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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.


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


● 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


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


● 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

● 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

● 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)


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

Case reports

● 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


59 year old woman with atrial mass

Contributed by: Dr. Claudia Mendez (Colombia)

Micro description

● 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


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


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

● CD19, CD20, CD22, CD79a
● Also light chain restriction, CD10 (3060%); bcl6 (6090%), IRF4/MUM1 (3565%)
● 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

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


● 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

● 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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