Familial Multiple Trichoepitheliomas Across Three Generations With a Pathogenic CYLD Variant Identified in One Affected Family Member: A Case Report

Familial multiple trichoepithelioma (FMT) is a rare autosomal dominant genodermatosis characterized by the progressive development of multiple benign cutaneous adnexal tumors with follicular differentiation, predominantly involving the central face.FMT is currently recognized as a phenotypic manifestation of CYLD cutaneous syndrome (CCS), a hereditary tumor predisposition disorder associated with pathogenic germline variants in the tumor-suppressor gene CYLD.Cutaneous tumors typically begin to develop around puberty or early adulthood and progressively accumulate over subsequent decades, potentially resulting in substantial facial disfigurement and functional impairment.We report FMT affecting three consecutive generations of the same family.Case 1, a 74-year-old female, exhibited extensive facial involvement characterized by numerous papules, nodules, and large confluent tumors that had progressively accumulated over several decades, producing marked alteration of facial contours and substantial cosmetic and functional impairment.Case 2, her daughter, presented with multiple centrofacial papules and small nodules, with a considerably lower tumor burden.Case 3, her grandson, also exhibited multiple facial papules, representing the third consecutive clinically affected generation.Representative facial lesions from all three affected individuals underwent biopsy, with histopathological findings consistent with trichoepithelioma in each case.The specimens demonstrated dermal basaloid proliferations with follicular differentiation and keratin-containing cystic structures.Molecular genetic testing performed exclusively in Case 3 identified the heterozygous pathogenic germline nonsense variant CYLD c.2806C>T, p.(Arg936Ter), previously associated with phenotypes within the CCS spectrum.Cases 1 and 2 did not undergo molecular testing; therefore, segregation of this specific variant across all three generations was not directly established.Because of the extensive tumor burden in Case 1, staged surgical excision of the largest and most deforming lesions was performed, resulting in substantial postoperative improvement in facial contour and reduction in tumor burden.This family illustrates the characteristic multigenerational presentation of CCS and the considerable cumulative burden that may develop over decades.Differences in tumor burden across generations should be interpreted cautiously because age-related tumor accumulation represents an important confounding factor.The convergence of clinical morphology, histopathological findings, vertical familial transmission, and molecular confirmation in one affected descendant highlights the importance of clinicopathological correlation, accurate genetic interpretation, individualized treatment, genetic counseling, and long-term dermatologic surveillance.