Leukocyte DisordersPart 2

Lymphomas and Other Disorders

Walter C. Bell, MD

Normal Lymph Node

Acute Nonspecific Lymphadenitis

• Lymph node enlargement due to infection• Most often involves cervical nodes (teeth,

tonsils) or axillary nodes (skin infections involving arms)

• Nodes are enlarged due to edema and tender due to capsular distension

• Nodes may develop abscesses with redness of overlying skin, drainage through fistula tract

Chronic Lymphadenitis

• Follicular Hyperplasia:– Rheumatoid arthritis, toxoplasmosis, early HIV

• Paracortical Hyperplasia:– Viral infections (mono), vaccinations

• Sinus histiocytosis:– Filling of sinuses with histiocytes– Non-specific

Reactive Follicular Hyperplasia

Lymphoma

• Lymphoid neoplasm producing a mass either through enlargement of lymph nodes or involvement of another organ

• Lymphocytic leukemia vs lymphoma– Leukemia circulating, lymphoma mass effect– In reality, much overlap

• Non-Hodgkin or Hodgkin: broad grouping

Lymphoma

• Classified by cell type (B or T), growth pattern, immunophenotype, and genetic aberrations

• 5 broad categories– Precursor B-cell neoplasms (immature B cells)– Peripheral B-cell neoplasms (mature B cells)– Precursor T-cell neoplasms– Peripheral T-cell and NK cell neoplasms– Hodgkin lymphoma

• Histologic examination of tissue required for diagnosis

Lymphoma

• Vast majority of lymphoid neoplasms are of B-cell origin (80-85%)

Follicular Lymphoma

• 45% of adult lymphoma; most common form of lymphoma in the US

• Older patients• Generalized lymphadenopathy, spleen frequently

involved• Indolent, but difficult to cure• Bone marrow almost always involved at diagnosis• Characteristic translocation t(14;18)• Transformation into more aggressive diffuse large

B-cell lymphoma with survival of less than 1 yr.

Follicular Lymphoma

Diffuse Large B-cell Lymphoma

• 20% of adult lymphomas

• Older pts as well as children

• Diffuse growth pattern

• Extranodal disease seen

• Marrow involvement uncommon at diagnosis

• Aggressive, but up to 50% are curable

• May be associated with immunodeficiency

Diffuse Large B-cell Lymphoma

Burkitt Lymphoma

• Three types– Endemic African Burkitt lymphoma– Sporadic Burkitt lymphoma– HIV associated

• Histologically identical• All forms associated with c-MYC

translocations on chromosome 8 (t(8;14) most common)

• EBV infection seen in all endemic cases and 20-25% of other types

Burkitt Lymphoma

• Children and young adults • 30% of childhood NHL in US• Endemic

– Mass involving mandible; also frequently involves abdominal organs – kidneys, ovaries, adrenals

• Sporadic– Abdominal mass involving ileocecum and peritoneum

• Bone marrow involvement uncommon• In general, children and young adults can be

cured with chemotherapy, older patients have a poorer prognosis

Burkitt Lymphoma“Starry Sky” Appearance

Mantle Cell Lymphoma

• 3% of all NHL in US

• Older males

• Painless lymphadenopathy; GI tract frequently involved

• Most have t(11;14)

• Aggressive

Mantle Zone Lymphoma

Hodgkin Lymphoma

• Arises in a single node and spreads to contiguous nodes

• In advanced stages may spread to extranodal sites

• Reed-Sternberg cells (1-5% of tumor mass)– B-cell origin– Induce accumulation of reactive lymphocytes,

histiocytes and granulocytes

Hodgkin Lymphoma

• Four subtypes:– Nodular sclerosing: most common– Mixed cellularity: most common over age 50– Lymphocyte predominance– Lymphocyte depletion: rare

Hodgkin Lymphoma

• Tumor stage at diagnosis predicts outcome

• Low stage – 90% cure

• Advanced stage – 60 – 70% 5 year disease free survival

• Long term survivors have increased risk of developing second cancers secondary to radiation and chemotherapy (breast cancer particularly high in females treated with chest radiation as adolescents)

Reed-Sternberg Cells

Clinical Differences Between Hodgkin’s and Non-Hodgkin’s Lymphomas

Hodgkin’s Disease

• More often localized to a single axial group of nodes(cervical, mediastinal, para-aortic)

• Spreads by contiguity• Mesenteric nodes and

Waldeyer’s ring rarely involved

• Extranodal involvement uncommon

Non-Hodgkin’s Lymphoma

• More frequent involvement of multiple peripheral nodes

• Noncontiguous spread• Waldeyer’s ring and

mesenteric nodes commonly involved

• Extranodal involvement common

Multiple Myeloma

• Plasma cell disorder characterized by multiple masses of neoplastic plasma cells throughout the skeletal system (plasmacytoma if solitary)

• Can spread to lymph nodes and skin• Incidence higher in older men and people

of African descent

Multiple Myeloma

• Infiltration of bone, punched out defects on radiographs– Pathologic fractures– Hypercalcemia

• Production of excess immunoglobulins– M protein on protein electrophoresis– Rouleaux formation in peripheral blood– Renal failure (light chains toxic to renal tubular

epithelial cells)• Suppression of normal humoral immunity

– Bacterial infections

Multiple Myeloma

Rouleaux Formation

Langerhans Cell Histiocytoses

• Clonal proliferation of Langerhans cells which are dendritic antigen-presenting cells in many organs, including skin

• Old name: Histiocytosis X

Langerhans Cell Histiocytoses

• Multifocal multisystem type– Usually in children before the age of 2 yrs– Cutaneous lesions on back, trunk, scalp– Hepatospenomegaly, lymphadenopathy,

pulmonary lesions, destructive bone lesions– Infiltration of marrow leads to anemia,

thrombocytopenia, infection (otitis media mastoiditis)

– Rapidly fatal, 50% 5 year survival with therapy

Langerhans Cell Histiocytoses

• Unifocal/Multifocal type– Eosinophilic granuloma– Accumulation within medullary cavity of bone with

associated eosinophilic infiltrate• Pulmonary disease seen in adult smokers

– Can regress spontaneously on cessation of smoking

– Polyclonal, likely reactive• Langerhans cells contain the characteristic

Birbeck granule by electron microscopy and stain for CD1a and S-100

Birbeck Graunules

Pathology of the Spleen

• Acute Splenitis: Associated with bloodborne infections– May be painful with necrosis and abcess

formation

• Congestive Splenomegaly:– Systemic: due to right sided heart failure– Cirrhosis– Partal vein thrombosis

Splenic Infarcts

• Due to emboli from thrombi in the heart

• May be septic if associated with bacterial endocarditis

• Wedge shaped infarcts• May also be associated

with splenomegaly due to outgrowing blood supply

Splenic Pathology

• Primary neoplasms are rare– Hemangioma most common primary

neoplasm

• Accessory spleens: common, 20-30%

• Rupture– Usually associated with crushing injury,

severe blow– Extensive intraperitoneal hemorrhage;

surgical emergency

Thymic Pathology

Thymic Pathology

• Hyperplasia– Follicular hyperplasia with prominent lymphoid

follicles– Associated with myasthenia gravis (present in

70% of cases)– Occasionally seen in other autoimmune

disorders

Thymoma

• Neoplasm of thymic epithelial cells

• Tumors of adults usually over the age of 40.

• Occur in the anterior superior mediastinum

• Most are benign, may be malignant (thymic carcinoma)

• Present due to compression of mediastinal structures.

• Associated with myasthenia gravis.

Case 1

• A 67- year old male presents with weakness, fatigue, and weight loss worsening over several months.

• Headaches

Slide 15.19

Multiple Myeloma

Case 2

• A 12 year old male presents with a mandibular mass.

X-Ray

• 7 cm expansile mass in mandible

Biopsy

Bx Interpretation

• Lymphoid neoplasm with “starry sky” appearance, c/w Burkitts lymphoma

• Diagnosis confirmed by flow cytometry (monoclonal B cell population) and cytogenetics (t8:14)

Case 3

• A 4 year old child has been increasingly listless for about a week. He now complains of pain when picked up and has bruising on his arms and legs.

CBC

• Anemia• Thrombocytopenia• Blasts on smear

Flow Cytometry

• Blasts are CD19 positive (B-cell marker)

Case 3

• Dx: ALL

Case 4

• A 45 year old male experienced gradual weight loss, weakness, anorexia increasing over several months. Physical exam reveals splenomegaly

CBC

• Nl Hct, platelets

• White count 168,000 ( normal 4000-11000)

Smear

Case 4

• Dx: CML

• Patient treated with chemotherapy with resolution of symptoms

Case 5

• A 38 year old female presents with dyspnea.

Chest radiograph

• Mediastinal widening

• CT- 10 cm mediastinal mass impinging on trachea

Biopsy

Case 5

• Dx: Hodgkin’s Lymphoma

End