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J Neurol Surg B Skull Base 2019; 80(01): 010-017
DOI: 10.1055/s-0038-1655759
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Proposal for Modification of Cahan's Criteria Utilizing Molecular Genetic Analyses for Cases without Baseline Histopathology: A Unique Method Applicable to Primary Radiosurgery

Aaron E. Rusheen
1   Medical Scientist Training Program, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States
,
James B. Smadbeck
2   Biomarker Discovery Program, Center of Individualized Medicine, Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States
,
Lisa A. Schimmenti
3   Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, United States
,
Eric W. Klee
2   Biomarker Discovery Program, Center of Individualized Medicine, Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States
,
Michael J. Link
3   Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, United States
4   Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, United States
,
George Vasmatzis
2   Biomarker Discovery Program, Center of Individualized Medicine, Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States
,
Matthew L. Carlson
3   Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, United States
4   Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, United States
› Author Affiliations
Further Information

Publication History

11 March 2018

17 April 2018

Publication Date:
31 May 2018 (online)

Also available atMedOne
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Abstract

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.

Keywords

Cahan's criteria - radiation-induced malignancy - radiosurgery - Gamma-Knife - sarcoma - vestibular schwannoma

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Financial Support

Mayo Clinic Center for Individualized Medicine.