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Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 4 December 2011, last major update November 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● b cell lymphoma #2
● Proto-oncogene at 18q21.3
● Encodes 25 kDa protein, mainly localized to inner mitochondrial membrane; also endoplasmic reticulum and nuclear envelope


● Prevents cells from undergoing apoptosis
● bcl2 overexpression increase lifespan of B cells; may maintain memory B cells, plasma cells and neurons by prolonging life span without cell division
● May participate in ion channel formation and alteration of membrane permeability, necessary for initiation of apoptosis
● Non-phosphorylated bcl2 inhibits apoptosis, and Bax homodimers normally cause apoptosis; Bax can bind to and inhibit non-phosphorylated bcl2, promoting apoptosis
● Epstein-Barr virus latent membrane protein-1 (LMP-1) interacts with bcl2 promoter, leading to prolonged lifespan for B cells
● Surprisingly, bcl2 overexpression in osteoblasts causes osteocyte apoptosis (PLoS One 2011;6:e27487)


Two main pathways to apoptosis

Mitochondrial control of apoptosis

bcl2 translocation in follicular lymphoma


● Nuclear and cytoplasmic staining

Uses by Pathologists

● (1) Distinguish follicular hyperplasia of lymph node (germinal centers are bcl2 negative) from follicular lymphoma (germinal centers are bcl2+); bcl2 usually overexpressed in follicular lymphoma due to t(14,18)(q32;q21), which brings bcl2 gene adjacent to active immunoglobulin heavy chain (IgH) gene; however, some follicular lymphomas are bcl2 negative (Am J Surg Pathol 2011;35:1691, Am J Surg Pathol 2009;33:591)
● (2) Detect immature enteric ganglion cells in pediatric intestinal pseudo-obstruction (Am J Surg Pathol 2005;29:1017)
● (3) Diffuse large cell lymphoma: adverse prognostic factor in some studies (Mod Pathol 2005;18:1113, Clin Cancer Res 2011 Sep 20 [Epub ahead of print])
● (4) Myelodysplastic syndrome: increased expression associated with progression
● (5) May have prognostic value in early stage breast cancer (Br J Cancer 2010;103:668)

Micro images

Normal: left-human tonsil, right-lymph node (mantle zone and T cells are positive but germinal center is negative)

Various images

Burkitt lymphoma (left: negative, the predominant patter; right: positive, occasionally seen

Cervix-tuboendometrial metaplasia

Collecting duct carcinoma-kidney

Diffuse large B cell lymphoma

Follicular lymphoma

Follicular lymphoma of thyroid: t(14;18) negative / bcl2 negative (left) versus positive (right)

Primary cutaneous follicular cell lymhoma: leg type (left) and classic type (right)

Solitary fibrous tumor: left/middle-ear, right-CNS

Spindle cell epithelioma of vagina

Synovial sarcoma: left-lung, right-pericardium

Thyroid gland-CASTLE

Positive staining - normal

● Lymph node: small B lymphocytes in mantle zone and cells within T cell areas
● Adrenal cortex, melanocyties, thymus-medullary cells, thyroid gland solid cell nests
● Immature (but not mature) small ganglion cells

Positive staining - disease

Hematopoietic: follicular lymphoma (germinal centers stain); also acute lymphoblastic leukemia, angiotropic / intravascular lymphoma, Burkitt lymphoma (occasionally, Indian J Pathol Microbiol 2011;54:290), diffuse large B cell lymphoma (variable), extranodal NK/T-cell lymphoma, nasal-type: 39% (Am J Clin Pathol 2008;130:343), Hodgkin lymphoma (classical): 27% (Hum Pathol 2007;38:103), mantle cell lymphoma, marginal zone lymphoma (variable), persistent polyclonal lymphocytosis, plasmablastic lymphoma, SLL

Other: adrenal cortical adenoma and carcinoma (Mod Pathol 1998;11:716), atrioventricular node tumor of heart, basal cell carcinoma (skin and prostate, Am J Surg Pathol 2007;31:697), breast-benign stromal spindle cell tumor, breast-columnar cell lesions, breast-micropapillary carcinoma, breast-phyllodes tumor (stromal cells), cervix-mesonephric remnants / rests, cervix-tuboendometrial metaplasia, collecting duct carcinoma-kidney, colorectal adenomas / carcinomas, dermatofibrosarcoma protuberans

● Giant cell angiofibroma, hemangiopericytoma, large cell neuroendocrine carcinoma (salivary glands), low grade fibromyxoid sarcoma of soft tissue, lymphoepithelioma-like carcinoma, melanoma (uvea, Arch Pathol Lab Med 1996;120:497), myofibroblastoma, pheochromocytoma (variable)

● Sclerosing epithelioid fibrosarcoma, small cell carcinoma (breast), solitary fibrous tumor, spindle cell epithelioma of vagina (Arch Pathol Lab Med 2001;125:547), squamous cell carcinoma (uterus), squamous papilloma (conjunctiva, Ann NY Acad Sci 2004;1030:419), synovial sarcoma (Hum Pathol 1996;27:1060), thyroid gland-CASTLE

Negative staining

● Anaplastic lymphoma, apocrine benign / malignant lesions, benign fibrous histiocytoma, lymphoid hyperplasia (marginal zone cells in hyperplastic areas are bcl2+, germinal centers are bcl2-), lymphoplasmayctic lymphoma

End of Stains > bcl2

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