A Pediatric Intra-Axial Malignant SMARCB1-Deficient Desmoplastic Tumor Arising in Meningioangiomatosis

Abstract

SMARCB1 inactivation is a well-established trigger event in atypical teratoid/rhabdoid tumor. Recently, a role for SMARCB1 inactivation has emerged as a mechanism of clonal evolution in other tumor types, including rare brain tumors. We describe an unusual malignant intra-axial SMARCB1-deficient spindle cell desmoplastic neoplasm, occurring in a 6-year-old child with meningioangiomatosis and a long history of seizures. Striking features of the tumor were a storiform pattern and strong CD34 expression. Undifferentiated round cell areas with isolated rhabdoid cells showing high mitotic index and focal necrosis with INI1 expression loss were present. The meningioangiomatosis component showed few chromosomal imbalances, including chromosomal 22 monosomy (where SMARCB1 maps) and gain at 6q14.3. In addition to these abnormalities, the spindle cell desmoplastic neoplasm and its dedifferentiated SMARCB1-deficient component shared several other aberrations, including homozygous deletion at 9p21.3, losses at 1p, 3p, 3q, 10p, and 13q, gains and losses at 5p and 11p. In line with INI1 loss, the dedifferentiated component showed remarkably decreased levels of SMARCB1 transcript. The residual SMARCB1 allele was wildtype. Our findings suggest progression from the meningioangiomatosis to the malignant desmoplastic neoplasm through the occurrence of complex chromosomal abnormalities, and point to functional silencing of SMARCB1 in the dedifferentiation component.

An update on the CNS manifestations of neurofibromatosis type 2

“…Molecular analyses of the meningioangiomatosis and sarcoma in this case showed that the meningioangiomatosis exhibited multiple recurrent chromosomal alterations including monosomy 22, 6q gain, and 5q loss. Interestingly, monosomy 22 and 6q gain were also observed in the sarcomatous lesion, in addition to numerous other chromosomal alterations, suggesting that the tumor may have arisen from the underlying meningioangiomatosis through acquisition of additional chromosomal alterations and silencing of SMARCB1 expression [113].…”

Meningioangiomatosis Combined with Calcifying Pseudoneoplasms of Neuraxis

“…Only six cases occurred in the occipital lobe (9.68%). Intracranial lesions coexisting with MA have been reported in 17 patients [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], and meningioma was the most common combined tumor (11/17, 64.71%) [ 9 , 10 , 13 , 14 , 15 ]. Notably, the perivascular spread of meningioma-associated-type MA should not be interpreted as evidence of a grade II meningioma.…”

“…For instance, Lucila Domecq Laplace et al [ 27 ] reported three cases of CAPNON located in the posterior fossa with perilesional edema, and the vast majority were cured after total resection. However patients may experience recurrence because of incomplete evacuation [ 28 ], neoplastic malignancy [ 12 ], or coexisting with other malignant tumors [ 20 , 21 ]. In addition to surgery, medical treatment and follow-up observations have been reported [ 1 , 29 , 30 , 31 ].…”

A case of desmoplastic myxoid tumor, SMARCB1 mutant, in the pineal region

“…SMARCB1/INI1 is a component of the SWI/SNF complex that is involved in chromatin remodeling and transcriptional regulation 4 . Inactivation of SMARCB1/INI1 has been detected in many CNS tumors, including AT/RT, extraskeletal myxoid chondrosarcomas (EMC), poorly differentiated chordomas (PDC), malignant rhabdoid tumors, cribriform neuroepithelial tumors (CRINET), pleomorphic xantoastrocytomas (PXA), gangliogliomas, high‐grade gliomas, ependymomas, and meningeal SMARCB1‐deficient tumors 5–8 . According to the clustering analyses, some of the abovementioned tumors were similar to the AR/RT molecular subgroups such as CRINET and AT/RT‐TYR, DMT, SMACRB1 mutant, and AT/RTMYC 3,5 .…”