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59 Cards in this Set
- Front
- Back
Define lymphoma.
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Clonal (neoplastic) lymphoproliferative disorders primarily involving solid lymphoid organs
-- lymph nodes -- spleen -- tonsil -- thymus May also arise from lymphocytes/lymphoid tissue in extranodal sites other than the spleen, tonsil, and thymus -- skin -- lung -- GI tract May secondarily involve peripheral blood and BM |
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What areas do leukemias involve?
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Peripheral blood and BM, but may spread to lymphoid organs
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The majority of lymphomas present with...?
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lymphadenopathy
-- 1/3 arise in extranodal sites such as GI (MALT lymphoma) |
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Two major lymphoma categories?
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1. Hodgkin
2. Non-Hodgkin These two are morphologically, immunophenotypically, and clinically distinct |
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Non-Hodgkin lymphomas and maturation?
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They relate to normal stages of B or T cell maturation
-- distinct morphology -- distinct immunophenotype |
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The Dx of lymphoma requires...?
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1. Histologic evaluation of biopsy material
2. Immunophenotyping of biopsy material is helpful 3. Molecular diagnostic analysis may be required to -- demonstrate clonality OR -- detect distinct genetic lesion |
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What are the steps involved in the Dx of lymphoma?
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1. Biopsy of lymphoid tissue
Algorithm: -- Benign vs. malignant -- lymphoid vs. non-lymphoid malignancy (carcinoma, melanoma) -- Hodgkin vs. Non-Hodgkin Lymphoma -- Subtype of lymphoma (classification) based on cell type, anatomic compartment, immunophenotype 2. Clinical staging -- Evaluation of peripheral blood and BM -- Radiologic studies 3. Prognostic index -- classification -- stage -- age -- LDH |
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Morphology of Non-Hodgkin lymphoma (NHL)?
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1. Lymphoid infiltrate w/ loss of normal architecture
2. Abnormal growth patterns -- nodular OR -- diffuse 3. Cellular composition -- homogeneity -- size -- nuclear shape **Features that favor a reactive process include preservation of the normal architecture and cellular heterogeneity |
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Immunophemotype of NHL?
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1. B or T cell lineage
2. Monoclonal -- kappa/lambda Ig light chain 3. Abnormal phenotype -- ex: CD5 (T cell marker) positive B lymphocytes in CLL/SLL |
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Genotype/cytogenetics of NHL?
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1. Clonality
-- Ig/T-cell receptor gene rearrangement 2. Cytogenetic aberration -- t(14;18)(q32;q21) BCL-2 Follicular lymphoma -- t(8;14)(q24;q32) C-MYC Burkitt lymphoma -- t(11;18)(q21;q21) MALT-1 MALT lymphoma -- t(11;14)(q13;q32) CYCLIN D1 Mantle cell lymphoma |
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Major lymphoma classifications of NHL?
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1. Morphology (Rappaport) 1966
2. Cell lineage and differentiation (Kiel; Lukes-Collins) 1974 3. Clinical features (Working Formulation) 1982 4. Combination of morphology, immunophenotype, genetics, and clinical features (REAL/WHO) 1994/2001 |
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What is the basis of the Working Formulation for clinical usage classification of NHL?
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1. Separates lymphomas into three major clinical prognostic groups or "clinical grades"
2. Within each group further sub-classification was based on: -- pattern of growth --> nodular or diffuse -- size of cells --> small, large, mixed small and large -- proliferative rate |
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What are the three "clinical grades" of NHL.
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Low grade
Intermediate grade High grade |
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Describe low grade NHL
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-- Predominantly small lymphocytes
-- nodular growth pattern 1. lymphoma, small lymphocytic 2. lymphoma, follicular, predominantly small cleaved cell 3. lymphoma, follicular, mixed small celaved and large cell |
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Describe intermediate grade NHL.
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-- predominantly large lymphocyte
-- diffuse growth 1. lymphoma, follicular, predominantly large cell 2. lymphoma, diffuse, small cleaved cell 3. lymphoma, diffuse, mixed small and large cell 4. lymphoma, diffuse, large cell |
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Describe high grade NHL.
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-- large proliferative fraction
1. lymphoma, large cell, immunoblastic 2. lymphoma, lymphoblastic 3. lymphoma, small noncleaved cell (SNC) |
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What are the difficulties with the WHO classification?
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1. Not distinct disease entities
2. Some of the more recently recognized lymphomas (mantle cell, MALT) are not included in the classification |
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What is the revised European-American Classification of Lymphoid Neoplasms (REAL)?
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1. well defined "real" diseases
2. distinct clinicopathological entities based on a combination of: -- morphology -- immunophenotype -- cytogenetic and molecular studies -- biological behavior |
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Which classification is preferred for NHL?
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Currently the WHO classification is preferred (based on similar principles as its predecessor, REAL)
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List the WHO B cell neoplasms.
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PRECURSOR B-CELL NEOPLASMS
1. B-lymphoblastic leukemia/lymphoma** MATURE B-CELL NEOPLASMS 1. B-cell CLL/SLL* 2. Hairy cell leukemia 3. Extranodal marginal zone lymphoma (MALT lymphoma) 4. Follicular lymphoma* 5. Plasma cell myeloma 6. Diffuse large B-cell lymphoma* 7. Burkitt lymphoma* *most common in adults **most common in children |
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List the WHO T cell neoplasms.
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PRECURSOR T-CELL NEOPLASMS
1. T-precursor lymphoblastic leukemia/lymphoma** MATURE T-CELL AND NK-CELL NEOPLASMS 1. mycosis fungoides/Sezary syndrome **more common in children |
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How are NHLs categorized?
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Based on LINEAGE, they are divided into two major categories:
1. B-cell lymphomas 2. T/NK-cell lymphomas Based on DIFFERENTIATION STAGE, the above are further divided into: 1. B- or T-precursor lymphoblastic leukemia/lymphoma (ALL/LBL) 2. Peripheral or mature B- or T-cell lymphomas |
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Clinical presentation of follicular lymphoma (FL)?
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MOST COMMON NHL in the U.S.
Median age 50-60yrs Males = females Generalized painless lymphadenopathy |
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FL morphology?
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Closely resembles the normal germinal center of lymphoid follicles
-- effacement of normal nodal architecture -- nodular (follcicular) growth pattern; may be diffuse or both nodular and diffuse Composed of mixture of follicle center cells --centroblasts (large non-cleaved cells) -- centrocytes (small cleaved cells) Lack apoptosis/tingible body macrophages |
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FL immunophenotype
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B cell (CD19+, CD20+)
-- CD10(+) Monoclonal kappa or lambda light chain BCL2 protein + |
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FL genotype?
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t(14;18)(q32;q31)
BCL2 rearrangement |
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FL classification?
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WORKING FORMULATION
1. Low grade -- follicular, predominantly small cleaved cell -- follicular, mixed small cleaved and large cell 2. Intermediate grade -- follicular, predominantly large cell -- diffuse, mixed small and large cell -- diffuse, large cell REAL/WHO CLASSIFICATION -- follicular lymphoma, nodular and/or diffuse -- Grades I, II and III based on number of large cells present -- most are low grade (I-II) at presentation |
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FL staging?
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Most present w/ advanced stage (75% at stage IV)
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FL pathogenesis?
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BCL-2 gene rearrangement t(14;18)
-- leads to BCL-2 overexpression -- BCL-2 inhibits apoptosis -- prolinged survival of follicle center cells |
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FL clinical course?
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Median survival or 7-9 yrs
NOT cured by therapy 30-50% progress to diffuse large cell lymphoma -- median survival <1yr |
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Describe diffuse large cell B cell lymphoma.
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Heterogeneous group of tumor composed of a predominance of large lymphocytes w/ dispersed (vesicular) chromatin and prominent nucleoli
-- represents 30-40% NHLs Some transformed from a lower grade lymphoma -- ex: follicular lymphoma Also forms a subset of lymphomas occuring in HIV infected individuals Aggressive by may be curable |
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Clinical presentation of small lymphocytic lymphoma (SLL)?
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Overlap btwn CLL and SLL
-- morphologically and immunophenotypically and genotypically indistinguishable -- primarily differ in degree of peripheral blood lymphocytosis at presentation CLL: peripheral blood or BM involvement, but may have or develop lymphadenopathy SLL: primarily affects lymphoid tissues but may involve BM and peripheral blood |
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SLL morphology?
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Diffuse (NOT follicular) effacement by a monotonous infiltrate of small lymphocytes
Small round (non-cleaved) lymphoctes Pseudonodules "growth center": prolymphocytes, paraimmunoblasts Features of low grade lymphoma -- low mitotic activity -- absence of necrosis |
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Clinical presentation of Burkitt lymphoma?
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30% of childhood NHL
A subset of lymphomas occurring in HIV infected Most tumors manifest at extranodal sites |
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Two major clinical types of Burkitt lymphoma?
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1. African (endemic)
-- Tropical equatorial Africa and New Guinea -- median age 7 yrs -- maxilla, mandible, ovaries, kidneys 2. Non-African (sporadic) -- non-endemic areas -- median age 11 yrs -- Ileocecum, peritoneum |
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Burkitt lymphoma morphology?
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Loss of normal architecture
-- diffuse lymphoid infiltrate Medium size cells w/ dispersed (vesicular) chromatin and prominent nucleoli -- round nuclei (small noncleaved cells) -- moderately abundant blue cytoplasm Admixed benign (tingible body) macrophages -- "starry sky" appearance High mitotic activity |
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Burkitt lymphoma immunophenotype?
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B-cell (CD19+, CD20+)
-- monoclonal kappa or lambda light chain -- CD10(+) -- BCL2(-) |
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Burkitt lymphoma classification?
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WORKING FORMULATION
high grade lymphoma, small noncleaved cell type |
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Burkitt lymphoma staging?
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variable stage at presentation
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Burkitt lymphoma pathogenesis
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C-MYC (8q24) translocation: t(8;14), t(8;22) or t(8;2)
EBV related -- African --> EBV genome present in 95% of the cases -- Non-African --> EBV genome present in 15% of the cases |
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Burkitt lymphoma clinical course?
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highly aggressive
curable w/ aggressive therapy |
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What is MALT lymphoma?
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Presents as extranodal disease in mucosa associated lymphoid tissue
Assoc w/ chronic inflammatory disorders -- H.pylori gastritis -- Autoimmune diseases: Sjogren, Hashimoto thyroiditis |
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MALT lymphoma clinical presentation?
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Extranodal
-- stomach (most common) -- salivary gland -- lung -- orbit -- skin |
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MALT lymphoma morphology?
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Infiltrate of:
-- centrocyte-like cells -- monocytoid B-cells -- plasma cells Reactive germinal centers Lymphoepithelial lesions -- lymphocytes infilt and destroy epith of crypts, ducts, and glands |
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MALT lymphoma immunophenotype?
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B-cell (CD19+, CD20+)
-- monoclonal surface Ig -- CD5(-), CD10(-) |
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MALT lymphoma classification?
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Not in Working Formulation (low grade)
Recognized in REAL classification |
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MALT lymphoma staging?
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usually localized
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MALT lymphoma etiology?
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Gastric MALToma associated w/ H.pylori infection
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MALT lymphoma clinical course?
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Indolent
Potential cure by : -- antimicrobial therapy -- surgical excision -- radiation May transform to higher grade, large cell lymphoma |
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What is Mycosis Fungoides (MF)/Sezary Syndrome?
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A mature T-cell lymphoma arising in the skin
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Mycosis Fungoides (MF)/Sezary Syndrome clinical features?
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Most common cutateous T-cell lymphoma
-- indolent, waxing, waning 8-9yrs -- progressive skin lesions from skin rash to plaques, and to tumor stages Involvement of peripheral blood: Sezary Syndrome |
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Mycosis Fungoides (MF)/Sezary Syndrome morphology?
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lymphoid infiltrate composed of:
-- small and large cells w/ "cerebriform" nuclei in the epidermis (epidermotropism and Pautrier's abscesses) -- AND in the upper dermis Circulating Sezary cells w/ cerebriform nuclei |
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Mycosis Fungoides (MF)/Sezary Syndrome immunophenotype?
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Mature helper T cells (CD4+, CD3+)
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Clinical features of Hodgkin lymphoma?
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20-30% of all lymphomas in the U.S.
Bimodal age incidence: -- 15 to 45 yrs -- >50 yrs Cervical lymphadenopathy or mediastinal mass -- spread via contiguous LNs -- "B" symptoms |
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Hodgkin lymphoma morphology?
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1. Reed-Sternberg cells
2. Reed-Sternberg cell variants -- mononuclear -- lacunar cell -- lymphocytic and histiocytic (L&H) 3. inflammatory background -- histiocytes -- plasma cells -- eosinophils |
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Hodgkin lymphoma classification?
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1. lymphocyte predominance HL (LPHL)
2. classic HL -- nodular sclerosis (NS) -- lymphocyte rich (LR) -- mixed cellularity (MC) -- lymphocyte depleted (LD) |
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Hodgkin lymphoma immunophenotype?
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L&H cells
-- LCA+, CD20+ RS cells and variants: -- LCA-, CD30+, CD15+, CD20- Rule out NHL, carcinoma, melanoma |
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Hodgkin lymphoma staging?
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Ann Arbor staging system
STAGE I: -- single lymph node region OR -- single extra-lymphatic site (Ie) STAGE II: -- 2 or more lymph node regions on the same side of the diaphragm OR -- involvement of limited contiguous extra-lymphatic site (IIe) STAGE III: -- lymph node regions of both sides of the diaphragm, which may involve spleen, AND/OR -- limited contiguous extra-lymphatic site (IIIe) STAGE IV: -- multiple or disseminated foci of involvement of 1 or more extralymphatic organs (liver, BM) OR -- tissues w/ or w/o lymphatic involvement |
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Hodgkin lymphoma etiology?
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Unknown cell of origin
Infectious/viral etiology EBV viral genome found in many cases Immunodeficiency (congenital and acquired) |