2021 NPB-15

This case was originally published in 2021. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.

A 47-year-old woman with history of a presumed clinoidal schwannoma diagnosed on imaging and treated with stereotactic radiosurgery in 2016 presented for routine follow-up imaging. On MR imaging, the lesion recurred and grew in size. The patient underwent a craniotomy and tumor resection. In addition to the immunostains shown in the images, tumor cells showed retained INI1 expression, focal immunoreactivity for progesterone receptor, and no staining for S100 or Melan-A.

Tissue Site
Brain, right clinoid process

The whole slide image provided is an H&E-stained image of the brain from the right clinoidal resection specimen.

T1-weighted MRI shows a dural-based, heterogenous, well-circumscribed lesion in the region of the clinoid process (Image A). H&E-stained sections show a tumor composed of rhabdoid cells with eccentric nuclei, dense eosinophilic cytoplasm, and distinct cell borders (Image B, Image C, and Image D). IHC stains for S100 and Melan-A are negative (not shown). Tumor cells are immunoreactive for EMA (Image E), PR (not shown), and vimentin (Image F), which highlights paranuclear globular/fibrillary inclusions. INI1 immunoreactivity is retained (not shown). The Ki-67 proliferation index for the tumor is high (Image G). This entity is best categorized as a rhabdoid meningioma.

Rhabdoid meningioma is a rare variant. On imaging, these tumors are dural-based with heterogenous enhancement and can either be well-circumscribed or show invasion of brain parenchyma. They can be supra- or infratentorial and can rarely occur in the spinal cord. Histologically, the tumor is predominantly composed of rhabdoid cells with eccentric nuclei, dense eosinophilic cytoplasm, and distinct cell borders. The paranuclear inclusions represent whorled bundles of intermediate filaments, most commonly vimentin. Tumor cells are also immunoreactive for EMA, variably immunoreactive for PR, and have intact INI1 staining. They frequently have high mitotic rates, necrosis, and anaplasia, sometimes having a papillary architecture. Meningiomas with these high-grade features have an aggressive clinical course, including an increased rate of recurrence and high mortality, and are thus categorized as World Health Organization (WHO) grade 3. However, rhabdoid meningiomas without other high-grade features follow a somewhat less aggressive course and are graded in the same manner as other meningiomas. For example, meningiomas with only focal rhabdoid features behave even less aggressively and should be classified as ‘meningioma with focal rhabdoid features, WHO grade 1’.

Recently, both germline and somatic alterations in the BRCA-1 associated protein (BAP1) tumor suppressor gene on chromosome 3p21 have been found in rhabdoid meningiomas. BAP1 encodes BAP1 protein which functions as a tumor suppressor deubiquitinating enzyme. Germline mutations in BAP1 cause a tumor predisposition syndrome that confers increased risk of developing uveal and cutaneous melanoma, mesothelioma, clear cell renal cell carcinoma, cholangiocarcinoma, papillary thyroid carcinoma, basal cell carcinoma, and other neoplasms. In rhabdoid meningiomas, mutations in BAP1 cause loss of protein expression, which can be assessed by immunostaining. In the current case, next-generation sequencing confirmed the presence of a BAP1 mutation. In the spectrum of meningiomas with rhabdoid features, correlation has been found between loss of BAP1 and greater extent of rhabdoid features, higher mitotic rate, and higher WHO grade. BAP1-deficient rhabdoid meningiomas have also been found to have mutations in other genes including NF2, FBXW7, and PBRM1, the latter of which is seen in papillary meningiomas and in some rhabdoid meningiomas with papillary architecture. BAP1-deficient tumors also have a worse prognosis when compared to BAP1-retained rhabdoid meningiomas, particularly regarding recurrence and mortality rates.

The differential diagnosis of rhabdoid meningioma includes atypical teratoid/rhabdoid tumor (AT/RT), gemistocytic astrocytoma or epithelioid glioblastoma, melanoma, and metastatic malignant rhabdoid tumor. The current case showed no INI1 loss and did not have SMARCB1 or SMARCA4 alterations on next-generation sequencing, findings which would be expected in AT/RTs and malignant rhabdoid tumors. Gemistocytic astrocytomas and epithelioid glioblastomas have cells with eccentric nuclei and dense eosinophilic cytoplasm, but the tumor cells are immunoreactive for GFAP and negative for EMA and PR. Melanomas can have rhabdoid morphology and are immunoreactive for SOX10 and Melan-A and negative for EMA and PR.

• Rhabdoid meningioma is a rare variant with poor prognosis and is classified as WHO grade 3 if associated with other malignant features. It is primarily composed of rhabdoid cells with eccentric nuclei, dense eosinophilic cytoplasm, and distinct cell borders.
• BAP1 mutations causing BAP1 loss have been identified in high-grade rhabdoid meningiomas. These BAP1-deficient meningiomas are more likely to have high-grade features and behave more aggressively with increased rates of recurrence and mortality.
• BAP1 germline variants are seen in a tumor predisposition syndrome which confers increased risk of developing uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, rhabdoid meningioma, and other neoplasms.

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