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Multiple familial pilomatrixomas in the absence of other clinical features: a case of familial benign pilomatrixoma

A pilomatrixoma is a calcifying epithelioma of the hair follicle. Cells within this neoplasm may differentiate to cells of hair matrix, hair cortex, follicular infundibulum, outer root sheath and hair bulge. Pilomatrixomas most commonly arise due to somatic activating mutations in the bcatenin gene (CTNNB1), resulting in the high expression in proliferating matrix cells, activating the Wnt signalling pathway. b-catenin is then downregulated as the cells differentiate. Most pilomatrixomas are benign. Differential diagnoses for solitary nodular skin lesions include sebaceous, dermoid, branchial or pre-auricular cysts, ossifying hematoma, chondroma, fibroxanthoma, giant cell tumor, osteoma cutis, lymphadenopathy or a foreign body reaction. While solitary pilomatrixomas are the most common benign superficial tumour in children, they comprise 0.12% of all cutaneous tumours. Multiple pilomatrixomas are rare, associated with genetic disorders, including familial adenomatous polyposis (FAP), myotonic muscular dystrophy type 1, Rubenstein–Taybi syndrome, Turner syndrome Kabuki syndrome and the childhood cancer syndrome constitutional mismatch repair deficiency (CMMRD). A 41-year-old man presented with multiple firm, asymptomatic, fleshy mobile lesions, ranging in size from 2– 30 mm in diameter, at the left pre-auricular area, left shoulder and upper lateral aspect of the left arm, along with two smaller lesions on his scalp. These began in his teens as small nodules, progressing slowly in size over many months or years. He had no other symptoms, normal fertility, normal intellect, no dysmorphism and no musculoskeletal abnormalities. Screening gastroscopy and colonoscopy were unremarkable. The lesions were excised; the histology was consistent with pilomatrixoma, with typical features of thick trabeculae of ghost-like squamous cells focally merging with basaloid squamous cells, with intervening inflamed stroma containing many foreign body giant cells and the partial calcification of the lesions (see Fig. 1). A computed tomography and positron emission tomography scan of his neck, chest, abdomen and pelvis showed no evidence of metastatic disease, no abnormal lymphadenopathy and no evidence of sarcoidosis. One of his three daughters aged 10 years similarly had multiple lesions, the largest measuring 12 mm in diameter on her right temple. These were asymptomatic and had developed over 5 years. These were excised and confirmed histologically to be pilomatrixomas. She is otherwise well. Neither of his other children (aged 7 and 3) nor other family members had similar skin lesions and there was no other significant family history. Genetic studies undertaken on the proband’s blood for the APC gene (FAP) revealed no pathogenic mutations and testing of the CTG repeats in the DMPK gene (myotonic dystrophy) showed CTG repeats within normal ranges. No further genetic testing was done since there were no phenotypical features of CMMRD, nor Rubenstein–Taybi or Kabuki syndrome. This report describes a father and daughter with multiple pilomatrixomas in the absence of any other known associations. While a familial pattern of multiple pilomatrixomas has been described, with no clinical evidence of other conditions, these previous reports did not include genetic studies. The primary management of multiple pilomatrixoma should exclude any of the existing associations described above. As clinical genetic practice moves from an iterative analysis of individual genes to next generation panels and filtered exome sequencing, we anticipate it will be possible to simultaneously test multiple genes, to confirm or negate the syndromic associations of multiple pilomatrixomas.