Cutaneous melanoma is highly immunogenic, yet primary melanomas and metastases develop successfully in otherwise immunocompetent patients. To investigate the local immunosuppressive microenvironment, we examined the presence of suppressor T lymphocytes and tolerising dendritic cells (DCs), the expression of immunosuppressive cytokines (IL-10, TGFb1 and TGFb2) and the enzyme indoleamine 2,3-dioxygenase (IDO) using qRT -PCR and immunohistochemistry in primary skin melanomas, negative and positive sentinel lymph nodes (SLN), and lymph nodes with advanced metastases. Our results indicate that tolerogenic DCs and suppressor T lymphocytes are present in melanoma at all stages of disease progression. They express transforming growth factor b receptor 1 (TGFbR1), and are therefore susceptible to TGFb1 and TGFb2 specifically expressed by primary melanoma. We found that expression of IDO and interleukin 10 (IL-10) increased with melanoma progression, with the highest concentration in positive SLN. We suggest that negative SLN contain immunosuppressive cells and cytokines, due to preconditioning by tolerogenic DCs migrating from the primary melanoma site to the SLN. In primary melanoma, TGFb2 is likely to render peripheral DCs tolerogenic, while in lymph nodes IDO and TGFb1 may have a major effect. This mechanism of tumourassociated immunosuppression may inhibit the immune response to the tumour and may explain the discrepancy between the induction of systemic immunity by anti-melanoma vaccines and their poor performance in the clinic.

Background: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors.

BIA-ALCL is a rare neoplasm with a good prognosis. Our data support the recommendation that stage I disease be managed with surgery alone. Adjuvant chemotherapy may be required for more invasive disease and our experience has shown the efficacy of Brentuximab as a second line treatment.

The recent discovery of activating mutations in the BRAF gene in many cutaneous melanomas led us to screen the genomic sequence of BRAF exons 11 and 15 in a series of 48 intraocular (uveal) melanomas, together with control samples from three cutaneous melanomas and the SK-Mel-28 cell line, which has a BRAF mutation. The same mutation was detected in two-thirds of our cutaneous melanoma samples, but was not present in any uveal melanomas. This finding further underlines the distinction between uveal and cutaneous melanomas, and suggests that BRAF inhibitors are unlikely to benefit patients with uveal melanoma.

Dupuytren's disease may present with well-defined subcutaneous cords or as more diffuse disease with involvement of the skin. Fasciectomy is the procedure commonly carried out for the full range of disease, but is associated with rates of recurrence of up to 66%. We reviewed 143 rays in 103 patients undergoing dermofasciectomy for diffuse disease with involvement of the skin. We found recurrence in 12 rays (8.4% of rays; 11.6% of patients) during a mean follow-up of 5.8 years, eight as cords and four as nodules. We suggest that dermofasciectomy is a better method of disease control than fasciectomy for the more diffuse type of disease with involvement of the skin.