Molecular Characteristics of Composite Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Yi Zhou, Rashmi Kanagal-Shamanna, Sylvia Hoeller, Alexander Tzankov, Daniela Hoehn, Steven H Swerdlow, Andreas Rosenwald, Zijun Y Xu-Monette, Roberto N Miranda, Carlos Bueso-Ramos, L Jeffrey Medeiros, Ken H Young. The University of Texas MD Anderson Cancer Center, Houston, TX; University of Basel Hospital, Basel, Switzerland; University of Pittsburgh School of Medicine, Pittsburgh, PA; University of Würzburg, Würzburg, Germany
Background: Mantle cell lymphoma (MCL) accounts for approximately 6-7% of all B-cell lymphomas. MCL occurs in patients with a median age of 60 years and with an incidence of 0.2-0.3 case per 100,000 person-years. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) accounts for 12% of all B-cell lymphomas, it occurs in patients with a median age of 65 years and with an incidence of 12.8 cases per 100,000 person-years. CLL/SLL and MCL are the diseases of elderly and share many morphologic and immunophenotypic features. Both can develop from B-cells that may (mutated) or may not (unmutated) have undergone somatic hypermutation. The clonal relationship between the MCL and CLL/SLL in rare composite cases is not well studied in the literature.
Design: Cases of composite MCL and SLL were identified through a multi-institutional collaboration. All cases were reviewed by at least three hematopathologists. Morphologic and immunophenotypic features of MCL and SLL were characterized separately. Immunoglobulin heavy chain variable region restriction fragment length polymorphism (RFLP/IgH) analysis was performed on microdissected MCL and SLL components to assess clonal relation.
Results: Seven cases of composite MCL and SLL were identified. All patients were men with a median age of 73 years. They all presented with lymphadenopathy, at least 4 had extranodal disease. Morphologic examination showed that the MCL components had a mantle zone (n=3), nodular and diffuse (n=2), or diffuse pattern (n=2); 4 of them had blastoid or pleomorphic morphology. The SLL component had an internodular (n=5), vaguely nodular (n=1), or diffuse pattern (n=1). All MCL were CD5+ and cyclin D1+ with t(11;14). All SLL were CD5+, CD23+ and cyclin D1-. RFLP/IgH analysis of microdissected paraffin section specimens showed that the MCL and SLL components displayed different fragment lengths in 6 of 7 cases, indicating that they were derived from different neoplastic B-cell clones. Result of the remaining one case was equivocal.
Conclusions: The lack of clonal relationship between the MCL and CLL/SLL components in composite lymphoma suggests that the MCL and CLL/SLL are two distinct disease processes. It therefore seems unlikely that MCL arises from CLL/SLL.
Monday, March 19, 2012 1:00 PM
Poster Session II # 197, Monday Afternoon