Development of squamous cell carcinomas in Darier disease: a new model for skin carcinogenesis?

This is the authors' abstract. We don't add key points for this paper.

E‐mail: mddoru@hotmail.com Conflicts of interest: none declared. Sir, Darier disease (DD) (follicular keratosis) represents a rare disorder of skin keratinization that stems from null mutations resulting in a haploinsufficiency of the ATP2A2 gene.1 Although DD was observed as an acquired paraneoplastic syndrome secondary to a carcinoma, squamous cell carcinomas (SCCs) of the scrotum, subungual region, vulva, oesophagus and oral cavity1 have been reported to develop in cutaneous or mucosal areas of DD. Genetic abnormalities present in DD may serve as a model of skin carcinogenesis. No aggressive SCC associated with DD has yet been reported on the extremities. A 63‐year‐old white man with DD since age 3 years presented with an SCC of the right leg supramaleolar region, featuring a 2‐cm telangiectatic translucent plaque, in an area affected by DD. He underwent three consecutive local resections, followed by radical resection, skin grafting and adjuvant local radiation. Two years later, a recurrence of the SCC developed in the grafted area, expanding deep into the soft tissues (Fig. 1a). An amputation of the leg below the knee was performed, revealing a 7·5 × 7·5 × 2·5 cm grey‐green necrotic mass extending to the bone. The surrounding skin was diffusely involved with hypertrophic DD. Two months later, he developed a rapidly growing right inguinal mass (Fig. 1b,c) with a maximum diameter of 9 cm which was resected and revealed metastatic SCC (Fig. 2). No evidence of a primary SCC was present, as the overlying epidermis showed no evidence of SCC in situ and no connection with the infiltrating tumour. E‐cadherin was expressed at a low level by areas of both SCC and DD (Fig. 2c). Adjuvant groin radiation (total of 45 Gy) was administered concomitantly with the anti‐epidermal growth factor receptor antibody cetuximab for 4 weeks. The patient’s DD has evolved slowly since early childhood, currently severely affecting the majority of cutaneous surfaces. Only modest improvement was achieved with systemic retinoids (isotretinoin and acitretin), which were discontinued several years before presentation. No immunosuppression, use of herbal remedies, carcinogenic exposures or drugs, history of smoking or family history of cancers were present.