Matrical Tumors: A Comparative Molecular Analysis of Six Cases With Histological Correlations.

Abstract

Abstract: Pilomatrical tumors include pilomatricoma, melanocytic matricoma, and pilomatrical carcinoma. Similar to the normal anagen hair follicle bulb, they may be associated with benign and, rarely, with atypical pigmented dendritic melanocytes. It has been recently suggested that the term "melanocytic matricoma" be replaced with "pilomatricoma with melanocytic hyperplasia" (PMMH). Occasional cases of PMMH show intermediate grades of histological atypia. Their clinical behavior is uncertain. Interestingly, we found in one of these atypical tumors a molecular characterization compatible with a malignant profile. In this study, we compare this case with the molecular profiles of two PMMHs, one atypical PMMH, whose histology was previously published, and of two unpublished cases: a pilomatrical carcinoma and a large matrical tumor of difficult categorization. We also correlate histology with the molecular results. Although histologically the six cases form a morphological continuum with increasing grades of architectural and cytological atypia, our molecular analysis distinctly segregates the lesions into two molecular groups. The first group exhibits only isolated alterations in CTNNB1, a low tumor mutational burden, and a relatively stable chromosomal profile. The second group, by contrast, demonstrates mutations of TP53, biallelic inactivation of CDKN2A or RB1, and an elevated tumor mutational burden, in addition to mutations in CTNNB1 or loss of APC. The tumors in the second group are clearly different from the benign PMMHs. Atypical PMMHs could represent an early stage in the development of tumors that, since their beginning, have a malignant molecular profile different from that of PMMHs and can progressively drive their evolution toward overt malignancy.