T regulatory cells mediate immunosuppresion by adenosine in peripheral blood, sentinel lymph node and TILs from melanoma patients.

T regulatory cells (Tregs), involved in tumour tolerance, can generate Adenosine by CD39/CD73 surface enzymes, which identify four Tregs subsets: CD39+CD73- nTregs, CD39+CD73+ iTregs, CD39-CD73+ oTregs and CD39-CD73- xTregs. In melanoma patients, increased Tregs levels are detected in peripheral blood (PB), sentinel lymph node (SLN) and tumour infiltrating lymphocytes (TILs), but Adenosine role was not investigated yet. We examined total Tregs and Adenosine subsets in PB, SLN and TILs from melanoma patients (n = 32) and PB from healthy donors (HD; n = 10) by flow cytometry. Total Tregs significantly increased in stage III-IV patients PB, in SLN and TILs, as compared to HD/stage I-II patients. Tregs subsets analyses showed that: 1) PB nTregs significantly increased in SLN and decreased in TILs; 2) iTregs significantly increased in stage III-IV patients PB and further significantly increased in SLN and TILs; 3) PB oTregs and xTregs significantly decreased in SLN and TILs. Patients clinical features did not significantly influence total Tregs, except SLN excision order. Results confirmed Tregs role in melanoma progression and indicate Adenosine generation as a novel escape mechanism, being nTregs and iTregs increased in PB/SLN/TILs.

CD4+FOXP3+ T regulatory cells decrease and CD3+CD8+ T cells recruitment in TILs from melanoma metastases after electrochemotherapy.

Electrochemotherapy (ECT) represents an effective local treatment for skin unresectable melanoma metastases with high overall objective response rate. ECT is based on the combination of anti-neoplastic drugs administration and cancer cells electroporation. Whether ECT can also activate the immune system is a matter of debate, however a significant recruitment of dendritic cells in melanoma treated metastases has been described. Herein we investigated immediate and late effects of ECT treatment on T cell subsets in ECT-treated lesions by fluorescent immunohistochemistry. Biopsies from melanoma patients (n = 10) were taken before ECT (t0), at d1 and d14 from treatment. At t0, CD3+CD4+ T cells were the most represented T cells, well detected in the perilesional dermis, particularly at tumour margin, while CD3+CD8+ T cells were less represented. CD4+FOXP3+ T regulatory (Treg) cells were present in the perilesional dermis and within the lesion. ECT induced a significant decrease of CD4+FOXP3+ Treg cells percentage in the perilesional dermis, observed at d1 and at d14 (p < 0.001). CD3+CD8+ T cells frequency significantly increased at d14 from treatment in the perilesional dermis (p < 0.001). Furthermore calreticulin translocation to the plasma membrane, a hallmark of immunogenic cell death, was observed in metastatic cells after ECT. The data reported here confirm that ECT induces a local response, with a lymphoid infiltrate characterized by CD4+FOXP3+ Treg cells decrease and CD3+CD8+ T cells recruitment in the treated lesions. These results might contribute to design novel combinational therapeutic approaches with ECT and immunotherapy in order to generate a systemic long-lasting anti-melanoma immunity.

'Animal-type' melanoma of the scalp with satellitosis and positive sentinel nodes in a 4-year-old child: case report and review of the literature.

BACKGROUND: Although showing a rapidly rising incidence, paediatric melanoma is relatively rare, accounting for 1-4% of all cases of melanoma and for 1-3% of all paediatric malignancies. The overall survival rate in paediatric patients seems to be similar to that recorded in adults. 'Animal-type' melanoma (ATM) is a rare melanoma subtype, occurring both in childhood and in adults, that shows a close histological resemblance to the heavily pigmented melanocytic tumours observed in grey and white horses. CASE PRESENTATION: We present a case of ATM of the scalp with satellitosis and two positive sentinel nodes in a 4-year-old male child. No other tumour deposits were found in the subsequent regional lymphadenectomy; the patient has been tumour free for 30 months. CONCLUSIONS: We treated our case of ATM in a child as the other types of paediatric melanoma, therefore as an adult melanoma. ATM is generally considered a neoplasm with an indolent course, that occasionally shows an aggressive behaviour, and patient deaths of ATM have been reported. Due to the rarity of ATM, further studies are needed to better define the biological behaviour of this particular melanoma subtype and the therapeutic and follow-up strategies.

Familial and sporadic melanoma: different clinical and histopathological features in the Italian population - a multicentre epidemiological study - by GIPMe (Italian Multidisciplinary Group on Melanoma).

BACKGROUND: Having a familial member affected by cutaneous melanoma is a risk factor for this neoplasm. Only a few epidemiological case-control studies have been carried out to investigate whether familial and sporadic melanomas show different clinical and histopathological features. OBJECTIVE: The aim of this study was to evaluate eventual different features and risk factors in subjects affected by familial and sporadic cutaneous melanoma. METHODS: A case-control multicentre study interesting 1407 familial (n = 92) and sporadic (n = 1315) melanomas in the Italian population. The analysis was made using t-test for continuous variables and chi-squared test for categorized ones. The variables which have shown statistically significant differences in the two groups in the univariate analysis were included in a multivariate model. RESULTS: The results showed some main significantly clinical differences between the two groups investigated: earlier age at diagnosis, a greater proportion of sunburns and a higher number of naevi were observed for the familial cases compared with sporadic ones. Nevertheless, we did not find a diagnostic anticipation in familial melanomas, in fact the invasion level and the thickness of melanomas was similar in the two groups. CONCLUSION: Some relevant clinical differences are observed between the two groups examined. The familial melanoma members, although carriers of constitutional risk factors, are not careful enough to primary and secondary prevention.

Dermatofibrosarcoma protuberans in childhood: two case reports and review of the literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer with intermediate malignancy, characterized by a progressive local growth and a propensity for local recurrence. DFSP is most frequent in adults; however, in recent years, DFSP in childhood emerged to be more common than previously believed. Unfortunately DFSP in children may be misdiagnosed, leading to a delay in the treatment. The authors report two cases of childhood DFSP with unusual clinical presentation: a congenital nodular variant and an atrophic variant developed at 2 years of age, both with acral localization. They highlight the importance of an early diagnosis by pediatricians and dermatologists to ensure an appropriate complete excision and reduce the risks of recurrences.

Comparison of two dressings in the management of partial-thickness donor sites.

This study evaluated and compared the performance of an adhesive hydro-cellular dressing with that of a paraffin gauze dressing in the treatment of partial-thickness skin-graft donor site wounds. Fifty patients were included in the study, each acting as his/her own control. Donor site area ranged from 20 cm2 to 71 cm2; half the area of each patient's donor site was treated with the trial dressing, the other half with paraffin gauze. Outcome measures assessed were: time to complete epithelialisation; ease of dressing removal; pain on removal; and appearance of the wound bed. The trial dressing demonstrated a significantly faster healing time (p < 10(-6)) and enhanced patient comfort.

First recurrence analysis of 840 cutaneous melanomas: a proposal for a follow-up schedule.

AIMS AND BACKGROUND: A correct follow-up schedule for patients who underwent an excision for stage I cutaneous melanoma might allow the early detection of local and distant metastases. At present, there is no general agreement on follow-up protocols. In order to work out a follow-up guide, we have retrospectively evaluated the records of 840 stage I cutaneous melanoma patients surgically treated and followed during the postoperative period in the Division of Plastic Surgery of the University of Florence from 1975 to 1992. METHODS: We evaluated the patients' records by analyzing time, pathway and site of any first recurrence in relation to the main prognostic factors such as patient sex, site, histological type and depth of invasion of each primary melanoma. A statistical analysis was performed. RESULTS: To summarize, the salient results were the following: 80% of relapses occurred in the first 3 years and they occurred significantly earlier when the primary melanoma was localized in the trunk and significantly later when the melanoma was localized in the lower limbs and for < 1.5 mm lesions. The first recurrence occurred earlier by the lymphatic than by the hematic pathway regarding the overall number of patients. The hematic pathway was the most frequent (with respect to the overall percentage of hematic metastases) for the melanomas localized in the head and neck region and for lentigo malignant melanomas, whereas the lymphatic pathway was most frequent for melanomas of the lower limbs and > 3 mm in thickness. CONCLUSIONS: We suggest a follow-up schedule taking into consideration the postoperative behavior of stage I cutaneous melanoma patients (in terms of time and pathway of the first recurrence) in relation to the site and depth of invasion of the tumor.