# Clinicopathologic and molecular characterization of a series of sporadic trichoblastic neoplasms

## TL;DR

This study characterizes sporadic trichoblastic neoplasms, identifying their clinicopathologic features, molecular profiles, and a rare case of malignant transformation.

## Contribution

The study reports a novel FOXK1::GRHL1 fusion in a trichogerminoma and high tumor mutational burden without UV signature in sporadic trichoblastic tumors.

## Key findings

- RNA sequencing revealed high tumor mutational burden and absence of UV-related mutational signature in sporadic trichoblastic tumors.
- A FOXK1::GRHL1 fusion was identified in a case of trichogerminoma.
- One case showed malignant transformation with increased atypia and mitotic activity.

## Abstract

Trichoblastoma (TB) is a benign primitive follicular neoplasm that can occur in the setting of Brooke-Spiegler syndrome (CYLD mutations), in association with nevus sebaceous (mosaic HRAS mutations), or sporadically. We studied the histopathologic and molecular features of 16 sporadic trichoblastic neoplasms, including a case of trichogerminoma and a case of trichoblastic carcinoma arising within a TB. Sixteen tumors were identified in nine males and seven females (median age 64 years, range 33–97 years) involving the scalp (4), back (2), nasolabial fold (1), cheek (1), skin overlying the parotid gland (1), nasal ala (1), ear (1), upper chest (1), gluteal region (1), thigh (1), leg (1), and ankle (1) with a median size of 1.6 cm (range 1.2–7.0 cm). Histologically, 16 cases consisted of a dermal multinodular growth of basaloid epithelial cells surrounded by fibrotic stroma without epidermal connection. Malignant transformation was observed in one case, characterized by increased atypia and mitotic activity. Another case exhibited focal areas of “cell balls,” indicative of trichogerminoma. RNA sequencing of six tumors showed a high tumor mutational burden (TMB) and lacked a UV-related mutational signature, which may help distinguish trichoblastic tumors from potential mimics. Additionally, a FOXK1::GRHL1 fusion was found in the case of trichogerminoma. Clinical follow-up (15/16 patients; 94%; median: 65 months; range 2.5–106.5 months) showed no evidence of residual or metastatic disease.