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Biclonal CLL/SLL

Posted on August 07 2013

Biclonal CLL/SLL
Case Study

Benign Atypical CD5+ B Cell Proliferation vs Biclonal Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/ SLL)

History:

An 85 year-old male with clinically suspicious adenopathy underwent bone marrow biopsy.

Microscopic Findings: 

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.

Special Studies:

Flow cytometry
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)

FISH:

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

Differential Diagnosis: 

Benign atypical CD5+ B cell proliferation versus biclonal chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/ SLL)

Diagnosis: 

Biclonal chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/ SLL)

Educational comments: 

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.

References: 

Hsi ED, Hoeltge G, and Tubbs RR. Biclonal Chronic Lymphocytic Leukemia. Am J Clin Pathol 2000; 113:798-804

Fig 1.  Extensive, patchy marrow involvement by small lymphocyte infiltrate.
Fig 2. Tumor cells are dimly CD20+

Fig 3. Tumor cells are PAX5+.
Fig 4.  Tumor cells are CD23+.
Fig 5. Tumor cells are CD5+.
Fig 6. Tumor cells are cyclin D1-

 

Fig 7. Bimodal CD5 staining highlights discrete CD5+ B cell subsets


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