Lymph Node Biopsy: Positive for cd20, cd3, bcl6, bcl2

A Healthtap Patient asked:

I had biopsy done of neck lump node. It has been present for over 8 months. No appetite and weight loss. Positive for cd20, cd3, bcl6, bcl2. Meaning?

CD 20 is an antigen present on a wide range of normal and neoplastic B lymphocytes. This could be lymphoma or reactive hyperplasia (not cancer).

Here is more information: 


From Wikipedia, the free encyclopedia
BCL-2 human.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases BCL2, Bcl-2, PPP1R50, B-cell CLL/lymphoma 2, apoptosis regulator
External IDs OMIM: 151430 MGI: 88138 HomoloGene: 527GeneCards: BCL2
Genetically Related Diseases
chronic lymphocytic leukemia[1]
Targeted by Drug
RNA expression pattern
PBB GE BCL2 203684 s at.png

PBB GE BCL2 203685 at.png

PBB GE BCL2 207005 s at.png

More reference expression data
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC) Chr 18: 63.12 – 63.32 Mb Chr 1: 106.54 – 106.71 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse
Bcl-2 (B-cell lymphoma 2), encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inducing (pro-apoptotic) or inhibiting (anti-apoptotic) apoptosis.[5][6] Bcl-2 is specifically considered an important anti-apoptotic protein but it is NOT considered a proto-oncogene because it is not a growth signal transducer.
Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomasOrthologs[7] (such as Bcl2 in mice) have been identified in numerous mammals for which complete genome data are available.
Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma.


The two isoforms of Bcl-2, Isoform 1, also known as 1G5M, and Isoform 2, also known as 1G5O/1GJH, exhibit a similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, suggest differences in antiapoptotic activity for the two isoforms [8]

Normal physiological function[edit]

BCL-2 is localized to the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. The pro-apoptotic proteins in the BCL-2 family, including Bax and Bak, normally act on the mitochondrial membrane to promote permeabilization and release of cytochrome C and ROS, that are important signals in the apoptosis cascade. These pro-apoptotic proteins are in turn activated by BH3-only proteins, and are inhibited by the function of BCL-2 and its relative BCL-Xl.[9]
There are additional non-canonical roles of BCL-2 that are being explored. BLC-2 is known to regulate mitochondrial dynamics, and is involved in the regulation of mitochondrial fusion and fission. Additionally, in pancreatic beta-cells, BCL-2 and BCL-Xl are known to be involved in controlling metabolic activity and insulin secretion, with inhibition of BCL-2/Xl showing increasing metabolic activity, but also additional ROS production; this suggests it has a protective metabolic effect in conditions of high demand.[citation needed]

Role in disease[edit]

Damage to the Bcl-2 gene has been identified as a cause of a number of cancers, including melanomabreastprostatechronic lymphocytic leukemia, and lung cancer, and a possible cause of schizophrenia and autoimmunity. It is also a cause of resistance to cancer treatments.[citation needed]


Cancer can be seen as a disturbance in the homeostatic balance between cell growth and cell death. Over-expression of anti-apoptotic genes, and under-expression of pro-apoptotic genes, can result in the lack of cell death that is characteristic of cancer. An example can be seen in lymphomas. The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone does not cause cancer. But simultaneous over-expression of Bcl-2 and the proto-oncogene myc may produce aggressive B-cell malignancies including lymphoma.[10] In follicular lymphoma, a chromosomal translocation commonly occurs between the fourteenth and the eighteenth chromosomes — t(14;18) — which places the Bcl-2 gene from chromosome 18 next to the immunoglobulin heavy chain locus on chromosome 14. This fusion gene is deregulated, leading to the transcription of excessively high levels of Bcl-2.[11] This decreases the propensity of these cells for apoptosis.

Auto-immune diseases[edit]

Apoptosis plays an active role in regulating the immune system. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the case of defective apoptosis, it may contribute to etiological aspects of autoimmune diseases.[12] The autoimmune disease type 1 diabetes can be caused by defective apoptosis, which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cells are the immune system’s most important antigen-presenting cells, their activity must be tightly regulated by mechanisms such as apoptosis. Researchers have found that mice containing dendritic cells that are Bim -/-, thus unable to induce effective apoptosis, suffer autoimmune diseases more so than those that have normal dendritic cells.[12]Other studies have shown that dendritic cell lifespan may be partly controlled by a timer dependent on anti-apoptotic Bcl-2.[12]


Apoptosis plays an important role in regulating a variety of diseases. For example, schizophrenia is a neurodegenerative disease that may result from an abnormal ratio of pro- and anti-apoptotic factors.[13] Some evidence suggests that this may result from abnormal expression of Bcl-2 and increased expression of caspase-3.[13]

Diagnostic use[edit]

Antibodies to Bcl-2 can be used with immunohistochemistry to identify cells containing the antigen. In healthy tissue, these antibodies react with B-cells in the mantle zone, as well as some T-cells. However, positive cells increase considerably in follicular lymphoma, as well as many other forms of cancer. In some cases, the presence or absence of Bcl-2 staining in biopsies may be significant for the patient’s prognosis or likelihood of relapse.[14]

Targeted therapies[edit]

Targeted and selective Bcl-2 inhibitors currently in the clinic include :


An antisense oligonucleotide drug Genasense (G3139) was developed by Genta Incorporated to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA that hybridises with and inactivates mRNA, preventing the protein from being formed.
Human lymphoma cell proliferation (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNAIn vitro studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.[15]
These showed successful results in Phase I/II trials for lymphoma. A large Phase III trial was launched in 2004.[16] As of 2016, the drug had not been approved and its developer was out of business.[17]

ABT-737 and Navitoclax (ABT-263)[edit]

In the mid-2000s, Abbott Laboratories developed a novel inhibitor of Bcl-2, Bcl-xL and Bcl-w, known as ABT-737. This compound is part of a group of BH3 mimetic small molecule inhibitors (SMI) that target these Bcl-2 family proteins, but not A1 or Mcl-1. ABT-737 is superior to previous BCL-2 inhibitors given its higher affinity for Bcl-2, Bcl-xL and Bcl-w. In vitro studies showed that primary cells from patients with B-cell malignancies are sensitive to ABT-737.[18] ABT-737 does not directly induce apoptosis; it enhances the effects of apoptotic signals and causes single-agent-mechanism-based killing of cells in small-cell lung carcinoma and lymphoma lines.[citation needed]
In animal models, it improves survival, causes tumor regression and cures a high percentage of mice.[19] In preclinical studies utilizing patient xenografts, ABT-737 showed efficacy for treating lymphoma and other blood cancers.[20] Because of its unfavorable pharmacologic properties ABT-737 is not appropriate for clinical trials, while its orally bioavailable derivative navitoclax (ABT-263) has similar activity on small cell lung cancer (SCLC) cell lines and has entered clinical trials.[21] While clinical responses with navitoclax were promising, mechanistic dose-limiting thrombocytopoenia was observed in patients under treatment due to Bcl-xL inhibition in platelets.[22][23][24]

Venetoclax (ABT-199)[edit]

Due to dose-limiting thrombocytopoenia of navitoclax as a result of Bcl-xL inhibition, Abbott Laboratories successfully developed the highly selective inhibitor venetoclax (ABT-199), which inhibits Bcl-2, but not Bcl-xL or Bcl-w.[25] Clinical trials studied the effects of venetoclax, a BH3-mimetic drug designed to block the function of the Bcl-2 protein, on patients with chronic lymphocytic leukemia (CLL).[26][27] Good responses have been reported and thrombocytopoenia was no longer observed.[27][28] A phase 3 trial started in Dec 2015.[29] It was approved by the US FDA in April 2016 for CLL associated with 17-p deletion.[30] This is the first FDA approval of a protein-protein inhibitor of BCL-2.[30]
Left supraclavicular lymph nodes:                                                                              
  Diffuse large B-cell lymphoma                                                                                
CLINICAL INFORMATION:                                                                                               
75 year-old female with mediastinal adenopathy and bilateral supraclavicular                                  
SPECIMEN SUBMITTED:                                                                                                
Received from Alliance Pathology Consultants, PasadenaTX, for consultation:                                 
– 6 paraffin blocks labeled “3842-FS1A, 1B, FS2A, 2B, 2C, 3”                                                  
– 7 glass slides labeled “S2003-3842-FS1A cryo, S2004-3842-1B, FS2A,                                          
FS2A cryo, 2B, 2C, 3″                                                 
– A one-page letter from Dr. Dorothy Willis dated 05-06-04                                                    
– A two-page surgical pathology report specimen “BM:S3842-04″                                                 
ADDITIONAL TECHNIQUES (block 3842-2C):                                                                        
CD3, CD10, CD20, CD30, CD45, Bcl-2, cytokeratin immunohistochemical
GROSS DESCRIPTION:                                                                                                 
See Alliance Pathology report S3842-04.                                                                        
MICROSCOPIC DESCRIPTION:                                                                                            
Histologic sections of the left supraclavicular lymph nodes show effacement of                                
lymph node architecture by large cells with irregular nuclear contour,                                         
vesicular nuclei with fine chromatin, and one to several nucleoli.  Frequent                                  
mitotic figures are seen.  Necrotic foci and bands of sclerosis are also found                                
in sections.                                                                                                   
Immunohistochemical stains, with adequate controls, show that the neoplastic                                  
cells are positive for CD20, CD45, and bcl-2. These cells are negative for                                   
CD3, CD10, and CD30.  Normal T cells (positive for CD3) are scattered                                         
throughout the sections.  No epithelial components are detected with                                           

Lymph node, right inguinal, biopsy:
– Benign reactive lymph node with follicular hyperplasia and sinus hyperplasia
Histologic sections of the (R) inguinal lymph node show preservation of lymph node architecture. The capsule is moderately thickened.  Follicular hyperplasia and sinus hyperplasia are noted. The follicles have well-formed mantle zone. No evidence of granuloma or necrosis is seen. Vascular proliferation is moderately increased.
Immunohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD10, CD20, and bcl-2.  The germinal centers are positive for CD20, CD10, and negative for bcl-2.  CD3 and bcl-2 are positive for lymphocytes in the interollicular areas.

Mod Pathol 2000;13(11):1244–1252

CD20-Positive Peripheral T-Cell Lymphoma: Report of a Case after Nodular Sclerosis Hodgkin’s Disease and Review of the Literature

Renee L Mohrmann M.D.1 and Daniel A Arber M.D.1
1Division of Pathology, City of Hope National Medical Center, Duarte, California
Correspondence: Renee L. Mohrmann, M.D., Division of Pathology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000 USA. fax: 626-301-8145; e-mail:
Accepted 9 June 2000.
Diffuse large B-cell lymphoma (DLBCL) is classified as a distinct lymphoma entity, according to the World Health Organization (WHO) classification. It is the most common subtype of non-Hodgkin lymphomas (NHLs), representing approximately 40% to 50% adult NHL cases. The incidence of NHL is currently increasing. It is now the fifth most frequent cancer worldwide.
Evidence suggests that DLBCL is not a single disease but rather a heterogeneous group of tumors with various clinical courses, histology and molecular and cytogenetic characteristics. Currently, the International Prognostic Index (IPI) model is most widely used to predict the outcome of DLBCL. However, even patients within identical IPI categories may exhibit striking variability in prognosis, suggesting the heterogeneity of this malignancy. Molecular and cytogenetic studies of NHLs have shown that chromosomal and genetic abnormalities are associated with the biological and clinical features of these diseases and that they could serve as useful prognostic markers.

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