Prognostic differences across sexes in melanoma patients: what has changed from the past?

Differences across the sexes include epidemiological trends, distribution of clinical features and prognostic relevance in melanoma patients. The aims of this single-institution hospital-based cohort study were as follows: to assess the trends over time of the male/female ratio; to analyse the clinicopathologic features according to sex and their modifications following the introduction in 1999 of sentinel lymph node biopsy; to ascertain the metastatic pathways across sexes and the prognostic role of sex in the disease-free interval (DFI), disease-specific survival (DSS) and survival after recurrence. The patient population included 4310 stage I-II melanoma patients, diagnosed, treated and followed up in our institution from 1975. Patients were divided into two groups on the basis of the introduction of sentinel lymph node biopsy in 1999. A female prevalence was observed until 1999; thereafter, the male/female ratio approached 1 (period 1999-2003), with a subsequent increasing trend suggesting a potential male prevalence. Longer DFI and DSS were observed after 1999 and men showed greater improvement compared with women. In multivariate analyses, sex showed a lower impact on DFI and survival after recurrence following the introduction on sentinel lymph node biopsy. No sex-related differences in terms of DSS were observed before and after 1999 among patients with melanoma located on the trunk. However, among patients with primary lesions not located on the trunk, sex maintained a significant prognostic role in both groups. The results of this study suggest that in the last few years, the prognosis of men could have improved more than that in women. The changing surgical/therapeutic interventions can influence sex disparities in melanoma.

Gauze-based negative pressure wound therapy: a valid method to manage pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is an uncommon ulcerative, non-infective chronic inflammatory skin disorder of unknown aetiology. Systemic therapies are necessary to control the associated medical diseases, and, due to the inflammatory nature of PG, topical or systemic immunosuppressant agents are effective, but wound healing is usually slow. Negative wound pressure therapy (NPWT) has become an important tool for the management of complex skin ulcers, and usage in PG has been recently described in the literature: we present four cases of classic PG in which NPWT in association with systemic therapy achieved wound healing and a drastic pain reduction.

Extracorporeal photopheresis for the treatment of erythrodermic cutaneous T-cell lymphoma: a single center clinical experience with long-term follow-up data and a brief overview of the literature.

Extracorporeal photopheresis (ECP) is a therapeutic procedure in which leukapheresed peripheral blood mononuclear cells are exposed to ultraviolet A in the presence of the photosensitizer 8-methoxypsoralen and then reinfused. Several guidelines recommend ECP as a treatment of choice in erythrodermic primary cutaneous T-cell lymphomas (E-CTCL). However, the level of evidence is low due to the rarity of this disease and the lack of randomized controlled trials. We performed a review of the English literature, restricting our analysis to studies including erythrodermic patients and more than 10 cases. Based on these criteria, we identified 28 studies, with a total of 407 patients. The median response rate in erythrodermic patients was 63% (range 31-86%), with a complete response rate ranging between 0 and 62% (median 20%). In our experience, we treated 51 patients with E-CTCL since 1992. A clinical response was obtained in 32 of 51 patients (63%), with a 16% complete response rate. The median time for response induction was eight months (range: 1-23). The median response duration was 22.4 months (range six months to 11 years). The treatment was generally well tolerated without systemic toxicities grade III-IV. The pretreatment parameters significantly associated with a higher likelihood to obtain a clinical response were the B-score in the peripheral blood, CD4/CD8 ratio, and amount of circulating CD3+CD8+ cells. Literature data together with our personal experience clearly support the clinical activity and tolerability of ECP in patients with E-CTCL. Prospective controlled clinical trials are strongly recommended to better document the evidence.

Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012.

PURPOSE: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. There is a need for multicenter trials involving defined patient populations using rigorous assessment criteria. We have investigated pegylated liposomal doxorubicin (PLD) in a clearly defined patient population with advanced MF. PATIENTS AND METHODS: Eligible patients had stage IIB, IVA, or IVB MF, refractory or recurrent after at least two previous systemic therapies. Patients were registered to receive a maximum of six cycles of PLD 20 mg/m2 on days 1 and 15, every 28 days (one cycle). The primary end point was response rate (RR). RESULTS: Nine centers recruited 49 eligible patients. The median number of chemotherapy cycles received was five. There were no grade 3 to 4 hematologic toxicities. Grade 3 or 4 nonhematologic/nonbiochemical toxicities included cardiac symptom (2%), allergy/hypersensitivity (2%), constitutional symptom (4%), hand and foot reaction (2%), other dermatologic toxicity (6%), other GI toxicity (4%), infection (4%), pulmonary embolism (2%), and cardiac ischemia (2%). Of 49 patients, 20 (40.8%) were responders (complete clinical response [CCR] or partial response [PR] as overall response): three (6.1%) experienced CCRs, and 17 (34.7%) experienced PRs. A 50% or greater reduction of cutaneous manifestations was observed in 26 (60.5%) of 43 assessable patients. Two early deaths were reported, resulting from related cardiovascular toxicity and disease progression. The lower limit of the one-sided 90% CI for RR was 31.2%. Median time to progression and median duration of response were 7.4 and 6 months, respectively. CONCLUSION: PLD has an acceptable safety profile in patients with advanced MF. The efficacy of PLD seems promising.

Epstein-Barr virus in cutaneous T-cell lymphomas: evaluation of the viral presence and significance in skin and peripheral blood.

The importance of viral agents in the development of cutaneous T-cell lymphomas (CTCL) is still debated. For this purpose, we retrospectively evaluated the Epstein-Barr virus (EBV) presence in Sézary syndrome (SS), mycosis fungoides (MF), inflammatory dermatoses (ID), and healthy donors (HD) using different approaches: EBV-DNA was quantified in skin biopsies and peripheral blood using real-time PCR, EBV-encoded small RNA (EBER) transcripts were detected by in situ hybridization (ISH), and latent membrane protein1-2 antigens were detected by immunohistochemistry. Skin biopsies were EBV-DNA-positive in 8/30 (27%) SS, 7/71 (10%) MF, and 2/18 (11%) ID patients and in none of the 25 normal skin samples. Positive mRNA (EBER) signals, always confined to cerebriform T lymphocytes, were found in 5/30 SS patients (17%), whereas signals in all MF and ID patients were negative. The presence of EBV-DNA in skin and blood samples was associated with a significantly lower survival in MF/SS patients. In evaluating EBV serological status, most (>70%) SS, MF, and ID patients showed a serological reactivation demonstrated by the presence of anti-EA IgG. In conclusion, although the finding of EBV-DNA in CTCL does not prove its etiopathogenetic role and may be related instead to immunosuppression, our study demonstrates that it has prognostic relevance.

TCRgamma-chain gene rearrangement by PCR-based GeneScan: diagnostic accuracy improvement and clonal heterogeneity analysis in multiple cutaneous T-cell lymphoma samples.

Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emerges within a multiple subclone pattern ("clonal heterogeneity"). PCR analysis has been shown to be useful in the diagnosis of mycosis fungoides (MF) and Sézary Syndrome (SS). Focusing the attention on clonal heterogeneity, the efficacy of the multiplex/heteroduplex (HD) PCR and the GeneScan (GS) capillary electrophoresis analysis was compared in the early diagnosis of MF/SS, using a multiple sample approach. Indeed, GS demonstrated TCRgamma gene rearrangement (GR) in all the 57 SS (100%) and in 123/146 (84%) of the MF samples, whereas the multiplex/HD PCR was less sensitive. An increase in clonality was observed in connection with both a worsening of the cutaneous disease (79% T1/T2; 100% T3/T4) and an increase in the histopathological score (HS < 5, 76%; HS > or = 5, 94%). Clonal heterogeneity with adjunctive reproducible skin TCRgamma-GRs was also observed. "Clonal instability," with different GRs, was present in a small percentage of patients. Therefore, it can be concluded that GS analysis in TCRgamma-GR is able to improve diagnosis in MF/SS patients and the multiple sample approach is helpful for a correct interpretation of clonal patterns in skin lesions, especially in early-stage MF and in SS skin/blood samples.

Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases.

BACKGROUND: Rituximab, a chimeric antibody directed against CD20, has a high therapeutic value in refractory/relapsed low-grade or follicular B-cell non-Hodgkin's lymphomas as a monotherapy or in combination with polychemotherapy. OBJECTIVES: We sought to evaluate the clinical activity and toxicity of a schedule foreseeing the use of intravenous rituximab preceded by single-dose cyclophosphamide in the treatment of patients with primary cutaneous B-cell lymphoma who progressed and relapsed after chemotherapy. METHODS: A total of 7 patients were treated; 4 had both cutaneous lesions and nodal or visceral involvement. All the patients had been previously treated with at least 1 standard chemotherapy regimen, and 4 with 2 or more, with a median response duration of 8 months. Immunohistochemistry on frozen sections was performed with monoclonal antibodies directed against CD20, CD55, and CD59 before rituximab treatment. RESULTS: The overall objective response rate was 85.7%, with a complete response in 5 patients; treatment was well tolerated in all cases. After a median follow-up of 13 months, 2 patients showed a cutaneous relapse. The response durations of the remaining patients who were disease-free are now 5, 7, 17, and 18 months. No relationship was found between CD55 and CD59 expression and the clinical outcome. CONCLUSION: Although a longer follow-up period is needed to confirm these data, our results are encouraging, particularly in terms of disease-free survival.