Abstract

Telomerase reverse transcriptase (TERT) activation plays an important role in oncogenesis by avoiding tumor cell replicative senescence and often correlates with tumor aggressiveness. TERT promoter hotspot mutations are commonly found in skin tumors including basal cell carcinoma (BCC). Among the spectrum of basaloid follicular neoplasms, BCC, trichoepithelioma (TE), trichoblastoma (TB), and fibroepithelioma of Pinkus (FEP) show varying degrees of similarities both in morphology and in molecular pathogenesis. This poses sometimes diagnostic challenges and leads to debates on tumor evolution and classification. TERT alterations have rarely been described in basaloid neoplasms other than BCC. Herein, we report the largest-to-date TERT promoter analysis in basaloid follicular neoplasms with a review of histology and immunohistochemistry. A total of 30 cases were analyzed and 3 of them failed due to insufficient nucleic acids. Among the 27 cases, activating hotspot mutations -124C>T and -146C>T were found in 40% BCCs (4/10), 25% FEPs (2/8) and 0% TE/TBs (0/9). While TERT positive rate in BCC is comparable to previously reported, this rate in TE/TBs is significantly lower (95% confidence interval: [0-28.3%]). Our results suggest that TERT promoter mutations are infrequent in TE/TB, in contrast to BCC, which may in part explain the difference in tumor aggressiveness. We also provide new evidence for the much-debated classification of FEP, suggesting FEP may be more closely related to BCC than TE/TB given the prevalence of TERT mutation among them.

Financial Disclosure: No current or relevant financial relationships exist.