Pachydermoperiostosis with cutaneous squamous cell carcinomas

A 46-year-old man visited our department with masses on the face and a skin problem. Approximately 15 years ago, he had noticed marked thickening of the skin on the face and scalp, which had exaggerated progressively to produce deep wrinklings with seborrhea (Fig. 1). He had profuse perspiration of the face, hands, feet, acid the upper aspects of the trunk. Three years earlier, he developed a single nodule on the nose, which progressed to an ulcerated mass. In addition, another tender nodule was noticed on the glabella 3 months prior to his visit. He had chronic epigastralgia and diffuse arthralgia, His brother, 52 years old, had similar lesions of pachydermia and cutis verticis gyrata with digital dubbings. His two sisters had no skin lesions, but suffered from congenital cyanotic heart disease and spinal deformity, respectively. Human leukocyte antigen (HLA) typings between the two affected brothers revealed almost identical HLA-A, HLA-B, acid HLA-C class I antigens. On physical examination, the patient was a short, underdeveloped man with a height of 153 cm and weight of 44 kg, The larger tumor on the nose was 3.0 x 3.5 cm in diameter, producing a perforated tunnel connecting to the nasal cavity, Facial follicular papules, blepharoptosis, palmoplantar blanching, plantar thickening with fissures, and swelling of the knees and ankles were also observed. Histopathologic findings of the main tumor revealed pleomorphic, atypical squamous cells with mixed inflammatory cells, and numerous horn pearls with abnormal keratinization in the epidermis and dermis (Fig. 2). The second tumor was a 1.0-cm-sized, deep-seated, firm nodule. The skin biopsy from this nodule showed the same findings as those of the larger tumor. In the thickened skin of the forehead, diffuse mucinous thickening of the dermis was remarkable, which exhibited a positive reaction to alcian blue stain at pH 2.5, and hypertrophied sebaceous glands were found in the dermis. Laboratory examinations showed findings of severe iron deficiency anemia, In serum electrophoresis, there was albumin/globulin inversion.(1) Bone studies showed thoracic scoliosis and cortical thickening of the long bones. There were peptic ulcers on the gastric pylorus and bulb of duodenum from gastroduodenoscopy. The chromosomal analysis, which is constitutional or stressed by UVB (3.2-19.2 J/m(2)), diepoxybutane (DEB, 0.1 mu g/mL),(2) and mitomycin (MMC, 0.1 mu g/mL), showed neither numerical nor structural aberrations; however, karyotyping in synchronized lymphocyte culture with methotrexate treatment (final concentration, 10(-7) M) showed 10 breakage points at five cells from 20 lymphocytes (Fig. 3). Electron microscopic study and tissue cultures searching for morphologic abnormality of the fibroblasts near the nodules showed no significant specific findings. For the reduction of the ulcerative tumor before surgical intervention, the patient was irradiated with an electron beam over 7 weeks (total dose, 7000 cGy). Also, the glabellar nodule was removed and facial rhytidectomy was performed. With a recommendation to avoid sunlight, no lesions had developed during follow-up for 1 year.