Malignant Mesothelioma With EWSR1-ATF1 Fusion in Two Adolescent Male Patients

Our plain-English summary of Malignant Mesothelioma With EWSR1-ATF1 Fusion in Two Adolescent Male Patients, by H. Ren, S.R. Rassekh, A. Lacson, et al (Pediatric and Developmental Pathology, 2021).

The study

• Authors: H. Ren, S.R. Rassekh, A. Lacson, C.H. Lee, B.C. Dickson, C.T. Chung, A.F. Lee
• Journal: Pediatric and Developmental Pathology
• Published: 2021;24(6):570-574
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a neoplasm of serosal surfaces, most commonly affecting the pleura. The peritoneum, pericardium, and tunica vaginalis are less frequently involved. Malignant mesothelioma with EWSR1-ATF1 fusion in young adults was recently reported in the literature. Here, we present two pediatric cases of EWSR1-ATF1 translocation-associated malignant mesothelioma in the peritoneum and pericardium respectively. Both cases lacked a known exposure history. Microscopy in both cases showed predominantly epithelioid morphology with ample eosinophilic cytoplasm, and immunohistochemistry was positive for pan-keratin, calretinin, and WT1. Both cases showed EWSR1-ATF1 gene rearrangement by RNA sequencing, which was instrumental in confirming the diagnosis of malignant mesothelioma and to exclude more common pediatric sarcomas, especially in the context of limited sampling.

In plain English

This case report described two 15-year-old male patients with malignant mesothelioma whose tumors carried a gene fusion called EWSR1-ATF1. Patient #1 had a mass in the small bowel mesentery and was diagnosed with malignant peritoneal mesothelioma. Patient #2 had a mass in the pericardium, the sac around the heart, and was diagnosed from core needle biopsies with primary pericardial mesothelioma. The article stated that both cases lacked a known exposure history. It did not describe asbestos or any other exposure for either patient. Under the microscope both tumors were mainly epithelioid, and stains for mesothelial markers, including calretinin and WT-1, were positive. In Patient #1, BAP1 protein was retained and markers of melanocytic differentiation were negative. RNA sequencing found the EWSR1-ATF1 fusion in both tumors, with different breakpoints in each. Patient #1's tumor partly resembled a type of sarcoma, and the authors stated that RNA sequencing was crucial for confirming the diagnosis. The authors concluded that these two patients are the youngest reported with this type of mesothelioma.

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 of two patients
• Who was studied: Two adolescent male patients, both 15 years old at diagnosis. Patient #1 had peritoneal mesothelioma presenting as a mesenteric mass. Patient #2 had pericardial mesothelioma. The article does not state where or when the patients were treated.
• Exposure: No known exposure history in either case. The article names no fiber type, product or job for these patients. The study focused on the EWSR1-ATF1 gene fusion in the tumors.
• Main results:
  • Patient #1: the tumor stained positive for mesothelial markers, and BAP1 protein was retained in the tumor cells.
  • Patient #1: markers for melanocytic differentiation were negative.
  • Patient #1: RNA sequencing identified an EWSR1-ATF1 fusion with breakpoints in exon 13 of EWSR1 and exon 5 of ATF1.
  • Patient #1: electron microscopy showed a poorly differentiated tumor with epithelioid features, including microvilli and desmosomes.
  • Patient #2: RNA sequencing identified an EWSR1-ATF1 fusion with breakpoints in exon 8 of EWSR1 and exon 4 of ATF1.
  • Patient #2: the findings supported a final diagnosis of primary pericardial mesothelioma.
  • The authors stated that RNA sequencing was crucial for confirming the diagnosis in Patient #1, whose tumor had areas resembling clear cell sarcoma.
• The authors' conclusion: The authors concluded that these two patients are the youngest reported with EWSR1-ATF1-associated mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Neoplasm, Serosal Surface, Pleura, Peritoneum, Pericardium, Tunica Vaginalis, Translocation.

Related studies

• 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)
• 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)
• 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)
• Malignant Peritoneal Mesothelioma in an Adolescent Male With BAP1 Deletion — S. Taylor, D. Carpentieri, et al. (2015)
• The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study — J. Ito, N. Asano, et al. (2016)

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