Multiple primary malignancies associated with a germline SMARCB1 pathogenic variant

• Published in: Familial cancer Vol. 18; no. 4; pp. 445 - 449
• Main Authors: Eelloo, Judith A., Smith, Miriam J., Bowers, Naomi L., Ealing, John, Hulse, Paul, Wylie, James P., Shenjere, Patrick, Clarke, Noel W., Soh, Calvin, Whitehouse, Richard W., Jones, Mark, Duff, Christopher, Freemont, Anthony, Gareth Evans, D.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2019; Springer Nature B.V
• Subjects: Anorexia; Biomedical and Life Sciences; Biomedicine; Biopsy; Cancer Research; Chemotherapy; Diagnosis; Epidemiology; Female; Fibroids; Genetic analysis; Genetic disorders; Hemangioma - genetics; Hemangioma - therapy; Horner Syndrome - diagnostic imaging; Human Genetics; Humans; Low back pain; Lymphoma; Middle Aged; Neoplasms, Multiple Primary - complications; Neoplasms, Multiple Primary - genetics; Neoplasms, Multiple Primary - pathology; Neoplasms, Multiple Primary - therapy; Neurilemmoma - complications; Neurilemmoma - genetics; Neurilemmoma - pathology; Neurilemmoma - therapy; Neuroendocrine tumors; Neurofibromatoses - complications; Neurofibromatoses - genetics; Neurofibromatoses - therapy; Neurofibromatosis; Neurofibrosarcoma - genetics; Neurofibrosarcoma - pathology; Neurofibrosarcoma - therapy; Neurological disorders; Original Article; Pain; Pelvis; Peripheral nerves; Positron emission tomography; Retroperitoneal Neoplasms - genetics; Retroperitoneal Neoplasms - therapy; Schwann cells; Skin Neoplasms - complications; Skin Neoplasms - genetics; Skin Neoplasms - therapy; Small intestine; SMARCB1 Protein - genetics; Surgery; Tomography; Torticollis; Tumors; Uterus; Vomiting; Follicular lymphoma; Schwannomatosis; Neurofibromatosis type 1; Malignancy; Neurofibromatosis type 2; MPNST; SMARCB1
• ISSN: 1389-9600; 1573-7292
• DOI: 10.1007/s10689-019-00138-4

A 51-year old presented with a 6-month history of increasing pelvic/lower back pain with nocturnal waking and episodes of anorexia and vomiting. Examination revealed right torticollis and Horner’s syndrome, and a large abdominal mass arising from the pelvis. Magnetic resonance and positron emission tomography imaging revealed (A) a 14 cm heterogeneous enhancing mass, abutting the left kidney with standardised uptake value max = 2.9, (B) a large heterogeneous enhancing pelvic mass (C) mesenteric adenopathy standardised uptake value max = 10.3 and (D) 6 cm right lung apex mass standardised uptake value max = 4.3. Computerised tomography-guided biopsy of lesion A was reported as neurofibroma with occasional atypia, lesion B a benign uterine leiomyoma and lesion C follicular lymphoma world health organisation Grade 2. Although she had been given the diagnosis of Neurofibromatosis Type-1 (NF1) 25-years previously following removal of an intradural extramedullary schwannoma she had no cutaneous stigmata of NF1. Genetic analysis of blood lymphocyte DNA identified a pathogenic variant in SMARCB1 confirming a diagnosis of schwannomatosis. Following 6-months chemotherapy for lymphoma, surgery was performed to remove lesion A. Histology revealed a malignant peripheral nerve sheath tumour with areas of low and high-grade change. An incidental, well-differentiated small bowel neuroendocrine carcinoma was also excised. Close surveillance continues with no recurrence after 6 years. This case study describes a novel finding of three separate synchronous primary malignancies in a patient with schwannomatosis and a proven SMARCB1 pathogenic variant.