A Rare Case of a Malignant Proliferating Trichilemmal Tumor: A Molecular Study Harboring Potential Therapeutic Significance and a Review of Literature.

Abstract

Malignant proliferating trichilemmal tumors (MPTTs), arising from the external root sheath of hair follicles, are exceptionally rare, with limited documentation of their genetic alterations. We present a case of a 64-year-old African American woman who initially presented with a gradually enlarging nodule on her posterior scalp. An initial biopsy at an outside hospital suggested metastatic adenocarcinoma or squamous cell carcinoma (SCC) of an uncertain origin. A subsequent wide local excision revealed a 2.0 cm tumor demonstrating characteristic trichilemmal keratinization, characterized by an abrupt transition from the nucleated epithelium to a laminated keratinized layer, confirming MPTT. Immunohistochemistry demonstrated diffuse p53 expression, patchy CD 34 expression, focal HER2 membranous expression, and patchy p16 staining (negative HPV ISH). A molecular analysis identified TP53 mutation and amplifications in the ERBB2 (HER2), BRD4, and TYMS. Additional gene mutations of uncertain significance included HSPH1, ATM, PDCD1 (PD-1), BARD1, MSH3, LRP1B, KMT2C (MLL3), GNA11, and RUNX1. Assessments for the homologous recombination deficiency, PD-L1 expression, gene rearrangement, altered splicing, and DNA mismatch repair gene expression were negative. The confirmation of ERBB2 (HER2) amplification in the MPTT through a molecular analysis suggests potential therapeutic avenues involving anti-HER2 monoclonal antibodies. The presence of the TP53 mutation, without the concurrent gene mutations typically observed in SCC, significantly aided in this differential diagnosis.