Lymphoma - B cell neoplasms - Diffuse large B cell lymphoma (DLBCL)

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Lymphoma - B cell neoplasms

B cell lymphoma subtypes

Diffuse large B cell lymphoma (DLBCL)

Reviewer: Nikhil Sangle, M.D., University of Utah and ARUP Laboratories (see Reviewers page)
Revised: 7 May 2014, last major update February 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Neoplasm of large B lymphoid cells with nuclei at least 2x size of lymphocyte

Terminology
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● Most cases have no accepted criteria for subdivision, and are called diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS)
● Variants described separately include: AIDS associated, CD5+, EBV positive, intravascular, lymphomatoid granulomatosis, mediastinal, primary cutaneous, primary effusion, primary CNS, T-cell/histiocyte-rich

Epidemiology
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● Common in Western countries (25-30% of adult non Hodgkin lymphoma)
● Affects all ages (most commonly elderly, median age 7th decade)

Etiology
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● Either germinal center B-like (bcl6+, CD10+, CD38+), activated B-like (IRF4+, FLIP+, bcl2+), or neither
● Arises de novo (common) or due to progression/transformation of a less aggressive non-Hodgkin lymphoma
● 1/3 arise from transformation of follicular lymphoma (germinal center-like), detectable by bcl2 rearrangement or bcl6/CD10 coexpression with strong and uniform bcl6 expression

Clinical features
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● 50% are stage III/IV at diagnosis
● Often presents as single, rapidly growing nodal mass
● 30%-40% are extranodal (skin, GI, GU, CNS) at diagnosis; also liver, spleen
● Bone marrow involvement in up to 27% (Eur J Haematol 2006;76:473); may show DLBCL morphology or low grade non-Hodgkin lymphoma phenotype
● Often difficult to diagnose on flow cytometry
● Overall 3 year survival ~ 78% in 2006 studies

Prognostic factors
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● Favorable: limited disease (no or <10% marrow involvement), favorable international prognostic index
● Favorable: germinal center gene expression (bcl6+, CD10+, negative for MUM1/IRF4, negative for CD138) versus activated B cell-like profile (Am J Surg Pathol 2004;28:464)
● Unfavorable: p53 mutations present
● Unfavorable: CD10+ and bcl2+ coexpression (Am J Clin Path 2001;116:183)

Treatment
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● Fatal if untreated; remission in 70% after chemotherapy, 50% cure rate

Case reports
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● Associated with Hepatitis C (Arch Pathol Lab Med 2000;124:1532)
● ALK+ but CD30- (Am J Surg Pathol 2003;27:1473; Mod Pathol 2003;16:828)
● Exhibiting Homer-Wright type rosettes (Arch Pathol Lab Med 2003;127:e411)
● Ovarian tumor with spindle cell morphology (Arch Pathol Lab Med 2003;127:e169)
● Composite tumor with Hodgkin lymphoma (Am J Clin Pathol 2006;126:222)
● Distinctive patterns of splenic and bone marrow involvement (Mod Pathol 2005;18:495)

Gross images
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59 year old woman with atrial mass

Contributed by: Dr. Claudia Mendez (Colombia)

Micro description
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● Diffuse growth pattern with large cells (usually 5 x normal lymphocytes) resembling immunoblasts (amphophilic cytoplasm, eccentric nuclei with one central nucleoli) or centroblasts (pale or basophilic cytoplasm, vesicular chromatin due to chromatin margination, 2-3 nucleoli, often near membrane), or rarely anaplastic, associated with neutrophils (Arch Pathol Lab Med 2000;124:735)
● May have plasmacytic differentiation or epithelioid granulomas (Mod Pathol 2002;15:750)
● ALK+: immunoblastic cells with intravascular growth pattern, often extensive necrosis, CD30 negative
● Anaplastic: resembles anaplastic large cell lymphoma or metastatic carcinoma
● Microvillous: sinus growth pattern with surface villi by EM
● T cell/histiocyte rich: see below

Micro images
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Classic histology Adrenal gland Atrial mass

Bone marrow shows interstitial pattern (unusual)

Ethmoid sinus

Lymph node, lymph node with neutrophils

Lymph node with widespread epithelioid granulomas

Paratesticular

Small intestine: starry sky pattern (unusual)

Spleen: involvement of red pulp cords and sinusoids

CD45 (LCA) CD20 CD20 IgM CD43 (T cells)

bcl6+ CD10+ CD10 (various)

Positive stains
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● CD19, CD20, CD22, CD79a
● Also light chain restriction, CD10 (30–60%); bcl6 (60–90%), IRF4/MUM1 (35–65%)
● 1/3 are bcl6+/CD10+ (Hum Pathol 2001;32:954)
● Variable CD45, variable surface Ig, variable bcl2
● CD3 highlights infiltrating T cells, not tumor cells
● CD68 highlights infiltrating histiocytes, which may be prominent

Negative stains
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● TdT, variable CD5, cytokeratin (rarely positive, Arch Pathol Lab Med 2001;125:1104)

Molecular
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● IgH and IgL are clonally rearranged, but may be difficult to document in T cell rich cases
● t(14;18)(q32;q21): affects IgH and bcl2; present in 30%, also in follicular lymphoma
● t(3;14)(p27;q32): affects bcl6 and IgH; present in 30%, also in follicular lymphoma
● Numerous other translocations involving bcl6 (3q27)

Differential diagnosis
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● Carcinoma (including nasopharyngeal), granulocytic sarcoma, melanoma, seminoma/dysgerminoma, thymoma
● Also infectious mononucleosis or other childhood viral infections (not monoclonal)

End of Lymphoma - B cell neoplasms > B cell lymphoma subtypes > Diffuse large B cell lymphoma

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