Diffuse large B cell lymphoma (DLBCL)

Lymphoma and plasma cell neoplasms
B cell lymphoma subtypes
Diffuse large B cell lymphoma (DLBCL)

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 6 September 2018, last major update February 2011

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: diffuse large B cell lymphoma

Table of Contents

Cite this page: Sangle, N. Diffuse large B cell lymphoma (DLBCL). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomadiffuse.html. Accessed October 16th, 2018.

Definition / general

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

Terminology

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

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

Etiology

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

20 year old male with pelvic mass (Arch Pathol Lab Med 2003;127:e411)
23 year old female with an ovarian mass (Arch Pathol Lab Med 2003;127:e169)
36 year old female (Mod Pathol 2003;16:828)
55 year old male diagnosed with chronic hepatitis C and cirrhosis (Arch Pathol Lab Med 2000;124:1532)
56 year old male with small intestinal tumor (Am J Clin Pathol 2006;126:222)
ALK+ but CD30- (Am J Surg Pathol 2003;27:1473)
Distinctive patterns of splenic and bone marrow involvement (Mod Pathol 2005;18:495)

Treatment

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

Gross images

Images hosted on other servers:

59 year old woman with atrial mass

Contributed by Dr. Claudia Mendez

Diffuse large B cell lymphoma

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

Images hosted on PathOut server:

CD20

Images hosted on other servers:

Classic histology

Adrenal gland

Atrial mass

Ethmoid sinus

Lymph node, lymph node with neutrophils

Paratesticular

CD45 (LCA)

CD20

IgM

CD43 (T cells)

Positive stains

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

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

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)