendothelioma
MALIGNANT NEOPLASMS
Angiosarcoma
Hemangiopericytoma

REVIEW TEST
_____1. Commissural fusion is a constant _____9. At 24-72 hours, myocardial infarct is

pathologic lesion of which valve disease? characterized by:
A. congenital mitral stenosis A. myocardial waviness
B. myxomatous mitral valve B. loss of striations and heavy
C. parachute mitral valve neutrophilic infiltration
D. rheumatic mitral stenosis C. dense fibrosis
D. cytomyolysis and macrophages
_____2. The leading cause of valvular cardiac
disease in the Philippines is which of these? _____10. The most common site of coronary
A. infective endocarditis artery atherosclerotic occlusion is the:
B. rheumatic valvular disease A. right main coronary artery
C. myxomatous mitral valve B. posterior descending branch
D. degenerative calcific valvular disease C. left anterior descending branch
D. left circumflex artery
_____3. The most commonly involved valve in
rheumatic heart disease:
A. mitral
B. aortic
C. pulmonary
D. tricuspid
_____4. Myxomatous changes in the spongiosa
layer of the mitral valve is characteristic of:
A. rheumatic valvular disease
B. mitral valve 1rolapsed
C. congenital mitral valve stenosis
D. senile degenerative changes in mitral
valve
_____5. Infective endocarditis of the mitral

valve may be complicated by:
A. systemic embolization
B. valvular insufficiency
C. both
D. neither
_____6. Acute left ventricular failure is

manifested by:
A. pulmonary edema
B. dilated internal jugular veins
C. nutmeg liver
D. congestive splenomegaly
_____7. Failure of the left ventricle after a

massive infarct can lead to which condition?
A. pulmonary arterial hypertension
B. pulmonary edema
C. pulmonary infarct
D. pulmonary hemorrhage
_____8. The imbalance in ischemic heart

disease is seen in the supply and demand of
the myocardium for which of these?
A. glucose
B. albumin
C. oxygen
D. carbon dioxide

PATHOLOGY OF THE LUNGS
(LUNG DISEASES)
JOCELYN MYRA R. CAJA, M.D.
PATHOLOGY OF THE LUNGS Edema Caused by Microvascular Injury
(LUNG DISEASES) • Injury to the capillaries of the alveolar septa
• Primary injury to vascular endothelium or
Congenital Anomalies damage to alveolar epithelial cells →
Developmental defects of the lungs: leakage of fluids & proteins in interstitium →
1. Agenesis or hypoplasia of both lungs, 1 lung alveoli
or single lobes • Edema localized in pneumonia
2. Tracheal & bronchial anomalies • Edema diffuse contribute to ARDS
3. Vascular anomalies
4. Congenital lobar overinflation (emphysema) Adult Respiratory Distress Syndrome (ARDS)
5. Congenital cysts or Diffuse Alveolar Damage (DAD)
6. Intralobar and extrapulmonary lobar • Diffuse alveolar capillary damage
sequestrations • Clinically: rapid onset of severe respiratory
insufficiency, cyanosis, severe arterial
Atelectasis hypoxemia
• Incomplete expansion of the lungs • Severe edema – non-cardiogenic, low
• Collapse of previously inflated lung pressure, high permeability
substance • Histology: hyaline membranes (mechanism
• Significant condition result to: different from RDS of newborns)
1. Reduced oxygenation • well-recognized complications of numerous
2. Predisposes to infection and diverse conditions:
1. Direct lung injuries
Types of Atelectasis: infection, O2 toxicity, inhaled toxins, other
1. Resorption atelectasis irritants and aspiration of gastric content
● From complete obstruction of an airay 2. Systemic
largely due to excessive seretions or Septic shock, shock due to trauma, hem.
exudates in smaller bronchi found in: pancreatitis, burns, complicated abdominal
a. bronchial asthma surgery, narcotic overdose, drug reactions,
b. chronic bronchitis hypersensitivity reactions
c. post-op status
d. aspiration of foreign bodies Morphology:
Initial: - congestion, interstitial and intra-
Mediastinum shifts toward atelectatic lung alveolar edema, inflammation
2. Compression atelectasis fibrin depositions
● Pleural cavity partly or completely filled by: - Alveolar walls become lined with waxy
fluid exudate, tumor, blood, air hyaline membrane
- Type II epithelial cells proliferate
Mediastinum shifts away from the affected lung Later: - organization of fibrin exudate →
3. Patchy atelectasis intra-alveolar fibrosis
● Develops when there is loss of surfactant as - marked thickening of alveolar septa,
in neonatal (RDS) and adult (ARDS) proliferation of interstitial cells, deposition of
4. Contraction atelectasis collagen
● When local or generalized fibrotic changes in
lung or pleura prevent full expansion Pathogenesis: final common pathway:
diffuse damage to alveolar capillary wall
Diseases of Vascular Origin Initial injury: capillary endothelium (most
Pulmonary Congestion & Edema frequently)
I. Hemodynamic disturbances
II. Microvascular injury Alveolar epithelium (occasionally)
Consequent: increased capillary permeability
Hemodynamic pulmonary edema Interstitial → intra alveolar edema
• most attributable to increased hydrostatic Fibrin exudation formation of hyaline
pressure, occurs in left-sided CHF membranes
Lesions cannot easily be resolved →
• heavy, wet lungs (fluid initially at basal organization and scarring (severe chronic
region) changes)
• histologic: alveolar capillaries engorge,
intravascular granular pink precipitate, Clinical course:
microhemmorhages, hemosiderophages (HF • Usually hospitalized (due to one of
cells) predisposing factors)
later: fibrosis & thickening of alveolar walls • Initially: no pulmonary symptoms
→ firm and brown lungs profound dyspnea, tachypnea
CXR may be normal
• Later: cyanosis, hypoxemia, respiratory
failure
USTFMS MEDICAL BOARD REVIEW 2019 1|PATHOLOGY
(LUNG DISEASES)
CXR: diffuse bilateral infiltrates Pulmonary Hypertension & Vascular Sclerosis
• Therapy is difficult (frequently fatal) • Normal: pulmonary BP is only 1/8 systemic
• high concentrations of O2 → oxygen toxicity BP
• progression from one phase to next can be • Pulmonary hypertension
rapid (few hours) - Pulmonary pressure reaches ¼ systemic
BP
Pulmonary Embolism, Hemorrhage & - Secondary to structural cardiopulmonary
Infarction conditions that
• occlusions of pulmonary arteries by blood ↑Pulmonary blood flow or pressure, pulm.
clots; embolic in origin vascular resistance, left heart resistance to
• usual source of emboli: thrombi in DV of leg blood flow
in >95% cases Causes:
• Consequences of embolic occlusion depend 1. Chronic obstructive or interstitial lung
on: diseases
1. Size of embolic mass - Emphysema
a. Large emboli may impact main 2. Antecedent congenital or acquired heart
pulmonary artery → sudden death disease
b. Smaller emboli travel out to - MS
peripheral vessels may or may not 3. Recurrent thromboemboli
cause infarction
2. General state of the circulation Primary pulmonary hypertension
a. Adequate cardiovascular status • idiopathic cause of endothelial dysfunction
- can sustain lung parenchyma • associated with autoimmune diseases, toxic
despite obstruction to pulmonary substances, genetic determinants
arterial system • common in women 20-40 y/o
- Hemorrhage may occur (no
infarction) Secondary pulmonary hypertension
b. Circulation is inadequate (heart or • initiating disorder:
lung disease) increased shear and mechanical injury
- Pulmonary infarcts associated with left-to-right shunts or
- Lower lobes (3/4 cases) biochemical injury produced by fibrin
- Multiple lesions (1/2 cases)
range: barely visible to the naked eye to Morphology:
massive involvement wedge shape with • common to both 1° and 2° arterioles and
apex toward hilus small arteries prominently affected
1. ↑ Muscular thickness of the media
Pulmonary Infarct (medial hypertrophy)
• hemorrhagic type 2. Intimal fibrosis
• early stage: raised red-blue area • plexogenic pulmonary arteriopathy – in 1°
pleura with fibrinous exudate pulm HPN or congenital heart disease with L
• after 48 hours: red-brown (hemosiderin → R shunt
produced)
• late stage: gray-white peripheral zone Clinical Course:
(fibrous replacement) • signs and symptoms only evident in
• histologic: ischemic necrosis of the lung advanced arterial disease
within area of hemorrhage • 1° = dyspnea & fatigue
= chest pain (anginal type)
Clinical Presentation: • in time: severe respiratory distress
• may mimic MI cyanosis, RVH, death (decompensated cor
• (large) severe chest pain, dyspnea, shock, pulmonale)
fever, ↑LDH • superimposed: thromboembolism &
• (small) transient chest pain, cough pneumonia
resolve via contraction and fibrinolysis
• Unresolved lead to pulmonary HPN, pulm. PULMONARY INFECTIONS
vascular sclerosis, Respiratory Tract Infections
chronic cor pulmonale  More frequent that infections of other organs
 Majority URT caused by viruses
Prevention:  Lung infections caused by:
• early ambulation in post-op, post-partum 1. viral
patients 2. Bacterial
• elastic stockings 3. mycoplasmal
• isometric leg exercise 4. fungal
• preventive anticoagulation for high-risk  Large cause of morbidity and rank among the
major immediate cause of death

(LUNG DISEASES)
Bacterial Pneumonia Lobar pneumonia
 Bacterial invasion of the lung parenchyma Stages:
evokes exudative solidification (consolidation) 1. Congestion – heavy, boggy, red vascular
 Variables: engorgement, numerous bacteria, few PMN’s
1. Specific etiologic agent
2. Host reaction 2. Red hepatization – massive confluent exudation
3. Extent of involvement with RBC’s (congestion) and PMN’s, fibrin in
alveolar spaces
Classification: - Red, firm, airless, liver-like consistency
 According to etiologic agent:
o Pneumococcal 3. Gray hepatization – progressive disintegration of
o Staphylococcal, etc. red cells, persistence of
 According to nature of the host reaction fibrinosuppurative exudate
 Gross anatomic distribution: - Grayish, brown, dry surface
o Bronchopneumonia
o Lobar pneumonia 4. Resolution – consolidated exudate within alveolar
Bronchopneumonia spaces (enzymatic digestion)
 Patchy consolidation of the lung - Pleural fibrinous reaction → organization,
 Extension of a preexisting bronchitis or thickening
bronchiolitis
 Common in injury or old age Bronchopneumonia
 Common finding in post mortem exam  Consolidated areas of acute suppurative
frequently terminates a long course of inflammation
progressive heart failure or disseminated tumor  “Patchy”, multilobar, bilateral
 Basal – gravitate into the lower lobes
Lobar pneumonia  3-4 cm, sl. elevated, dry, granular, gray-red to
 Acute bacterial infection of a large portion of a yellow poorly delimited margins
lobe or of an entire lobe  suppurative, neutrophil-rich exudate that fills the
 Classic type is infrequent because of bronchi, bronchioles, adjacent alveolar spaces
effectiveness of antibiotics
Complications of pneumonia:
 Lobular involvement may become confluent →
 Abscess formation
total lobar consolidation
 Empyema
 Organization → solid tissue
* Patterns overlap
 Bacteremic dissemination
* Important from clinical standpoint – identification
of the causative agent and determination of the
Clinical Course:
extent of the disease
 Malaise, fever, cough (productive)
 pleuritic pain, pleural friction rub (with pleuritis)
Pathogenesis
 CXR:
 Airways & alveoli exposed to >10,000 L of air
- Radiopaque, well-circumscribed lobe
containing hazardous dusts, chemicals,
- Focal opacities in bronchopneumonia
microorganisms
 Dramatically modified by antibiotics
 Normal lung is free from bacteria
Potent defense mechanisms to clear / destroy Viral & Mycoplasmal Pneumonia

bacteria (Primary Atypical Pneumonia)
 Nasal clearance  Atypical because lack of alveolar exudate
o Sneezing & blowing  Interstitial pneumonitis
o Swallowing Morphology
 Tracheobronchial clearance: mucociliary action  Interstitial nature of inflammatory reaction
o Swallowed or expectorated localized within the walls of the alveoli
3. Alveolar clearance: alveolar macrophage  Widened and edematous alveolar septa
 Infiltrates – mononuclear
Etiologic agent  Lymphocytes, histiocytes, plasma cells
Bronchopneumonia – Staph, Strep, Pneumococci, H.  Modified picture with superimposed bacterial
influenzae, P. aeruginosa, coliform bacteria infection
Lobar pneumonia Clinical course

 90-95% caused by Pneumococci (S. pneumonia)  Varied
types 1, 3, 7, 2 (type 3 common – virulent)  May masquerade as severe upper respiratory
 Occasionally K. pneumonia, Staph, Strep, H. tract infection
influenza, gram (-) organisms  Few localizing symptoms: (w/ or w/o cough)
 Spreads through pores of Kohn  Fever, headache, muscle ache, leg pains
 Symptoms out of proportion of scanty physical
findings
(LUNG DISEASES)
CHRONIC OBSTRUCTIVE PULMONARY Pathogenesis:
DISEASE  Chronic irritation by inhaled substance
 EMPHYSEMA  Microbiologic infection
 CHRONIC BRONCHITIS
 ASTHMA Hallmark and Earliest feature - hypersecretion of
 BRONCHIECTASIS mucus in the large airway
 Hypertrophy of submucosal glands
Emphysema  Increase in goblet cells in small bronchi and
 abnormal permanent enlargement of the bronchioles
airspaces distal to the terminal bronchiole.  both sexes and ages may be affected
 With destruction of septal wall  most frequent in middle age men
 Without fibrosis  Cigarette smoking remains the paramount
 if without destruction of wall - overinflation influence
 4 to 10 times more common in heavy smokers
Types of Emphysema:
 panacinar Other histologic findings
 paraseptal  Increase in the size of mucous glands - this can
 Irregular be assessed by:
 Reid index: ratio of the thickness of the mucous
Pathogenesis of emphysema: gland layer to the thickness of the wall between
 Protease- antiprotease theory the epithelium and the cartilage.
 Normal is 0.4
Effects of cigarette smoking:  Bronchiolitis obliterans - severe obstruction
 Smokers have greater number of neutrophils caused by mucous plugging
and macrophages in the alveoli
 Stimulates release of elastase from neutrophils Bronchial Asthma
 Enhance elastolytic protease activity in  Chronic relapsing inflammatory disorder
macrophages - hyperreactive airways
 Oxidants in cigarette and free radicals from - Episodic reversible constriction
neutrophils inhibit alpha1 anti-trypsin - Increase responsiveness of the
Tracheobronchial tree to various stimuli
Morphology: - associated with atopy
 Abnormal fenestration in the wall
 Complete destruction of the walls Symptoms are:
 Some bleb and bullae produced by fusion by  Disabling attacks of severe dyspnea
adjacent diseased alveoli  Coughing
 Wheezing because of bronchospasm
Clinical course:  Asymptomatic in between attacks
 Manifestation occur if 1/3 of parenchyma is  Status asthmaticus - state of unremitting attacks
affected
 Dyspnea is usually the first symptom in some Extrinsic asthma -
patient cough and wheezing  Initiated by type 1 hypersensitivity reaction
 Weight loss is common  Induced by exposure to an extrinsic antigen
 The only reliable and consistently present
findings is slowing of forced expiration. Habitus: Intrinsic asthma
pink puffers  Initiated by diverse non immune mechanism
 e.g exercise, cold, pulmonary infection, etc
Chronic bronchitis
 Common in smokers Pathogenesis:
 Associated with COPD  Have 2 major components:
 Lead to cor pulmunale and heart failure 1. Chronic airway inflammation
 Cause metaplasia and dysplasia of the 2. Bronchial hyperresponsiveness
respiratory epithelium
Nonatopic asthma
Definition:  Second large group
 Patient who has persistent cough with sputum  Frequently triggered by respiratory tract
production for at least 3 months in at least 2 infection. Viruses > bacterial
consecutive years  Usually with no family history of asthma
 Serum IgE is normal
Chronic asthmatic bronchitis - with hyper reactive  No associated allergies
airways and with intermittent bronchospasm and
wheezing Drug induced asthma
 Several pharmacologic agents provoke asthma
 Aspirin is uncommon

(LUNG DISEASES)
 Occurs in patient with allergic rhinitis and nasal MALIGNANT TUMOURS:
polyps also exhibit urticarial
 Triggered by inhibiting the cyclooxygenase SQUAMOUS CELL CARCINOMA
pathway  MOST CLOSELY associated with cigarette
smoking / hypercalcemia
Occupational asthma  Associated within the vicinity of bronchial
 Stimulated by fumes organic and chemical dust, dysplasia, squamous metaplasia and in situ
gases and formaldehyde carcinoma
 Include Type I IgD- mediated reaction  Frequently associated with bronchial collapse
and obstruction (narrowing) and consequent
Histologic features of asthma: pneumonia
 Lungs are overdistended  Metastasis occurs via regional
 Bronchi and bronchiole are occluded with lymphatics/hematogenous
mucous plugs  Histologic grade varies from well to poor
 Curschmann spiral - whorles of shreded
epithelium ADENOCARCINOMA
 Numerous eosinophils and Charcot-Leyden  Arise also from first & 2nd order bronchi but
crystals are present tends to occur peripherally
 Thickening of the basement membrane of the  Incidence in both sexes are equal
bronchial epithelium  Occurs in association with old trauma,
 Bronchial wall edema with inflammatory tuberculosis and infarctions
infiltrates particularly eosinophils  Growth is slower than SCC and tends to have a
 Increase in size of submucosal glands better prognosis
 Hypertrophy of bronchial wall muscle  Histologic grade varies from mucin-producing to
poorly differentiated
Bronchiectasis
 Chronic necrotizing infection of the bronchi or BRONCHIOLOALVEOLAR CARCINOMA
 Adenocarcinoma presenting as a pneumoniae
bronchioles leading to or associated with
abnormal dilatation of airway like picture (grossly and radiologically)
 Dilatation should be permanent  Uniformly cuboidal to columnar cells line the
 cough, fever and expectoration of copious alveolar spaces recapitulating terminal
bronchiolar histology
amount of foul smelling sputum.
 Diffuse growth pattern
Etiology  Maintain alveolar sacs and spaces
 Bronchial obstruction - tumor, foreign body,
asthma chronic bronchitis UNDIFFERENTIATED (ANAPLASTIC)
 Congenital or hereditary - cong. Bronchiectasis, CARCINOMA
cystic fibrosis and sequestration of the lungs  No distinguishing features of both SCC and
 Necrotizing infection - TB or Staph. adenoCA
 Poor prognosis and rapid clinical course
TUMORS OF THE PULMONARY SYSTEM
General Consideration: A. LARGE CELL UNDIFFERENTIATED CARCINOMA
 MOST tumours of the lungs are malignant (LCUC)
 Large sheets of round to polyhedral cells
 95% arise from large airways (1st & 2nd
 Giant cells present, prognosis is hopeless
bronchi)
 Epithelial malignancy
 Risk 20x in heavy cigarette smokers B. SMALL CELL UNDIFFERENTIATED CARCINOMA
(SCUC)
 Urban industrialized inhabitants also at risk
 OAT CELL TYPE – resembles small lymphocytes
 MOST cancer death in men are predominantly
lung in origin
C. INTERMEDIATE CELL TYPE – fusiform type
 Carcinogens involved:
 tumour cells contains dense core granules
a. benzopyrene in cigarette tar
similar to argentaffin cells of GIT
b. radioactive substance
 Secrete hormone and hormone – like substance
c. heavy metals
d. asbestos exposure  Produce paraneoplastic syndromes such as
Cushing’s syndrome (ACTH) syndrome of AIDH
(anti-diuretic hormone), myasthenic syndromes
BENIGN TUMOURS:
 HAMARTOMA: haphazard lobular proliferation of (Eaton-Lambert) and Horner’s syndrome (ptosis
and miosis)
MATURE hyaline cartilage, Adipose cells, smooth
muscle, respiratory epithelia
 LIPOMA PLEURAL TUMORS
 ARE MAINLY a result of metastasis e.g. breast,
 LEIOMYOMA
lungs, liver, ETC.

(LUNG DISEASES)
MALIGNANT MESOTHELIOMAs
• Identified with occupational exposure to
asbestos
• Diffusely spread over surface of both lungs
eventually encasing them in a thick rim of fibrous
stroma containing infiltrating nests and ducts of
malignant mesothelial cells
• Prognosis is poor

REVIEW TEST
_____1. Primary pulmonary hypertension is _____7. Which of the following is considered

caused by: triggering factor in non-atopic asthma?
A. chronic obstructive lung disease A. Dusts
B. recurrent thromboemboli B. Pollens
C. congenital heart disease C. Rhinovirus
D. unknown etiology D. Animal dander
_____2. This type of atelectasis is caused by _____8. Which one of these is characteristic of
partial or complete filling of the pleural cavity bronchial asthma?
by fluid exudate, tumor, blood or air. What is A. airway dilatation and scarring
this type? B. smooth muscle hyperplasia
A. resorption C. mucus gland hyperplasia
B. compression D. destruction of septal wall
C. patchy
D. contraction _____9. A 58 y.o. colonel sought consult due to
dyspnea. He has been experiencing this 2
_____3. The main difference between bacterial years prior to consult. He had occasional bouts
and viral pneumonia is the: of cough before. Chest x-ray showed increase
A. Initial stage of congestion radiolucency of both lung fields with normal
B. Lack of alveolar exudation in viral sized heart. Personal history: 35 pack years
pneumonia (tobacco alternate with cigarettes)
C. Great overlap between the two Which will be your most likely diagnosis?
D. Interstitial fibrosis in bacterial A. Chronic bronchitis
pneumonia B. Bronchiectasis
C. Asthma
_____4. This organism can cause a necrotizing D. Emphysema
type of pneumonia:
A. Streptococcus _____10. The major pathologic changes
B. Staphylococcus associated with bronchiectasis are:
C. Klebsiella A. mucus gland hyperplasia and
D. H. influenza hypersecretion
B. airway dilatation and scarring
_____5. A 66-year-old woman has had a C. smooth muscle hyperplasia, excessive
worsening non-productive cough with malaise mucus and inflammation
for the past week. Her temperature increases to D. airspace enlargement with wall
37.4 C. A chest radiograph reveals diffuse destruction
bilateral pulmonary interstitial infiltrates in all
lung fields. A sputum gram stain reveals normal
flora and few neutrophils. She recovers over
the course of the next two weeks without
sequelae. Infection with which of the following
organisms most likely caused her illness?
A. M. tuberculosis
B. C. neoformans
C. S. pneumonia
D. Influenza A virus
_____6. The most common major symptom

shared by COPD’s is:
A. cough
B. fever
C. dyspnea
D. wheezing

IMMUNOPATHOLOGY
I. Hypersensitivity Reactions
- Immune-mediated injury
1. Type I Immediate
Prototype: Anaphylaxis, allergies, atopic bronchial asthma
- Production of IgE antibody  immediate release of vasoactive amines and other mediators from mast
cells, late recruitment of inflammatory cells
- Pathologic lesions: vascular dilatation, edema, smooth muscle contraction, mucus production, tissue
injury, inflammation
- Rapid reaction within minutes after the combination of an antigen with antibody bound to mast cells in
those with previous sensitization
Early phase responses

Molecular Mediators:
Primary – in granules
Secondary – synthesized later
(w/in 1- few minutes)
Localized clinical response (Atopy)
atopic asthma:
urticaria (hives)
eczema (skin lesions)
atopic rhinitis
food allergies
Systemic clinical response
(anaphylaxis)
Late phase responses anaphylatic shock
-- 4-6 hours later
e.g.,
Erythema, etc
“peak flow rate” measurements
Due to:
-- Cytokines from mast cells
-- Recruited eosinophils & TH2
-- degranulation
Chronic Type I
-- eosinophilia
-- inflammation: damaged airways & mucous membranes
2. Type II Antibody-mediated (Cytotoxic)

Prototype: Autoimmune hemolytic anemia, EF, Goodpasture‟s
- Production of IgG, IgM  binds to antigen on target or tissue  phagocytosis or lysis of target cell by
activated complement or Fc receptors; recruitment of leukocytes
- Pathologic lesions: phagocytosis and lysis of cells, inflammation, in some diseases functional
derangements w/o cell or tissue injury
Ig binding to AG on cells
-- triggers cell lysis
Complement mediated
Macrophage mediated

IMMUNOPATHOLOGY
Examples of Antibody-Mediated Diseases (Type II Hypersensitivity)

Clinicopathologic
Disease Target Antigen Mechanisms of Disease Manifestations
Autoimmune hemolytic Red cell membrane proteins (Rh Opsonization and phagocytosis Hemolysis, anemia
anemia blood group antigens, I antigen) of red cells
Autoimmune Platelet membrane proteins Opsonization and phagocytosis Bleeding

thrombocytopenic (Gpllb: Illa integrin) of platelets
purpura
Pemphigus vulgaris Proteins in intercellular junctions Antibody-mediated activation Skin vesicles (bullae)
of epidermal cells (epidermal of proteases, disruption of
cadherin) intercellular adhesions
Vasculitis caused by Neutrophil granule proteins, Neutrophil degranulation and Vasculitis

ANCA presumably released from inflammation
activated neutrophils
Goodpasture syndrome Noncollagenous protein in Complement- and Fc Nephritis, lung

basement membranes of kidney receptor–mediated hemorrhage
glomeruli and lung alveoli inflammation
Acute rheumatic fever Streptococcal cell wall antigen; Inflammation, macrophage Myocarditis, arthritis
antibody cross-reacts with activation
myocardial antigen
Myasthenia gravis Acetylcholine receptor Antibody inhibits acetylcholine Muscle weakness,

binding, down-modulates paralysis
receptors
Graves disease TSH receptor Antibody-mediated stimulation Hyperthyroidism

(hyperthyroidism) of TSH receptors
Insulin-resistant Insulin receptor Antibody inhibits binding of Hyperglycemia,

diabetes insulin ketoacidosis
Pernicious anemia Intrinsic factor of gastric parietal Neutralization of intrinsic Abnormal
cells factor, decreased absorption erythropoiesis, anemia
of vitamin B12
3. Type III Immune complex disease

Prototype: Systemic lupus erythematosus, serum sickness,
Arthus reaction, some glomerulonephritis
- Deposition of Ag-Ab complexes  complement activation recruitment of leucocytes by complement
products and Fc receptors  release of enzymes and other toxic molecules
- Pathologic lesions: inflammation, necrotizing vasculitis (fibrinoid necrosis)

IMMUNOPATHOLOGY
Examples of Immune Complex–Mediated Diseases

Clinicopathologic
Disease Antigen Involved Manifestations
Systemic lupus Nuclear antigens Nephritis, skin lesions,
erythematosus arthritis, others
Poststreptococcal Streptococcal cell wall antigen(s); may be Nephritis

glomerulonephritis “planted” in glomerular basement membrane
Polyarteritis nodosa Hepatitis B virus antigens in some cases Systemic vasculitis
Reactive arthritis Bacterial antigens (e.g., Yersinia) Acute arthritis
Serum sickness Various proteins, e.g., foreign serum protein Arthritis, vasculitis, nephritis
(horse anti-thymocyte globulin)
Arthus reaction Various foreign proteins Cutaneous vasculitis

(experimental)
4. Type IV Cell-mediated (Delayed)

Prototype: TB, contact dermatitis, multiple sclerosis, type I DM, RA, IBD
- sensitized thymus derived T-lympho  activated T-lymphocytes to cause: 1. release of cytokines 2. T
cell mediated cytotoxicity  inflammation and macrophage activation
- Pathologic lesions: perivascular cellular infiltrates, edema, granuloma formation, cell destruction
- slow onset ~day(s) (if sensitized)

IMMUNOPATHOLOGY
Examples of T Cell–Mediated (Type IV) Hypersensitivity
Disease Specificity of Pathogenic T Cells Clinicopathologic Manifestations

Type 1 diabetes mellitus Antigens of pancreatic islet β cells Insulitis (chronic inflammation in islets),
(insulin, glutamic acid decarboxylase, destruction of β cells; diabetes
others)
Multiple sclerosis Protein antigens in CNS myelin (myelin Demyelination in CNS with perivascular
basic protein, proteolipid protein) inflammation; paralysis, ocular lesions
Rheumatoid arthritis Unknown antigen in joint synovium Chronic arthritis with inflammation,
(type II collagen?); role of antibodies? destruction of articular cartilage and
bone
Crohn disease Unknown antigen; role for commensal Chronic intestinal inflammation,
bacteria obstruction
Peripheral neuropathy; Protein antigens of peripheral nerve Neuritis, paralysis

Guillain-Barré syndrome? myelin
Contact sensitivity Various environmental antigens (e.g., Skin inflammation with blisters
(dermatitis) poison ivy)
Tuberculosis
-- Persistent Mycobacterium tuberculosis
Granuloma (tubercule) formation

TH1 cells and activated macrophages
„caseous‟ regions
extended tissue destruction

IMMUNOPATHOLOGY
II. Autoimmune Diseases

- Immune reaction against self antigens
- at least three requirements should be met before a disorder is categorized as truly due to
autoimmunity:
(1) the presence of an immune reaction specific for some self-antigen or self-tissue
(2) evidence that such a reaction is not secondary to tissue damage but is of primary pathogenic
significance
(3) the absence of another well-defined cause of the disease
Immune-Mediated Inflammatory Diseases

DISEASES MEDIATED BY ANTIBODIES AND IMMUNE COMPLEXES
Organ-specific autoimmune diseases
Autoimmune hemolytic anemia
Autoimmune thrombocytopenia
Myasthenia gravis
Graves disease
Goodpasture syndrome
Systemic autoimmune diseases

Systemic lupus erythematosus (SLE)
Diseases caused by autoimmunity or by reactions to microbial antigens

Polyarteritis nodosa
DISEASES MEDIATED BY T CELLS

Organ-specific autoimmune diseases
Type 1 diabetes mellitus
Multiple sclerosis
Systemic autoimmune diseases

Rheumatoid arthritis[*]
Systemic sclerosis[*]
Sjogren syndrome[*]
Diseases caused by autoimmunity or by reactions to microbial antigens

Inflammatory bowel disease (Crohn disease, ulcerative colitis)
Inflammatory myopathies
III. Immunologic Deficiency Syndrome

1. Primary – hereditary, bet. 6 mos – 2 yrs
2. Secondary – acquired altered immune function due to infections, malnutrition, aging,
immunosuppression, irradiation, chemotherapy, autoimmunity
3. X-linked agammaglobulinemia of Bruton
 Most common 1 IDS
4. Isolated IgA deficiency
5. DiGeorge‟s Syndrome (Thymic Hypoplasia)
6. AIDS

REVIEW TEST
_____1. Diabetes mellitus type I probably results _____8. Removal of immune complexes that are
from attacks on antigenic beta cells by: formed in an immune reaction is easily accomplished
A. Cytotoxic T cells by the:
B. Cytotoxic antibody A. Reticuloendothelial system
C. Macrophages B. Lymphatic drainage and antigen
D. NK cells neutralization
C. Rapid deterioration of immunoglobulins
_____2. The agonist state in Graves’ disease is due and antigens
to: D. Dendritic cells
A. Follicular cell membrane disruptions
caused by NK cells _____9. Which of the following statements is TRUE
B. Cytotoxic antibodies that destroy T about immunodeficiency states?
suppressor cells A. Most congenital immunodeficiency
C. Autoantibodies that stimulate the TSH diseases are X-linked and therefore
receptors mostly occur only in males.
D. Activation of complement fragments B. Patients with T-cell deficiencies are able
to mount responses to bacterial
_____3. The absence or paucity of T cells prevents infections in infancy from passively
an adequate response to intracellular bacteria, acquired lymphocytes.
viruses and fungi in: C. An increased incidence of cancers may
A. X-linked agammaglobulinaemia be due to paucity of cytotoxic T cells
B. IgA deficiency that normally recognize tumor antigens.
C. Chronic mucocutaneous candidiasis D. ALL OF THE ABOVE
D. DiGeorge syndrome
_____10. Skeletal muscle malfunction in myasthenia
_____4. A 12-yr-old healthy boy developed a 7 mm gravis results primarily from:
induration at the site of intradermal injection of PPD. A. Destruction of acetylcholine receptors by
What is his immune status? cytotoxic antibodies
A. Activated T cell deficiency B. Displacement of acetylcholine from
B. Lack of dendritic cells receptor sites
C. No previous exposure to tuberculin C. Active phagocytosis of acetylcholine
antigen molecules by activated macrophages
D. Recovery from tuberculous infection D. Muscle breakdown and reactive fibrosis
_____5. A streptococcal infection in the throat may

lead to cardiac damage because:
A. Direct cytopathic change induced by
microorganism
B. Specific antibodies developed in the
immune response mistake the cardiac
tissues for the bacterial antigens
C. Non-specific immunoglobulins attach to
the tissues and induce antibody-
dependent cell-mediated cytotoxicity
D. Fibrin deposited in the cardiac
interstitium is chemotactic for
neutrophils
_____6. Immune complexes indirectly cause tissue

damage by:
A. Inducing complement receptor
duplication in red blood cells
B. Stimulating immunoglobulin receptor
propagation in macrophages
C. Eliciting an acute inflammatory reaction
D. Providing a chemotactic target for
activated lymphocytes
_____7. In cell-mediated cytotoxicity the target cells

die as a result of attack by:
A. Activated CD4 lymphocytes
B. Activated CD8 lymphocytes
C. Epithelioid histiocytes
D. Giant cell activity
THE LOWER URINARY TRACT
ROLAN R. DELA ROSA, MD
THE LOWER URINARY TRACT retroperitoneal structures and causing

hydronephrosis
- composed of:  Secondary to drugs, inflammatory conditions
1. Ureters or malignant diseases
2. Urinary bladder  70% are primary or idiopathic
3. Urethra
URINARY BLADDER
URETERS  D/o are more disabling than lethal
 Cystitis more common in young women of
Congenital Anomalies reproductive age
 Found in 2-3% of all autopsies
 Contributes to obstruction of urine flow Congenital Anomalies
1. DIVERTICULA
1. DOUBLE AND BIFID URETERS  Diverticulum consists of a pouchlike
- Majority of double ureters are unilateral and of evagination of the bladder wall
no clinical significance  Congenital (d/t developmental failure) but
more commonly acquired caused by
2. URETEROPELVIC JUNCTION OBSTRUCTION persistent urethral obstruction
(UPJ)  Carcinoma may arise in bladder diverticuli
 Most common cause of hydronephrosis in
infants and children 2. EXSTROPHY
 Commonly in boys - Developmental failure in the anterior wall of the
 Bilateral in 20% of cases abdomen and the bladder
 Adult UPJ more common in women and most
often unilateral 3. VESICOURETERAL REFLUX
 Most common and serious anomaly
3. DIVERTICULA  Major contibutor to renal infxn & scarring
Saccular outpouchings of the ureteral wall  May create congenital vesicouterine fistulas
 Uncommon and asymptomatic 4. PATENT URACHUS
 Cause pockets of stasis and secondary  Creates fistulous urinary tract
infections  Connecting bladder with the umbilicus
 May give rise to urachal cyst and eventually
Inflammation bladder adenocarcinomas
- Typically not associated with infection
of little clinical consequence Inflammation
1. ACUTE AND CHRONIC CYSTITIS
1. URETERITIS FOLLICULARIS  More commonly in women because of
- The accumulation or aggregation of lymphocytes shorter urethras
forming germinal centers in the subepithelial  Triad of symptoms: frequency, lower
region abdominal pain, dysuria
 E. coli (most common cause) , Proteus,
2. URETERITIS CYSTICA Klebsiella and Enterobacter, TB, Candida
- Mucosa become sprinkled with fine cysts (1- albicans, cryptococcus, viruses, chlamydia,
5mm in diameter) mycoplasma and radiation
 Hemorrhagic cystitis - in patients receiving
Tumors and Tumor-like Lesions cytotoxic antitumor drugs
Primary tumors of ureters are rare  Follicular cystitis - aggregation of
 Small benign tumors are of mesenchymal lymphocytes into lymphoid follicles
origin  Eosinophilic cystitis - infiltration with
 Fibroepithelial polyp submucosal eosinophils
 Small mass projection into the lumen
 Often in children 2. INTERSTITIAL CYSTITIS (CHRONIC PELVIC PAIN
 More commonly uccurs in ureters SYNDROME)
 Majority of primary malignant tumors of the  Occurs most frequently in women
ureter are UROTHELIAL CARCINOMAS  A persistent, painful form of chronic cystitis
 Sixth and seventh decades of life  Frequency, urgency, hematuria and dysuria
 Causes obtruction of the ureteral lumen  Cystoscopic findings of fissures and punctate
hemorrhages in mucosa
OBSTRUCTIVE LESIONS  Hunner ulcers - chronic mucosal ulcers seen
- give rise to hydroureter, hydronephrosis and in late ulcerative phase
sometimes pyelonephritis
3. MALACOPLAKIA
1. SCLEROSING RETROPERITONEAL FIBROSIS  Refers to a peculiar pattern of vesical
 Characterized by a fibrous proliferative inflammatory reaction
inflammatory process encasing the  Characterized by soft, yellow, slightly raised
mucosal plaques 3-4 cm in diameter
stalk and are referred to as exophytic

 Michaelis-gutmann bodies present within papillomas
macrophages  Inverted papillomas consist of inter-
 Related to chronic bacterial infection, mostly anastomosing cords of cytologically bland
by e. Coli or occasionally by proteus urothelium that extend down into the lamina
 Occurs commonly in immunosuppressed propria
transplant recipients
B. Papillary Urothelial Neoplasms of Low Malignant
4. POLYPOID CYSTITIS Potential (PUNLMPs)
 Resulting from irritation to the mucosa  With thicker urothelium or diffuse
 Indwelling catheters are most common  nuclear enlargement compared with
cause papillomas
 Rare mitotic figures
Metaplastic Lesions  Larger than papillomas
1. CYSTITIS GLANDULARIS  May recur with same morphology and no
- Brunn nests grow downward into the lamina invasion
propria and undergo transformation of lining  Rarely recurs as high grade and with
into cuboidal or columnar epithelium invasion
C. Low-grade Papillary Urothelial Carcinomas
2. CYSTITIS CYSTICA  Orderly appearance both architecturally and
- Cystic spaces filled with clear fluid lined by cytologically
flattened urothelium  Cells are evenly spaced and cohesive
 Minimal nuclear atypia
3. INTESTINAL OR COLONIC METAPLASIA  Mild variation in nuclear size and shape
- Epithelium resembles intestinal mucosa and with  Rarely recurs and invades
goblet cells  Less than 10% are invasive
4. SQUAMOUS METAPLASIA D. High-grade Papillary Urothelial Cancers

 A response to injury  Cells are discohesive with large
 Replaced by squamous epithelium hyperchromatic nuclei, frank anaplasia
 frequent mitotic figures
5. NEPHROGENIC ADENOMA  disarrayed architecture with loss of polarity
 Result from shed renal tubular cells that  high incidence of invasion into the
implant in sites of injured urothelium muscularis propria and metastasizes
 Focally replaced by cuboidal epithelium w/c  80% are invasive
can assume a papillary growth pattern
E. Carcinoma in Situ (CIS or flat urothelial
NEOPLASMS carcinoma)
 95% are of epithelial in origin  Lesions that have malignant cytologic
 The remainder is mesenchymal in origin changes but are confined to the epithelium,
without basement membrane invasion
1. UROTHELIAL TUMORS  Malignant cells within a flat urothelium
 Represents about 90% of all bladder tumors  It can be full-thickness or
 2 distinctive precursor lesion to invasive  It may be scattered malignant cells in an
urothelial carcinoma: otherwise normal epithelium (pagetoid
spread)
a. Non-invasive papillary tumor  Lacks cohesiveness of cells
 Most common precursor lesion  50-75% progresses to muscle invasive
 Originates from papillary urothelial cancer if left untreated
hyperplasia
b. Flat non-invasive urothelial carcinoma F. Invasive Urothelial Cancer
 Referred to as carcinoma in situ  Associated with papillary urothelial cancer,
(CIS) usually high grade or CIS
 Considered to be high grade  Invasion into the muscularis mucosae is of
 Once muscularis propria invasion prognostic significance
occurs, there is a 30% 5-year  Extent of spread (staging) at the time of
mortality rate initial diagnosis is the most important factor
 Types of Urothelial (Transitional in determining the outlook of a patient
Cell) Tumors
OTHER EPITHELIAL TUMORS:
A. Urothelial Papillomas A. Squamous Cell Carcinoma
 Represent 1% or less of bladder tumors  Represent about 3 to 7 % of bladder cancers
 Usually seen in younger patients  Pure scc are nearly always associated with
 Typically arise singly, small (0.5 to 2 cm), chronic bladder irritation and infection
superficially attached to the mucosa by a

B. Mixed Urothelial Carcinomas with areas of  EMBRYONAL RHABDOMYOSARCOMA
Squamous Carcinoma - Most common sarcoma in infancy or

 More frequent than pure SCC childhood
 Most are invasive, fungating or are - LEIOMYOSARCOMA
infiltrative and ulcerative - Most common sarcoma in the
C. Adenocarcinoma bladder in adults
 Rare 3. SECONDARY TUMORS
 Some arise from urachal remnants or in  By direct extension from primary lesions in
association with extensive intestinal nearby organs
metaplasia  Lymphomas involving the bladder –
D. Small-cell Carcinomas  maybe as A a part of systemic disease
 Indistinguishable from small-cell carcinomas
of the lungs OBSTRUCTION
 Arise in the bladder often in association with - most important cause:
urothelial, squamous or adenocarcinoma  males: prostate enlargement
 females: cystocele of the bladder
Epidemiology and Pathogenesis
 Incidence higher in men, urban dwellers and URETHRA
in developed countries Inflammation
 Between ages 50 and 80 years  Gonococcal urethritis
 Not familial  Nongonococcal urethritis
- E. coli, Chlamydia, Mycoplasma
Risk factors:  REITER SYNDROME triad:
 Cigarette smoking - most impt factor  Urethritis
 Exposure to arylamines (2-naphthylamine)  Arthritis
 cancers - appear 15 to 40 years after  onjunctivitis
exposure Tumors and Tumor-like Lesions
 Schistosoma haematobium  URETHRAL CARUNCLE
 Long-term use of analgesics  an inflammatory lesion
 Heavy long-term exposure to  small, red, painful mass
cyclophosphamides  typically in older females
 Prior exposure to irradiation  Benign epithelial tumors
 chromosome 9 deletions –the only  squamous and urothelial papillomas
genetic changes present frequently in  inverted urothelial papillomas
superficial papillary tumors and occasionally  condylomas
in noninvasive flat tumors  PEYRONIE DISEASE – results in fibrous bands
involving the corpus cavernosum of the penis
Clinical course:  Primary carcinoma of the urethra
 Painless hematuria – classic sx  Uncommon
 Have tendencies to recur and may  Squamous cell carcinoma - if found
show a higher grade within the distal urethra
 98% 10-yr survival: papillomas, punlmps,
and low-grade papillary urothelial cas
 Death in 25% of cases with high THE MALE GENITAL TRACT
grade papillary urothelial cas
 30% mortality rate – invasive urothelial PENIS
carcinomas; once tumor invades into the Congenital Anomalies
lamina propria  HYPOSPADIAS
 Worst prognosis - squamous cell  urethral opening on the ventral
carcinoma and adenocarcinoma surface of the penis
 Bacillus calmette-guerin (bcg) – used to  more common than epispadias
elicit a local inflammatory reaction that  EPISPADIAS
destroys the tumor  urethral opening on the dorsal surface of the
 Radical cystectomy: penis
 Tumor invading the muscularis propria  PHIMOSIS
 Cis or high-grade papillary cancer  when the orifice of the prepuce is
refractory to bcg too small to permit normal retraction
 Cis extending into the prostatic  may result from anomalous devt or
urethra and extending down the prostatic repeated attacks of infection
ducts
 Chemotherapy:for advanced bladder Inflammation
ca  STDs: syphilis, gonorrhea, chancroid, granuloma
2. MESENCHYMAL TUMORS inguinale, lymphopathia venerea, genital herpes
 benign tumor: Leiomyoma  BALANOPOSTHITIS
 Sarcomas – tend to produce large masses - refers to infection of the glans and
prepuce caused by organisms  sterility

- Candida albicans, anaerobic  testicular cancer
bacteria, Gardnerella, and pyogenic bacteria  tx: Orchiopexy preferably
before 2 years of age
Tumors  does not guarantee fertility
 Benign tumors: but protects from developing
- CONDYLOMA ACUMINATUM cancer
- caused by HPV types 6
(more common) and 11 Regressive Changes
- hyperkeratosis, acanthosis ATROPHY AND DECREASED FERTILITY
and koilocytosis -causes:
 Malignant tumors: 1. Atherosclerotic blood supply
 CARCINOMA IN SITU (CIS) 2. Inflammatory orchitis
 2 distinct lesions with CIS 3. Cyptorchidism
features 4. Hypopituitarism
 BOWEN DISEASE 5. Malnutrition or cachexia
 strong association with HPV 16 6. Irradiation
 men and women over 35 7. Antiandrogens
 solitary, thickened, gray-white opaque 8. Increased fsh
plaque  Atrophy occasionally occurs as a primary failure
 can develop into an invasive carcinoma of genetic origin
 BOWENOID PAPULOSIS  Atrophy is an end-stage pattern of testicular
 sexually active adults injury
 younger age  Inflammation
 multiple, reddish brown  Gonorrhea and tuberculosis almost invariably
papular lesions arise in the epididymis
 HPV 16 related  Syphilis affects first the testis
 never develops into an invasive  Nonspecific epididymitis and orchitis
carcinoma o childhood: assoc with congenital
 regresses spontaneously genitourinary abnormality and infxn
 INVASIVE CARCINOMA with gram-neg rods
 SQUAMOUS CELL CARCINOMA (SCC) o <35 y/o: C. trachomatis and N.
 10-20% of male malignancies in Asia Gonorrhea
 circumcision confers protection o >35 y/o: E. coli and Pseudomonas
 HPV DNA detected in 50%of cases  GRANULOMATOUS (AUTOIMMUNE) ORCHITIS
 HPV type 16 (most common) and 18  middle age
 cigarette smoking elevates risk  presents as a moderately tender
 ages 40-70 testicular mass of sudden onset
 VERRUCOUS CARCINOMA  GONORRHEA
 variant of SCC that has low  MUMPS
malignant potential  orchitis may develop in postpubertal
 locally invasive, rarely mets males 20-30% of cases
 acute interstitial orchitis develops
TESTIS AND EPIDIDYMIS about 1 week after infxn
 inflammatory diseases: most impt and  TUBERCULOSIS
frequent conditions affecting epididymis -almost invariably begins in the
 tumors: most impt and frequent conditions epididymis and may spread to testis
affecting testis  SYPHILIS
 testis is involved first by the infxn
Congenital Anomalies  2 forms:
 CRYPTORCHIDISM o Gummas
 complete or incomplete failure of the o diffuse interstitial
intra-abdominal testes to descend into the inflammation
scrotal sac
2 phases of testicular descent: Vascular Disorders
1. Transabdominal phase – controlled  TORSION
mullerian-inhibiting substance -2 types:
2. Inguinoscrotal phase – controlled by 1. Neonatal torsion – no associated anatomic defect
Androgen 2. Adult torsion – associated with
 cyptorchidism is only rarely bilateral anatomic defect (bell-clapper
associated with a well-defined hormonal abnormality)
disorder  urologic emergency!!!
 unilateral mostly  must be untwisted before 6 hours
 bilateral in 25% of cases to remain viable
 complications:

Spermatic Cord and Paratesticular Tumors Pathologic Classification of Common Testicular

 LIPOMA –more commonly involves the Tumors
proximal spermatic cord
 ADENOMATOID TUMOR – most common GERM CELL TUMORS
benign paratesticular tumor ● Seminomatous Tumors
 RHABDOMYOSARCOMA –most common - Seminoma
malignant paratesticular tumor in children - Spermatocytic seminoma
 LIPOSARCOMAS – most common ● Nonseminomatous Tumors
paratesticular tumor in adults - Embryonal Carcinoma
- Yolk sac (Endodermal Sinus) Tumor
Testicular Tumors - Choriocarcinoma
-2 major categories: - Teratoma
1. Germ cell tumors – 95% SEX CORD-STROMAL TUMORS
- most are aggressive but ● Leydig Cell Tumor
curable ● Sertoli Cell Tumor
-2 subdivisions:  25% hav c-KIT activating mutations
1. seminomas  (+) PLAP and HCG
2. nonseminomas  produce bulky masses
2. Sex cord-stromal tumors
-most are generally benign  SPERMATOCYTIC SEMINOMA
 GERM CELL TUMORS  uncommon tumor
 most common tumor of men in 15-  over age 65
34y/o  slow-growing tumor
 associated with a spectrum of disorders  does not produce metastasis
known as TESTICULAR  excellent prognosis
 EMBRYONAL CARCINOMA
DYSGENESIS SYNDROME  occurs mostly in 20-30 y/o
 syndrome includes:  more aggressive than seminoma
a. cryptorchidism  smaller tumor
b. hypospadias  YOLK SAC TUMOR
c. poor sperm quality  aka ENDODERMAL SINUS TUMOR
 strong family predisposition  most common testicular tumor in
infants and children up to 3 y/o with
Classification and Pathogenesis very good prognosis
 SEMINOMA – composed of cells that  microscopic finding: SCHILLER-DUVAL
resemble primordial bodies, hyaline-like bodies
germ cells or early gonocytes  (+) AFP
 most common testicular tumor  CHORIOCARCINOMA
 NON-SEMINOMATOUS  highly malignant form of testicular
 TUMORS – composed of tumor
undifferentiated cells that resemble  pure form is rare; <1%
embryonic stem cells or differentiate  morphology:no testicular enlargement,
into various lineages small palpable nodule
 INTRATUBULAR GERM CELL  (+) HCG
 NEOPLASIA – lesions where most  TERATOMA
testicular germ cell tumors originate  more than one germ layer
essentially a type of CIS  occurs at any age
 pure forms are common in infants and
SEMINOMA children
 most common type of germ cell tumor  morphology: large, heterogenous
 50%  “teratoma with malignant
 peak: 3rd decade transformation” – where a malignant
 almost never occur in infants non-germ cell tumor may arise in
 identical with dysgerminoma teratoma
 contain isochromosome 12p  child: differentiated mature teratomas
 express OCT3/4 and NANOG usually follow a benign course
 postpubertal male: all teratomas are
regarded as malignant capable of
metastasizing
 MIXED TUMORS
 about 60% of testicular tumors
 composed of more than one “pure”
patterns

 common mixtures include teratoma,  TESTICULAR LYMPHOMA

embryonal carcinoma and yolk sac  uncommon tumor of the testis
tumor; seminoma with embryonal  NON-HODGKIN
carcinoma; and embryonal carcinoma  5% of testicular tumors
with teratoma (teratocarcinoma)  most common form of testicular
neoplasms in men over the age of 60
 clinical features of germ cell testicular  higher incidence of CNS involvement
tumors:
 painless enlargement of the testis MISCELLANEOUS LESIONS OF TUNICA
 any solid testicular mass should be VAGINALIS
considered neoplastic unless proved  HYDROCELE
otherwise - accumulation of serous fluid in tunica vaginalis
 biopsy is associated with a risk of  HEMATOCELE
tumor spillage -presence of blood in tunica vaginalis
 management: radical orchiectomy -from direct trauma to testis or torsion
 lymphatic spread: common to all forms  CHYLOCELE
of testicular tumors -accumulation of lymph in the tunica
 retroperitoneal para-aortic nodes are -seen in patients with elephantiasis
first to be involved, then mediastinal  SPERMATOCELE
and supraclavicular nodes -small cystic accumulation of sperm in
 hematogenous spread- primarily to the dilated efferent ducts or ducts in the rete
lungs, but liver, brain and bones may testis
alse be involved  VARICOCELE
 dilated vein in the spermatic cord
seminomas tend to remain localized to the testis  may be asymptomatic
for a long time and metastasis involves lymph node  contibutes to infertility
 extremely radiosensitive  can be surgically repaired
 good prognosis
 PROSTATE
non-seminomatous metastasize early and use  weighs approx 20g
hematogenous route frequently and are  androgens control growth and survival of
radioresistant prostatic cells
 poor prognosis
 the rare pure choriocarcinoma is the Inflammation
most aggressive  ACUTE BACTERIAL PROSTATITIS
 E. coli, gram neg rods, enterococci and
TUMORS OF SEX CORD- GONADAL STROMA staphylococci
 fever, chills, dysuria
LEYDIG CELL TUMORS  prostate: tender and boggy
 may elaborate androgens, estrogens
and corticosteroids  CHRONIC BACTERIAL PROSTATITIS
 may arise at any age but commonly  low back pain, dysuria, perineal,
between 20 and 60 y/o suprapubic discomfort
 most common presenting feature is  hx of recurrent UTI
testicular swelling or gynecomastia  dx depends on demonstration of
 in children, sexual precocity is the leukocytosis in the expressed
dominating feature secretions and (+) culture
 morphology: circumscribed nodules,
golden brown,  CHRONIC ABACTERIAL PROSTATITIS
 cytoplasm contains rod-shaped  most common form of prostatitis
crystalloids of Rainke  no hx of recurrent UTI
 most are benign; only 10% are invasive  secretions contain <10/hpf
and metastasize leukocytes
 SERTOLI CELL TUMORS  bacterial cultures negative
 most are hormonally silent and present
as testicular mass  GRANULOMATOUS PROSTATITIS
 morphology: firm, small nodules, gray-  instillation of BCG is a common
white to yellow cause
 most are benign, approx 10% pursue a  FUNGAL granulomatous prostatitis
malignant course – seen in immunocompromised
hosts
GONADOBLASTOMA
 rare neoplasm containing mixture of
germ cells and gonadal stromal elements,
that almost always arise in gonads with
some form of testicular dysgenesis
BENIGN ENLARGEMENT o PSA is the most important test

used in the diagnosis and
 BENIGN PROSTATIC HYPERPLASIA (BPH) OR management of prostate CA
NODULAR HYPERPLASIA o serum PSA level of 4 ng/mL is used
 common d/o of men over age 50 as a cut-off point between normal
 commonly in periurethral region and abnormal
 originates in the inner aspect of the o Tx: surgery, radiation or hormonal
prostate gland (transition zone) manipulations
 seen in 20% of men age 40, 70% of
men age 60 and 90% men age 80 Miscellaneous Tumors and Tumor-like
 etiology and pathogenesis: impaired cell Conditions
death  DUCTAL ADENOCARCINOMA
 dihydrotestosterone (DHT) – main  arise in peripheral ducts
androgen in the prostate -relatively has poor prognosis
 stromal cells (produce FGF-7) are
responsible for androgen-dependent  COLLOID CARCINOMA
prostatic growth  cancer that reveal abundant
 prostate weighs between 60 and 100g mucinous secretions
 microscopic: hallmark of BPH is  SMALL CELL CARCINOMA
nodularity  most aggressive variant of prostate
 NOT considered to be a premalignant CA
 rapidly fatal
TUMORS
 ADENOCARCINOMA  UROTHELIAL CA
 most common form of cancer in men  most common to secondarily
 typically a disease of men over involve the prostate
age 50
 screening: recommended at age 40
 uncommon in Asians
 hereditary and environmental fxs
 androgens play an impt role in prostate
cancer
 men with germline mutations of the
tumor suppressor gene BRCA2 have a
20-fold increased risk of prostate CA
 most common epigenetic alteration in
prostate CA is hypermethylation of
glutathione S-transferase (GSTP1)
 Prostatic Intraepithelial Neoplasia (PIN)
– a precursor lesion
 70% arises in the peripheral zone of the
gland, classically in the posterior
location where it may be palpable on
rectal exam
 metastases first spread via lymphatics
initially to the obturator nodes and
eventually to the para-aortic nodes
 hematogenous spread accurs chiefly to
the bones (axial skeleton) and is
typically osteoblastic
 GLEASON SYSTEM – used in grading prostate

CA
 gleason score remains stable for a period
of several years
 grade and stage are the best prognostic
predictors
 Clinical course:
o asymptomatic when localized
o urinary symptoms come in late
because of peripheral location
o back pain caused by vertebral
metastases
o biopsy is required to confirm
diagnosis

REVIEW TEST
ROLAN R. DELA ROSA, M.D
MALE AND LOWER URINARY TRACT _______8. What is the only genetic changes present
REVIEW TEST frequently in superficial papillary tumors and
occasionally in noninvasive flat tumors of the
bladder?
_______1. Which of the following is the most A. Genetic polymorphisms at the xp27
common developmental abnormality involving the B. Chromosome 9 deletions
testis? C. Germline mutation of brca2
A. Anorchism D. Hypermethylation of glutathiones
B. Cyptorchidism transferase
C. Synorchism
D. All of the above _______9. This is the term used for squamous
carcinomas in situ of the shaft of the penis:
_______2. Which of the following is referred to as A. Bowen disease
an anomaly in which the opening of the urethra is B. Berger disease
found On the ventral surface of the penile shaft? C. Beckwith-wiedemann syndrome
A. Hypospadias D. Warthin tumors
B. Epispadias
C. Both _______10. True of verrucous carcinoma except:
D. None of the above A. Variant of squamous cell carcinoma
B. Rarely metastasize
_______3. What is peyronie disease? C. High malignant potential
A. Inflammation of the testis and epididymis D. Locally invasive
B. Fribromatosis involving the fascia of the
penile shaft _______11. Most common type of hpv associated
C. Vesicles over the glans that ulcerate and with penile cancer?
heal by formation of crusts A. Type 6
D. Urethritis caused by n.gonorrhea B. Type 11
C. Type 16
_______4. True of ureteropelvic junction obstruction D. Type 18
except:
A. Most common cause of hydronephrosis in _______12. True of testicular torsion except:
infants and children A. Neonatal torsion has no associated
B. Adult upj more common in women and anatomic defect
most often unilateral B. Adult torsion is associated with bilateral
C. Bilateral in 20% of cases anatomic defect
D. Commonly in girls C. Urologic emergency
D. Must be untwisted before 24 hours to
_______5. A condition known as developmental remain viable
failure in the anterior wall of the abdomen and the
Bladder: _______13. What is the most common
A. Exstrophy paratesticular tumor?
B. Diverticula A. Adenomatoid tumor
C. Urachal cyst B. Rhabdomyosarcoma
D. Hamartoma C. Lipoma
D. Liposarcoma
_______6. True about patent urachus except:
A. Creates fistulous urinary tract _______14. What is the most common type of
B. Connecting bladder with the umbilicus germ cell tumor of the testis?
C. May give rise to urachal cyst A. Yolk sac tumor
D. May give rise to 30% of bladder B. Embryonal carcinoma
adenocarcinomas C. Seminoma
D. Teratoma
_______7. These are laminated mineralized
concretions resulting from deposition of calcium in _______15. True of teratoma of the testis except:
enlarged A. Pure forms are common in infants and
A. Lysosomes:Psamomma bodies children
B. Schiller-duval bodies B. Differentiated mature teratomas usually
C. Hyaline globule bodies follow a benign course in children
D. Michaelis-gutmann bodies C. All teratomas are regarded as malignant
capable of metastasizing in postpubertal
male
D. Occurs in young age

REVIEW TEST
_______16. What is the most common neoplasm of

the male genital tract?
A. Seminoma
B. Prostatic carcinoma
C. Urothelial carcinoma
D. None of the above
_______17. What is the most common form of

testicular neoplasm in men over the age of 60?
A. Non-hodgkin lymphoma
B. Teratoma
C. Seminoma
D. Squamous cell carcinoma
_______18. The classification system used in

grading prostate carcinomas:
A. Bethesda classification
B. Gleason classification
C. Fuhrman classification
D. Jones criteria
_______19. What is the most common form of

prostatitis?
A. Acute bacterial prostatitis
B. Chronic bacterial prostatitis
C. Chronic abacterial prostatitis
D. Ganulomatous prostatitis
_______20. What is the most common location of

rostatic carcinoma?
A. Transition zone
B. Peripheral area
C. Periurethral area
D. Middle area
E. Periurethral area Middle area

THE LOWER URINARY TRACT FEMALE
GENITAL TRACT and BREAST
I. Female Genital Tract Extramammary Paget’s are rare lesions

Diseases of the female genital tract are best of the vulva with similar skin presentation as
studied with the review of basic anatomy and that of the breast
histology of the system. These are extremely
common lesions in the practice of medicine. Malignant Melanoma is a rare lesion in
the vulva
A. Infections of the Female Genital Tract –
Different organisms infect the female genital tract, C. Vaginal Lesions – Lesions of this segment are
many of which are sexually transmitted. relatively free of infection or primary lesion
1. Confined to the Lower Genital Tract (lesions of 1. Congenital Anomalies will be taken up in
the vulva, vagina and cervix) greater detail in OB/GYNE
a. Herpes simplex is common and has
increased in incidence among the young 2. Pre/Malignant – Vaginal Intraepithelial
reproductive age group. Neoplasia (VaIN),/Squamous Cell
b. Mycotic and yeast infections are common Carcinoma, Adenocarcinoma,
among diabetics, those with OCP and Embryonal Rhabdomyosacroma - are
pregnant patients extremely uncommon lesions of the area
c. Trichomonas vaginalis are flagellated
protozoa which cause purulent vaginal D. Cervical Lesions – Lesions of this part of the
discharge and discomfort genital tract are quite common and may be
d. Mycoplasma sp. and Gardnerella vaginalis considered of high prevalence and concern
2. Involving the Upper and Lower Genital Tract – 1. Inflammation of the Cervix may be
is a condition known as Pelvic Inflammatory labeled as Acute and Chronic Cervicitis,
Disease (PID) and characterized by pelvic pain, or lead to formation of Endocervical
adnexal tenderness. It results more from an Polyps
ascending infection by any of the group of
organisms: N. gonorrhea, Chlamydia, enteric 2. Pre/Malignant – Cervical
organisms. Intraepithelial Neoplasia (LSIL, HSIL),
Squamous Cell Carcinoma – the risk
B. Vulvar Lesions - The lesions of this part are factors and carcinogenesis of the lesion are
applications of basic lesions that can occur in the important
said anatomic area.
E. Body of the Uterus (Endomyometrium)
1. Bartholin’s Cyst is a consequence of an
acute inflammation of the Bartholin gland. 1. Review of the Endometrial Histology in
the Menstrual Cycle
2. Lichen Sclerosus is a consequence of
atrophy and inflammation. 2. The condition, Functional Endometrial
Disorders (DUB) may be brought about by
Lichen simplex chronicus is a chronic any of the following causes:
condition resulting from rubbing and scratching a. Anovulatory cycle
the skin to relieve pruritus.
b. Endometrial Changes Induced
3. Neoplasms are the most important lesions of by Oral Contraceptives
the vulva. c. Menopausal and Postmenopausal
Changes
a. Benign tumor, specifically Condyloma
acuminatum is sexually transmitted 3. Inflammation of the Endometrium:
and appear as wartlike gross ChronicEndometritis (pathogenesis)
appearance. Etiologic agent is that of
HPV, types 6 & 11. The virus has a 4. Endometriosis is the finding of
cytopathic effect forming “koilocytic endometrial tissue insinuating between the
atypia” (nuclear atypia with perinuclear myometrium and Adenomyosis are
vacuolization) interweaving bundles of smooth muscle and
b. Pre/Malignant – Vulvar endometrial tissue forming localized nodule
within the myometrium
Intraepithelial Neoplasia (VIN) are
premalignant lesions of the vulva 5. Endometrial Polyps are benign
localized overgrowths that project from the
Squamous Cell Carcinoma are endometrial surface into the endometrial
uncommon lesions of the vulva cavity

6. Endometrial Hyperplasia refers to a benign, of borderline malignancy (also

morphological continuum that ranges from called atypical proliferating or of low
simple glandular crowding to a conspicuous malignant potential), and malignant.
proliferation of atypical glands, which are They account for over 90% of ovarian
difficult to distinguish from early carcinoma cancers and nearly 60% of all ovarian
(know the pathogenesis) tumors.
7. Malignant Tumors of the b. Germ Cell Tumors – These
Endometrium – Endometrial carcinoma is constitute a fourth of all ovarian
the single most common gynecologic tumors. In adult women, germ cell
malignancy. It is linked to prolonged tumors are virtually all benign (mature
estrogenic stimulation of the endometrium. cystic teratoma/ dermoid cyst),
It may grow in a diffuse or polypoid pattern. whereas in children and young adults
are largely malignant.
8. Tumors of the Endometrium with
Stromal Differentiation c. Sex Cord-Stromal Tumors – These
Endometrial stromal sarcoma accounts for are derived from either the primitive
less than 2 % of all uterine malignancies. sex cords or the mesenchymal stroma
Some are pure stromal sarcomas, whereas of the developing gonad. They
others exhibit intimate admixtures of account for 10% of all ovarian tumors.
sarcomatous (stromal) and carcinomatous
(epithelial) elements. I. Gestational and Placental Disorders
9. Tumors of the Myometrium 1. Disorders of Early Pregnancy
a. Leiomyomas are benign tumor of a. Spontaneous Abortion – This term
smooth muscle origin, is the most applies to a pregnancy that terminates
common tumor of the female genital before the fetus is capable of
tract. Also known as a myoma or a extrauterine life, which currently is
fibroid. about the 22nd week of gestation.
Know the principal factors that are
b. Leiomyosarcoma is a malignancy responsible for abortion.
of smooth muscle origin. It accounts
for nearly 2% of uterine b. Ectopic Pregnancy
malignancies.
2. Disorders of Late Pregnancy – This topic
G. Fallopian Tubes will be emphasized more in OB/GYNE.
1. Inflammations- Salpingitis typically is the
a. Placental Abnormalities and Twin
result of ascending infections of the lower
Placentas
genital tract. The common causative agents
b. Placental Inflammation and Infections
are: N. gonorrhea, E. coli, Chlamydia,
c. Toxemia of Pregnancy (Pre
Mycoplasma
eclampsia/Eclampsia)
2. Tubal pregnancy is also called ectopic d. Intrauterine Growth Restriction
pregnancy wherein there is implantation
that develops outside the endometrium 3. Gestational Trophoblastic Disease – It is
particularly the fallopian tube. important to know the pathogenesis and its
increased prevalence in our own local
3. Tumors and Cysts – Tumors of the setting (Philippines). The term gestational
fallopian tube are rare and the most trophoblastic disease embraces the
common of which is an adenomatoid tumor. spectrum of trophoblastic disorders
Paratubal cysts are common incidental characterized by abnormal proliferation and
finding. maturation of trophoblast, as well as
H. Ovaries – It is important to know from where neoplasms derived from trophoblast.
the tumors arise from and what triggers its
formation. a. Hydatidiform mole (complete/partial)
– Complete H-mole is a placenta that
1. Non-Neoplastic and Functional Cysts – has grossly swollen chorionic villi,
Cysts are the most common cause of resmbling bunches of grapes, in which
enlarged ovaries. Excluding cysts that arise there are varying degrees of
from the invaginated surface epithelium of trophoblastic proliferation. Partial H-
the ovary (serous cyst), almost all arise from mole is now a recognized to be a
ovarian follicles. distinct form of mole. It is important to
2. Ovarian Tumors distinguish this from complete H-mole,
since it does not evolve into
a. Tumors of Mullerian Epithelium – choriocarcinoma.
These can be broadly classified as

b. Invasive mole is a H-mole in which e.g. in juvenile (virginal) hypertrophy- There is

the villous trophoblast has invaded the unusual tissue response to hormonal changes
underlying myometrium. during puberty
5. Amastia
c. Choriocarcinoma is a malignant tumor
derived from the trophoblast. It is a C. Inflammation – It is important to know the
tumor allograft in the host mother and etiopathogenesis.
thus unique among human cancers.
1. Mastitis
II. Breast (Female)
A. Normal Anatomy & Histology of the Breast
• During early stage of nursing, breast is
rendered vulnerable to bacterial infection
esp. by Staphylococcus aureus
• Composed of 6 to 10 major duct systems
• ABSCESS- results from rupture of mammary
• Each duct is divided into lobules (functional ducts
unit of mammary parenchyma)
• The ductal system drains through main
• Periareolar abscess associated with
squamous metaplasia of lactiferous ducts
excretory duct or lactiferous sinus
• There is branching of the large ducts distally • Histology: purulent inflammation with
which leads to terminal ducts Before multiple abscesses, fibrotic breast
menarche it ends blindly parenchyma and obliteration of lobular
After menarche it ends as ductules & acini pattern
(TDLU) • Clinical presentation: erythematous, warm,
• The nipple and areola complex is covered may be associated with retraction of skin
by stratified squamous epithelium. and nipple, i.e. they may be mistaken for
neoplasm (CA)
• It is pigmented & supported by smooth
muscle • Treatment: I & D, antibiotics, bromcriptine,
• The Areolar glands (of Montgomery) cessation of breast feeding
function in nipple lubrication and become 2. Mammary Duct Ectasia
prominent during pregnancy • Occurs in the 5th to 6th decade of life
The stratified squamous orifice is double layer of

• Among multiparous, premenopausal women
cuboidal epithelium with basement membrane & • Clinical presentation: inversion & retraction
myofilaments (myoepithelial cells) (Normally, of nipple
there is single layer of cuboidal to attenuated • Histology: dilated ducts, inspissated breast
cells in the TDLU) secretions, marked periductal and interstitial
• The breast stroma is composed of dense chronic granulomatous inflammation,
fibroconnective tissue admixed with adipose tissue calcifications
containing elastic fibers supporting the large ducts
3. Fat Necrosis
• LOBULES- enclosed by breast- specific
hormonally responsive loose, delicate, myxomatous • Associated with trauma, prior surgery,
stroma containing scattered lymphocytes. radiation
• Focal inflammatory reaction to cystic ductule
LOBULES, morhologic changes contents
• Histology: foamy macrophages infiltrating
1. follicular phase- quiescent partially necrotic adipose tissue forming
chalky firm, ill-defined nodules and
2. After ovulation- cellular hyperplasia as hemorrhage
well as increasing acini per lobule and
lobular stroma edema is marked
• Clinical presentation: may be confused for a
tumour
3. Menstruation- epithelial apoptosis,
4. Granulomatous mastitis – may be caused by any
appearance of stromal edema,
of the following:
lymphocytic infiltration & overall
regression in size of lobules • Tuberculosis
B. Disorders of Development
• Foreign body reaction
1. Supernumerary breasts or nipples (ECTOPIA) • Sarcoidosis
Seen along the “milkline”, i.e. axilla to • Deep fungal mycosis: Actinomycosis,
perineum Coccidioidomycosis, Histoplasmosis
2. Accesory axillary breast tissue
3. Congenital inversion of the nipples • Parasitic: Schistosomiasis, Hydatid cysts,
4. Macromastia Cysticercosis

D. Tumours of the Breast 8. Oral contraceptive use

BENIGN No convincing evidence in influencing the
1. Nipple duct adenoma / papilloma evolution or survival of patients with breast
2. Intraductal papilloma carcinoma
3. Fibroadenoma
4. Tubular adenoma 9. Estrogen & Progesterone receptor status
Robbins New Classification of Benign 10. DNA content

Epithelial Lesions
1. Non-proliferative (Fibrocystic Change) 11. Expression of oncogenes / loss of suppressor
2. Proliferative Breast Disease without Atypia genes:
3. Proliferative Breast Disease with Atypia erb-B2(Her2/Neu), c-myc, ras-p21, p53 and
(includes DCIS) INT2
4. Clinical Significance of Benign Breast Epithelial
Changes 12. Angiogenesis
MALIGNANT 13. Proteases
A. In- situ Carcinomas Breast (Male) – It should be noted that breast

(15 to 30 % of ALL cancers) lesions among male individuals are also seen
1. Ductal carcinoma- in- situ 80% A. Gynecomastia
2. Lobular carcinoma- in- situ 20% B. Carcinoma
B. INVASIVE CARCINOMA (Important to know

the more common malignancies)
(Account for about 70 – 80% of all breast
cancers)
a. Ductal carcinoma 79%
b. Lobular carcinoma 10%
c. Tubular carcinoma 6%
d. Mucinous (colloid) CA 2%
e. Medullary Carcinoma 2%
f. Papillary Carcinoma 1%
g. Paget’s disease of the nipple
h. Inflammatory carcinoma
C. STROMAL TUMOURS
a. Phyllodes tumour, low grade
b. Phyllodes tumour, high grade
CLINICAL COURSE & PROGNOSIS

1. Axillary lymph node status
Negative node involvement: 70- 80% 10 yr.
Survival
1-3 positive nodes : 35-40%
>10 positive nodes : 10-15%
2. Patient’s age
<50 yrs. of age is known to have a better
prognosis
3. Tumour size
<1 cm size has a 98% 5 yr. Survival
4. Histologic subtype
30 yr. Survival: 60% for tubular, colloid,
mucinous, medullary, papillary, lobular
<20% for invasive ductal carcinoma
5. Tumour (microscopic) grade, Tumor stage
6. Presence of lymphovascular invasion
7. Pregnancy
The occurrence of breast carcinoma during
pregnancy has a poorer prognosis.

REVIEW TEST
FEMALE GENITAL TRACT

REVIEW TEST
CASE: A 57 year-old woman complains of postmenopausal bleeding, necessitating the use of 2-3
pads per day. On internal examination, the uterus is slightly enlarged. Blood is coming out of the
os. There is a mass palpated at the left adnexa.
For the questions that follow, choose your answer from among these choices:
A. Endometrial polyp
B. Leiomyoma
C. Endometrial hyperplasia
D. Endometrial carcinoma
____ 1. Which lesion is least likely to cause the bleeding?
____ 2. Which is most common in occurrence?
____ 3. Which has a pre-malignant potential?
____ 4. Which is amenable to simple enucleation, if small in number and size?
____ 5. Which is characterized microscopically by presence of thick-walled blood vessels in clusters?
____ 6. Which can be submucosal in location?
____ 7. Which is composed purely of mesenchymal cells, with no epithelial elements?
____ 8. Which lesion has to be graded and staged?
____ 9. Which has to be evaluated on the basis of nuclear atypia, mitotic activity and tumor necrosis to
determine its biologic behavior?
____10. Which of the other three lesions is usually preceded by endometrial hyperplasia?

PATHOLOGY OF THE KIDNEY AND
LOWER URINARY TRACT
MARIA SARAH L. LENON, MD
I. RENAL BIOPSY
4. Acute renal failure - characterized by oliguria or
The diagnosis of glomerular diseases involves the anuria with recent onset of azotemia.
use of the following techniques as well as correlation 5. Chronic renal failure - characterized by prolonged
with the clinical and laboratory findings: (>3 months) symptoms and signs of uremia
6. Renal tubular defect - dominated by polyuria,
1. Light Microscopy: using the following stains: nocturia, and electrolyte disorders
a. H and E- used as the routine stain 7. Urinary tract infections - characterized by
b. Silver impregnation stain - outlines the bacteriuria and pyuria
glomerular and tubular basement 8. Nephrolithiasis - characterized by renal colic,
membranes (splitting, spikes and domes) hematuria, and recurrent stone formation
c. Trichrome stain – assess presence of fibrosis
d. Periodic Acid-Schiff stain(PAS) - outlines the C. STAGES OF RENAL FAILURE:
basement membranes of glomeruli and 1. Diminished renal reserve - GFR is about 50% of
tubules and highlights the mesangial matrix. normal; serum BUN and creatinine values are
This is the best stain to assess the normal; patients are asymptomatic
mesangial matrix. 2. Renal insufficiency - GFR is 20 to 50% of normal;
characterized by azotemia, anemia, hypertension,
2. Immunofluorescence - localize types of polyuria and nocturia
immunoglobulin (IgA, IgM, IgG), antigens, 3. Renal failure - GFR is less than 20 to 25% of
complement (C3, C1q), fibrin-related compounds, normal; patients develop edema, metabolic
and cell surface markers acidosis, and hypocalcemia; overt uremia may
ensue
3. Electron microcopy - defines ultra-structural 4. End-stage renal disease - GFR is less than 5% of
changes and specific location of electron-dense normal; terminal stage of uremia
deposits
Morphologic lesions III. GLOMERULAR DISEASES
1. Diffuse - involves almost all the glomeruli
2. Focal - involves only several glomeruli A. CLASSIFICATION
(usually less than 50%) 1. Primary glomerulopathies
3. Segmental - involves a portion of a a. Acute diffuse proliferative
glomerulus glomerulonephritis
4. Global - involves the entire glomerulus i. Post streptococcal
ii. Non streptococcal
II. CLINICAL MANIFESTATIONS OF RENAL b. Rapidly progressive (crescentic)
DISEASES glomerulonephritis
c. Lipoid nephrosis (minimal change disease)
A. DEFINITION OF TERMS d. Focal segmental glomerulosclerosis
1. Azotemia - biochemical abnormality that e. Membranous glomerulopathy
refers to an elevation of the BUN f. Membranoproliferative glomerulonephritis
and creatinine levels. It is related g. IgA nephropathy
largely to a decreased GFR. h. Chronic glomerulonephritis
2. Uremia - azotemia associated with
constellation of clinical signs and 2. Systemic diseases
symptoms and biochemical a. Systemic lupus erythematosus
abnormalities b. Diabetes mellitus
c. Amyloidosis
B. MAJOR RENAL SYNDROMES d. Goodpasture’s syndrome
1. Acute nephritic syndrome - glomerular syndrome e. Polyarteritis nodosa
characterized by: f. Wegener’s granulomatosis
- Hematuria, red cell casts, variable levels g. Henoch-Schonlein purpura
of proteinuria, acute or chronic renal h. Bacterial endocarditis
failure, hypertension
- Classic presentation of acute post 3. Hereditary disorders
streptococcal glomerulonephritis a. Alport’s syndrome
2. Nephrotic syndrome - characterized by heavy b. Fabry’s disease
proteinuria (> 3.5 gm per day), hypoalbuminemia
(less than 3 gm dl), severe edema, hyperlipidemia, B. PATHOGENESIS OF GLOMERULAR INJURY
and lipiduria Immune mechanisms underlie most cases of
3. Asymptomatic hematuria or proteinuria - usually a primary GN and many of the secondary
manifestation of subtle or mild glomerular glomerular involvement.
abnormalities
Immune Mechanisms of Glomerular Injury
I. Antibody-mediated injury
a. In situ immune complex deposition
(fixed intrinsic tissue antigens or planted antigens)
LOWER URINARY TRACT
b. Circulating immune-complex deposition

(exogenous or endogenous antigens) 3. Membranous Glomerulonephritis
(Membranous Nephropathy)
II. Cell-mediated injury - A major cause of nephrotic syndrome in
III. Activation of Alternative Complement adults; 85% is idiopathic while the rest may
Pathway
be associated with carcinoma, SLE,
C. SUMMARY OF IMPORTANT SPECIFIC
exposure to inorganic salts (gold, mercury),
PRIMARY GLOMERULOPATHIES
drugs (penicillamine, captopril), infections,
1. Acute Post streptococcal (Proliferative)
metabolic disorders
Glomerulonephritis
- Caused by certain strains of group A beta - Morphology:
hemolytic streptococci usually to types 12, 4 and 1 Light microscopy - diffuse capillary wall
thickening
- Usually affects children
- Characterized clinically by oliguria and hematuria IF - granular IgG and C3; diffuse
1-2 weeks after recovery from a sore throat or skin EM – sub epithelial deposits forming
infection “spikes and domes”
4. Minimal Change Disease
- Associated with periorbital edema and mild to
(Lipoid Nephrosis/ Nil Disease)
moderate hypertension; patient exhibit red cell casts
- Most frequent cause of nephrotic syndrome
in the urine and mild proteinuria
in children; proteinuria is usually highly
- Morphology: selective
a. Light microscopy - enlarged hypercellular - Morphology:
glomeruli with leucocytic infiltration Light Microscopy - normal glomeruli; lipid
b. IF - granular IgG and C3 in GBM and in tubules
mesangium (starry sky pattern) IF – negative (cytokine mediated)
c. EM - subepithelial humps EM – loss (fusion) of foot processes; no
electron-dense deposits
- Prognosis: spontaneous total recovery in 95% of
prognosis:
children and 60% in adults; 1-2% of children
- 90% of children exhibit rapid response to
develop chronic GN; less than 1% develop RPGN
corticosteroid therapy
2. Rapidly Progressive (Crescentic)
5. Focal Segmental Glomerulosclerosis
Glomerulonephritis
- 10 to 15% are idiopathic; the rest may be
- Clinico-pathologic syndrome characterized by: associated with another primary glomerular
A. Clinical - rapid and progressive decline in lesion, loss of renal mass, heroin abuse and
renal function, frequently with severe HIV infection
oliguria or anuria, usually resulting in - Morphology:
irreversible renal failure in weeks or months Light microscopy - focal and segmental
sclerosis and hyalinosis
B. Morphologic - formation of IF - focal; IgM and C3
a. Light microscopy- glomerular crescents EM - loss of foot processes; epithelial
(20-50%) due to proliferation of parietal denudation
cells and migration of monocytes and
macrophages into Bowman’s space. Differences from minimal change disease:
b. IF- depends on type 1. higher incidence of hematuria, reduced GFR,
c. EM- rupture of the GBM and hypertension
2. proteinuria is more often non-selective
3 TYPES of RPGN: 3. responds poorly to corticosteroid therapy
1. Type I- Anti-GBM antibody 4. may progress to chronic GN; 50% develop
2. Type II- Immune Complex end-stage renal disease within 10 years
3. Type III- Pauci-immune 5. deposits of IgM and C3 in IF
causes:
6. Membrano-proliferative GN
 Post infectious RPGN
(MPGN; Mesangio-capillary GN)
 Systemic diseases
- Accounts for 5-10% of cases of idiopathic
- SLE
nephrotic syndrome in children and adults
- Goodpasture’s syndrome
- Morphology
- Vasculitis
- Wegener’s granulomatosis
Light microscopy - mesangial proliferation;
- Henoch-Schonlein purpura
basement membrane thickening; splitting
- Essential cryoglobulinemia
 Idiopathic RPGN

LOWER URINARY TRACT
(“tram-track”) There are three types based on IF change consists of widespread thickening
and EM findings: of capillary wall
Type I - IF: IgG + C3; C1 + C4
EM: sub endothelial deposits 2. Diabetic Glomerulosclerosis
- major renal lesions
Type II -  Glomerular lesions
EM: also called Dense deposit (Basic: Basement membrane thickening)
Disease (intramembranous 1. Diffuse glomerulosclerosis – most
deposits) common lesion
Type III - exhibit both subendothelial 2. Nodular glomerulosclerosis
and subepithelial deposits; (Intercapillary glomerulosclerosis or Kimmelstiel-
associated with GBM disruption and Wilson disease) - virtually pathognomonic of
reduplication diabetes
3. Exudative lesions
7. IgA Nephropathy a. Arteriolosclerosis
- Frequent cause of recurrent gross or b. UTI – pyelonephritis and papillitis
microscopic hematuria; mild proteinuria is
usually present 3. Henoch-Schonlein Purpura
- may be considered the most common - renal lesions are virtually similar to IgA
cause of glomerulonephritis worldwide nephropathy; associated with purpuric skin
- Morphology lesions, abdominal manifestation, and non-
a. Light microscopy - normal or mesangial migratory arthralgia
widening (focal segmental GN or
mesangio-proliferative) 4. Goodpasture’s syndrome
b. IF - prominent IgA deposits in the - consists of:
mesangium; IgG, IgM and C3 may be 1. Rapidly progressive glomerulonephritis
present 2. Necrotizing hemorrhagic interstitial
c. EM - mesangial and para mesangial Pneumonitis
dense deposits - lesions are caused by anti-basement membrane
antibodies (peptide in the non - collagenous portions
8. Chronic Glomerulonephritis of the alpha 2 chain of type IV collagen)
- end-stage pool of glomerular disease
characterized by chronic renal failure IV. DISEASES AFFECTING TUBULES AND
- morphology INTERSTITIUM
 Gross - usually bilaterally contracted
kidneys; cortical surface shows diffuse, A. ACUTE TUBULAR NECROSIS
fine regular granularity or scars - Clinico-pathologic entity characterized
 Microscopic - hyalinized glomeruli; morphologically by destruction of tubular
tubular atrophy; interstitial fibrosis and epithelial cells and clinically by acute
leucocytic infiltration suppression of renal function
- Fully reversible
D. GLOMERULAR LESIONS ASSOCIATED WITH - morphologic patterns:
SYSTEMIC DISEASE
a. Ischemic ATN - characterized by focal tubular
1. Systemic Lupus Erythematosus necrosis at multiple points with skip areas associated
- most common causes of death are renal with tubulorrhexis and presence of casts (patchy);
failure and inter current infections clinically associated with shock
- IF- FULL HOUSE (IgA, IgG, IgM, C3, C1q,
Fibrinogen) b. Nephrotoxic ATN - characterized by extensive
- renal lesions (WHO morphologic necrosis along the proximal tubular segments;
classification) usually caused by drugs, antibiotics, radiographic
o Class I - normal contrast agents, poisons and organic solvents
o Class II - Mesangial lupus GN – mildest
of the lesions characterized by - 3 phases: Initiation phase, maintenance phase,
mild hematuria or transient recovery phase
proteinuria
o Class III - Focal proliferative GN B. TUBULO INTERSTITIAL NEPHRITIS
o Class IV - Diffuse proliferative GN - most
serious of the renal lesions, occurring in 1. Acute pyelonephritis
35-40% of biopsied patients; epithelial - Hematogenous vs. ascending infection
crescents are common - Predisposing conditions: urinary obstruction,
o Class V - Membranous GN - usually instrumentation, vesico-ureteric reflux,
associated with severe proteinuria with pregnancy, patient’s age and sex, pre-
nephrotic syndrome; principal histologic existing renal lesions, diabetes mellitus,
immunosupression and immunodeficiency.
LOWER URINARY TRACT
- Morphologic hallmark: patchy interstitial VII. Urolithiasis (Renal Calculi, Stones)

suppurative inflammation and tubular
necrosis A. Cause:
- the most important determinant is increased
- Complications: papillary necrosis (seen urinary concentration of the stone’s
mainly in diabetics and urinary tract constituents (supersaturation)
obstruction), pyonephrosis (usually in almost
complete obstruction), perinephric B. Main types of calculi:
abscesses
- 85% due to normal Gram negative GI flora (mucoprotein matrix is present in all calculi)
(E. coli, Klebsiella, Proteus)
1. Calcium stones (75%) - most common;
2. Chronic pyelonephritis composed mostly of calcium oxalate
- Chronic tubulointerstitial inflammation with 2. “Triple stones” or struvite stones (15%) -
scarring and associated with involvement of composed of magnesium ammonium
calyces and pelvis phosphate; formed largely following
- Gross morphology: coarse, discrete irregular infection by urea-splitting bacteria;
scars overlying dilated, blunted or deformed associated with staghorn calculi
calyces; 3. Uric acid stones (6%) - more than half of
- usually unilateral; if bilateral, the patients with urate calculi have neither
involvement is asymmetric hyperuricemia nor increased urinary
- Microscopic: thyroidization of tubules, excretion of uric acid
tubular atrophy, interstitial fibrosis with 4. Cystine (1-2%) - associated with genetic
chronic inflammatory cells defect.
V. DISEASES OF BLOOD VESSELS

VIII. TUMORS OF THE KIDNEY
A. BENIGN NEPHROSCLEROSIS A. Benign Tumors - usually incidental findings at
- benign hypertension autopsy
- morphology: hyaline arteriolosclerosis, 1. Cortical adenoma
fibroelastic hyperplasia 2. Renal fibroma or hamartoma
B. MALIGNANT NEPHROSCLEROSIS 3. Angiomyolipoma - present in 25-50% of
- malignant or accelerated phase of patients with tuberous sclerosis
hypertension 4. Oncocytoma
- morphology: necrotizing arteriolitis (fibrinoid
necrosis of arterioles), hyperplastic B. Malignant tumors
arteriolitis (“onion skinning”)
- “flea-beaten” gross appearance of the 1. Renal Cell Carcinoma
kidney (Hypernephroma, Adenocarcinoma of the Kidney)
- accounts for 85-90% of all renal cancers in adults
VI. Urinary Tract Obstruction (Obstructive - predisposing factors:
Uropathy) 1. cigarette, pipe, and cigar smoking
2. genetic factors: 60% of patients with
A. Clinical Importance: von Hippel-Lindau syndrome
3. classic clinical diagnostic features:
1. Increases susceptibility to infection costovertebral pain, palpable mass,
2. Increases susceptibility to stone formation hematuria (in 90% of cases)
3. Almost always leads to permanent renal - prognosis: tendency to metastasize widely before
atrophy (hydronephrosis or obstructive giving rise to any local symptoms or signs;
uropathy) - average 5-year survival rate – 45%
B. Causes: 2. Wilm’s Tumor

- most common primary renal tumor of childhood
congenital anomalies, urinary calculi, benign (usually between 2-5 years)
prostatic hypertrophy, tumors, inflammation, - predisposing congenital malformations:
sloughed papillae or blood clots, normal pregnancy, 1. WAGR syndrome - aniridia, genital
uterine prolapse and cystocele, functional disorders. anomalies, and mental retardation
2. Denys-Drash syndrome - gonadal
C. Hydronephrosis dysgenesis and nephropathy
 dilatation of the renal pelvis and calyces 3. Beckwith-Wiedemann syndrome -
associated with progressive atrophy of the enlargement of body organs,
kidney due to obstruction of urine outflow. hemi hypertrophy, renal medullary
cysts, adrenal cytomegaly

LOWER URINARY TRACT
IX. Bladder Epithelial Tumors
Urothelial (Transitional) Cell Tumors:

o Inverted papilloma
o Papilloma (exophytic)
o Urothelial tumors of low malignant Potential
(PUNLMP)
o Papillary urothelial carcinoma
o Carcinoma in situ
o Squamous cell carcinoma
o Mixed Carcinoma
o Adenocarcinoma
o Small cell carcinoma
Grading of Urothelial (Transitional Cell)

Tumors
WHO/ISUP Grades
Urothelial papilloma
Urothelial neoplasm of low malignant potential
Papillary urothelial carcinoma, low grade
Papillary urothelial carcinomas, high grade

REVIEW TEST
CHOOSE THE BEST ANSWER C. Henoch-Schonlein Purpura

D. Post streptococcal GN
_____ 1. A 2-year-old female presented with a left
upper quadrant abdominal mass. The child had no _____ 5. A 7-year-old child presents with
previous history of medical illness. An abdominal hypoalbuminemia, edema, hyperlipidemia, and
ultrasound was done that showed a markedly proteinuria. The edema is in the periorbital region
deformed left kidney with a 12 cm nonhomogenous initially and eventually spreads to the rest of the
soft tissue mass arising from the upper pole. There body. The patient is given steroid therapy and the
was medial displacement of the bowel loops. Which disease goes away. What is a key morphological
of the following is the most likely diagnosis for this feature of the patient’s disease?
case? A. Fusion of the foot processes
A. Nephroblastoma B. Destruction of the basement membrane
B. Teratoma C. Destruction of the glomerulus
C. Neuroblastoma D. Hemosiderin laden macrophages in the
D. Rhabdomyosacrcoma kidney
E. Hepatoblastoma
_____ 6. A 25-year-old Asian male is noticed to have
_____ 2. A 45-year-man noticed blood in his urine.
CT of the lower abdomen and pelvis showed a mass recurrent gross hematuria. The patient has fatty
in the superior pole of the kidney was discovered. stools, indicating some sort of malabsorption
syndrome. He sometimes has arthritis. There are no
Surgical resection of the renal mass was done that
showed a large yellow tan tumor with areas of remarkable findings on physical examination.
hemorrhage. The tumor is made up mainly of large Urinalysis shows a pH of 6.5; specific gravity 1.018;
3+ hematuria; 1+ proteinuria; and no glucose or
irregular cells, some with granular cytoplasm, and
others with large vacuoles. The nuclei vary in size ketones. Microscopic examination of the urine shows
and shape. Some are pyknotic and some are RBCs and no WBCs, casts, or crystals. A renal biopsy
specimen from the glomeruli of this patient is most
displaced to the periphery of the large vacuolated
cells characteristic of this disease. What is likely to show which of the following alterations
the BEST diagnosis? A. Sub epithelial electron-dense deposits
B. Granular staining of the basement
A. Collecting (Bellini) duct carcinoma membrane by anti-IgG antibodies
B. Papillary carcinoma C. Mesangial IgA staining by
C. Clear cell carcinoma immunofluorescence
D. Chromophobe renal carcinoma D. Diffuse proliferation and basement
E. Wilm's tumor membrane thickening
E. Thrombosis in the glomerular capillaries
_____ 3. A 27-year-old female presents with malar
rash, photosensitivity, oral ulcers, arthritis, and signs _____ 7. A diabetic patient presents with macro
of nephritic syndrome. Upon examination of his albuminuria. He also has hypertension and his GFR
kidney, there appears to be crescent formation. Test has decreased a lot. He has retinopathy. His kidney
samples reveal antibodies against DNA, ANA, and glomerular basement membrane is thickened and
snRNA. What is the pathogenic mechanism of the there appears to be sclerosing. What is a key
disease? feature of his syndrome?
A. Immune complex mediated A. Kimmelsteil-Wilson nodules
B. Infection B. Heberden Nodes
C. Tumor C. Bouchard nodes
D. None of the above D. All of the above
_____ 4. A 7-year-old boy is recovering from _____ 8. A 49-year-old female underwent an

impetigo and manifested with few honey-colored emergency surgery of a renal tumor that went into
crusts on his face. Culture of these skin lesions was sudden rupture and subsequent bleeding. The tumor
done with growth of Group A Streptococcus was sent for histopathologic examination and
pyogenes. He is treated with antibiotics. One week showed tri phasic elements of benign adipose
later, he develops malaise with nausea and a slight tissues, smooth muscle and variably sized vessels.
fever and passes dark brown urine. Laboratory This patient also manifested with skin lesions and
studies show a serum anti streptolysin O titer of episodes of seizure. What is the likely diagnosis for
1:1024. Which of the following is the most likely the renal tumor?
diagnosis? A. Renal adenoma
A. Lupus Nephritis B. Renal fibroma
B. IgA Nephropathy C. Angiomyolipoma
D. Oncocytoma
REVIEW TEST
_____ 14. A 62-year-old man has had several

_____ 9. A 30-year-old man suddenly develops episodes of painless hematuria over the past week
severe abdominal pain and passed out red colored with no other accompanying symptoms. Urinalysis
urine. Physical examination was unremarkable. The shows 4+ hematuria. The urine culture is negative.
patient noted a 0.5-cm stone that passed out in his A cystoscopy is performed, and 2.5 cm friable mass
urine that is sent for analysis. The chemical is seen on the right bladder wall. Microscopically, -
composition is found to be calcium oxalate. What this mass showed dyscohesive cells with large
underlying condition is most likely to be present?
A. Gout hyperchromatic nuclei, some appearing highly
B. Idiopathic hypercalciuria anaplastic. Which of the following risk factors is
C. Acute cystitis
most important in the pathogenesis of this bladder
D. Diabetes Mellitus
lesion?
_____ 10. Which of the following renal calculi is A. Schistosomiasis
commonly associated with urea-splitting bacteria? B. Cigarette smoking
C. Diabetes Mellitus
A. Cystine
D. Chronic bacterial cystitis
B. Struvite Stones
C. Calcium Stones
_____ 15. A 60-year-old man presents with a feeling
D. Uric acid stones
of fullness in his abdomen and a 5-kg weight loss
_____ 11. A 72-year-old woman died of an acute over the past 6 months. Physical examination is
myocardial infarction. At autopsy, both kidneys were normal. Laboratory studies show hemoglobin of 8.2
decreased in size (about 120 g each) with a finely g/dL, hematocrit of 24%, and MCV of 70 μm3.
granular cortical surface. Microscopicallly, the renal Urinalysis shows 3+ hematuria, but no protein,
vessels showed hyalinization of arteriolar walls and glucose, or leukocytes. Abdominal CT scan shows an
fibroelastic hyperplasia. Which of the following 11-cm mass in the upper pole of the right kidney. A
clinical abnormalities most likely accompanied this right nephrectomy is performed, and on gross
lesion? examination the mass appears hemorrhagic that
A. Oliguria invades the renal vein. Microscopic examination of
B. Benign hypertension the tumor cells in complex, arborizing, finger-like
C. Malignant hypertension projection with delicate fibrovascular stroma with
D. Hematuria psammomatous calcifications. Which of the following
E. Flank pain is the likely pathologic diagnosis?
A. Angiomyolipoma
_____ 12. A 58-year-old man is in a stable condition
B. Renal Cell Carcinoma, Clear Cell Type
after an acute myocardial infarction. Two days later,
C. Renal Cell Carcinoma, Papillary Type
his urine output decreases, and the serum urea
D. Renal Adenoma
nitrogen level increases to 3.3 mg/dL. Oliguria
persists for 5 days, followed by polyuria for 2 days. _____ 16. Autopsy findings in an 82-year-old man
He is discharged from the hospital. Which of the showed gross appearance of the right kidney of
following renal lesions best explains these renal ureteral, pelvic and calyceal dilatation. The
abnormalities? appearance of the right kidney is most suggestive of
A. Acute tubular necrosis renal injury from which of the following?
B. Benign nephrosclerosis
A. Benign Nephrosclerosis
C. Acute renal infarction
B. Chronic pyelonephritis
D. Hemolytic-uremic syndrome
C. Ureteral obstruction
D. Diabetes Mellitus
_____ 13. What histomorphologic type of urothelial
tumor is usually associated with Schistosomiasis? _____ 17. What neoplasm of the urinary bladder is
A. Adenocarcinoma highly associated with urachal remnants?
B. Papilloma A. Adenocarcinoma
C. Papillary urothelial carcinoma B. Papilloma
D. Squamous carcinoma C. Papillary urothelial carcinoma
D. Squamous carcinoma

REVIEW TEST
_____ 18. What is the MOST COMMON location of

metastases from renal cell carcinoma?
A. Liver
B. Bone
C. Brain
D. Lung
E. Lymph nodes
_____ 19. A 30-year-old woman has had fever and

body malaise for the past month. This was
accompanied by myalgia and arthralgias. She
likewise had a 4-kg weight loss. Serum complement
levels are decreased. CBC showed anemia, -
thrombocytopenia and mild leukocytosis. A renal
biopsy specimen shows a diffuse proliferative

glomerulonephritis with extensive granular immune
deposits of IgG and C1q in capillary loops and
mesangium. After being treated with
immunosuppressive therapy consisting of prednisone
and cyclophosphamide, her condition improves.
Which of the following serologic studies is most
likely to be positive in this patient?
A. Anti-centromere antibody
B. Anti–double-stranded DNA antibody
C. Anti–DNA topoisomerase I antibody
D. Anti–glomerular basement membrane
antibody
_____ 20. A 17-year-old woman has had a fever and

chills accompanied by right flank pain for the past 3
days. Significant physical examination finding of
costovertebral angle tenderness is noted. Urinalysis
shows a pH of 6.5; specific gravity 1.018; and no
protein, blood, glucose, or ketones. Microscopic
examination of the urine shows many WBCs and
WBC casts. Which of the following factors is most
important in the pathogenesis of the renal disease
affecting this patient?
A. Age
B. Sex
C. Vesicoureteral reflux
D. Blood pressure
E. Lung infection

BONE, JOINT, SOFT TISSUE
AND SKIN PATHOLOGY
CELESTINE MARIE G. TRINIDAD, MD
BONE, JOINT, AND SOFT TISSUE PATHOLOGY  Osteocytes – osteoblasts that are
completely embedded in bone matrix and
BASIC STRUCTURE OF BONE isolated in a lacuna
- detect mechanical forces and
Constituents of bone: translate them into biologic activity
 Extracellular Matrix (mechanotransduction)
 Specialized Cells responsible for production  Osteoclasts – specialized multinucleated
and maintenance of the matrix macrophages responsible for bone
resorption
Matrix
 Extracellular component of bone Bone Formation and Growth
 Made up of:  Endochondrondral ossification -bones
o Organic component (osteoid) (35%) develop from a cartilage mold (anlagen)
 Predominantly type I  Intramembranous ossification-responsible
collagen with smaller for the development of flat bones (no
amounts of cartilage anlagen)
glycosaminoglycans and
other proteins DEVELOPMENTAL ABNORMALITIES OF BONE
 Only osteopontin AND CARTILAGE
(osteocalcin) unique to the Disorders of the Growth Plate
bone; marker of  Achondroplasia – autosomal dominant
osteoblastic activity disorder
o Mineral component (65%) -most common skeletal dysplasia and cause
 Hydroxyapatite of dwarfism
[Ca10(PO4)6(OH)2]; -gain-of-function mutations in FGFR3
Imparts hardness (unique -reduction in the proliferation of the
feature of bone matrix) chondrocytes in the growth plate
 Serves as a repository for Delayed Maturation of Bone
99% of the body’s calcium  Osteogenesis Imperfecta (Brittle Bone
and 85% of its phosphorus Disease) – autosomal dominant disorder
 Synthesized in two forms: - extracellular structural protein deficiency
o Woven leading to deficiency in the synthesis of type
o Lamellar 1 collagen
-fundamental abnormality: too little bone,
LAMELLAR WOVEN extreme skeletal fragility
Arrangement of Parallel Irregular - Also affects other tissues rich in type I
Type I collagen
collagen (joints, eyes, ears, teeth, skin)
Osteocytes in Few Numerous
matrix o Blue sclera
Osteocyte Uniform Pleomorphic o Hearing loss
morphology o Dental imperfections
 Osteoporosis - decreased bone mass 2.5
Deposition/ Slow Rapid
Production standard deviations below peak bone mass
Tensile strength Strong Low -increased porosity of the skeleton
Present in adult Normal Abnormal predisposing the bone to fractures
skeleton  Osteopetrosis - Marble Bone Disease,
Found in bone Rare Usual Albers-Schönberg disease
forming tumor -reduced bone resorption and diffuse
Pathologic Reaction to Reaction to
symmetric skeletal sclerosis due to impaired
formation persistent rapidly
stress and growing activity of osteoclasts
slowly tumor or -Erlenmeyer flask deformity
growing virulent  Paget’s Disease of the Bone (Osteitis
tumors infection Deformans) – disorder of increased, but
disordered and structurally unsound, bone
Cells mass
 Osteoblasts – synthesize, transport and -3 phases: osteolytic, mixed and sclerotic
assemble the matrix and regulate its -mosaic pattern of lamellar bone (seen in
mineralization sclerotic phase)

AND SKIN PATHOLOGY
DISEASES ASSOCIATED WITH ABNORMAL vertebrae, sparing the lamina spines and the
MINERAL HOMEOSTASIS adjacent vertebrae
 Renal Osteodystrophy – describes all the -infection breaks through intervertebral discs
skeletal changes of chronic renal disease to affect multiple vertebrae and extends into
-Cause skeletal abnormalities through these the soft tissues; destruction of discs and
mechanisms: vertebrae frequently results in permanent
o Tubular dysfunction: renal tubular compression fractures, scoliosis or kyphosis,
acidosis; low pH dissolves neurologic deficits
hydroxyapatite; causes osteomalacia
o Generalized renal failure: secondary
hyperparathyroidism
o Decreased production of secreted  Syphilis (Treponema pallidum) and
factors: Vitamin D yaws (Treponema pertenue)
 Osteomalacia and Rickets – Vitamin D -Congenital Syphilis – bone lesions appear
deficiency or abnormal metabolism about the 5th month of gestation and are fully
- rickets (disorder in children) developed at birth
- osteomalacia (disorder in adults) -Acquired Syphilis- bone disease may begin
- decreased mineral content of bone early in the tertiary stage, usually 2 to 5 years after
 Hyperparathyroidism-3 interrelated the initial infection; affect nose, palate, skull, and
skeletal abnormalities: osteoporosis, brown extremities (especially tibia)
tumor (mass of reactive tissue) and osteitis -characterized by edematous granulation
fibrosa cystic tissue containing numerous plasma cells and
 Paget Disease (Osteitis Deformans) - necrotic bone; gummas – centers of coagulated,
disorder of increased, but disordered and necrotic material and margins composed of plump,
structurally unsound, bone mass palisading macrophages and fibroblasts surrounded
- 3 phases: osteolytic, mixed, osteosclerotic by large numbers of mononuclear leukocytes
-Hallmark: mosaic pattern of lamellar bone -frequently involves the nose (saddle nose
(seen in the sclerotic phase); Jigsaw-like deformity due to destruction of the vomer), palate,
pattern: produced by unusually prominent skull and extremities (-saber shin: massive
cement lines periosteal bone deposition on the medial and
anterior surface of the tibia causing anterior bowing)
BONE INFECTIONS (OSTEOMYELITIS)
FRACTURES
 Sequestrum: dead bone Healing of fractures:
 Involucrum: shell of living tissue (reactive Hematoma  Soft Callus  Hard Callus  Healing
bone) around a sequestrum
 Brodie abscess: small intraosseous OSTEONECROSIS (Avascular Necrosis /
abscess that frequently involves the cortex Aseptic Necrosis) – Infarction of bone and marrow
and is walled off by reactive bone -Stem from fractures or corticosteroid administration
 Sclerosing osteomyelitis of Garré:
develops in the jaw, associated with BONE TUMORS AND TUMOR-LIKE
extensive new bone formation that obscures CONDITIONS OF BONE
much of the underlying osseous structure Non-Neoplastic Conditions
Organisms:  Simple Solitary/Unicameral Bone Cyst
 Staphylococcus spp – most common -Location: proximal metadiaphysis of
pathogen; responsible for 80% to 90% of humerus
the cases of culture-positive pyogenic -X-ray: fallen fragment sign
osteomyelitis -Gross: usually unilocular, cystic bone cavity
 Mycobacterium tuberculosis – direct –Micro: lined by a fibrous membrane and
extension (e.g., from a pulmonary focus into filled with serous or sero-sanguinous fluid,
a rib or from tracheobronchial nodes into or white chylous material
adjacent vertebrae) or spread via the  Aneurysmal Bone Cyst
circulation -Location: most frequently develops in the
- Findings similar to pulmonary tuberculosis: metaphysis of long bones and the posterior
granulomas, caseous necrosis, Langhan’s elements of vertebral bodies
giant cells -Gross: multiloculated blood-filled cystic
-Pott Disease (Tuberculous Spondylitis): spaces
tuberculosis affecting the bodies of the

AND SKIN PATHOLOGY
-Micro: spaces separated by septa of plump lucency thick cortical

uniform fibroblasts, multinucleated surrounded by bone)
osteoclast-like giant cells, and reactive thick cortical
woven bone; differentiated from bone)
Symptoms Relieved by Not relieved by
hemangioma and arterio-venous
aspirin and NSAIDs
malformation because of absence of NSAIDs
endothelial lining
 Eosinophilic Granuloma – Unifocal and  Osteosarcoma – Most common primary
multifocal unisystem Langerhans cell malignant tumor of the bone exclusive of
histiocytosis myeloma and lymphoma
- Micro: proliferations of Langerhans cells -bimodal age distribution – 1st peak: 70%
admixed with variable numbers of occurs in patients younger than 20 y/o; 2nd
inflammatory cells, eosinophils are usually, occurs in older adults, frequently suffer from
but not always, a prominent component of conditions known to predispose to
the infiltrate osteosarcoma—Paget disease, bone infarcts,
- Langerhans cells have abundant, often and prior radiation
vacuolated cytoplasm and vesicular nuclei -associated with mutations of the RB gene
containing linear grooves or folds; presence -Location: about 60% occur about the knee
of Birbeck granules in the cytoplasm on EM (distal femur and proximal humerus,
Fibrous Dysplasia – - May be monostotic metaphyseal region
(involvement of a single bone), polyostotic -X-ray: permeative growth pattern;
(involvement of multiple bones) Codman’s triangle (due to periosteal
- Micro: Composed of curvilinear trabeculae upliftment); soft tissue component (due
of woven bone surrounded by a moderately to rapid growth- doubling time is only about
cellular fibroblastic proliferation 3-4 weeks); sunburst appearance (due to
-"Chinese characters" - shapes of the osteophyte formation in the soft tissue
trabeculae mimic Chinese characters, bone component)
lacks prominent osteoblastic rimming -Micro: Formation of bone (osteoid matrix)
by the tumor cells is diagnostic
Neoplastic Conditions -may have 4-fold increase in serum alk
Metastatic (Secondary) Bone Tumors - Most phos levels (due to bone matrix
common form of skeletal malignancy, greatly production)
outnumbering primary bone cancers
-Radiographic appearance of metastases Chondroid (Cartilage) forming tumors
may be:  Osteochondroma – most common benign
o Purely lytic (bone destroying): bone tumor; benign cartilage-capped tumor
carcinomas of the kidney, lung, and that is attached to the underlying skeleton
gastrointestinal tract and malignant by a bony stalk
melanoma  Chondroma - benign tumors of hyaline
o Purely blastic (bone forming): cartilage that usually occur in bones of
prostate adenocarcinoma enchondral origin
o Mixed lytic and blastic -Enchondroma- arise within the medullary
Primary Matrix Producing Bone Tumors cavity
-Juxtacortical chondroma- arise on the
Osteoid (Bone) Matrix Producing surface of the bone
 Osteoid Osteoma and Osteoblastoma –  Chondrosarcoma - malignant tumors that
benign bone-producing tumors that have produce cartilage
identical histological features, but differ in -Age: usually in their 40s or older,
the following: Males>Females
Osteoid Osteoblastoma -Location: axial skeleton, especially the
Osteoma pelvis, shoulder, and ribs; rarely in distal
Size <2 cm >2 cm
extremities
Site of Appendicular Posterior spine
-X-ray: ―popcorn appearance‖
origin skeleton, (laminae and
femur, tibia pedicles) -Micro: tumors vary in cellularity, cytologic
X-ray Associated No nidus (small atypia, and mitotic activity and are assigned
with a nidus round lucency a grade from 1 to 3
(small round surrounded by

AND SKIN PATHOLOGY
Tumors of Unknown Origin -most commonly affected: knee followed by

 Giant cell tumor of the bone – hip
-Age: patients 20s to 40s, arises in patients - X-ray: kissing bones due to narrowing of
with fused bone plates the joint space
- Location: arise in the epiphysis, majority  Gout – caused by deposition of urate
arise around the knee (distal femur and crystals in the joints
proximal tibia) -most commonly affected: big toe followed
-X-ray: ―soap bubble‖ appearance, tumors by knees
often destroy the overlying cortex, -clinical course: 1) asymptomatic
producing a bulging soft tissue mass hyperuricemia ( BUA), 2) acute gouty
delineated by a thin shell of reactive bone arthritis, 3) intercritical gout, and 4) chronic
-Micro: Histology is dominated by tophaceous gout
multinucleated osteoclast-type giant cells -Tophi: foreign body granulomas
(synonym: osteoclastoma) surrounding urate crystals in the affected
joint
Small Round Cell Tumors of the Bone
 Multiple Myeloma – most common SOFT TISSUE PATHOLOGY
primary malignant bone tumor Tumors of Adipose Tissue/Fat
-malignant tumor of plasma cells  Lipoma - benign
-Bone lesions appear radiographically as  Liposarcoma – 3 morphologic subtypes:
punched-out defects well-differentiated, myxoid, pleomorphic
 Ewing Tumor and Primitive -H&E: immature fat cells or lipoblasts
Neuroectodermal Tumor (PNET) -Cytogenetics: amplification of 12q13-q15
-Age: Youngest average age at (well-differentiated) and t(12;16) (myxoid)
presentation, approximately 80% are
younger than 20 years, Males>Females Tumors of Fibrous Tissue
-Location: diaphysis of long tubular bones  Fibroma – benign
-X-ray: destructive lytic tumor with  Fibrosarcoma-malignant
permeative margins that extends into the -H&E: pleomorphic spindle-shaped cells in a
surrounding soft tissues; ―onion skin herringbone pattern (45 angle insertion)
appearance‖ (characteristic periosteal with mitotic figures present
reaction produces layers of reactive bone) -Special Stains: Trichrome-Masson (green)
-Micro: primitive round cells without obvious -Cytogenetics: trisomies in Chromosomes 8,
differentiation 11 and 17
-Genetics: Most contain a (11;22) (q24;q12)
translocation generating in-frame fusion of Tumors of Skeletal Muscle
the EWS gene on chromosome 22 to the  Rhabdomyoma – benign
FLI1 gene  Rhabdomyosarcoma – malignant
-3 morphologic subtypes: embryonal
DISEASES OF THE JOINT (sarcoma botryoides, ―bunch of grapes‖),
 Osteoarthritis – single most common form alveolar, pleomorphic
of joint disease -H&E: tadpole-shaped/racket-shaped
-slowly progressive destruction of the rhabdomyoblasts characterized by
articular cartilage (eburnation) that is abundant eosinophilic cytoplasm;
manifested in the weight bearing joints 3 morphologic subtypes: embryonal
and fingers of older persons or the joint of (sarcoma botryoides, ―bunch of grapes‖),
younger persons subjected to trauma alveolar, pleomorphic
 Rheumatoid arthritis – systemic, -Immunohistochemistry: desmin, MYOD1,
autoimmune, chronic inflammatory disease myogenin
in which chronic polyarthritis involves
diarthrodial joints bilaterally Tumors of Smooth Muscle
-rice bodies (due to hyperplasia of the  Leiomyoma - benign
synovial tissues)  Leiomyosarcoma - malignant
 Infectious arthritis – Staphylococcus sp. -H&E - spindle cells with blunt-ended cigar
is the most common pathogen shaped nuclei intersecting at right (90) angles
-synovial fluid can become purulent -Immunohistochemistry - smooth muscle
actin, desmin, caldesmon

AND SKIN PATHOLOGY
-Munro microabscesses: neutrophils

Tumors of Uncertain Differentiation within the parakeratotic stratum corneum
 Synovial Sarcoma -2 types: monophasic  Lichen Planus – 6 Ps: Pruritic, Purple,
Polygonal, Planar, Papules, Plaques
and biphasic pattern (showing spindle cells
- papules are often highlighted by white
and epithelial cells) dots or lines called Wickham striae
- Immunohistochemistry: Cytokeratin, EMA -Micro: interface dermatitis, sawtoothing of
-Cytogenetics: chromosomal translocation dermoepidermal interface
t(x;18)(p11;q11) producing SS18-SSX1 - colloid/Civatte bodies: anucleate, necrotic
 Undifferentiated Pleomorphic Sarcoma basal cells may become incorporated into
– -diagnosis of exclusion the inflamed papillary dermis
-still represents the largest category of
Blistering Diseases
sarcomas  Pemphigus vulgaris – suprabasal
-previously called Malignant Fibrous nonacantholytic blister
Histiocytoma - ―row of tombstones” single layer of
intact basal cells that forms the blister base
SKIN PATHOLOGY -IF: fishnet-like pattern
 Bullous pemphigoid – subepidermal
Important Microscopic Terms blister
 Acanthosis: diffuse epidermal hyperplasia -tense bullae filled with clear fluid
 Erosion: discontinuity of the skin showing -IF: linear deposition of complement
incomplete loss of the epidermis along the dermoepidermal junction
 Ulceration Discontinuity of the skin  Dermatitis herpetiformis –
showing complete loss of the epidermis subepidermal blister
revealing dermis or subcutis - fibrin and neutrophils accumulate
 Hyperkeratosis: thickening of the stratum selectively at the tips of dermal papillae
corneum -IF: discontinuous, granular deposits of lgA
 Parakeratosis: keratinization with retained that selectively localize in the tips of dermal
nuclei in the stratum corneum papillae
 Papillomatosis: surface elevation caused
by hyperplasia and enlargement of Infections
contiguous dermal papillae  Verruca - squamoproliferative disorders
 Spongiosis: intercellular edema of the caused by human papillomaviruses
epidermis -shows epidermal hyperplasia that is often
undulant in character, koilocytosis,
Inflammatory Dermatoses prominent and apparently condensed
Acute Inflammatory Dermatoses keratohyaline, jagged eosinophilic
 Urticaria - localized mast cell degranulation intracytoplasmic keratin aggregates
and resultant dermal microvascular  Molluscum Contagiosum – caused by a
hyperpermeability poxvirus
-angioedema (edema of the deeper dermis -molluscum body:
and the subcutaneous fat) ellipsoid, homogeneous, cytoplasmic
 Erythema multiforme - uncommon self- inclusion in cells of the stratum granulosum
limited hypersensitivity reaction to certain and the stratum corneum
infections and drugs (eosinophilic in the blue-purple stratum
-―target lesions” granulosum and acquire a pale blue hue in
- Stevens-Johnson syndrome: febrile the red stratum corneum)
form associated with extensive
involvement of the skin Disorders of Melanocytes
- toxic epidermal necrolysis: diffuse  Melanocytic Nevus – benign
necrosis and sloughing of cutaneous and -maturation sequence: junctional nevus 
mucosal epithelial surfaces compound nevus  intradermal nevus
Chronic Inflammatory Dermatoses  Dysplastic Nevus – exhibit both
 Psoriasis - typical lesion: pink to salmon- architectural and cytologic atypia, linear
colored plaque covered by loosely adherent fibrosis surrounding the epidermal rete
silver-white scale ridges that are involved by the nevus
-multiple, minute, bleeding points when the  Melanoma – most deadly of all skin
scale is lifted from the plaque (Auspitz cancers
sign) due to abnormal proximity of vessels - strongly linked to acquired mutations
within the dermal papillae caused by exposure to UV radiation in
-Micro: acanthosis with regular downward sunlight
elongation of the rete ridges - clinically, show ABCDE:
-Kogoj spongiform pustules: neutrophils A – assymetry
within slightly spongiotic foci of the B - border irregularity
superficial epidermis C - color change
AND SKIN PATHOLOGY
D - diameter >6mm
E - elevation
-2 phases:
o Radial growth phase: horizontal
spread of melanoma within the
epidermis and superficial dermis
o Vertical growth phase: tumor
cells invade downward into the
deeper dermal layers as an
expansile mass
-Types: superficial spreading (most
common), lentigo maligna, nodular,
acral lentiginous
-probability of metastasis correlates with
depth of invasion (Breslow thickness)
- Determinants of a more favorable
prognosis: thinner tumor depth, no or
very few mitoses (< 1 per mm2), a brisk
tumor infiltrating lymphocyte
response, absence of regression, lack of
ulceration
Epithelial Tumors
 Seborrheic keratosis –middle-aged or
older individuals
- composed of sheets of small cells that
most resemble basal cells of the normal
epidermis
-hyperkeratosis, horn cysts, invagination
cysts
 Fibroepithelial Polyp/Acrochordon -
consist of fibrovascular cores covered by
benign squamous epithelium
 Actinic Keratosis – cytologic atypia seen
in lowermost layers of the epidermis (not all
levels of the epidermis), parakeratosis
-superficial dermis contains thickened, blue-
gray elastic fibers (elastosis), a probable
result of abnormal elastic fiber synthesis by
sun-damaged fibroblasts
 Squamous Cell Carcinoma - cells with
atypical nuclei involve all levels of the
epidermis (in situ), or may be invasive
 Basal Cell Carcinoma – most common
invasive cancer in humas
-advanced lesions may ulcerate (―rodent
ulcers”)
-may show multifocal or nodular growth
-embedded in a mucinous matrix
-cells show peripheral palisading,
retraction spaces/clefts

REVIEW TEST
BONE, SOFT TISSUE AND SKIN PATHOLOGY
_____1. Which of the following is TRUE about _____8. A 17-year-old male comes in for consult
lamellar bone? due to pain around the right knee for the past 3
A. The arrangement of collagen fibers in months. A radiograph of the right leg shows an ill-
lamellar bone imparts more structural defined mass involving the metaphyseal area of the
integrity than collagen fibers in woven bone. distal right femur, with lifting of the adjacent
B. It is produced rapidly such as in fracture periosteum, and a soft tissue mass described as
repair. having “sunburst” appearance. If a bone biopsy is to
C. Collagen fibers are arranged haphazardly. be done on this patient, what are the expected
D. Its presence in an adult is always histologic findings?
pathologic. A. Sheets of plasma cells in lesions and in
bone marrow
_____2. Osteopetrosis refers to a group of genetic B. Hyperchromatic, pleomorphic spindle
diseases characterized by reduced bone resorption cells forming an osteoid matrix
and diffuse symmetric skeletal sclerosis. This is due C. Uniform oval mononuclear cells and
to the impaired function of which cellular component numerous osteoclast-type giant cells
of the bone? D. Sheets of uniform, primitive, small,
A. Osteoblast round cells
B. Osteoclast
C. Osteocyte _____9. A 6-year-old boy is brought in for consult
D. Chondrocyte for a 5-cm mass in the right lateral neck, which was
noted to be rapidly enlarging in the last six months.
_____3. This is a manifestation of vitamin D A biopsy of the mass showed sheets of both
deficiency in children: primitive round cells with eosinophilic cytoplasm and
A. Rickets spindled, “tadpole-shaped” cells, some of which
B. Osteomalacia have prominent cross-striations.
C. Osteopenia Immunohistochemical staining was positive for
D. Dysostosis desmin, myogenin and myo-D1. What is the most
likely diagnosis?
_____4. Which of the following is TRUE about A. Rhabdomyosarcoma
endochondral ossification? B. Leiomyosarcoma
A. This is the process in which bones are C. Synovial sarcoma
formed directly from a fibrous layer of D. Fibrosarcoma
tissue derived from mesenchyme,
without a cartilage anlagen. _____10. Metastatic prostate adenocarcinoma to the
B. The primary center of ossification is bone on radiographic imaging is predominantly:
located at both longitudinal ends of the A. Purely lytic
bone. B. Purely blastic
C. This is responsible for the development of C. Mixed lytic and blastic
flat bones. D. Neither lytic nor blastic
D. The plate of the cartilage anlage that
becomes entrapped between the two _____11. Which of the following is consistent with a
expanding centers of ossification forms diagnosis of eosinophilic granuloma?
the growth plate. A. Multiloculated blood-filled cystic spaces
separated by septa of plump uniform
_____5. This is the most common form of skeletal fibroblasts, multinucleated osteoclast-like
malignancy: giant cells, and reactive woven bone
A. Osteosarcoma B. Randomly interconnecting trabeculae of
B. Multiple Myeloma woven bone prominently rimmed by a
C. Chondrosarcoma single layer of osteoblasts
D. Metastatic tumors C. Proliferation of cells with vesicular nuclei
containing linear grooves or folds,
_____6. Osteosarcomas typically arise in this region admixed with variable numbers of
of the long bone: eosinophils, lymphocytes, plasma cells,
A. Epiphysis C. Diaphysis and neutrophils
B. Metaphysis D. Subdiaphysis D. Curvilinear trabeculae of woven bone
with a “Chinese character” appearance
_____7. This is a a small intraosseous abscess that and lacking osteoblastic rimming
frequently involves the cortex and is
walled off by reactive bone: _____12. A 30-year-old male patient comes in for
A. Sclerosing osteomyelitis of Garré consult due to right knee pain for a month.
B. Pott Disease Radiograph of the right leg showed a well-defined 7-
C. Albers-Schönberg abscess cm mass in the epiphysis of the distal femur, with a
D. Brodie abscess “soap bubble” appearance and a sclerotic rim.
Microscopic examination of a biopsy specimen of the
REVIEW TEST
lesion shows multinucleated cells in a stroma _____18. A 45-year-old woman has a nodule on her
predominantly composed of spindle-shaped back that has become larger over the past 2
mononuclear cells. What is the most likely months. The lesion has irregular borders and an
diagnosis? irregular brown-to-black color. An excisional
A. Ewing sarcoma biopsy showed radial growth of large round
B. Giant cell tumor malignant cells singly and in nests in the epidermis
C. Osteosarcoma and superficial papillary dermis. These cells have
D. Chondrosarcoma prominent red nucleoli and fine granular brown
cytoplasmic pigment. What is the most likely
_____13. A 75-year-old woman loses her balance diagnosis?
and falls to the floor. She immediately has marked A. Basal cell carcinoma
pain in the right hip. Imaging on admission shows a B. Actinic keratosis
right femoral neck fracture. Bone mass is shown to C. Squamous cell carcinoma
be 2.5 standard deviations below mean peak bone D. Melanoma
mass in young adults. Mineral content of the bone,
however, is normal. What is the diagnosis? _____19. Bullous pemphigoid is characterized by
A.Osteomalacia blisters that are:
B. Osteopenia A. Suprabasal
C. Osteodystrophy B. Subepidermal
D. Osteoporosis C. Dermal
D. Subgranular
_____14. Patients with osteosarcoma may present
with a four-fold increase in its serum levels: _____20. This term refers to surface elevation
A. Alkaline phosphatase caused by hyperplasia and enlargement of
B. Uric acid contiguous dermal papillae:
C. Inorganic phosphorus A. Parakeratosis
D. Osteocalcin B. Orthokeratosis
C. Papillomatosis
_____15. A 33-year-old woman noted malaise, D. Acanthosis
fatigue, and joint pain for the past 5 months,
accompanied by progressive, symmetric, loss of joint
motion, especially in the hands and feet. Joint
capsule tissue was excised, and showed that the
synovium was grossly edematous, thickened, and
hyperplastic, with bulbous villi that appeared similar
to rice grains. What is the most likely diagnosis?
A. Septic arthritis
B. Osteoarthritis
C. Gouty arthritis
D. Rheumatoid arthritis
_____16. Which of the following refers to

neutrophils within slightly spongiotic foci of the
superficial epidermis?
A. Wickham striae
B. Munro microabscesses
C. Kogoj spongiform pustule
D. Auspitz sign
_____17. A 50-year-old woman presents with a

discolored area of skin on her forehead which she
has noticed for the past 3 years. The biopsy
specimen microscopically shows basal cell
hyperplasia, with some of the basal cells exhibiting
nuclear atypia. The upper dermal collagen and
elastic fibers show homogenization with elastosis.
What is the most likely diagnosis?
A. Basal cell carcinoma
B. Actinic keratosis
C. Squamous cell carcinoma
D. Melanoma

MBR 2019 - Pathology Handouts

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

MBR 2019 - Pathology Handouts

Uploaded by

Copyright:

Available Formats

CELL ADAPT, INJURY, HEMODYNAMICS,

PATHOLOGY NOTES: CELLULAR RESPONSES TO INJURY

CELLULAR ADAPTATION and INJURY

*Adaptive change reverts back to normal once

*Pure hypertrophy without hyperplasia

USTFMS MEDICAL BOARD REVIEW 2019 1 | PATHOLOGY

INTRACELLULAR ACCUMULATIONS CLINICALLY IMPORTANT FORMS OF EDEMA

USTFMS MEDICAL BOARD REVIEW 2019 2 | PATHOLOGY

MAJOR CLINICAL FORMS OF HEMORRHAGE COMMON SITES OF SYSTEMIC INFARCTION FROM

*BENIGN TUMORS THAT CAN

Bone; Pleomorphic adenoma (salivary glands)

Composed of One Parenchymal Cell type Fibroma Fibrosarcoma

Endothelial and related tissues

Tumors of epithelial origin Squamous cell papilloma Squamous cell or epidermoid

USTFMS MEDICAL BOARD REVIEW 2019 4 | PATHOLOGY

More than one Neoplastic Cell Type-Mixed

MAIN ROUTES OF METASTASIS 5. Healing. Restoration of injured tissue to its

1. Infections concentration of red cells in small

USTFMS MEDICAL BOARD REVIEW 2019 7 | PATHOLOGY

1.3.2. Recognition of Microbes and secretions of mesothelial cells lining the

USTFMS MEDICAL BOARD REVIEW 2019 8 | PATHOLOGY

Time of healing 3-7 days Prolonged 2.1.1. Persistent infections by

USTFMS MEDICAL BOARD REVIEW 2019 9 | PATHOLOGY

2.2. Morphologic Features ● Platelet-Activating Factor

USTFMS MEDICAL BOARD REVIEW 2019 10 | PATHOLOGY

o Leukocytosis o Eg. Allergies and autoimmune

USTFMS MEDICAL BOARD REVIEW 2019 11 | PATHOLOGY

Type I collagen, 10% osteocalcin, 2.2. Delayed Maturation of Bone

USTFMS MEDICAL BOARD REVIEW 2019 12 | PATHOLOGY

4.2.3. Skeletal Syphilis – – Osteoid Osteoma – benign, asso with a

USTFMS MEDICAL BOARD REVIEW 2019 13 | PATHOLOGY

USTFMS MEDICAL BOARD REVIEW 2019 14 | PATHOLOGY

H&E - spindle cells with blunt-ended cigar

Immunohistochemistry - vimentin, smooth

9.6. SYNOVIAL SARCOMA – tissue of origin:

Immunohistochemistry - 1) (+) Vimentin 2) (+)

USTFMS MEDICAL BOARD REVIEW 2019 15 | PATHOLOGY

CELL ADAPT, INJURY AND DEATH, C. Glomerular capillary hydrostatic pressure

UST FMS MEDICAL BOARD REVIEW 2019 | PATHOLOGY

UST FMS MEDICAL BOARD REVIEW 2019 | PATHOLOGY

_____35. A 19 y/o man comes to the emergency

_____36. A patient who has had an aortic valve

_____37. What is the main cause of Acute Tubular

UST FMS MEDICAL BOARD REVIEW 2019 | PATHOLOGY

I. Neoplastic Hematopathology Malignant Lymphomas

malaria, typhoid fever, leukemia and acute Other causes:

Classification of Anemia Biochemical:

UST FMS MEDICAL BOARD REVIEW 2019 2 | PATHOLOGY

♣ Neutrophils are larger than normal ♣ Results from failure or suppression of

♣ Several variants alpha chain synthesis; precipitated as Heinz

Immunohemolytic anemia microangiopathic hemolytic anemia and

CHOOSE THE BEST ANSWER:

_______ 3. Which of the following is increased or

_______ 4. Hemoglobin Bart is composed of 4

________ 5. The beta globulin gene is located in

________6. All of the following globulin gene locus

________ 7. Which of the following cell normally

________ 8. The most common type of non-

UST FMS MEDICAL BOARD REVIEW 2019 | PATHOLOGY

I. Human Genetic Architecture  less than 2% of the human genome encodes

UST FMS MEDICAL BOARD REVIEW 2019 1 | PATHOLOGY

Another species of gene-silencing RNA, called small a. Mutations

UST FMS MEDICAL BOARD REVIEW 2019 3 | PATHOLOGY

__5. i(X)(q10)chromosome E. Deletion