Distinguishing Syndromic Pilar Tumors from Cutaneous Squamous Cell Carcinoma: A Focus on Multiple Pilar Cysts and Proliferating Pilar Tumors

Summary: A 39-year-old female with a lifelong history of cutaneous facial cysts presented with rapidly enlarging posterior neck and forehead masses. Initial biopsy of the neck mass suggested cutaneous squamous cell carcinoma (cSCC), based on atypia of squamous epithelium and growth pattern. However, review of the wide local excision specimen allowed for more accurate classification of an atypical proliferating trichilemmal tumor (aPTT), identified by a dermal-based, lobular, proliferation of solid and cystic trichilemmal lined tumor with no overlying in situ disease and no definitive infiltrative growth. Additionally, background trichilemmal cysts were present. An excision of the forehead mass revealed similar histopathologic features. PTTs are usually sporadic but can be autosomal-dominantly inherited tumors caused by mutations in the PLCD1 tumor suppressor gene, ranging from benign to malignant forms. Malignant PTTs (MPTTs) histologically mimic cSCCs with keratinocytes exhibiting invasion and variable atypia but are differentiated by lack of overlying in situ disease, occurring in pre-existing trichilemmal cysts, trichilemmal keratinization, cystic growth pattern, low tumor mutational burden, and absence of UV signature of TP53 mutations. Although the patient lacked leukonychia, ciliary dystrophy or family history of pilar cysts, providers must also consider germline mutations and familial inheritance patterns associated with genodermatoses including FLOTCH Syndrome.