Lymphoma & related disorders
Mature B cell neoplasms
DLBCL and large B cell lymphomas with high grade features
DLBCL-NOS
Author: Nikhil Sangle, M.D.
Topic Completed: 1 February 2011
Minor changes: 1 September 2020
Copyright: 2001-2020, PathologyOutlines.com, Inc.
PubMed Search: diffuse large B cell lymphoma
Table of Contents
Definition / general | Terminology | Epidemiology | Etiology | Clinical features | Prognostic factors | Case reports | Treatment | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosisCite this page: Sangle N. DLBCL-NOS. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomadiffuse.html. Accessed September 23rd, 2020.
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
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
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)
