A case of ovarian mesothelioma with VHL mutation diagnosed by immunohistochemistry and literature review

Our plain-English summary of A case of ovarian mesothelioma with VHL mutation diagnosed by immunohistochemistry and literature review, by Y. Yao, H. Yan, J. Xiong, et al (Frontiers in Oncology, 2024).

The study

• Authors: Y. Yao, H. Yan, J. Xiong, Y. Duan
• Journal: Frontiers in Oncology
• Published: 2024;14:1471978
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

The malignant mesothelioma mainly develops in the pleura and peritoneum, while primary ovarian mesothelioma is very rare. Here, we report the first case of primary ovarian mesothelioma (clear cell variant) with VHL mutations in the world based on the results of histomorphology, immunohistochemistry, and genetic testing. This is an extremely rare type of tumor that has not been reported so far. Through the literature search, we reviewed primary ovarian mesothelioma, focusing on its differential diagnosis and molecular genetics. The purpose of this paper is to deepen the flexible selection and application of immunohistochemical markers in mesothelioma, so as to reduce missed diagnosis and misdiagnosis.

Copyright © 2024 Yao, Yan, Xiong and Duan.

In plain English

This article is a case report combined with a review of published cases. The authors described a 40-year-old woman, treated at hospitals in China, whose right ovarian mass was found on a CT scan in April 2022. She had no history of asbestos exposure. After staging surgery, pathology showed a 2 cm tumor in the right ovary and a 0.5 cm nodule in the omentum. Three hospitals tested the tissue with different immunohistochemical stains and reached different diagnoses: ovarian clear cell carcinoma, likely mesothelioma, and clear cell papillary cystadenoma related to VHL syndrome. Gene testing found two mutations in the VHL gene. A multidisciplinary team made the final diagnosis of ovarian mesothelioma, clear cell type, with VHL gene mutation. She received six cycles of pemetrexed and cisplatin, and no recurrence was found on CT more than 20 months after surgery. The authors found 26 earlier reported ovarian mesothelioma cases, and seven mesotheliomas with VHL mutations, none of them ovarian. They called this the first such case. They concluded that diagnosis should combine tissue appearance, immunohistochemistry and genetic testing.

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 one patient with a literature review of previously reported primary ovarian mesothelioma cases and mesotheliomas with VHL mutations
• Who was studied: One 40-year-old woman with a right ovarian lesion found on CT in early April 2022, seen at a local hospital, the Affiliated Hospital of Tongji Medical College (Wuhan), and a Shanghai hospital
• Exposure: No asbestos exposure: the authors report the patient had no history of asbestos exposure. No fiber type was studied.
• Main results:
  • The patient's serum CA125 was slightly elevated at 62 U/ml before surgery.
  • After surgery, pathology found a right ovarian tumor 2 cm in diameter and a 0.5 cm nodule in the greater omentum.
  • The local hospital diagnosed ovarian clear cell carcinoma, based on the clear cell appearance, positive PAX-8 and negative WT-1.
  • At the second hospital, re-staining for WT-1 was positive and new stains (CK5/6, HBME-1, weak BAP1, negative NapsinA) indicated a high possibility of mesothelioma.
  • Targeted gene sequencing found two mutations in the first exon of the VHL gene: p.N78S (c.233A>G, mutant abundance 29.36%) and p.S65L (c.194C>T, 27.38%).
  • The Shanghai hospital changed the diagnosis to clear cell papillary cystadenoma of the ovary related to VHL syndrome.
  • A multidisciplinary team made the final diagnosis of ovarian mesothelioma (clear cell type) with VHL gene mutation.
  • The patient received six cycles of pemetrexed 500 mg/m2 with cisplatin 70 to 75 mg/m2. Postoperative survival exceeded 20 months, with no recurrence, metastasis or ascites found on CT follow-up.
  • In the literature review, 26 previously reported primary ovarian mesothelioma cases had ages at onset of 16 to 74 years, with a median of 50.5 years.
  • Among the 26 previously reported ovarian mesothelioma cases, Ber-EP4 was positive in 11 of 17 tested (65%).
  • The authors found seven previously reported mesotheliomas with VHL mutations (six peritoneal, one pleural) and no ovarian mesothelioma with VHL mutation.
• The authors' conclusion: The authors concluded that primary ovarian mesothelioma and clear cell mesothelioma with VHL mutations are both extremely rare. They concluded that diagnosis needs to combine histomorphology, immunohistochemistry and genetic testing, and that the immunohistochemical marker panel should be expanded because the disease is easily confused with ovarian clear cell carcinoma.
• Limitations the authors state:
  • The authors note that the omental lesion may reflect seeding from a primary ovarian tumor or may have originated in the peritoneum; they favor the ovarian origin.
  • Only 1 of the 26 previously reported ovarian mesothelioma cases had PAX-8 staining, limiting comparison for this patient's positive PAX-8 result.
  • The authors state that further studies are needed to determine whether VHL genotype is related to the clear cell appearance.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Immunohistochemistry, Pleura, Peritoneum, Differential Diagnosis, Misdiagnosis.

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