Pilomatrixomas: syndromic associations and a guide to germline genetic testing

Pilomatrixomas are benign tumours derived from hair matrix cells of the skin. These neoplasms are typically isolated and sporadic in nature but can also occur in association with several genetic syndromes, when they often present as multiple lesions. The presentation of multiple pilomatrixomas in childhood or adulthood can therefore be the first manifestation of an underlying multisystem disorder. The syndromic associations of these lesions include myotonic dystrophy type 1, familial adenomatous polyposis and several rare developmental disorders. Diagnosing these rare disorders in otherwise healthy individuals who present with multiple pilomatrixomas therefore presents clinicians with diagnostic and counselling challenges. We review the known and evolving syndromic associations of pilomatrixomas and the molecular pathology of these lesions, and propose a practical guideline for the use of germline genetic testing.