Citations

Epstein-Barr virus–associated smooth-muscle tumors are rare tumors seen in immunocompromised patients. Most cases occur in the context of AIDS and organ transplantation, and very rarely in the setting of congenital immunodeficiency, with only 5 case reports of the latter published so far in the literature. The authors report the case of a previously healthy 8-year-old girl with headaches and precocious puberty who was found to have a large skull base lesion. There was a synchronous left adrenal lesion. She underwent resection of the skull base lesion and a left adrenalectomy. Thorough evaluation for immunodeficiency was negative for a known congenital immunodeficiency syndrome. She had a short course of intravenous immunoglobulin and has had no recurrence of disease or new lesions in the 17 months since presentation. Continued surveillance for the development of opportunistic infections and new or recurrent lesions is warranted in this case. Repeat surgery for surgically accessible tumors or chemoradiation would be recommended for any additional lesions.

Background Cahan's criteria have been utilized since 1948 to establish causality between prior radiation treatment and the development of secondary malignancy. One major criterion specifies that histological and radiographic evidence collected before and after radiation treatment must confirm separate tumor types; however, pretreatment biopsy is rarely obtained prior to radiosurgery for vestibular schwannoma and many other skull base and cranial lesions. Therefore, in these cases Cahan's criteria cannot be validly applied. Objective This article proposes an update to Cahan's criteria using modern molecular genetic analysis for cases lacking baseline histopathology. Methods Mate-pair sequencing and whole exome sequencing of a cerebellopontine angle undifferentiated high-grade pleomorphic sarcoma (UHGPS) that developed after stereotactic radiosurgery of a presumed benign vestibular schwannoma. Results Mate-pair sequencing and whole exome sequencing of the sarcoma revealed complex chromosomal aberrations. Notably, the tumor contained a deletion in the NF2 gene at 22q12 and an in-frame deletion on exon 5 of the remaining copy of NF2. Biallelic events impacting NF2 are atypical for UHGPS but are characteristic for vestibular schwannoma. These findings help support the conclusion that the UHGPS arose from a benign vestibular schwannoma all along. Conclusions Next-generation sequencing can be successfully applied to a radiation-induced sarcoma when both the original and malignant tumors harbor separate signature genetic markers. As our understanding of the genetic profile of various tumors expand, we believe that next-generation sequencing and other genomic tools will play an increasingly important role in establishing causality between radiation and the development of secondary malignancy.