No abstract

OBJECTIVES To report a retrospective series of 130 Chinese patients with penoscrotal extramammary Paget’s diseases (EMPD), with a long‐term follow‐up, and thus improve the diagnosis and therapy of this disease. PATIENTS AND METHODS The history, clinical presentation, pathology, treatment, and prognosis of 130 patients were analysed. All cases were confirmed by skin biopsy, and then the patients had local wide resection to remove the involved skin and subcutaneous tissue. The large defective wound was reconstructed using a split‐thickness skin graft or local flap. RESULTS Forty‐five patients were evaluated by frozen‐section biopsy of the margins during surgery, five of whom had positive margins and then had an extended resection immediately. Most of these patients had local skin or adjacent scrotal flaps to cover their skin defects. Of the 130 patients, 81 had a mean (range) follow‐up of 3.2 (0.5–10) years after surgery. Five of nine patients with positive margins and three (4%) of 72 with negative margins had tumour recurrence. Five patients died from metastatic disease. CONCLUSIONS Penoscrotal EMPD needs be differentiated from other chronic dermatitis. A 3 cm surgical margin should be sufficient and frozen‐section pathological examinations are necessary for some complicated conditions. Skin grafts or local flaps are good for large skin defects.

Objective: Mutations in chromosome X open reading frame 6 (CXorf6), a recently described candidate gene involved in the development of male genitalia, have been found in patients with complex 46,XYdisorders of sexual development (46,XY DSD) including micropenis, bifid scrotum, and penoscrotal hypospadias. The objective of this work was to identify genomic variants of CXorf6 in patients with isolated hypospadias, severe or non-severe. Design and methods: Forty-one patients with glandular to perineal hypospadias and thirty controls were studied. Direct sequencing for coding exons 3-6 of CXorf6 and their flanking splice sites was performed on DNA extracted from foreskin collected from surgery. Secondary and tertiary structures of the protein were predicted using NNpredict and Protein Homology/analogY Recognition Engine engines. Results: Four mutations (9.7% of cases) were identified. One missense mutation (1295TOC, V432A) and two deletions (325delG, predicted to cause a stop codon L121X) occurred in patients with penoscrotal and proximal hypospadias. One patient with subcoronal hypospadias had CAG-repeat amplification in the second polyglutamine domain of CXorf6. Secondary structure prediction indicated that this insertion occurred in a helix element of the protein. The tertiary structure prediction showed an alteration of the shape of the protein and crowding between domains. Conclusion: CXorf6 mutations are associated with isolated hypospadias of varying severity. However, the pathophysiology of these mutations and the function of the CXorf6 gene product remain to be investigated. European Journal of Endocrinology 159 453-458