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

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.