Giant Pediatric Rhabdoid Meningioma Associated with a Germline BAP1 Pathogenic Variation: A Rare Clinical Case

Our plain-English summary of Giant Pediatric Rhabdoid Meningioma Associated with a Germline BAP1 Pathogenic Variation: A Rare Clinical Case, by A.C. Ravanpay, A. Barkley, G.A. White-Dzuro, et al (World Neurosurgery, 2018).

The study

• Authors: A.C. Ravanpay, A. Barkley, G.A. White-Dzuro, P.J. Cimino, L.F. Gonzalez-Cuyar, C. Lockwood, L.M. Halasz, F.M. Hisama, M. Ferreira
• Journal: World Neurosurgery
• Published: 2018;119:402-415
• Type of article: Case report
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Rhabdoid meningiomas are rare World Health Organization grade 3 tumors that tend to follow an aggressive course, with an increased likelihood for local recurrence, remote metastasis, and cerebrospinal fluid dissemination. Genetic testing has found certain genes associated with reduced time to tumor recurrence. BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene that is associated with multiple tumors, including rhabdoid meningiomas.

Case Description: We present a case of a pediatric patient who presented with a rhabdoid meningioma occurring in the right tentorium and invading multiple venous structures, including the right jugular vein. The patient underwent 5 separate operations for management of this tumor. The first surgery was an intracranial tumor debulking with reconstruction of venous structures. Postoperatively, the patient was unable to have the ventricular catheter removed and underwent placement of a ventriculoperitoneal shunt. Significant recurrence of the intracranial portion of tumor was found during preoperative imaging for her second stage procedure. She underwent a second craniotomy for resection of the tumor. Her postoperative magnetic resonance imaging showed significant residual tumor and the patient therefore underwent a third craniotomy for total tumor resection, which involved reconstruction of the superior sagittal sinus. She did well after this surgery, with no new neurologic deficits. Her final operation involved resection of the residual tumor in the neck and chest by both otolaryngology and cardiothoracic surgery. This surgery involved opening the jugular vein and resecting residual tumor from the intima. Pathologic results from all surgeries were consistent with rhabdoid meningioma; however, the tissue from the biopsy and first craniotomy lacked the high-grade features that were found on subsequent resections. Genetic analysis found loss of both BAP1 tumor suppressor genes. Peripheral blood testing showed that this patient was a germline carrier of a pathogenic BAP1 variant.

Discussion: Pediatric rhabdoid meningiomas represent a rare disease and are found on recurrent tumors in conjunction with lower-grade meningioma disease. Our patient presented with what was initially believed to be a low-grade meningioma with rhabdoid features, which then transformed into a World Health Organization grade III rhabdoid meningioma on recurrence. This tumor was discovered to have a biallelic loss of BAP-1 mutation and the patient was found to have a germline mutation in 1 of her BAP-1 alleles. Germline mutations in BAP-1 are associated with a cancer syndrome that involves uveal and cutaneous melanoma, malignant mesothelioma, atypical Spitz tumors, and clear-cell renal cell carcinoma. Patients with this mutation are encouraged to undergo annual eye examinations starting at the age of 11 years. The BAP-1 tumor predisposition syndrome is most commonly an inherited mutation associated with incomplete penetrance and variation with nonoverlapping tumor types.

Conclusions: Rhabdoid meningiomas are unlikely to be found in children and have a high rate of local recurrence. Gross total resection has to be balanced with risk of postoperative deficit. Genetic testing of this rare entity should be performed to identify any hereditary germline mutations.

Published by Elsevier Inc.

In plain English

This was a case report of a 12-year-old girl treated in Seattle for a giant rhabdoid meningioma, a rare tumor of the brain's lining. It grew from the right tentorium into several veins and down the jugular vein to the superior vena cava. She had five operations: an initial tumor removal, a shunt to drain fluid from the brain, two repeat skull operations, and a combined neck and chest operation. These were followed by proton beam radiation. The first tissue showed low tumor activity and could not be given a definite grade. Later samples showed WHO grade III features. Tumor sequencing found both copies of the BAP1 gene inactivated. Blood testing showed she was a germline carrier of a harmful (pathogenic) BAP1 variant. Neither parent was tested. In January 2018 she was doing well, with no signs of recurrence on imaging. Mesothelioma was mentioned only as part of a BAP1 cancer syndrome described in other studies. Asbestos exposure was not discussed. The authors concluded that genetic testing of this rare tumor should be done to identify hereditary germline mutations.

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)
• Who was studied: One 12-year-old girl brought to Harborview Medical Center and transferred to Seattle Children's Hospital (Seattle, Washington, USA). She was treated from December 2014, with follow-up to January 2018.
• Exposure: No asbestos or other environmental exposure is reported. The article concerns a germline pathogenic BAP1 variant found in the patient.
• Main results:
  • The initial intracranial specimen showed a meningioma with rhabdoid features. It had low mitotic activity (up to one mitotic figure in ten consecutive high-power fields).
  • The initial specimen also had a low Ki-67 proliferative index of approximately 3-4%. A definitive WHO grade was difficult to assign.
  • Later excisions showed definitive WHO grade III features. The first tentorial excision had up to seven mitotic figures per ten high-power fields.
  • The second tentorial excision had up to nine mitotic figures per ten high-power fields.
  • In the neck mass excision, all 17 lymph nodes were negative for meningioma.
  • After the fourth operation, gross total resection of the intracranial portion of the tumor was achieved.
  • Tumor sequencing showed both copies of BAP1 inactivated. One copy had a variant causing a premature stop (p.Q392*), and the other allele was deleted (loss of heterozygosity on the short arm of chromosome 3).
  • Blood testing found the same p.Q392* variant, showing the patient is a germline carrier of a pathogenic BAP1 variant.
  • The patient received six weeks of proton beam therapy to 59.4 Cobalt Gray Equivalent.
  • At the January 2018 visit she was doing well, with no radiographic signs of recurrence.
  • Neither parent was tested. The mother's testing was denied by insurance, and the father was not available.
• The authors' conclusion: The authors concluded that rhabdoid meningiomas are unlikely in children and have a high rate of local recurrence, and that gross total resection must be balanced against the risk of post-operative deficit. They also concluded that genetic testing of this rare tumor should be done to identify hereditary germline mutations. They suggested that earlier surveillance screening for people with BAP1 tumor predisposition syndrome may be warranted.

Topics

Medical terms in this study, explained in our Lexicon: Rhabdoid, BAP1, Metastasis, Tumor Suppressor Gene, Biopsy, Germline Mutation, Malignant Mesothelioma, Carcinoma.

Related studies

• Germline BAP1 mutations induce a Warburg effect — A. Bononi, H. Yang, et al. (2017)
• SMARCB1/INI1/BAF47- deficient pleural malignant mesothelioma with rhabdoid features — N. Kimura, M. Hasegawa, et al. (2018)
• BAP1 gene mutations in Egyptian patients with advanced sporadic malignant pleural mesothelioma (MPM): relation with clinical outcomes and survival — A.A. Bahnasy, R.S. El-Din, et al. (2018)
• Tumours associated with BAP1 mutations — R. Murali, T. Wiesner, et al. (2013)
• Clinical Implications of Real-time Integrative Sequencing in Management of Patients With Suspected Germline BAP1 Mutations — S. Sengupta, A.C. Weyand, et al. (2019)
• Medullary thyroid cancer, leukemia, mesothelioma and meningioma associated with germline APC and RASAL1 variants: a new syndrome? — A. Angelousi, N. Settas, et al. (2017)

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