Genetic and Immunohistochemical Profiling of Malignant Mesothelioma With Brain Metastasis: A Report of Two Cases

Our plain-English summary of Genetic and Immunohistochemical Profiling of Malignant Mesothelioma With Brain Metastasis: A Report of Two Cases, by P.M. Harary, Y.S. Hori, R. Jain, et al (Cancer Reports, 2026).

The study

• Authors: P.M. Harary, Y.S. Hori, R. Jain, A.H. Kattaa, M.H. Gephart, M.F. Gensheimer, S.G. Soltys, D.J. Park, S.D. Chang
• Journal: Cancer Reports
• Published: 2026;9(5):e70571
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Brain metastasis (BM) occurs in < 3% of malignant mesothelioma (MM) cases and is associated with an aggressive disease course. While genomic profiling has provided insight into molecular alterations in MM, the characteristics of MM with brain involvement remain unexplored. Data are particularly limited for MM of pericardial origin, an exceedingly rare tumor which comprises < 1% of mesotheliomas.

Cases: We describe the clinical course and genetic profiles of two patients with BM from MM, both of whom exhibited atypical presentations, including neurological symptoms, diagnosis at extremes of age for this condition, and absence of prior asbestos exposure. In Case 1, a 20-25-year-old male with pericardial MM presented for left arm shaking, with brain MRI at this time revealing 14 total lesions, 85.7% of which had vasogenic edema. He underwent whole-brain radiotherapy (WBRT), passing away 21.25 months following initial diagnosis. In Case 2, an 85-90-year-old male reported expressive aphasia and was found to have a large hemorrhagic frontotemporal lesion. He was subsequently diagnosed with pleural MM and received stereotactic radiosurgery (SRS) for management of BM, with a favorable treatment response on follow-up imaging. He succumbed to systemic progression 6 months after diagnosis of BM. Next-generation sequencing identified a missense mutation in RAD51C in Case 1, and NF2 splice-site and TP53 frameshift mutations in Case 2.

Conclusion: To our knowledge, this represents the first reported genetic profiling of MM with BM. The TP53 frameshift mutation is unusual for MM, and its potential association with rapid disease progression warrants further investigation. Given the aggressive nature of MM, SRS may be preferable to WBRT due to its shorter treatment time and ease of combination with systemic regimens.

© 2026 The Author(s). Cancer Reports published by Wiley Periodicals LLC.

In plain English

This case report, by researchers at Stanford University, described two men whose malignant mesothelioma had spread to the brain, with tumor gene testing and tissue staining. Neither man had a reported history of asbestos exposure. Case 1, aged 20–25, had mesothelioma of the pericardium (the sac around the heart). Brain imaging showed 14 lesions, 85.7% with surrounding swelling (edema). He received whole-brain radiotherapy (30 Gy in 10 fractions) and died 21.25 months after his initial diagnosis. Testing found a RAD51C variant that the authors described as of uncertain significance. Case 2, aged 85–90, first complained of difficulty speaking (expressive aphasia). A bleeding brain lesion was found, and pleural mesothelioma was then diagnosed. He received targeted radiation (stereotactic radiosurgery) to two brain lesions, and the first treated lesion shrank in volume by 16%. He died 6 months after the brain spread was diagnosed. His tumor had NF2 and TP53 mutations. The authors concluded this was the first reported genetic profiling of mesothelioma with brain metastasis and that the TP53 mutation warrants further investigation.

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 (retrospective, with tumor genetic sequencing and immunohistochemistry)
• Who was studied: Two male patients with malignant mesothelioma and brain metastasis: one aged 20–25 with pericardial mesothelioma and one aged 85–90 with pleural mesothelioma. The cases were reported by authors at Stanford University, but the article does not explicitly state where the patients were treated. Dates of treatment are not given.
• Exposure: Neither patient had a reported history of asbestos exposure, occupational or personal. No fiber type is discussed for these patients.
• Main results:
  • Case 1 (pericardial mesothelioma): brain imaging showed 14 lesions, 85.7% of which had vasogenic edema
  • Case 1 was treated with whole-brain radiotherapy, 30 Gy in 10 fractions
  • Case 1 died 21.25 months after his initial diagnosis of pericardial mesothelioma
  • Case 1 genetic testing found a RAD51C alteration (p.F164L), which the authors said is considered a variant of uncertain significance
  • Case 2's chief complaint was expressive aphasia, and mesothelioma was diagnosed afterwards. Biopsy confirmed pleural mesothelioma in the right lower lung.
  • Case 2 genetic testing found an NF2 splice-site mutation (variant allele frequency 23%) and a TP53 frameshift mutation (variant allele frequency 27%)
  • Case 2: after stereotactic radiosurgery, follow-up showed a 16% volume reduction in the treated brain lesion, but two new brain metastases appeared
  • Case 2 entered hospice care and died 6 months after diagnosis of brain metastasis
• The authors' conclusion: The authors concluded that this is the first report of genetic profiling of mesothelioma with brain metastasis. They said the TP53 frameshift mutation warrants further investigation for a possible link with increased metastatic spread. They added that early and aggressive treatment may be warranted for mesothelioma that has spread inside the skull.
• Limitations the authors state:
  • The genetic analysis relied on variant allele frequency; the authors said copy number variant analysis would give stronger evidence of loss of TP53 function
  • The benefit of whole-brain radiotherapy in Case 1 was hard to judge because follow-up was short
  • There was insufficient evidence to say whether genetic background or the primary site drove brain spread in Case 1

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Metastasis, Pericardial, Asbestos Exposure, Next-Generation Sequencing (NGS), Disease Progression.

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