Track

Case Reports

Abstract

Malignant proliferating trichilemmal tumor (MPTT), originating from the external root sheath of hair follicles is extremely rare. The genetic alterations of the tumor are not well documented in the literature. Here we describe a case of MPTT with molecular studies. The patient is a 64-year-old African-American female who presented with a gradually enlarging nodule on the posterior scalp. Initial biopsy at outside hospital suggested metastatic adenocarcinoma versus squamous cell carcinoma (SCC) of uncertain origin. Subsequent wide local excision was performed. The histologic examination of the 2.0 cm scalp mass displayed characteristic trichilemmal keratinization, marked by an abrupt transition from a nucleated epithelium to a densely laminated keratinized layer without an intermediate granular layer. The diagnosis of MPTT was rendered. Immunohistochemistry showed the tumor with diffuse p53 expression, focal HER2 complete membranous staining, and focal p16 expression (negative result on HPV RNA in situ hybridization). Molecular analysis by next generation sequencing (NGS) revealed ERBB2 (HER2), BRD4 and TYMS amplification as well as TP53 mutation. Other gene mutations found with unknown significance and decreasing frequencies were: HSPH1, ATM, PDCD1 (PD-1), BARD1, MSH3, LRP1B, KMT2C (MLL3), GNA11, and RUNX1. Beyond genomic variants, assessments for homologous recombination deficiency, PD-L1 expression, gene rearrangement, altered splicing, and expression of DNA mismatch repair genes yielded negative results. In conclusion, the confirmation of ERBB2 (HER2) amplification by NGS in MPTT is suggestive of potential therapeutic utility with Anti-HER2 monoclonal antibody. The finding of TP53 mutation with no other gene mutations typically seen in SCC significantly helps with the differential diagnosis.