Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity
Dermawan JKK, Dinapoli SEE, Sukhadia P, Mullaney KAA, Gladdy R, Healey JHH, Agaimy A, Cleven AHH, Suurmeijer AJH, Dickson BCC, Antonescu CRR (2023)
Publication Type: Journal article
Publication year: 2023
Journal
DOI: 10.1002/gcc.23102
Abstract
Among mesenchymal tumors, MAML2 gene rearrangements have been described in a subset of composite hemangioendothelioma and myxoinflammatory fibroblastic sarcoma (MIFS). However, we have recently encountered MAML2-related fusions in a group of seven undifferentiated malignant epithelioid neoplasms that do not fit well to any established pathologic entities. The patients included five males and two female, aged 41-71 years old (median 65 years). The tumors involved the deep soft tissue of extremities (hip, knee, arm, hand), abdominal wall, and the retroperitoneum. Microscopically, the tumors consisted of solid sheets of atypical epithelioid to histiocytoid cells with abundant cytoplasm. Prominent mitotic activity and necrosis were present in 4 cases. In 3 cases, the cells displayed hyperchromatic nuclei or conspicuous macronucleoli, and were admixed with background histiocytoid cells and a lymphoplasmacytic infiltrate. By immunohistochemistry (IHC), the neoplastic cells had a nonspecific phenotype. On targeted RNA sequencing, MAML2 was the 3 ' partner and fused to YAP1 (4 cases), ARHGAP42 (2 cases), and ENDOD1 (1 case). Two cases with YAP1::MAML2 harbored concurrent RAF kinase fusions (RBMS3::RAF1 and AGK::BRAF, respectively). In 2 cases with targeted DNA sequencing, mutations in TP53, RB1 and PTEN were detected in 1 case, and PDGFRB mutations, CCNE1 amplifications and CDKN2A/2B deletion were detected in another case, which showed strong and diffuse PDGFRB expression by IHC. Of the 4 cases with detailed clinical history (median follow-up period 8 months), three developed distant metastatic disease (one of which died of disease); one case remained free of disease 3 years following surgical excision. In conclusion, we describe a heterogeneous series of MAML2-rearranged undifferentiated malignant epithelioid neoplasms, a subset of which may overlap with a recently described MIFS variant with YAP1::MAML2 fusions, further expanding the clinicopathologic spectrum of mesenchymal neoplasms with recurrent MAML2 gene rearrangements.
Authors with CRIS profile
Involved external institutions
Memorial Sloan Kettering Cancer Center
United States (USA) (US)
Sinai Health System
Canada (CA)
University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen
Netherlands (NL)
University of Toronto
Canada (CA)
United States (USA) (US)
Sinai Health System
Canada (CA)
University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen
Netherlands (NL)
University of Toronto
Canada (CA)
How to cite
APA:
Dermawan, J.K.K., Dinapoli, S.E.E., Sukhadia, P., Mullaney, K.A.A., Gladdy, R., Healey, J.H.H.,... Antonescu, C.R.R. (2023). Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity. Genes Chromosomes & Cancer. https://doi.org/10.1002/gcc.23102
MLA:
Dermawan, Josephine K. K., et al. "Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity." Genes Chromosomes & Cancer (2023).
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