Clinicopathologic Characterization of Cyclin D1-Negative Mantle Cell Lymphoma
Alejandra Carvajal-Cuenca, Itziar Salaverria, Cristina Royo, Guillem Clot, Alba Navarro, Elena M Hartmann, Nicola Trim, Renata Woroniecka, Wendy Erber, Philippe Gaulard, Iwona Wlodarska, Grzegorz Rymkiewicz, German Ott, Andreas Rosenwald, Armando Lopez-Guillermo, Leticia Quintanilla-Fend, Judith A Ferry, Nancy L Harris, Elaine S Jaffe, Reiner Siebert, Elias Campo, Silvia Bea. Hospital Clínic, University of Barcelona, Barcelona, Spain; Institute of Pathology, Würzburg, Germany; Addenbrooke's Hospital, Cambridge, United Kingdom; MSCM Cancer Centre and Institute, Warsaw, Poland; Henri Mondor Hospital, Creteil, France; Center of Human Genetics, Leuven, Belgium; Robert-Bosch-Krankenhaus, Stuttgart, Germany; Institute of Pathology, Tübingen, Germany; Massachusetts General Hospital, Boston; National Cancer Institute, Bethesda; Christian-Albrechts-University Kiel, Kiel, Germany
Background: Cyclin D1-negative mantle cell lymphoma (MCL) is not well characterized due in part to the difficulties in its recognition. SOX11 has been recently identified as a reliable biomarker of MCL, including the cyclin D1-negative variant. The aims of this study were to define the clinicopathologic characteristics of cyclin D1-negative MCL and to determine its relationship to conventional MCL.
Design: We investigated 42 cyclin D1-negative lymphomas that had similar morphology and phenotype (CD5 positive) to conventional MCL. All cases were negative for cyclin D1 expression and t(11;14). SOX11 and p27 expression was examined by immunohistochemistry. FISH studies for CCND2, CCND3, IGH, IGK and IGL were performed in all cases. The genomic profile was investigated in 35 cases using high-resolution copy number arrays (Agilent 1M).
Results: SOX11 was positive in 38 cases, negative in 3 and not evaluable in 1. The SOX11+ tumors had a classical morphology in 34 cases, marginal zone-like in 3 and blastoid in 1. All cases had diffuse or nodular growth pattern except one case with a mantle zone pattern. p27 was negative or weaker than in the associated T cells in 19/23 examined. CCND2 rearrangements were detected in 21/38 (55%) SOX11+ cases and in the case non-evaluable for SOX11. CCND2 was translocated to IGK, IGL, IGH and an undetermined partner in 10, 5, 3 and 4 cases, respectively. The genomic profile of these cases was similar to that described in cyclin D1-positive MCL with frequent gains of 3q, 18q, 8q and losses of 13q, 9p, 1p, 11q, 6q. These tumors presented more frequently in males (74%), with advanced stage (78%, stage IV), extranodal involvement (79%) and had a poor outcome (median survival 37 months).
Conclusions: SOX11+ Cyclin D1-negative MCL has similar clinical, pathologic, and secondary genetic alterations to conventional MCL. CCND2 is frequently translocated in these tumors using IG light chain genes as partners.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 211, Monday Morning