High Frequency and Unique Subtypes of Meningioma in Patients with BAP1 Tumor Predisposition Syndrome

Our plain-English summary of High Frequency and Unique Subtypes of Meningioma in Patients with BAP1 Tumor Predisposition Syndrome, by K.A. Ramsey, L. Byrne, O.B. Taylor, et al (medRxiv, 2025).

The study

• Authors: K.A. Ramsey, L. Byrne, O.B. Taylor, A. Soliman, E. Schreiner, I. Gray, A. Latham, R. Sheikh, S.S. Ahmadian, R.R. Lonser, J.D. Palmer, M.I. Carlo, C.M. Cebulla, M.H. Abdel-Rahman
• Journal: medRxiv
• Published: 2025
• Read it: PubMed · Publisher · Free full text

Abstract

Background: BAP1-tumor predisposition syndrome (BAP1-TPDS) is associated with four main cancers: uveal melanoma, cutaneous melanoma, malignant mesothelioma, and renal cell carcinoma. However, there are additional cancers found more rarely in BAP1-TPDS patients. The aim of this study was to investigate the association, clinical, and pathologic characteristics of meningioma in BAP1-TPDS.

Methods: We conducted a retrospective chart review of meningiomas in two independent cohorts of patients with germline BAP1 pathogenic or likely pathogenic (P/LP) variants at The Ohio State University Wexner Medical Center and at the Memorial Sloan Kettering Cancer Center from October 1st, 2010 date to April 21st, 2025. Additionally, we conducted a literature review of meningioma case studies for individuals with germline BAP1 (P/LP) variants.

Results: In a cohort of 237 subjects with BAP1-TPDS, we identified 6.8% (16/237) with history of meningiomas. The average age of diagnosis was 45.8 years (17-71). For patients with available pathology, 61.5% (8/13) of the tumors were grade II/III. Patients with available tumor tissue 83.3% (5/6) showed evidence of BAP1 biallelic inactivation. Family history of meningioma was reported in 18.8% (3/16) of patients. Three cases of meningioma were identified during meningioma surveillance imaging. Published cases were consistent with the early age of onset, high-grade tumors, and clinical phenotype of tumors.

Conclusions: This study provides additional evidence that high-grade brain and spinal meningiomas are part of the clinical spectrum of BAP1-TPDS. Craniospinal imaging surveillance in the BAP1-TPDS population should be considered starting around puberty, enabling early detection and management for individuals with BAP1-TPDS.

In plain English

This preprint, not yet peer reviewed, studied meningioma (a tumor of the coverings of the brain and spinal cord) in people who carry inherited harmful variants of the BAP1 gene. Those variants cause BAP1 tumor predisposition syndrome, which is linked to mesothelioma and other cancers. The authors reviewed medical records at Ohio State and Memorial Sloan Kettering, plus published case reports. Of 237 carriers, 16 (6.8%) had a meningioma. Their mean age at presentation was 45.1 years, and 75% were female. Of 13 tumors with pathology, 5 were rhabdoid and 1 was both rhabdoid and papillary. Of 10 tumors that were graded, 8 were high grade. Five of six re-examined tumors had lost BAP1. Three patients had a recurrence. Three tumors were found on screening scans in patients without symptoms. Two of the 16 patients had also had mesothelioma. The study did not look at asbestos exposure. The authors concluded that high-grade meningiomas are part of this syndrome and that brain and spine imaging should be considered from around puberty. They noted some lesions were diagnosed only by imaging.

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: Retrospective chart review of two hospital cohorts of carriers of germline BAP1 pathogenic or likely pathogenic variants, plus a review of published case reports
• Who was studied: 237 people with germline BAP1 pathogenic or likely pathogenic variants: 195 at The Ohio State University Wexner Medical Center (Columbus, OH) and 42 at Memorial Sloan Kettering Cancer Center (New York), with records from October 1, 2010 to April 21, 2025. 16 had meningioma. A separate literature review found 13 published patients.
• Exposure: Inherited (germline) loss-of-function BAP1 variants. No asbestos or fiber exposure was studied.
• Main results:
  • Meningioma frequency among BAP1 variant carriers was 6.7% (13/195) at Ohio State, 7.1% (3/42) at Memorial Sloan Kettering and 6.8% (16/237) combined
  • Mean age at presentation in the 16 patients was 45.1 years (median 46). The authors cite a mean of 66 years for the general population.
  • 75% of the 16 patients with meningioma were female and 25% were male
  • Among 13 pathology-confirmed meningiomas, 5/13 were rhabdoid, 4/13 atypical with unspecified subtype, 1/13 papillary, 1/13 both papillary and rhabdoid, and 1/13 transitional/mixed
  • Of 10 tumors with WHO grading, 2 were grade I, 4 were grade II and 4 were grade III (8/10 high grade)
  • Of 6 Ohio State tumors with tissue re-examined, 5 showed BAP1 loss and 1 kept BAP1 expression
  • Local recurrence occurred in 3 patients, 2 of them with rhabdoid tumors
  • Three tumors were found on surveillance imaging in patients without symptoms
  • 10 of the 16 patients with meningioma had another primary tumor, including mesothelioma in 2/16 and kidney cancer in 5/16
  • 13 of the 16 patients had a first- or second-degree relative with a BAP1-associated cancer (mesothelioma in 5/16). Only 3/16 had a relative with meningioma.
  • 4/16 cohort patients and 3/12 literature cases were diagnosed before age 30, the youngest at 17
  • The literature review found 13 published patients with germline BAP1 variants and pathology-confirmed meningioma. Of the 10 with histopathology reported, 6 were predominantly rhabdoid, 2 were papillary and 2 were both.
• The authors' conclusion: The authors concluded that high-grade brain and spinal meningiomas are part of BAP1 tumor predisposition syndrome. They said brain and spine imaging surveillance should be considered starting around puberty.
• Limitations the authors state:
  • The Ohio State cohort was enriched for uveal melanoma and for personal or family cancer histories typical of the syndrome, while Memorial Sloan Kettering included patients with diverse cancers
  • Follow-up information was missing for some patients, and only part of the cohort had standardized brain and spine screening
  • Some lesions were diagnosed only by imaging, without tissue confirmation

Topics

Medical terms in this study, explained in our Lexicon: BAP1 Tumor Predisposition Syndrome, BAP1, Mesothelioma, Carcinoma, Memorial Sloan Kettering, Pathology.

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• High frequency and unique subtypes of meningioma in patients with BAP1 tumor predisposition syndrome — K.A. Ramsey, L. Byrne, et al. (2026)
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