Coexistence of a novel STRN-ALK, NBEA-ALK double-fusion in an ovarian malignant mesothelioma patient: a case report and review

Our plain-English summary of Coexistence of a novel STRN-ALK, NBEA-ALK double-fusion in an ovarian malignant mesothelioma patient: a case report and review, by X. Wu, Q. Wang, X. Xu (Frontiers in Oncology, 2023).

The study

• Authors: X. Wu, Q. Wang, X. Xu
• Journal: Frontiers in Oncology
• Published: 2023;13:1156329
• Type of article: Case report
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Primary ovarian mesothelioma (POM) is a rare malignant tumor with poor prognosis. Although anaplastic lymphoma kinase gene (ALK) double-fusion partners have been found in various tumors, it is rarely reported in mesothelioma. In this article, we describe the coexistence of a novel STRN-ALK, neurobeachin (NBEA)-ALK double-fusion in a patient with primary ovarian mesothelioma. A 30-year-old woman was found to have pelvic masses for more than a year. Color Doppler ultrasound showed mixed mass in the left ovary and multiple solid masses in the right ovary. the patient underwent laparoscopic surgery, including total hysterectomy, bilateral salpingo-oopherectomy, pelvic lymph node and abdominal aortic lymph node resection, omentum resection and abdominal focus resection. Pathologic examination revealed bilateral ovarian malignant mesothelioma and no evidence of malignancy in the resected bilateral round/broad ligaments, bilateral parametrial tissues, vaginal stump, bilateral fallopian tubes, pelvic and paraaortic lymph nodes. Immunohistochemistry showed that it was positive for Calretinin, VIM, WT1, PAX8, mesothelin, CK5/6, PCK, CK7, MLH1, PMS2, MSH2, MSH6, weakly positive for BAP1, while being negative for Napsin A, P504S, CEA, D2-40, GATA3. The sequencing analysis identified STRN-ALK (intron3:intron19) and NBEA-ALK (intron1:intron16) double-ALK fusion. To the best of our knowledge, this is the first report that a novel NBEA-ALK and EML4-ALK coexist in one patient with POM. The patient has completed 6 cycles of continuous chemotherapy and is in stable condition. Whether ALK inhibitors can bring promising benefits to POM patients in the future deserves further study.

Copyright © 2023 Wu, Wang and Xu.

In plain English

This case report from Wuhan, China, described a 30-year-old woman admitted in June 2022 with a pelvic mass present for about a year. The article states she had no history of asbestos or radiation exposure. In July 2022 she had laparoscopic surgery removing the uterus, both ovaries and tubes, lymph nodes and omentum. Pathology showed malignant mesothelioma in both ovaries and no malignancy in the other tissues specifically listed, such as the fallopian tubes and lymph nodes. The diagnosis was primary ovarian mesothelioma. Tumor sequencing found two fusions involving the ALK gene: STRN-ALK (mutation abundance 27.74%) and NBEA-ALK (49.26%). She then received pemetrexed and nedaplatin chemotherapy every 3 weeks. A pelvic MRI on October 14, 2022 showed no recurrence. By the time of writing she had completed 6 cycles and was stable, with no obvious adverse symptoms; no ALK-targeted drug had been given. Follow-up was continuing. The authors concluded this was, to their knowledge, the first report of this double ALK fusion in primary ovarian mesothelioma, and that whether ALK inhibitors could benefit such patients deserves further study.

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 (single patient), with a discussion of previously published cases
• Who was studied: one 30-year-old woman with a pelvic mass present for about one year, admitted in June 2022 to Tongji Hospital, Wuhan, China
• Exposure: No asbestos exposure reported: the patient had no history of asbestos or radiation exposure. The study concerned gene changes (ALK fusions) in the tumor.
• Main results:
  • After surgery, pathology showed malignant mesothelioma in both ovaries. It found no evidence of malignancy in the specifically listed tissues: the round/broad ligaments, parametrial tissues, vaginal stump, fallopian tubes, and pelvic and paraaortic lymph nodes.
  • Immunohistochemistry of the tumor was positive for markers including Calretinin, VIM, WT1, CK5/6 and PCK, weakly positive for BAP1, and negative for CEA. The Ki67 index was 10%. The tumor was diagnosed as primary ovarian mesothelioma.
  • Next-generation sequencing of the tumor found a STRN-ALK fusion (intron 3 to intron 19) with mutation abundance 27.74% and an NBEA-ALK fusion (intron 1 to intron 16) with mutation abundance 49.26%.
  • The patient received pemetrexed (500 mg/m2) and nedaplatin (80 mg/m2) every 3 weeks.
  • A pelvic MRI on October 14, 2022 showed no recurrence of the tumor.
  • By the time of writing the patient had completed 6 cycles of chemotherapy. Her condition was stable, no obvious adverse symptoms had been observed, and follow-up was still in progress.
  • No tumor recurrence or metastasis had been found, so no targeted drug therapy was given.
• The authors' conclusion: The authors concluded that, to their knowledge, this was the first report of an NBEA-ALK and STRN-ALK double ALK fusion in a primary ovarian mesothelioma patient, and that whether ALK inhibitors can benefit such patients deserves further study.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Prognosis, Doppler Ultrasound, Bilateral, Omentum, Immunohistochemistry, Calretinin, Mesothelin.

Related studies

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• STRN-ALK Fusion in a Case of Malignant Peritoneal Mesothelioma: Mixed Response to Crizotinib, Mode of Resistance, and Brigatinib Sequential Therapy — V. Gerthofer, A. Scheiter, et al. (2021)
• A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review — C. Miyagawa, H. Takaya, et al. (2021)
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• Efficacy and safety of novel multiple-chain DAP-CAR-T cells targeting mesothelin in ovarian cancer and mesothelioma: a single-arm, open-label and first-in-human study — T. Xu, T. Tian, et al. (2024)
• Novel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer — D. Mauricio, J. Harold, et al. (2021)

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