Lhara Sumarriva Lezama1, Karen M Chisholm2, Eugene Carneal3, Alexandra Nagy3, Michael J Cascio4, Jie Yan5, Chung-Che Chang6, Athena Cherry3, Tracy I George5, Robert S Ohgami3. 1. Department of Pathology, Mount Sinai Health System, New York, NY, USA. 2. Department of Laboratories, Seattle Children's Hospital, Seattle, WA, USA. 3. Department of Pathology, Stanford University Medical Center, Stanford, CA, USA. 4. Department of Pathology, Oregon Health and Science University, Portland, OR, USA. 5. Department of Pathology, University of New Mexico, Albuquerque, NM, USA. 6. Department of Pathology, Florida Hospital, University of Central Florida, Orlando, FL, USA.
Abstract
AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive neoplasm with leukaemic features and frequent skin involvement. Translocations involving the MYC locus have been recently identified as recurrent cytogenetic abnormalities in this entity. The aim of this study was to assess the clinicopathological, immunophenotypic and genetic features in MYC-rearranged BPDCN cases. METHODS AND RESULTS: Pathology archives from six major institutes were queried for cases of BPDCN with 8q24 MYC translocations, and two cases were identified. A literature review identified 14 cases. Clinicopathological features, immunophenotype and cytogenetic and molecular data were reviewed. In these 16 MYC-rearranged cases, the median age at diagnosis was 70.5 years, and there was a male predominance. Whereas all cases showed marrow involvement, skin lesions (62.5%) and lymphadenopathy (50%) were variably seen. The median survival was 11 months. The median percentage of blasts in peripheral blood was 9%. All cases showed expression of CD4, with 10 of 16 being positive for CD56. HLA-DR, CD123, TCL1 and CD303 were positive in all cases tested. Cytogenetic analysis revealed a single recurrent translocation partner of MYC at 6p21 in 11 cases (69%), whereas four cases showed different MYC translocation partners (2p12, Xq24, 3p25, and 14q32). Interestingly, the group of patients with t(6;8)(p21;q24) showed an older median age at diagnosis (74 years) and a remarkably shorter median survival (3 months). CONCLUSIONS: Translocations involving the 8q24 MYC locus more frequently manifest as t(6;8)(p21;q24), and, given its association with specific clinicopathological features suggesting even more aggressive behaviour, t(6;8)(p21;q24) indicate a genetically defined subgroup within BPDCN.
AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive neoplasm with leukaemic features and frequent skin involvement. Translocations involving the MYC locus have been recently identified as recurrent cytogenetic abnormalities in this entity. The aim of this study was to assess the clinicopathological, immunophenotypic and genetic features in MYC-rearranged BPDCN cases. METHODS AND RESULTS: Pathology archives from six major institutes were queried for cases of BPDCN with 8q24 MYC translocations, and two cases were identified. A literature review identified 14 cases. Clinicopathological features, immunophenotype and cytogenetic and molecular data were reviewed. In these 16 MYC-rearranged cases, the median age at diagnosis was 70.5 years, and there was a male predominance. Whereas all cases showed marrow involvement, skin lesions (62.5%) and lymphadenopathy (50%) were variably seen. The median survival was 11 months. The median percentage of blasts in peripheral blood was 9%. All cases showed expression of CD4, with 10 of 16 being positive for CD56. HLA-DR, CD123, TCL1 and CD303 were positive in all cases tested. Cytogenetic analysis revealed a single recurrent translocation partner of MYC at 6p21 in 11 cases (69%), whereas four cases showed different MYC translocation partners (2p12, Xq24, 3p25, and 14q32). Interestingly, the group of patients with t(6;8)(p21;q24) showed an older median age at diagnosis (74 years) and a remarkably shorter median survival (3 months). CONCLUSIONS: Translocations involving the 8q24 MYC locus more frequently manifest as t(6;8)(p21;q24), and, given its association with specific clinicopathological features suggesting even more aggressive behaviour, t(6;8)(p21;q24) indicate a genetically defined subgroup within BPDCN.
Authors: Justin Taylor; Michael Haddadin; Vivek A Upadhyay; Erwin Grussie; Neha Mehta-Shah; Andrew M Brunner; Abner Louissaint; Scott B Lovitch; Ahmet Dogan; Amir T Fathi; Richard M Stone; Martin S Tallman; Raajit K Rampal; Donna S Neuberg; Kristen E Stevenson; Steven M Horwitz; Andrew A Lane Journal: Blood Date: 2019-06-26 Impact factor: 22.113