Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report

Abstract

Malignant mesothelioma with EWSR1-ATF1 fusion is a rare malignancy described in young adults without asbestos exposure. To the best of our knowledge, outcomes to local and systemic therapies for this subtype of malignant mesothelioma have not been described. This case report describes the clinical course of a 19-year-old man diagnosed with malignant peritoneal mesothelioma with EWSR1-ATF1 fusion localized to the abdomen. His disease followed an aggressive course and resulted in limited survival (18 mo). There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma and biologically targeted MET inhibition with crizotinib. More research is required in this rare subtype of peritoneal mesothelioma.

NR4A3 fusions characterize a distinctive peritoneal mesothelial neoplasm of uncertain biological potential with pure adenomatoid/microcystic morphology

“…Features of high‐grade malignancy (brisk mitotic activity and necrosis) were absent. Notably, the tumor cells in each case had patchy to negative expression of calretinin and retained nuclear expression of BAP1 16–18,22,23 . In‐frame fusion transcripts involved EWSR1 exon 7/8 and YY1 exon 2/3 16–18,22,23 .…”

“…Notably, the tumor cells in each case had patchy to negative expression of calretinin and retained nuclear expression of BAP1. [16][17][18]22,23 In-frame fusion transcripts involved EWSR1 exon 7/8 and YY1 exon 2/3. [16][17][18]22,23 Methylation studies showed clustering of EWSR1/FUS::ATF1-and EWSR1::YY1fusion-positive mesotheliomas that was similar to conventional mesotheliomas, indicating that they likely are part of the heterogeneous mesothelioma genetic spectrum.…”

“…[16][17][18]22,23 In-frame fusion transcripts involved EWSR1 exon 7/8 and YY1 exon 2/3. [16][17][18]22,23 Methylation studies showed clustering of EWSR1/FUS::ATF1-and EWSR1::YY1fusion-positive mesotheliomas that was similar to conventional mesotheliomas, indicating that they likely are part of the heterogeneous mesothelioma genetic spectrum. Only limited follow-up was available, and it suggested an indolent course of disease.…”

“…22,23 Most of these tumors were peritoneal in origin and they affected young to middle-aged adults, who had no history of asbestos exposure. [16][17][18]22,23 Histologically, these tumors were conventional cellular epithelioid mesotheliomas showing variable mixtures of solid, tubular, papillary, and trabecular growth within fibrous stroma, and were characterized by polygonal cells with eosinophilic cytoplasm and a centrally located nucleus. Features of high-grade malignancy (brisk mitotic activity and necrosis) were absent.…”

“…With the evolving genetic landscape of mesothelioma, gene fusions have been increasingly recognized in a rare subset of cases. In addition to tumors harboring EWSR1/FUS::ATF1 fusions, 16–18 five mesothelioma cases harboring an EWSR1::YY1 fusion have been reported 22,23 . Most of these tumors were peritoneal in origin and they affected young to middle‐aged adults, who had no history of asbestos exposure 16–18,22,23 .…”