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

Our plain-English summary of Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report, by H. Ke, A.J. Gill, C. McKenzie, et al (JTO Clinical and Research Reports, 2021).

The study

• Authors: H. Ke, A.J. Gill, C. McKenzie, J.G. Kench, R.C.F. Chan, N. Pavlakis, M. Fulham, C. Koh, S. Kao
• Journal: JTO Clinical and Research Reports
• Published: 2021;2(11):100236
• Type of article: Case report
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2021 The Authors.

In plain English

This case report described a 19-year-old male student with no known history of asbestos exposure who was diagnosed with epithelioid primary peritoneal mesothelioma, a cancer of the abdominal lining. Genetic testing of the tumor found a fusion of two genes, EWSR1 and ATF1. He was treated with surgery to remove the tumor from the abdomen combined with heated chemotherapy inside the abdomen (cisplatin and mitomycin). This was followed by platinum and pemetrexed chemotherapy, after which imaging showed no remaining disease. The cancer was found again in the abdomen 2 months after chemotherapy. The disease progressed during immunotherapy with ipilimumab and nivolumab. It then did not respond to crizotinib, a MET-inhibitor drug. He died 18 months after diagnosis, 10 months after the cancer returned. The authors stated that the case matched other reported cases of this very rare cancer in young age, no asbestos exposure, and epithelioid type. The authors concluded that no known treatments currently target this genetic change and that more research is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (one patient)
• Who was studied: One 19-year-old male student with primary peritoneal mesothelioma. The authors are based in Sydney, Australia, and ethics approval came from the Sydney Local Health District Ethics Committee. Dates of diagnosis are not given.
• Exposure: No asbestos exposure was known. The tumor carried an EWSR1-ATF1 gene fusion.
• Main results:
  • The tumor was epithelioid mesothelioma that retained BAP1 staining. A fluorescence in situ hybridization test showed rearrangement at the EWSR1 gene, and next-generation sequencing confirmed an EWSR1-ATF1 fusion.
  • The peritoneal cancer index was 26 at diagnostic laparoscopy and 34 during surgery. The patient had cytoreductive peritonectomy with hyperthermic intraperitoneal chemotherapy using cisplatin and mitomycin.
  • Imaging before and after adjuvant platinum and pemetrexed chemotherapy showed no residual disease. Asymptomatic peritoneal recurrence was then found during stoma reversal, 2 months after chemotherapy.
  • Treatment with ipilimumab 1 mg/kg every 6 weeks and nivolumab 3 mg/kg every 2 weeks was followed by further peritoneal disease progression on imaging after 12 weeks.
  • Third-line crizotinib 250 mg twice daily did not produce a response. Less than 2 months later the patient was admitted with small bowel obstruction and mesenteric bleed.
  • The patient died 18 months from diagnosis, which was 10 months after recurrence.
• The authors' conclusion: The authors concluded that this case showed treatment resistance to standard chemotherapy, ipilimumab and nivolumab, and crizotinib, with limited survival. They stated that no known treatments currently target this driver mutation and that more research is required.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Malignant Mesothelioma, Asbestos Exposure.

Related studies

• EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity — J.K. Dermawan, D. Torrence, et al. (2022)
• A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions — P. Desmeules, P. Joubert, et al. (2017)
• RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14;22)(q32;q12) — I. Panagopoulos, J. Thorsen, et al. (2013)
• Malignant Mesothelioma With EWSR1-ATF1 Fusion in Two Adolescent Male Patients — H. Ren, S.R. Rassekh, et al. (2021)
• Generation of human embryonic stem cell models to exploit the EWSR1-CREB fusion promiscuity as a common pathway of transformation in human tumors — F. Vanoli, B. Meskauskaite, et al. (2021)
• The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review — C. Fisher (2014)

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