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. 2012 Jul;138(1):132-9.
doi: 10.1309/AJCPIVKZRMPF93ET.

Chronic lymphocytic leukemia/small lymphocytic lymphoma with cyclin D1 positive proliferation centers do not have CCND1 translocations or gains and lack SOX11 expression

Joel F Gradowski  1 , Rachel L Sargent, Fiona E Craig, Kathleen Cieply, Kim Fuhrer, Carol Sherer, Steven H Swerdlow
Affiliations

Chronic lymphocytic leukemia/small lymphocytic lymphoma with cyclin D1 positive proliferation centers do not have CCND1 translocations or gains and lack SOX11 expression

Joel F Gradowski et al. Am J Clin Pathol. 2012 Jul.

Abstract

Cyclin D1 expression, usually absent in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), has been described in the proliferation centers (PC) of some CLL/SLL. The prevalence of this finding is uncertain, as is the explanation for its occurrence and whether these cases have any other unique features. Cyclin D1 immunohistochemical staining was therefore investigated in 57 extramedullary CLL/SLL biopsies. In 6 cases, cyclin D1 immunofluorescence followed by CCND1 fluorescence in situ hybridization (FISH) and PC targeted analysis was performed using a Bioview Duet system. Excluding the prospectively selected cases that had the targeted FISH studies, cyclin D1+ PC were identified in 20% of cases. The cyclin D1+ CLL did not appear pathologically or phenotypically distinctive, though 46% had an interfollicular growth pattern. The cyclin D1+ PCs were SOX11- and lacked CCND1 translocations and gains in 5 of 5 informative cases. The recognition of cyclin D1 expression in PC of a significant minority of CLL/SLL can be a diagnostic aid and should not lead to the diagnosis of focal mantle cell lymphoma.

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Figures

Image 1
Image 1
Partial preservation of lymph node architectural features. A (Case 2), Note the patent sinuses. B (Case 4), Prominent reactive germinal centers are present. (H&E, ×100)
Image 2
Image 2
A and B (Case 1), The distinct proliferation centers showed weak to moderate intensity cyclin D1 staining. C and D (Case 2), In contrast, in this case, the proliferation centers are somewhat confluent and have moderate to strong cyclin D1 staining. (A and C, H&E, ×40; B and D, immunohistochemistry with hematoxylin counterstain, ×500.)
Image 3
Image 3
Immunofluorescence in situ hybridization analysis showing the green cyclin D1+ cells in the immunohistochemical stain (A) and the results of the CCND1 break-apart probe in this specific region (B). Cells with split signals indicating a CCND1 translocation are not seen. Note 2 fusion signals in all informative cells in the region of the cyclin D1 positive proliferation center. The cells with a single fusion signal or rare cells with a single red or green signal represent truncation. (A, fluorescence cyclin D1 stain, ×1,000; B, cyclin D1 break-apart probe, ×1,000.)
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