Clinical management of desmoplastic myxoid tumor, SMARCB1-mutant

SMARCB1 (SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily B, member 1), also known as INI1, is a tumor suppressor gene that encodes a core subunit of the SWI/SNF chromatin-remodeling complex, which functions as an essential epigenetic regulator during development.1 Biallelic inactivation of SMARCB1 has been associated with the growth of benign and malignant tumors in children and adults.1 Intracranial SMARCB1-deficient tumors primarily arise in children and include malignant atypical teratoid/rhabdoid tumor (ATRT), benign cribriform neuroepithelial tumor, and poorly differentiated chordoma.1 The recent description of adult intracranial SMARCB1-deficient tumors with unique histology and indeterminate prognostic data2–4 would suggest these tumors to be part of a developmental spectrum of which ATRT is the most malignant. Herein, we describe the clinical management of one such adult intracranial SMARCB1-deficient tumor that has yet to be described by the World Health Organization Classification of Central Nervous System Tumors, desmoplastic myxoid tumor (DMT), SMARCB1-mutant. Available demographic data (Table 1) from all prior cases indicate no gender differences (F: 6; M: 4) and an average age of onset of 36.6 years (range 15-61 years old). Of note, all prior cases have been in the pineal region. The surgical management of DMT, SMARCB1-mutant cases has included subtotal resection (4/10) or gross total resection (6/10). Only 2 cases were initially treated with an endoscopic third ventriculostomy due to obstructive hydrocephalus. Adjuvant chemotherapy (1/10) or radiotherapy (4/10) have been provided in a minority of cases. Reports to date have not defined the coordinated use of radiotherapy with surgery. Our previously reported case5 has been the only case with cerebrospinal fluid (CSF) dissemination, which presented a therapeutic challenge. We chose to treat this patient with a subtotal resection followed by curative intent craniospinal irradiation with a radiation boost to the primary tumor region. In total, 36 Gy was delivered to the neuraxis in 20 fractions and an additional 19.8 Gy was given to the primary tumor volume in 11 fractions. Our patient remains clinically well with a significant reduction in tumor size with no signs of intracranial CSF dissemination or spinal drop metastases on MRI following surgical resection and radiotherapy. We were able to obtain more recent follow-up data on one additional previously reported case,4 who remains disease-free at 12-month post-GTR and radiotherapy. With a median follow-up of 29.5 months (0 months-7 years), 30% (3/10) of tumors have resulted in death, while the remainder are alive with stable disease or no signs of recurrence.