Unusual Dual Brain Tumor Morphologies in an MEN1 Patient: A Case Report of Diagnostic Challenges and Methylation Insights

TL;DR

A rare case of a patient with MEN1 who developed both a pituitary adenoma and an ATRT tumor is reported, highlighting the diagnostic challenges and the use of molecular techniques for accurate identification.

Contribution

This is the first documented case of ATRT co-occurring with MEN1, expanding the understanding of tumor associations in this syndrome.

Findings

The patient had two distinct tumors in the pituitary gland: a pituitary adenoma and an atypical teratoid/rhabdoid tumor (ATRT).

Methylation profiling and next-generation sequencing were critical in confirming the ATRT diagnosis.

The case highlights the importance of advanced molecular techniques in diagnosing rare tumor co-occurrences in MEN1 patients.

Abstract

Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant disorder commonly associated with tumor development in the parathyroid glands, pancreas, and pituitary gland. While pituitary adenomas are frequently observed in MEN1 patients, the presence of additional tumors within the pituitary gland is unusual. Moreover, the co-occurrence of a pituitary adenoma with an atypical teratoid/rhabdoid tumor (ATRT) has not been previously documented. ATRT is a rare, aggressive neoplasm predominantly affecting young children and is typically associated with inactivating mutations in the SMARCB1 or SMARCA4 tumor suppressor genes. These mutations result in uncontrolled cellular proliferation, which underlies the malignancy’s rapid progression. In adults, ATRT is exceedingly rare, making this case particularly noteworthy for its uniqueness in both tumor type and patient demographics. ATRTs are now classified into three molecular subgroups—MYC, SHH, and TYR—each with distinct epigenetic and clinical features, further refining diagnostic and prognostic assessments. In this case report, we describe a case of a female patient with MEN1 who experienced several recurrences of pituitary adenoma, ultimately necessitating surgical resection. Detailed pathological evaluation of the resected tissue revealed two distinct neoplasms within the pituitary gland: one typical of a pituitary adenoma, and the other confirmed as ATRT. The diagnosis of ATRT was established through extensive workup including immunohistochemical analysis, next-generation sequencing and methylation profiling, which served as essential tools in distinguishing ATRT from other potential differential diagnoses. This case illustrates the complex diagnostic journey and challenges encountered in identifying ATRT in the context of MEN1, underscoring the importance of using advanced molecular and immunohistochemical techniques in atypical presentations. Furthermore, it expands the understanding of potential tumor associations within MEN1, providing insight for pathologists and clinicians into the rare possibility of concurrent tumors in addition to pituitary adenoma in MEN1 patients. Raising awareness of such co-occurrences could prompt earlier diagnostic considerations by refining the differential diagnosis in patients with MEN1 presenting with unusual tumor types.

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