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Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma: common cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall
Author(s) -
Chuang WenYu,
Chang Hung,
Chang GwoJyh,
Wang TzuHao,
Chang YuSun,
Wang TongHong,
Yeh ChiJu,
Ueng ShirHwa,
Chien HuiPing,
Chang ChiuYueh,
Wan YungLiang,
Hsueh Chuen
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13161
Subject(s) - cyclin d1 , mantle cell lymphoma , biology , lymphoma , cancer research , immunohistochemistry , chromosomal translocation , diffuse large b cell lymphoma , cyclin d2 , pathology , cancer , medicine , genetics , cell cycle , immunology , gene
Aims To characterize the clinicopathological and genetic features of pleomorphic mantle cell lymphoma ( PMCL ), which morphologically mimics diffuse large B cell lymphoma ( DLBCL ). Methods and results We screened systematically 500 B cell lymphomas morphologically compatible with DLBCL using an immunohistochemical algorithm of three markers ( CD 5, cyclin D1 and SOX 11). Ten cases of PMCL were identified for further study and, surprisingly, four (40%) of them were cyclin D1‐negative. These 10 patients were mainly elderly males with advanced disease, and their median survival was only 11 months. All cyclin D1‐positive PMCL s tested showed an IGH – CCND 1 translocation, whereas one of the four cyclin D1‐negative PMCL s had a translocation involving CCND 2 and a high CCND 2 mRNA level ( P < 0.1). The genomewide copy number profiles of both cyclin D1‐positive and cyclin D1‐negative PMCL s were similar to those of classical mantle cell lymphoma ( MCL ) reported previously, confirming the diagnosis. Secondary genetic alterations involved in oncogenic pathways of MCL were observed more frequently in these PMCL s, possibly decreasing the dependence on the driving CCND 1 translocation and accounting for the common cyclin D1 negativity. Copy number gains of PIK 3 CA and CCDC 50 were detected in all cyclin D1‐negative PMCL s but in only 40% of the cyclin D1‐positive PMCL s. These additional oncogenic signals may compensate for the common absence of CCND 2 translocation in cyclin D1‐negative PMCL . Conclusion We demonstrate for the first time that cyclin D1 negativity is surprisingly common in PMCL morphologically mimicking DLBCL , and the use of a simple immunohistochemical algorithm can prevent misclassification and inappropriate treatment.