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: 3 April 2017, last major update February 2011

Copyright: (c) 2001-2017, PathologyOutlines.com, Inc.

PubMed Search: diffuse large B cell lymphoma

Table of Contents

Cite this page: Diffuse large B cell lymphoma (DLBCL). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomadiffuse.html. Accessed June 23rd, 2017.

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

Diffuse large B cell lymphoma,
contributed by Dr. Claudia Mendez (Colombia)

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

Bone marrow shows interstitial pattern (unusual)

Ethmoid sinus

Lymph node with widespread epithelioid granulomas

Lymph node, lymph node with neutrophils

Paratesticular

Small intestine: starry sky pattern (unusual)

Spleen: involvement of red pulp cords and sinusoids

CD45 (LCA)

CD20

IgM

CD43 (T cells)

BCL6+

CD10+

CD10 (various)

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)