DNA Methylation Profiling in Rare Sellar Tumors

Abstract

The histologic diagnosis of sellar masses can be challenging, particularly in rare neoplasms and tumors without definitive biomarkers. Moreover, there is significant inter-observer variability in the histopathological diagnosis of many tumors of the CNS, and some rare tumors risk being misclassified. DNA methylation has recently emerged as a useful diagnostic tool. To illustrate the clinical utility of machine-learning-based DNA methylation classifiers, we report a rare case of primary sellar esthesioneuroblastoma histologically mimicking a non-functioning pituitary adenoma. The patient had multiple recurrences, and the resected specimens had unusual histopathology. A portion of the resected sellar lesion was profiled using clinically validated whole-genome DNA methylation and classification. DNA was extracted from the tissue, hybridized on DNA methylation chips, and analyzed using a clinically validated classifier. DNA methylation profiling of the lesion showed that the tumor classified best with the esthesioneuroblastoma reference cohort. This case highlights the difficulty in diagnosing atypical sellar lesions by standard histopathological methods. However, when phenotypic analyses were nonconclusive, DNA methylation profiling resulted in a change in diagnosis. We discuss the growing role of DNA methylation profiling in the classification and diagnosis of CNS tumors, finding that utilization of DNA methylation studies in cases of atypical presentation or diagnostic uncertainty may improve diagnostic accuracy with therapeutic and prognostic implications.