GRHL-rearranged sebaceoma: expanding the clinical and morphologic spectrum

Abstract

Sebaceoma is a benign sebaceous neoplasm with broad architectural variability, and outside of mismatch repair (MMR)-deficient tumors, its molecular features have remained poorly defined. Recent work identified recurrent GRHL1/GRHL2 rearrangements in a subset of sebaceomas, suggesting the presence of a molecularly distinct group. We report three additional sebaceomas harboring RCOR1::GRHL2 fusions identified by RNA-based next-generation sequencing and integrate the clinical, morphologic, and molecular features of all 11 currently known GRHL-rearranged sebaceomas. Patients ranged from 40 to 84 years; two tumors arose on the head and neck, and one represented the first documented extracranial example (axilla). All tumors were macronodular to multinodular basaloid proliferations with variably complex corded (“organoid”) architecture; infundibulocystic structures were present in one case. One tumor demonstrated partially cystic growth and rounded basaloid nests, expanding the recognized morphologic spectrum. All three tumors were microsatellite stable without pathogenic MMR gene alterations. Across the combined cohort, no recurrences have been reported. These findings broaden the clinicopathologic spectrum of GRHL-rearranged sebaceoma and support this group as a sporadic, MMR-proficient subset characterized by distinctive organoid-patterned architecture. Further studies are needed to determine whether GRHL rearrangements represent a unifying driver of organoid morphology in sebaceoma.