[1578] ALK Positive Large B-Cell Lymphomas (ALK+ LBCL) Express the Terminal Plasma Cell Differentiation Program but Lack MYC Rearrangements

Alexandra Valera, Lluis Colomo, Antonio Martinez, Daphne de Jong, Olga Balague, Gabriel Matheu, Monica Martinez, Lekidelu Taddesse-Heath, Elaine S Jaffe, Carlos E Bacchi, Elias Campo. Hospital Clínic of Barcelona, Barcelona, Spain; Netherlands Cancer Institute, Amsterdam, Netherlands; Hospital de Manacor, Manacor, Spain; Laboratorio de Hematopatología, Mendoza, Argentina; Howard University Hospital, Washington, DC; National Cancer Institute, Bethesda; Consultoria em Patologia, Sao Paulo, Brazil

Background: ALK+ LBCL is an uncommon and aggressive variant of DLBCL characterized by the presence of ALK rearrangements and a terminal B-cell differentiation phenotype. MYC rearrangements are frequent in plasmablastic lymphomas (PBL), advanced multiple myeloma and a subgroup of aggressive DLBCL but its presence in ALK+ LBCL is unknown. MYC expression is downregulated by BLIMP1, a master regulator of plasma cell differentiation. The aim of this study was to investigate whether MYC rearrangements and protein overexpression may play a role in the pathogenesis of ALK+ LBCL.
Design: We investigated MYC rearrangement and protein expression in 12 ALK+ LBCL, 11 PBL and 16 ABC-DLBCL. The terminal B-cell differentiation program was evaluated by ICH using IRF4, CD138, PRDM1/Blimp1 and Xbp-1. MYC expression was assessed using the monoclonal Y69 antibody. ALK and MYC rearrangements were investigated by FISH.
Results: All 12 ALK+ LBCL had granular cytoplasmic ALK expression. The 11 evaluable cases had ALK rearrangements. Double ALK rearrangements were observed in 3/11 cases and 5' deletion in 2/11 cases. Extra copies of ALK were detected in 5/11 cases (2 simple-rearranged, 2 double-rearranged and one with 5' deletion). IRF4 was expressed in 8/10 cases, whereas PRDM1/Blimp1 and XBP1s were positive in 10/12 and 9/11, respectively. Seven of 10 cases had simultaneous expression of the 3 markers and 2 additional cases expressed at least two. CD138 was expressed in all cases and IgA in 8/11. MYC rearrangements were not identified in any ALK+ LBCL but in 4/11 PBL and 1/16 ABC-DLBCL. MYC gains were detected in 6/11 ALK+DLBCL, 5/11 PBL and 1/16 ABC-DLBCL. MYC protein was expressed with weak/moderate intensity in all ALK+LBCL and in 7/16 ABC-DLBCL. Strong MYC protein expression in >50% tumor cells was only observed in 6/11 PBL (4 MYC-rearranged, 1 gained, 1 normal) but in any ALK+ LBCL or ABC-DLBCL.
Conclusions: ALK+LBCL express the secretory and plasma cell differentiation program but, contrary to PBL, do not have MYC rearrangements or strong protein expression.
Category: Hematopathology

Monday, March 19, 2012 9:00 AM

Platform Session: Section C, Monday Morning


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