Handout 3

Hodgkins Lymphoma

RS cell is the neoplastic cell in Hodgkins lymphoma Nodular sclerosis type is the most common type Fever, night sweats and weight loss often confused with tuberculosis Prognosis corresponds with number of RS cells, type of HL and most importnantly stage Patients usually develop second malignancy as a result of treatment (becomes COD) Prognosis in general LP > NS>MC>LD

HL subtype
Lymphocyte predominant

Epidemiology
5% of cases Occurs mainly in males 60% of cases (MC type) Occurs mainly in females

Clinical Findings
Asymptomatic adult male with cervical or supraclavicular nodes Best survival Usually involves anterior mediastinal nodes and either cervical or supraclavicular nodes 75% 5 year survival 50% 5 year survival

Morphology
Difficult to find classic RS cells RS cell variant: Popcorn or L and H cell present Classic RS cells infrequent Lacunar cells present Collagen bands separate the lymphnode into nodular areas Classic RS cells numerous Increased Eosinophils, plasma cells and histiocytes Very few lymphocytes but numerous RS cells

Nodular Sclerosis

Mixed cellularity

30% cases Men >50 years Strong EBV association Least common type of HL Men >40-50 years old

Lymphocyte Depleted

Most aggressive HL 20% 5 year survival

Non-Hodgkins lymphoma
Type
B- Cell NHL
Handout # 4

Description/Immunophenotype
EBV relationship Characteristic translocation: t(8;14) 14 has immunoglobulin heavy chain gene 8 has c myc oncogene (DNA transcriptor)

Clinical findings
American Variant: Abdominal organ; GI tract and retroperitoneum Not usually associated with EBV High incidence in HIV positives African Variant: Involves the jaw 100% association with HBV Generalized lymphadenopathy Nonspecific complaints Hypogammaglobulinemia Autoimmune hemolytic anemia and thrombocytopenia Indolent course with prolonged survival May transform into DLBCL : Richter syndrome

Burkitt's Lymphoma 30% children with NHL

Chronic lymphocytic leukemia/Small lymphocytic lymphoma Patients usually >60 years of age

Neoplasm of small mature B cells SLL if confined to lymphnodes CLL if leukemic phase is present Tumor cells positive for CD 19, 20 and T cell marker CD 5

Follicular lymphoma MC NHL in the USA Usually occurs in elderly patients

Characteristic translocation: t(14;18) 14 has immunoglobulin heavy chain gene 18 has bcl-2 Translocation results in over-expression of antiapoptosis gene BCL2 Inhibition of apoptosis -->longer survival of cells. Derives from germinal center Bcells

Presents as generalized lymphadnopathy Leukemia less common than in SLL. Indolent course but difficult to cure.

Diffuse large B cell lymphoma Occurs in elderly and in childhood

Marginal Zone lymphoma

Occurs in extranodal sites involved by chronic inflammation or autoimmune disease. Salivary gland,Thyroid,Stomach. Most common site: Mucosa associated lymphoid tissue of GI tract ,most commonly stomach. Associated with H.pylori infection. Mantle Zone lymphoma Arises from mantle zone of lymphoid follicles Characteristic translocation t(11;14) Chromosome 11 has bcl-1 (cyclin D1) Chromosome 14 has immunoglobulin heavy chain gene.

Localized disease with extranodal involvement forming large mass: GI tract, Brain Progesses rapidly if untreated Leukemic phase very uncommon Special subtypes: Immunodeficiency associated DLBCL Body cavity large B cell lymphoma: 80% cases ,lymphoma regresses after H pylori eradication

Manifests as: disseminated disease (generalized lymphadenopathy) with aggressive course. It is incurable and survival is only a few years

T- Cell NHL
Adult T cell leukemia/lymphoma Seen in Japan and Caribbean Mycosis fungoides/Sezary syndrome 40-60 years of age A malignant T cell disorder (CD4 T cells) Due to HTLV-1 infection Skin lesions, hypercalcemia, enlarged lymphnodes, liver and spleen.

MC cutaneous lymphoma (Low grade T cell lymphoma of the skin) Involves CD4 T helper cells

Sequence of skin changes: Inflammatory eczematous lesions --> plaque stage --> tumor nodule stage

Anaplastic Large cell lymphoma Occurs in Handout children and #4 young adults

Cell of origin: Cytotoxic T cells (CD8 cells) Involves rearrangement of ALK gene on chr 2.

Morphology

Handout # 4

Both types have clasic Starry sky appearnace Bone marrow involvement and leukemic phase is common. Tumor cells have vacuoles containg lipid (positive for Oil red O)

SLL: Diffuse lymphoma Tumor cell diffusely infiltrate the lymphnode and destroy the architecture Tumor cells are small lymphid cells with scant amount of cytoplasm CLL: Peripheral blood lymphocytosis ; Smudge cells Tumor cell form follicles Two types of cells: centrocytes and centroblasts Neoplastic cells express bcl-2 oncoprotein due to t(14;18)

Composed of large cells with diffuse growth pattern. Aggressive but curable in 50% cases

Hyperlobated lymphocytes in PB

Tumor cells in epidermis (epidermotropism). Aggregates of cells : Pautrier micro abscesses Tumor cells have cerebriform nuclei Sezary syndrome: MF with a leukemic phase. Characterized by presence of neoplastic cells in peripheral blood

Composed of large anaplastic cells. Some cell contain horseshoe shaped nuclei with abundant cytoplasm = Hallmark cell. # 4 Handout