Lymphoma & related disorders

Mature B cell neoplasms

DLBCL and large B cell lymphomas with high grade features


Topic Completed: 1 February 2011

Minor changes: 14 October 2021

Copyright: 2001-2021,, Inc.

PubMed Search: diffuse large B cell lymphoma

Nikhil Sangle, M.D.
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Cite this page: Sangle N. DLBCL-NOS. website. Accessed November 27th, 2021.
Definition / general
  • Neoplasm of large B lymphoid cells with nuclei at least 2× 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)
Case reports
  • Fatal if untreated; remission in 70% after chemotherapy, 50% cure rate
Gross images

Contributed by Dr. Claudia Mendez

Diffuse large B cell lymphoma

Images hosted on other servers:

59 year old woman with atrial mass

Microscopic (histologic) description
  • Diffuse growth pattern with large cells (usually 5× 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
Microscopic (histologic) images

AFIP images


Images hosted on other servers:

Classic histology

Atrial mass

CD45 (LCA)



CD43 (T cells)

Positive stains
Negative stains
Molecular / cytogenetics description
  • 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)
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