Bcl-2

Bcl-2 (B-cell leukemia/lymphoma 2) is a mitochondrial membrane protein involved in blocking apoptotic death of certain cells.  Over expression is associated with multiple lymphomas.  Follicular Lymphoma (FL) is the most important diagnostically.  The vast majority of FLs express bcl-2.  In contrast, benign germinal centers are negative for bcl-2 (except for small follicular T-cells). 
 
In small lymphoid cells, there is little to no specificity to support a benign or malignant diagnosis with bcl-2, and the stain is not helpful in that setting.
Bcl-2 Expression Patterns
  • Follicular Lymphoma (bcl-2 expressed), some high grade tumors may be negative
    • Grade 1 = 87% +
    • Grade 2 = 81% +
    • Grade 3 = 73% +
  • Normal B-cells (non-germinal centers)
  • Normal T-cells
  • Burkitt Lymphoma (NEGATIVE)
  • DLBCL (independent adverse prognostic indicator)
Skin
Bcl-2 is expressed in most basal cell carcinomas of the skin, compared to squamous cell carcinomas, which are negative.  Bcl-2, like BerEP4 may be helpful in differentiating basal cell carcinoma from squamous cell carcinoma.
Microscopic Images
Bcl-2 Follicular Lymphoma
Bcl-2 expression in follicular lymphoma (high power).
Bcl-2 Tonsil
Bcl-2 expression (high power) in reactive tonsil.
Bcl-2
Bcl-2 expression in a benign tonsil.
Bcl-2
Bcl-2 expression in a benign tonsil.
Bcl-2 Follicular Lymphoma
Low power view of Bcl-2 expression in follicular lymphoma.

References
Chuang S-S, Ye H, Du M-Q, Lu C-L, Dogan A, Hsieh P-P, et al. Histopathology and immunohistochemistry in distinguishing Burkitt lymphoma from diffuse large B-cell lymphoma with very high proliferation index and with or without a starry-sky pattern: a comparative study with EBER and FISH. Am J Clin Pathol. 2007;128: 558–564. doi:10.1309/EQJR3D3V0CCQGP04
 
Boyd SD, Natkunam Y, Allen JR, Warnke RA. Selective immunophenotyping for diagnosis of B-cell neoplasms: immunohistochemistry and flow cytometry strategies and results. Appl Immunohistochem Mol Morphol. 2013;21: 116–131. doi:10.1097/PAI.0b013e31825d550a
 
Chan JKC, Ip YT, Cheuk W. The Utility of Immunohistochemistry for Providing Genetic Information on Tumors. International Journal of Surgical Pathology. 2013;21: 455–475. doi:10.1177/1066896913502529
 
Bone Marrow IHC.  Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009.  pp. 226.
 
Tellechea, O., Reis, J.P., Domingues, J.C., Baptista, A.P. (1993).  Monoclonal antibody Ber EP4 distinguishes basal-cell carcinoma from squamous-cell carcinoma of the skin.  American Journal of Dermatopathology.  Oct;15(5):452-5. 
 
Berglund, M., Thunberg, U., Amini, R.-M., Book, M., Roos, G., Erlanson, M., et al. (2005). Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 18(8), 1113–1120. doi:10.1038/modpathol.3800396