PATHOLOGY PRACTICALS

BONES AND CARTILAGE

leiomyoma
chondroma
lipoma
osteosarcoma
LEIOMYOMA/FIBROIDS, UTERUS
• HMGIC (chromosome 12q14) gene mutation
• HMGIY (chromosome 6p) gene mutation
ETIOLOGY • MED12 gene mutation

CELLS OF ORIGIN: Smooth muscles

• interlacing bundles of uniform spindle cells

• whorled-pattern of smooth muscles
MICRO • non-encapsulated
• mitoses do not appear
• oval nucleus

• well-circumscribed, round whorled-pattern

• usually has no necrosis

GROSS • occur within the:

• myometrium à intramural
• beneath endometrium à submucosal
• beneath serosa à subserosal
• abnormal vaginal bleeding
• frequency in urination (tumor compress bladder)
CLINICAL MANIFESTATION
• infarction manifesting as sudden pain (if large or pedunculated)
• impaired fertility

• most common tumor in women

• may undergo enlargement during the reproductive years and regress
after menopause
• Malignant transformation: Leiomyosarcoma
CHONDROMA, BONE
CELLS OF ORIGIN: endochondral
ETIOLOGY ARISES FROM: metaphyses
COMMON SITE: short tubular bones of hands and feet

well-circumscribed nodules of hyaline cartilage containing

MICRO
cytomorphologically benign chondrocytes

• formation of bone by tumor cell (pathognomonic)

GROSS • smaller than 3 cm
• gray-blue and translucent

• typically appear as solitary metaphyseal lesions of long bones of the

hands and feet
• non-hereditary disorders characterized by multiple enchondromas
• Ollier disease – syndrome of multiple enchondromas
CLINICAL MANIFESTATION
• Maffucci syndrome – with spindle/ soft tissue hemangiomas
• RADIOGRAPHIC FEATURE: C or O ring sign
• enchondroma à within medullary cavity
• juxtacortical chondroma à on surface of bone

• benign neoplasm involving hyaline cartilage, most commonly developing

in bones of enchondral origin
• most common cartilage tumor within bones
LIPOMA
• composed of cells that are well-differentiated and are hardly
distinguishable from normal adipocytes
• rarely more than a few centimeters in size
• SUBCLASSIFICATIONS:
o Conventional Lipoma à most common subtype that usually
MICRO
arises in the subcutis of the proximal extremities and trunk
o Fibrolipoma
o Angliolipoma
o Spindle cell Lipoma
o Myelolipoma

• well-circumscribed and resembles the tissue of origin (fat)

GROSS • consist of mature adipocytes forming a slowly growing, soft, mobile
and localized mass which is often a incidental finding

any symptoms may relate to a mass effect with compression on an

CLINICAL MANIFESTATION
adjacent structure

• most common soft tissue tumor of adulthood

• COMMON LOCATIONS: superficial extremity, trunk
 OSTEOSARCOMA, BONE
• RB and p53 gene mutation

• PREDISPOSING FACTORS:
o paget disease
ETIOLOGY
o bone infarcts
o prior irradiation
o men to women ratio (1.6:1)
• TUMORS ARISE FROM: metaphyseal region of long bones
• large hyperchromatic nuclei
• neoplastic bone usually has a coarse, lace-like architecture
MICRO
• formation of bone by tumor cells (pathognomonic) with coarse, lace-
like pattern

• gritty, gray-white big bulky tumors

GROSS
• often with areas of hemorrhage and cystic degeneration

• painful, progressively enlarging masses

• sometimes a sudden fracture of the bine is the first symptom
CLINICAL MANIFESTATION • reactive periosteal bone formation
• codman triangle – triangular shoadow between the cortexand raised
ends of periosteum

• TYPE OF SPREAD: hematogenous

• 50% occur in the knee
ENDOCRINE SYSTEM
Hashimoto thyroiditis
Papillary carcinoma
HASHIMOTO THYROIDITIS, THYROID
• breakdown of tolerance of thyroid self-antigens
ETIOLOGY • gene polymorphism: CTLA4 (most significant) and PTPN22 – code for
proteins that regulate responses of T cells
• extensive mononuclear inflammatory infiltrate
MICRO • well-developed germinal centers
• Hurthle cells – abundant eosinophilic and granular cytoplasm

• thyroid diffusely enlarged

GROSS • capsule intact, gland well demarcated
• pale, yellow-tan, firm and nodular

• diffuse, painless enlargement of the thyroid glands

• gradual development of hypothyroidism
• manifestation may appear before hypothyroidism caused by the
CLINICAL MANIFESTATION disruption of thyroid follicles
• increased T3 and T4
• decreased TSH
• decreased radioactive iodine uptake

• TYPE OF HYPERSENSITIVITY: Type II

• IMMUNOASSAY: Antiglobulin antibodies
PAPILLARY CARCINOMA (metastatic to the LN)
• RET or NTRK1 receptor tyrosine kinase gene mutation
• BRAF of serine/threonine kinase gene mutation
ETIOLOGY
TISSUE OF ORIGIN: Thyroid follicles

• finger-like processes àfibrovascular core

• Orphan Annie nuclei – ground glass appearance due to finely
dispersed chromatin
MICRO
• psammoma bodies (deposit of calcium) present
• single to stratified well-differentiated cuboidal epithelial cells
(whote arrows)

• papillary/ finger-like projections

GROSS
• well-formed papillae

• thyroid nodules not associated with other symptoms

CLINICAL MANIFESTATION
• initial presentation may be cervical lymphadenopathy
CENTRAL NERVOUS SYSTEM
Acute pyogenic meningitis
Meningioma
ACUTE PYOGENIC MENINGITIS
• neonates – E. coli and group B streptococci
ETIOLOGY • adolescents and young adults - N. meningitidis
• Elderly – Streptococcus pneumoniae and Listeria monocytogenes

• neutrophils in subarachnoid space surrounding the dilated leptomeningeal

MICRO vessels
• edema

• inflamed leptomeninges (pia and arachnoid)

GROSS
• yellow-tan clouding of meninges

• systemic manifestations of infection

• evidence of irritation of meninges with accompanying neurologic
impairment
• Waterhouse-Friderichsen syndrome
CLINICAL MANIFESTATION ü septicemic spread of infection with involvement of the adrenal
glands in the form of hemorrhagic infarction, accompanied by
petechiae on the skin
ü most commonly associated with N. meningitidis and S.
pneumoniae-caused meningitis
MENINGIOMA, CEREBRUM
• loss of long arm of chromosome 22 (chr 22q12) containing NF2 gene à higher
ETIOLOGY histologic grades and more chromosomal instability
• TRAF7 à lower histologic grade and less chromosomal instability

• numerous psammoma bodies from the calcification of the nests of neoplastic

mengiothelial cells (white arrow)
• neoplastic meningiothelial cells (black arrows)
• bosselated or polypoid appearance

• HISTOLOGIC PATTERNS:
MICRO
o Syncytial à meningioepithelial
o Fibroblastic à with elongated cells and abundant collagen deposit
o Transitional à combined syncytial and fibroblastic
o Psamommatous à calcification of the cyncytial nests
o Secretory à with PAS positive intracytoplasmic droplets
o Microcystic à loose spongy appearance

• rounded masses that are well-defined causing compression of the underlying

GROSS
brain

CLINICAL slow growing lesions with vague non-localizing symptoms or focal findings
MANIFESTATION referable to compression of underlying brain

• benign neoplasm most commonly in adults that is most commonly adherent to

the dura, arising from meningothelial cells of arachnoid
• considered WHO grade I/IV
BLOOD VESSEL
Atheroma
Hemorrhoids
Cavernous Hemangioma
Monckeberg Medial Sclerosis
ATHEROMA, CORONARY ATERTY AND AORTA
ETIOLOGY conditions leading to hypercholesterolemia

• cholesterol clefts (hallmark)

• fatty streak
MICRO • foam cells at the side of fibrous cap
• necrotic core with lipid deposits, foam cells and
smooth m cells

GROSS white-yellow lesion

• TARGETS: major elastic arteries and muscular arteries

• symptoms are apparent if obstruction involves
CLINICAL arteries supplying major organs such as the heart,
CONSEQUENCES brain and kidneys
• MAJOR CONSEQUENCES: MI, cerebral infarction or
stroke and gangrene of lower extremities

• ACCUMULATED SUBSTANCE: cholesterol

• LOCATION OF ATHEROMA: Tunica intima
• TYPE OF LESION: atheromatous plaque
ATHEROMA, CORONARY ATERTY AND AORTA
• age
o between 40-60 have 5x increased risk
• gender
NON-MODIFIABLE
o premenopausal women are relatively protected against
RISK FACTORS
atherosclerosis
• genetics
o most significant independent risk factor
• hyperlipidemia
MODIFIABLE MAJOR • hypertension
RISK FACTORS • cigarette smoking
• diabetes mellitus
• inflammation
o CRP levels – most important marker of inflammation
• hyperhomocystinemia
o associated with higher predisposition to coronary atherosclerosis
and peripheral vascular disease as well as stroke and venous
thrombosis
• metabolic syndrome
o includes resistance to insulin, high blood pressure,
hypercholesterolemia, hypercoagulability and a pro-inflammatory
ADDITIONAL RISK
state
FACTORS
o dyslipidemia, hyperglycemia and hypertension à cardiac risk
factor
o systemic coagulable and pro-inflammatory state à dysfunction
and/or thrombosis
• lipoprotein A
• disorders of hemostasis
• lack of exercise
• competitive, stressful lifestyle
• obesity
HEMORRHOIDS, ANUS
persistent elevated venous pressure within hemorrhoidal plexus

PREDISPOSING FACTORS:
ETIOLOGY
o pregnancy
o straining
o increased venous pressure
• thin-walled, dilated submucosal vessels with thrombi
• Internal Hemorrhoids: Simple Columnar (from embryonic endoderm),
superior hemorrhoidal plexus
MICRO • External Hemorrhoids: Stratified Squamous Non-Keratinized (from
ectoderm), inferior hemorrhoidal plexus
• LINES OF ZAHN – represent pale platelet and fibrin deposits alternating
with darker red cell rich layes

GROSS Anal tag/Fibrous polyp – healing of a thrombosed hemorrhoid

• pain
CLINICAL MANIFESTATION • presence of bright red blood (not excessive thus not an emergency)
• COMPLICATION: Hemorrhage

• HEMODYNAMIC CHANGE: Thrombosis

CAVERNOUS HEMANGIOMA, LIVER
ETIOLOGY CELL OF ORIGIN: endothelial cell

• endothelial proliferation (hallmark)

• non-encapsulated with infiltrative borders
MICRO
• less well-circumscribed and frequently involve deep structures
• intravascular thrombosis with associated dystrophic calcification is common

• red blue, soft spongy masses

GROSS
• 1-2 cm in diameter

• have little clinical significance

• but prone to traumatic ulceration and bleeding (complication)
• one of the components of con Hippel-Lindau disease
CLINICAL MANIFESTATION
• characterized by vascular lesions in the cerebellum, brainstem, retina,
pancreas and liver
• SHOULD NOT BE MISTAKEN FOR MALIGNANT NEOPLASM
• Destructive and show NO spontaneous tendency to regress, some may
require surgery.
• Little clinical significance.
• Cosmetic disturbance and vulnerable to traumatic ulceration and bleeding.
• Cavernous hemagioma is a component of Von Hippel Lindau disease –
occurring within the cerebellum, brain stem or retina, along with similar
angiomaatous lesions or cystic neoplasms in the pancreas and liver. Also
associated with renal neoplasms.
MONCKEBERG MEDIAL SCLEROSIS

ETIOLOGY hypercalcemia

• calcium deposits in tunica media (hallmark)

MICRO
• amorphous, basophilic calcium deposits

• Location of lesion: tunica media of muscular arteries

• Type of calcification: dystrophic calcification
• Serum calcium level: Normal
LIVER AND BILIARY TRACT
Hepatocellular carcinoma
Post-necrotic cirrhosis
Chronic cholecystitis
HEPATOCELLULAR CARCINOMA (HEPATOMA)
• inactivation of p53 (60%)
ETIOLOGY
• activation of B-catenin (40%)

• pseudoglandular pattern of tumor cells (white arrow) separated

MICRO from the normal hepatocytes (black arrow) by fibrous tissue
(arrowhead)

• liver enlarged and pale

• patterns of growth
GROSS • unifocal mass
• multifocal with widely distributed nodules
• diffusely infiltrative

• usually masked by underlying cirrhosis and chronic hepatitis

• most patients with upper abdominal discomfort, malaise, easy
fatigability and loss of weight
CLINICAL MANIFESTATION
• some complain of feeling of abdominal fullness
• jaundice, fever, GI bleeding or bleeding esophageal varices may or
may not occur
• cachexia
CAUSE OF DEATH • hemorrhage
• liver failure à hepatic coma
POST-NECROTIC CIRRHOSIS, LIVER
• chronic hepatitis B and C
ETIOLOGY • non-alcoholic fatty liver disease
• alcoholic liver disease

• diffuse fibrosis which eventually link portal tracts (white arrow)

MICRO • regenerating hepatocytes (black arrow) which when surrounded by the
fibrous bands is grossly seen as nodules

• bridging fibrous septa

GROSS
• regenerating hepatocytes

CLINICAL MANIFESTATION jaundice and portal hypertension

• Pathogenesis: portohepatic shunting

• Terminal events leading to death:
o hepatic encephalopathy
o bleeding from esophageal varices
o bacterial infections (damage to mucosal barrier and Kupffer cell
dysfunction)
o Major enzyme for alcohol metabolism: alcohol dehydrogenase and
acetaldehyde dehydrogenase
o Type of tissue repair involved: regeneration as a form of compensatory
hyperplasia
CHRONIC CHOLECYSTITIS, GALLBLADDER
• recurrent episodes of acute cholecystitis
ETIOLOGY • associated with cholelithiasis à calculous cholecystitis (90%)
• E coli and enterococci (isolated from bile in 1/3 cases)

• subepithelial and subserosal fibrosis with mononuclear cell infiltration

• reactive proliferation of the mucosa à mucosal folds fuse à crypts of
MICRO
epithelium buried within the gallbladder wall
• prominent Rokitansky-Aschoff sinuses

• recurrent attacks of pain in either the epigastric or RUQ area, with fatty
food intolerance, nausea and vomiting
• COMPLICATIONS:
o bacterial superinfection with cholangitis or sepsis
o perforation of the gallbladder with abscess formation
o rupture of GB à peritonitis
CLINICAL MANIFESTATION o fistula formation à drainage of bile into adjacent organs with
air and bacteria
o aggravation of pre-existing co-morbid illness
o porcelain GB à risk of malignant transformation

• CHOLELITHIASIS – condition commonly associated with the

development of this lesion
GASTROINTESTINAL TRACT
Acute appendicitis
Adenocarcinoma
Hemorrhoids
Tuberculosis
ACUTE APPENDICITIS
• overt luminal obstruction by fecalith
ETIOLOGY
• helminth obstruction (children)

• PMNs in muscularis externa (hallmark) (white arrow)

• lymphoid nodules with germinal center
MICRO
• dilated subserosal blood vessel (arteriole/muscular artery) (black
arrows)

• swollen and hyperemic appendix with purulent exudates

GROSS
• inflamed appendix

CLINICAL MANIFESTATION Mcburney’s sign, periumbilical pain at RLQ, nausea, increased WBC

• Type of Inflammation: Acute Suppurative Inflammation

• Morphologic change: Suppurative
• Predominant Inflammatory Cells: neutrophils
• Location: muscularis
• Hemodynamic Change: Hyperemia
• Age group showing atypical clinical presentation: very young and old,
immunocompromised
• Early major substance responsible for vasodilation: histamine
 ADENOCARCINOMA, COLON
• APC/B-catenin pathway à familial adenomatous polyposis (FAP
ETIOLOGY
• DNA mismatch repair deficiency à microsatellite instability à HNPCC or Lynch syndrome

• atypical glands lined by layers of columnar cells

MICRO
• invasion of mesenteric LN (black arrow) normal colonic glands

• right side (proximal colon): polypoid “cauliflower-like” or exophytic mass (white arrow)
GROSS
• left side (distal colon): grows in annular “napkin ring” lesions

LEFT SIDED LESION:

• obstruction
• Occult bleeding
• Changes in bowel habits
• Cramping left lower quadrant discomfort

CLINICAL RIGHT SIDED LESION:

MANIFESTATION • Fatigue
• Microcytic, hypochromic anemia (weakness d/t iron deficiency anemia)

PROGNOSTIC FACTOR:
1. depth of invasion
2. absence/ presence of lymph node
metastases
• most common malignancy of the GIT
• responsible for nearly 10% of all cancer deaths
• Benign Counterpart: Adenoma Colon
• Most common site of metastasis: Liver
• less glands means it is less differentiated
• tumor marker: Carcinoembryonic antigen (CEA)
HEMORRHOIDS
persistent elevated venous pressure within hemorrhoidal plexus

PREDISPOSING FACTORS:
ETIOLOGY
o pregnancy
o straining
o increased venous pressure
• thin-walled, dilated submucosal vessels with thrombi
• Internal Hemorrhoids: Simple Columnar (from embryonic endoderm),
superior hemorrhoidal plexus
MICRO • External Hemorrhoids: Stratified Squamous Non-Keratinized (from
ectoderm), inferior hemorrhoidal plexus
• LINES OF ZAHN – represent pale platelet and fibrin deposits alternating
with darker red cell rich layes

GROSS Anal tag/Fibrous polyp – healing of a thrombosed hemorrhoid

• pain
CLINICAL MANIFESTATION • presence of bright red blood (not excessive thus not an emergency)
• COMPLICATION: Hemorrhage

• HEMODYNAMIC CHANGE: Thrombosis

TUBERCULOSIS, COLON

ETIOLOGY Mycobacterium tuberculosis

• epithelioid cells
• peripherally located Langhan’s giant cells
MICRO
• randomly scattered foreign body giant cell
• central area of caseation necrosis in the muscle layer

GROSS • cheese-like appearance

• PATHOGENESIS: effects of Type IV hypersensitivity

• Type of necrosis: Caseous
• Lesion: tubercle
• Type of Inflammation: Chronic Granulomatous
• Segment most commonly involved: ileum/ileocecal