Multiple primary malignancies associated with a germline SMARCB1 pathogenic variant.

Area of Science:

• Oncology
• Genetics
• Neurology

Background:

• Schwannomatosis is a rare genetic disorder characterized by the development of multiple schwannomas.
• Neurofibromatosis Type-1 (NF1) is a distinct genetic condition, though some overlapping features can occur.
• SMARCB1 gene mutations are causative in a subset of schwannomatosis cases.

Observation:

• A 51-year-old female with a history of NF1 and a confirmed SMARCB1 pathogenic variant presented with pelvic pain and an abdominal mass.
• Imaging revealed multiple masses, including a large pelvic mass, mesenteric adenopathy, and a lung apex mass.
• Biopsies identified neurofibroma with atypia, uterine leiomyoma, and follicular lymphoma.

Findings:

• The patient was diagnosed with schwannomatosis due to the SMARCB1 variant, despite lacking typical NF1 stigmata.
• Post-chemotherapy for lymphoma, surgical resection of the pelvic mass revealed a malignant peripheral nerve sheath tumor.
• An incidental small bowel neuroendocrine carcinoma was also excised, totaling three synchronous primary malignancies.

Implications:

• This case demonstrates a rare instance of multiple synchronous primary malignancies in a patient with schwannomatosis.
• It underscores the importance of genetic testing (SMARCB1) for accurate schwannomatosis diagnosis.
• The findings suggest a potential link between schwannomatosis, SMARCB1 variants, and an increased risk of diverse cancers.