Wen-Yu Chuang1,2,3, Hung Chang4, Gwo-Jyh Chang2, Tzu-Hao Wang5, Yu-Sun Chang6, Tong-Hong Wang7, Chi-Ju Yeh1, Shir-Hwa Ueng1, Hui-Ping Chien1, Chiu-Yueh Chang1, Yung-Liang Wan8, Chuen Hsueh1,6,7. 1. Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan. 2. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 3. Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 4. Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan. 5. Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 6. Chang Gung Molecular Medicine Research Center and Graduate Institute of Basic Medical Sciences, Chang Gung University, Taoyuan, Taiwan. 7. Tissue Bank, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 8. Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Abstract
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 (CD5, cyclin D1 and SOX11). 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 PMCLs tested showed an IGH-CCND1 translocation, whereas one of the four cyclin D1-negative PMCLs had a translocation involving CCND2 and a high CCND2 mRNA level (P < 0.000001). The genomewide copy number profiles of both cyclin D1-positive and cyclin D1-negative PMCLs 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 PMCLs, possibly decreasing the dependence on the driving CCND1 translocation and accounting for the common cyclin D1 negativity. Copy number gains of PIK3CA and CCDC50 were detected in all cyclin D1-negative PMCLs but in only 40% of the cyclin D1-positive PMCLs. These additional oncogenic signals may compensate for the common absence of CCND2 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.
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 (CD5, cyclin D1 and SOX11). 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 PMCLs tested showed an IGH-CCND1 translocation, whereas one of the four cyclin D1-negative PMCLs had a translocation involving CCND2 and a high CCND2 mRNA level (P < 0.000001). The genomewide copy number profiles of both cyclin D1-positive and cyclin D1-negative PMCLs 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 PMCLs, possibly decreasing the dependence on the driving CCND1 translocation and accounting for the common cyclin D1 negativity. Copy number gains of PIK3CA and CCDC50 were detected in all cyclin D1-negative PMCLs but in only 40% of the cyclin D1-positive PMCLs. These additional oncogenic signals may compensate for the common absence of CCND2 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.
Authors: Sietse M Aukema; Giorgio A Croci; Reiner Siebert; Wolfram Klapper; Susanne Bens; Kathrin Oehl-Huber; Rabea Wagener; German Ott; Andreas Rosenwald; Philip M Kluin; Eva van den Berg; Anneke G Bosga-Bouwer; Mels Hoogendoorn; Eva Hoster; Iris Bittmann; Inga Nagel; Eva M Murga Penas; Markus Kreuz; Julia Bausinger; Wilfried Belder; Ilske Oschlies; Martin J S Dyer; Sandrine Jayne Journal: Virchows Arch Date: 2021-02-02 Impact factor: 4.064
Authors: Preetesh Jain; Shaojun Zhang; Rashmi Kanagal-Shamanna; Chi Young Ok; Krystle Nomie; Graciela Nogueras Gonzalez; Omarya Gonzalez-Pagan; Holly A Hill; Hun Ju Lee; Luis Fayad; Jason Westin; Loretta Nastoupil; Frederick Hagemeister; Wendy Chen; Onyeka Oriabure; Maria Badillo; Changying Jiang; Yao Yixin; Shaoying Li; Guilin Tang; C Cameron Yin; Keyur P Patel; Leonard Jeffrey Medeiros; Ranjit Nair; Sairah Ahmed; Swaminathan P Iyer; Selvi Thirumurthi; Richard Champlin; Guofan Xu; Pan Tinsu; David Santos; Ruiping Wang; Guangchun Han; Jianhua Zhang; Xingzhi Song; Sattva Neelapu; Jorge Romaguera; Andy Futreal; Christopher Flowers; Nathan Fowler; Linghua Wang; Michael L Wang Journal: Blood Adv Date: 2020-03-24
Authors: Haige Ye; Aakash Desai; Dongfeng Zeng; Krystle Nomie; Jorge Romaguera; Makhdum Ahmed; Michael L Wang Journal: J Exp Clin Cancer Res Date: 2017-12-15
Authors: Giovanni Carulli; Eugenio Mario Ciancia; Francesco Caracciolo; Paola Sammuri; Cristiana Domenichini; Maria Immacolata Ferreri; Alessia Di Vita; Virginia Ottaviano; Martina Rousseau; Mario Petrini Journal: Hematol Rep Date: 2018-01-03