Cyclin D1 Expression in LP Cells of Nodular Lymphocyte Predominant Hodgkin's Lymphoma
Benjamin B Cho, Robin D LeGallo, Teresa A Goldin, Nadine S Aguilera. University of Virginia Health System, Charlottesville, VA
Background: Cyclin D1 is a cell cycle regulatory protein that is expressed commonly in mantle cell lymphoma, occasionally in multiple myeloma and hairy cell leukemia, and rarely in proliferation centers of chronic lymphocytic leukemia. Cyclin D1 expression has also been documented in 2-20% of classical Hodgkin's lymphomas (CHL), with variable percentages of Reed-Sternberg (RS) cells showing positivity with cyclin D1 immunohistochemistry (IHC). However, reports of cyclin D1 expression in nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) have been conspicuously absent.
Design: Twelve of 66 NLPHL cases diagnosed at our institution from 2002 to 2012 had paraffin-embedded tissue blocks available for use in this study. For each of these 12 cases, diagnoses were confirmed prior to inclusion; all cases met criteria using 2008 WHO classification. Cyclin D1 IHC (clone SP4) was performed on all NLPHL cases as well as 6 control cases [3 cases of CHL (2 nodular sclerosis, 1 mixed cellularity) and 3 cases of T cell/histiocyte-rich large B cell lymphoma (THRLBCL)]. Fluorescence in situ hybridization (FISH) was performed using the Vysis LSI IgH/CCND1 dual color fusion probe (10 cases) or the Vysis LSI CCND1 dual color XT break apart probe (2 cases). Large cells were selected on Dapi and 30 consecutive cells were scored for enumeration and rearrangements of the probe signals.
Results: Patients aged 6 to 74 years (median 34.5 years); M:F=7:5. 9/12 cases were initial diagnoses. All NLPHL cases (12/12) were cyclin D1 positive in the majority of lymphocyte-predominant (LP) cells (>80%) showing a strong nuclear staining pattern. 3/3 cases of CHL were cyclin D1 positive in RS cells, though in a smaller proportion of malignant cells (5-20%) than in the NLPHL cases. 3/3 cases of THRLBCL were cyclin D1 negative. FISH showed a proportion of the large cells (range=18-32%, mean=24%) with three copies of non-fused IgH and CCND1 signals or intact CCND1 break apart signals. No rearrangements or fusions were identified.
Conclusions: We found that the majority of LP cells in NLPHL strongly express cyclin D1 without an associated translocation of CCND1. FISH revealed no genetic rearrangements or amplification to account for this increased protein expression. The significance of the three probe signals for both CCND1 and IgH is unclear but suggests possible triploidy in these cells, a finding seen in some cyclin D1+ plasma cell myelomas. Although the significance of these findings needs more investigation, at present cyclin D1 expression may be of diagnostic utility in differentiating NLPHL from THRLBCL.
Monday, March 4, 2013 2:45 PM
Proffered Papers: Section C, Monday Afternoon