Chromosome 22q Deletions in Atypical Teratoid/Rhabdoid Tumors in Adults

Abstract

Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors that usually occur in the posterior fossa. Both AT/RT and the analogous tumor outside the brain, malignant rhabdoid tumor, share a polyphenotypic immunoprofile and frequent 22q deletions with inactivation of the IN11/hSNF5 gene. Reports, so far, indicate that AT/RTs occur almost exclusively in children, most of whom are 5-years-old or less. The rarity of the tumor and the polyphenotypic immunoprofile, characterized by antigen expression that is often patchy, make diagnosis in adults difficult and controversial. We describe three AT/RTs in adults in which the diagnoses were supported by detection of 22q11.2 deletions, INI1 mutation and/or loss of INI1 protein expression. Two patients were female, ages 20 and 31 and one was male, age 45. Two tumors occurred in the sella or sellar region and one in the cerebellum. In all cases, fluorescence in situ hybridization with probes to the BCR (22q11.2) and NF2 (22q12) regions of chromosome 22 revealed single copy deletions of BCR with normal dosages of NF2 and, in all cases, immunohistochemistry demonstrated loss of INI1 protein expression. In one case, a single base pair deletion was detected in the INI1/hSNF5 gene. These molecular findings confirm the occurrence of AT/RTs in adults. Although rare, AT/RT should be considered in the differential diagnosis of poorly differentiated intracranial tumors in adults.

Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis

“…12 We found nuclear expression of SMARCB1/INI1 in all glioblastomas (four of four) and oligodendrogliomas Altogether, the findings suggest that immunohistochemistry with an antibody to the SMARCB1/INI1 gene product is a sensitive and specific means of identifying atypical teratoid/rhabdoid tumors.…”

INI1 expression is retained in composite rhabdoid tumors, including rhabdoid meningiomas

“…The 29-year-old patient was an unlikely candidate for a diagnosis of malignant rhabdoid tumor, although not impossible, since we and others have encountered rare examples in adult patients. 20,[39][40][41][42][43][44][45][46][47][48][49][50] Lastly, INI1/hSNF5 mutation analysis was also attempted on this case, but the DNA did not amplify well (data not shown). In a recent study of pediatric CNS tumors, there was one case of an oligodendroglioma with loss of expression and a second case of mixed oligoastrocytoma with focal loss.…”

Atypical Teratoid/Rhabdoid Tumors in Adult Patients: CT and MR Imaging Features

“…17 To our knowledge, only 29 cases of primary AT/RT of the CNS in adults have been reported (On-line Table). [18][19][20][21][22][23][24][25][26][27][28][29][30] The On-line Table summarizes the clinical and imaging data from our patients and from those in the literature.…”

“…10,18,19,24 To our knowledge, there are only limited case reports describing the imaging features of this entity in adults. 8,9,18,19,[21][22][23][24][25][26][27][28][29][30][31] The goal of this study was to characterize the CT and MR imaging features of CNS AT/RT in 5 adults. …”