Hematopoietic and Lymphoid

Pathology
Diseases of Red Cells
 Anemia
• General term, indicating a decrease in red blood cell
volume (hematocrit) or concentration of hemoglobin

• Usually an indication of underlying systemic disease

 Anemia – Clinical Features
• Pallor of the skin or mucosa

• Brittle, spoon-shaped nails (koilonychia)

• Fatigue, dyspnea
Anemia – Clinical Features
Anemia – Clinical Features
 Thalassemia
• Inherited disorder of hemoglobin synthesis

• Similar to sickle cell anemia, carriers of the trait are

resistant to the malarial organism

• Mediterranean, African, Indian, and Southeast Asians

are more often affected
 Thalassemia
• Alpha thalassemia • Beta thalassemia
– 1 gene mutation – – 1 gene mutation –
No disease detected Thalassemia minor
– 2 genes mutated – – 2 genes mutated –
Alpha thalassemia
trait Thalassemia major
(Cooley’s anemia,
– 3 genes mutated –
Hb H disease Mediterranean fever)
– 4 genes mutated –
Hydrops fetalis
 Thalassemia – Clinical Features
• Dependant upon the
subcategory

• “Hair-on-end”
radiograph

• Bone marrow
hyperplasia
 Thalassemia – Clinical Features
• Dependant upon the
subcategory

• “Hair-on-end”
radiograph

• Bone marrow
hyperplasia
 Thalassemia – Clinical Features
• Dependant upon the
subcategory

• “Hair-on-end”
radiograph

• Bone marrow
hyperplasia
Thalassemia – Clinical Features
 Thalassemia – Clinical Features
• Hepatosplenomegaly, lymphadenopathy

• Tissue hypoxia

• Bacterial infections

• High-output cardiac failure

Thalassemia – Clinical Features
 Thalassemia – Treatment

• Frequent blood transfusions

• Iron chelating agents (to treat hemochromatosis

secondary the multiple transfusions)

• Bone marrow transplantation

 Sickle Cell Anemia
• Genetic disorder of • Deoxygenated
hemoglobin synthesis hemoglobin subject to
molecular aggregation
• Thymine is substituted and polymerization
for adenine – Sickle shape to the
– Codes for valine red cells
instead of glutamic
acid in the beta-
globin chain of
hemoglobin
 Sickle Cell Anemia
• Codominant gene • Frequently affects
– Sickle cell trait – One patients in Africa,
allele affected Mediterranean basin,
and Asia
– Sickle cell disease –
Both alleles affected • 8% African Americans
carry the trait
• Abnormal gene confers
a resistance to malaria
 Sickle Cell Anemia – Clinical Features
• Reduced blood flow to
organs and tissues

• Susceptibility to
infections secondary to
spleen destruction

• Sickle cell crisis

 Sickle Cell Anemia – Clinical Features
• Reduced blood flow to
organs and tissues

• Susceptibility to
infections secondary to
spleen destruction

• Sickle cell crisis

 Sickle Cell Anemia – Clinical Features
• Radiographic
appearance
– Reduced trabeculae
pattern

– “Hair-on-end” skull
radiograph
 Sickle Cell Anemia – Clinical Features
• Radiographic
appearance
– Reduced trabeculae
pattern

– “Hair-on-end” skull
radiograph
Sickle Cell Anemia – Clinical Features
 Sickle Cell Anemia – Histology
• Sickle or boomerang-
shape erythrocytes in
blood smear
 Sickle Cell Anemia – Histology
• Sickle or boomerang-
shape erythrocytes in
blood smear
 Sickle Cell Anemia – Treatment and
Prognosis
• Sickle cell crisis – Supportive, rule out infection

• Penicillin therapy and polyvalent pneumococcal

vaccination

• Avoid crisis-precipitating events

• Variable prognosis
 Iron Deficiency Anemia
• Very common • Decreased serum Fe
condition, especially in
women • Microcytic,
hypochromic anemia
• Secondary to chronic
blood loss, decreased
dietary intake of iron
(Fe), decreased
absorption of Fe
 Iron Deficiency Anemia – Treatment

• Iron supplementation

• Determine and treat underlying cause

• Response to treatment is usually rapid

 Plummer-Vinson Syndrome

• Iron deficiency anemia in conjunction with glossitis

and dysphagia

• Associated with a high incidence of oral and

esophageal squamous cell carcinoma
 Plummer-Vinson Syndrome – Clinical
Features
• Females, 30-50

• Burning sensation of
the tongue and oral
mucosa

• Angular cheilitis
 Plummer-Vinson Syndrome – Clinical
Features
• Females, 30-50

• Burning sensation of
the tongue and oral
mucosa

• Angular cheilitis
 Plummer-Vinson Syndrome – Clinical
Features
• Females, 30-50

• Burning sensation of
the tongue and oral
mucosa

• Angular cheilitis
 Plummer-Vinson Syndrome – Clinical
Features
• Dysphagia (esophageal
webs)

• Brittle nails and

koilonychia

• Fatigue
 Plummer-Vinson Syndrome – Treatment

• Iron supplementation

• Esophageal dilation may be necessary

• Periodic oral cancer screening.

 Pernicious Anemia
• Condition caused by poor absorption of cobalamin
(vitamin B12, extrinsic factor), which is necessary for
normal maturation of rbc’s and other cells.

• Most patients lack intrinsic factor, which is necessary

for the absorption of extrinsic factor
 Pernicious Anemia – Clinical Features
• Fatigue, weakness,
headache

• Paresthesia, tingling, or
numbness of the
extremities
 Pernicious Anemia – Clinical Features
• Fatigue, weakness,
headache

• Paresthesia, tingling, or
numbness of the
extremities
 Pernicious Anemia – Clinical Features
• Oral symptoms
– Burning sensations of
the tongue, lips,
buccal mucosa

– Erythema or atrophy
 Pernicious Anemia – Treatment
• Intramuscular injection of cyanocobalamin

• Rapid resolution is usually expected

• Pernicious anemia is associated with an increased

risk of stomach cancer
Bleeding Disorders
 Thrombocytopenic Purpura
• Decrease in circulating platelets

• Ideopathic or secondary to any of a number of conditions

• Secondary to decreased production or increased

destruction

• Patients have an abnormal platelet function assay (PFA)

 Thrombocytopenia – Clinical Features
• Submucosal
hemorrhage

• Epistaxis

• Hemoptysis

• GI or urinary bleeding
 Thrombocytopenia – Clinical Features
• Submucosal
hemorrhage

• Epistaxis

• Hemoptysis

• GI or urinary bleeding
 Thrombocytopenia – Clinical Features
• Submucosal
hemorrhage

• Epistaxis

• Hemoptysis

• GI or urinary bleeding
 Thrombocytopenia – Treatment

• If drug-induced, cessation of the offending agent

• Corticosteroid therapy and platelet transfusion

 Polycythemia Vera
• Ideopathic increase in red blood cell mass, usually
concurrently with uncontrolled platelet and
granulocyte production

• Probably secondary to the behavior of an abnormal

progenitor stem cell
 Polycythemia Vera – Clinical Features
• Older adults • Ruddy complexion

• Nonspecific early • Erythromelalgia

symptoms
• Excess hemorrhage
• Thrombus formation (gingival, epistaxis,
ecchymosis)
• Hypertension,
splenomegaly
Polycythemia Vera
 Polycythemia Vera - Treatment
• Phlebotomy to reduce red blood cell mass

• Aspirin (anticoagulant)

• Myelosuppressive therapy

• Average survival – 10-12 years, with possible

development of acute leukemia
 Hemophilia
• Bleeding disorder secondary to a genetic deficiency
of clotting factors

• Major types
– Hemophilia A – Deficiency of factor VIII
– Hemophilia B (Christmas disease) – Deficiency of
factor IX
– Von Willibrand’s disease – Deficiency of von
Willibrand’s factor
Hemophilia
Hemophilia
 Hemophilia – Clinical Features
• Hemophilia A
– X-linked

– Severity depends
upon the extent of
the deficiency

– Increased partial
thromboplastine
time (PTT)
 Hemophilia – Clinical Features
• Hemophilia A
– X-linked

– Severity depends
upon the extent of
the deficiency

– Increased partial
thromboplastine
time (PTT)
 Hemophilia – Clinical Features
• Hemophilia A
– X-linked

– Severity depends
upon the extent of
the deficiency

– Increased partial
thromboplastine
time (PTT)
 Hemophilia – Clinical Features
– Pseudotumor of
hemophilia

– Hemarthrosis

– Increased bleeding
from many dental
procedures
 Hemophilia – Clinical Features
– Pseudotumor of
hemophilia

– Hemarthrosis

– Increased bleeding
from many dental
procedures
Hemophilia – Treatment and Prognosis

• Replacement therapy if severe

• Optimal dental care, restrict aspirin

• Unfortunate complication involved the contraction of

HIV
Hemophilia – Treatment and Prognosis
 von Willebrand’s Disease
• Common bleeding disorder secondary to decreased
or defective von Willebrand’s factor

• The disorder results in abnormal coagulation and

platelet function

• Autosomal dominant inheritance pattern

• Increased PTT, prothrombin time (PT) and abnormal

PFA
Hereditary Hemorrhagic Telangiectasia
(Osler-Weber-Rendu Syndrome)

• Autosomal dominant condition caused by a mutation

in the endoglin (HHT1) or ALK-1 (HHT2) genes

• Characterized by numerous vascular hamartomas of

skin and mucosa
 Hereditary Hemorrhagic Telangiectasia –
Clinical Features
• Numerous red papules
which blanch upon
diascopy

• Epistaxis

• Predisposition for
arteriovenous fistulas of
the lung, liver, and brain
 Hereditary Hemorrhagic Telangiectasia –
Clinical Features
• Numerous red papules
which blanch upon
diascopy

• Epistaxis

• Predisposition for
arteriovenous fistulas of
the lung, liver, and brain
 Hereditary Hemorrhagic Telangiectasia –
Clinical Features
• Numerous red papules
which blanch upon
diascopy

• Epistaxis

• Predisposition for
arteriovenous fistulas of
the lung, liver, and brain
 Hereditary Hemorrhagic Telangiectasia –
Clinical Features
• Numerous red papules
which blanch upon
diascopy

• Epistaxis

• Predisposition for
arteriovenous fistulas of
the lung, liver, and brain
 Hereditary Hemorrhagic Telangiectasia –
Clinical Features
• Numerous red papules
which blanch upon
diascopy

• Epistaxis

• Predisposition for
arteriovenous fistulas of
the lung, liver, and brain
 Hereditary Hemorrhagic Telangiectasia -
Diagnosis

• Any 3 of the following criteria

– Recurrent spontaneous epistaxis
– Telangiectasias of the mucosa and skin
– Arteriovenous malformation involving the lungs,
liver, or CNS
– Family history of HHT
 Hereditary Hemorrhagic Telangiectasia –
Treatment
• None necessary for mild • Dental consideration
cases – 1% of patients will
develop brain
• Nasal surgery for more abscesses, which
severe cases may indicate
antibiotic prophylaxis
• Blood transfusion
Diseases of White Cells
 Leukemia
• Heterogeneous group of malignancies of
hematopoietic stem cell derivation

• Probably due to genetic and environmental factors

– Philadelphia chromosome – t(9;22), CML
Leukemia
 Leukemia
• Classified according to histogenesis and clinical
behavior

• Clinical course – Acute vs. chronic

• Histogenesis – Myeloid vs.

lymphocytic/lymphoblastic
– Myeloid – Granulocytic, monocytic, erythrocytic
Leukemia
 Leukemia – Clinical Features
• M>F

• CLL – Most common,

elderly adults

• ALL – Children
 Leukemia – Clinical Features
• M>F

• CLL – Most common,

elderly adults

• ALL – Children
 Leukemia – Clinical Features
• Symptoms related to
reduction of normal red
and white blood cells
(infections, bleeding,
fatigue, oral ulceration)

• Hepatosplenomegaly,
lymphadenopathy
 Leukemia – Clinical Features
• Symptoms related to
reduction of normal red
and white blood cells
(infections, bleeding,
fatigue, oral ulceration)

• Hepatosplenomegaly,
lymphadenopathy
 Leukemia – Histology and Diagnosis
• Diffuse infiltration and
destruction by sheets of
abnormal cells

• Diagnosis through
blood smear
 Leukemia – Histology and Diagnosis
• Diffuse infiltration and
destruction by sheets of
abnormal cells

• Diagnosis through
blood smear
 Leukemia - Treatment
• Chemotherapy
– Induction

– Maintenance

• Prognosis – Variable and dependant upon the type

Disorders of Lymph Nodes and
Lymphoid Tissue
 Non-Hodgkin’s Lymphoma
• Heterogeneous group of lymphoreticular
(lymphocytes and their precursors) malignancies

• Usually arise in lymph nodes and grow as solid

masses

• Variable etiology

• More common in the immunocompromised

 Lymphoma - Classification
• Most lymphomas are of B cell origin.

• Complex classification, now primarily dependent

upon cytogenetic markers.

• The classification is important for determining the

optimal treatment.
 Lymphoma – Clinical Features
• Primarily adults

• Nodal vs. extranodal

(oral)

• Slowly growing mass

 Lymphoma – Clinical Features
• Primarily adults

• Nodal vs. extranodal

(oral)

• Slowly growing mass

 Lymphoma – Clinical Features
• Ultimately will spread
to different sites and
tissues (bone, liver,
lung, etc.)
 Lymphoma – Clinical Features
• Oral lesions
– Extranodal

– “Boggy” swelling,
usually normal or
purplish in color

– May occur in bone

 Lymphoma – Clinical Features
• Oral lesions
– Extranodal

– “Boggy” swelling,
usually normal or
purplish in color

– May occur in bone

 Lymphoma - Treatment
• Dependant upon grade and stage

• Radiation (localized) and/or chemotherapy

• High grade lesions are more aggressive, but more

likely to be cured; Overall, the cure rate is not
considered high
 Hodgkin’s Lymphoma (Disease)

• Poorly understood malignancy

• Lesional cell (Reed-Sternberg cell) makes up only 1-

3% of cells
 Hodgkin’s Lymphoma – Staging
• I – Single lymph node • III – Lymph node
region regions on both sides of
the diaphragm
• II – 2 or more lymph
node regions on the • IV – Disseminated
same side of the involvement
diaphragm
• A, B – Absence or
presence of systemic
signs
 Hodgkin’s Lymphoma – Clinical Features

• M>F

• Almost uniformly begins

in lymph nodes,
especially the cervical
and supraclavicular

• Fever, night sweats,

pruritis
 Hodgkin’s Lymphoma – Clinical Features

• M>F

• Almost uniformly begins

in lymph nodes,
especially the cervical
and supraclavicular

• Fever, night sweats,

pruritis
 Hodgkin’s Lymphoma – Clinical Features

• M>F

• Almost uniformly begins

in lymph nodes,
especially the cervical
and supraclavicular

• Fever, night sweats,

pruritis
 Hodgkin’s Lymphoma – Clinical Features

• M>F

• Almost uniformly begins

in lymph nodes,
especially the cervical
and supraclavicular

• Fever, night sweats,

pruritis
 Hodgkin’s Lymphoma – Treatment and
Prognosis
• Depends upon stage
– Stage I or II – Local radiation

– Stage III or IV – Combined chemotherapy (MOPP,

ABVD)

• Prognosis – Good, depends on stage and histologic

type
 Multiple Myeloma
• Malignancy of plasma cell origin

• Monoclonal proliferation results in production of

abnormal immunoglobulin (monoclonal
gammopathy, M-protein)

• Single lesions are referred to as plasmacytoma

 Multiple Myeloma – Clinical Features
• Older men; Blacks >
Whites

• Bone pain, pathologic

fracture

• Petechiae

• Fever
 Multiple Myeloma – Clinical Features
• Older men; Blacks >
Whites

• Bone pain, pathologic

fracture

• Petechiae

• Fever
 Multiple Myeloma – Clinical Features
• Radiograph
– Multiple punched-
out radiolucencies
 Multiple Myeloma – Clinical Features
• Radiograph
– Multiple punched-
out radiolucencies
 Multiple Myeloma – Treatment and
Prognosis
• Chemotherapy (radiation for solitary lesions –
plasmacytoma)

• Bone marrow transplant

• Improved prognosis, based upon risk categories.

Standard risk patients may expect to survive 6-7
years; high risk 2-3
 Langerhans Cell Histiocytosis (Langerhans
Cell Disease, Histiocytosis X)

• Neoplastic proliferation of Langerhans cells

• Langerhans cells – Dendritic mononuclear cells

normally found in the epidermis, mucosa, lymph
nodes, and bone marrow
 Langerhans Cell Histiocytosis – Clinical
Features

• Three traditional forms

– Letterer-Siwe disease – Acute, disseminated

– Hand-Schuller-Christian disease – Chronic,

disseminated

– Eosinophilic granuloma (monostotic or

polyostotic)
Langerhans Cell Histiocytosis – Clinical
Features
• Single organ involvement – typically bone or
skin
–Unifocal disease
–Multifocal disease
• Multi-organ disease
–No organ dysfunction
–Organ dysfunction
• Low-risk (skin, bone, lymph nodes and/or pituitary
gland)
• High-risk (lung, liver, spleen, and/or bone marrow
 Langerhans Cell Histiocytosis – Clinical
Features
• M=F; Less than 15 years
old

• Solitary or multiple
bone lesions

• “Floating in air”
radiograph
 Langerhans Cell Histiocytosis – Clinical
Features
• M=F; Less than 15 years
old

• Solitary or multiple
bone lesions

• “Floating in air”
radiograph
 Langerhans Cell Histiocytosis – Clinical
Features
• M=F; Less than 15 years
old

• Solitary or multiple
bone lesions

• “Floating in air”
radiograph
 Langerhans Cell Histiocytosis – Clinical
Features
• Dull pain and
tenderness often
accompany bone
lesions

• Ulcerative or
proliferative gingival
masses may also be
seen
Langerhans Cell Histiocytosis – Clinical
Features
Langerhans Cell Histiocytosis – Clinical
Features
 Langerhans Cell Histiocytosis – Treatment

• Curettage is often • Prognosis of bone

adequate lesions alone is good

• Radiation • Poorer prognosis for

acute disseminated
• Chemotherapy for form
disseminated forms