Benign Atypical CD5+ B Cell Proliferation vs Biclonal Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/ SLL)
An 85 year-old male with clinically suspicious adenopathy underwent bone marrow biopsy.
A decalcified core biopsy demonstrated atypical cellularity averaging approximately 70% comprised predominantly of 75% well differentiated lymphocytes. Scattered myeloid, erythroid and megakaryocytic elements were present with maturation. Paraffin immunohistochemistry revealed extensive PAX5+ CD5+ CD23+ cyclin D1‐ lymphocyte staining with diminished patchy CD20+ staining, sparse faint bcl6+ staining but negative CD10 staining.
Demonstrated an 11% population of atypical CD5+ B lymphocytes with both surface kappa and surface lambda light chain staining. One might consider this a polytypic B cell population; however, careful gating and interpretation revealed two distinct monoclonal CD5+ B cell subsets.
a. 7.7% of sample (18% of lymphocytes), CD45+, CD19+, CD20+/‐ (dim), CD5+, CD10‐, CD23+, FMC7‐, CD38‐, HLA DR+, sIg lambda+ (dim)
b. 2.9% of sample (7% of lymphocytes), CD45+(dim), CD19+, CD20+/‐ (dim), CD5+(dim), CD23+(dim), FMC7‐, CD38‐, HLADR+, sIg kappa+ (dim)
NEGATIVE for CLL associated abnormalities
NEGATIVE for IGH/BCL2 t(14;18) - No structural or numerical abnormality involving 14q32 or 18q and no abnormality involving loci examined on chromosomes 6, 11, 12, 13 or 17
Benign atypical CD5+ B cell proliferation versus biclonal chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/ SLL)
Biclonal chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/ SLL)
Based on flow cytometry alone, one might easily misinterpret the findings to represent a benign polytypic CD5+ B cell population with mixed surface kappa and surface lambda light chain staining. However, morphology clearly demonstrates a malignant small B cell marrow infiltrate with paraffin immunostaining highly characteristic of chronic lymphocytic leukemia/ small lymphocytic lymphoma. Careful gating and analysis of the flow cytometry findings based on bimodal CD5+ intensity staining reveals two distinct B cell subsets with different intensity staining for CD5, CD45, and CD23 and with discordant surface light staining.
Only rare cases of biclonal CLL/SLL with discordant kappa and lambda light chain expression have been described. There is no known clinical or prognostic significance to these cases. However, one must wonder if they arise through clonal evolution if they might be associated with risk for disease progression.
Fig 7. Bimodal CD5 staining highlights discrete CD5+ B cell subsets