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Background The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary syndrome (SS) patients makes it difficult both to ascertain the presence of clonal cells and to quantify the tumour burden in the peripheral blood. In previous reports we showed that the lack of CD26 (dipeptidyl-aminopeptidase IV) is a characteristic feature of circulating Sézary cells (SC). Objectives The purpose of this study was to ascertain, by means of high-resolution two-, three- or four-parameter flow cytometry, the relationship between CD26 expression on peripheral blood lymphocytes and peripheral blood involvement in cutaneous T-cell lymphoma patients and to assess its significance in SS diagnosis. Methods The patient population included 52 SS patients, 151 mycosis fungoides (MF) patients at different clinical stages (including 14 with blood involvement, B1-MF), 88 patients with erythrodermic inflammatory skin diseases (EISD) and 72 healthy donors (HD). CD26+ values were available in all cases, whereas CD4+ CD26– level measurement was performed in 23 SS, 141 MF, 71 EISD and 72 HD. Results CD4+ CD26– percentage values were higher than 30% in all but one B1-MF and higher than 40% in all SS cases, whereas HD, EISD and B0-MF patient values were always lower than 30%. A statistically significant difference was found in both CD26– and CD4+ CD26– percentage and absolute values between SS and HD, EISD and B0-MF patients. The CD26– and CD4+ CD26– percentage values (but not the absolute values) were significantly higher in B1-MF compared with HD, EISD and B0-MF patients (P < 0·001). Moreover, CD26– absolute values and CD4+ CD26– percentage and absolute values were significantly higher in SS than in B1-MF (P < 0·001). A statistically significant direct relationship was found between CD4+ CD26– percentage... [ABSTRACT FROM AUTHOR]

Background Although regulatory T cells (Tregs) are affected in several autoimmune skin diseases, only two studies have been performed in patients with bullous pemphigoid ( BP) with contrasting results. Objective To characterize Tregs and to determine the serum levels of regulatory cytokines in patients with BP. Methods In BP lesional skin, immunohistochemistry and confocal microscopy were performed for CD4+, CD25+, forkhead/winged helix transcription factor ( FOXP3)+, transforming growth factor ( TGF)-β+ and interleukin ( IL)-10+ cells. In addition, the number of CD4+ CD25++ FOXP3+ Tregs in peripheral blood was assessed by flow cytometry, and the levels of TGF-β and IL-10 were determined in serum samples by enzyme-linked immunosorbent assay before and after steroid therapy. Controls included patients with psoriasis, atopic dermatitis ( AD) and healthy donors. Results The frequency of FOXP3+ cells was significantly reduced in skin lesions from patients with BP ( P < 0.001) compared with psoriasis and AD. Moreover, the number of IL-10+ cells was lower in BP than in psoriasis ( P < 0.001) and AD ( P = 0.002), while no differences were observed in the number of TGF-β+ cells. CD4+ CD25++ FOXP3+ Treg in the peripheral blood of patients with BP was significantly reduced compared with healthy controls ( P < 0.001), and augmented significantly after steroid therapy ( P = 0.001). Finally, TGF-β and IL-10 serum levels were similar in patients with BP compared with healthy controls. However, after therapy, BP patients showed significantly higher IL-10 serum levels than before therapy ( P = 0.01). Conclusions These data suggest that the depletion of Tregs and of IL-10 in patients with BP may be an important factor in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Background The prognostic significance of regression in primary melanoma has been debated over the past few years. Once it was considered to be a negative prognostic factor, as it may have prevented proper melanoma thickness measurement, therefore affecting the staging of the tumours. For this reason, it was considered to be an indication for sentinel lymph node biopsy ( SLNB) in melanoma < 1 mm. Objectives To ascertain the utility of SLNB in thin melanoma and to clarify the role of regression in disease-free survival ( DFS) and overall survival ( OS) in our series. Methods We analysed data collected from 1693 consecutive patients with AJCC (American Joint Committee on Cancer) stage I-II melanoma. Results Globally, SLNB was performed in 656 out of 1693 patients. Regression was present in 349 patients and 223 of them were characterized by thin lesions. SLNB was performed in 104 cases of thin melanoma with regression. The majority of regional lymph node metastases were observed in patients who did not undergo SLNB (89 out of 132). Among the remaining 43 'false negative' patients only three showed regression in the primary. Using the Cox multivariate model, histological regression maintained a significant protective role [hazard ratio ( HR) 0·62, P = 0·012 for DFS; HR 0·43, P = 0·008 for OS] when corrected for the principal histopathological and clinical features, despite SLNB. Conclusions We confirmed that regression alone should not be a reason to perform SLNB in thin melanoma and, on the contrary, it can be considered a favourable prognostic factor in patients with AJCC stage I-II melanoma. [ABSTRACT FROM AUTHOR]

Background Development of more than one primary melanoma in a sole patient is frequent, accounting for 1.2-8.2% of melanoma patients in most recent series. Objective and methods Clinical, histological and epidemiological characteristics of 270 multiple primary melanomas patients were reviewed. Results Two-hundred and seven patients (76.7%) had two melanomas, whereas in the remaining 63 the number of primary ranged from three to eight; on the whole, 639 multiple primary melanomas were identified. Synchronous melanomas developed more frequently in patients with three or more lesions; median age was significantly lower in the group of patients with more than three melanomas than in the others. Mean Breslow's thickness significantly decreases ( P < 0.001) from the first (1.77 ± 1.76 mm) to subsequent primaries (0.85 ± 1.25 mm for the second and 0.66 ± 0.48 mm for the third melanoma). Percentage of ' in situ' melanomas was 5.6% as first diagnosis, but increased to 24.8% for the second melanoma; number of nodular melanomas was significantly lower for succeeding diagnosis. AJCC stage at diagnosis showed a statistical prognostic significance, whereas outcome and survival did not depend on the number of primary lesions. Multivariate analysis confirmed the prognostic role of Breslow's thickness, ulceration, gender and patient age, and the better prognosis of patients with multiple melanomas, respect to those with single primary melanoma. Conclusions Skin examination and long-term follow-up are mandatory for patients affected by melanoma, with the intent to promptly diagnose not only a disease progression but also possible new primary melanomas. [ABSTRACT FROM AUTHOR]

Background Sentinel lymph node (SLN) status is the most important prognostic factor for subjects with primary melanoma thicker than 1 mm. Objective We focused our study on patients with disease progression after negative SLN biopsy (SLNB), with the aim of elucidating their clinical and histopathological characteristics, outcome and real incidence of false negative. Methods A total of 688 melanoma patients who underwent SLNB (1 May 1998-31 December 2008) were analysed; all patients had Breslow >1 mm or Breslow <1 mm and at least one of the following features: regression, ulceration and/or Clark level IV-V. Results Progression developed in 114 of 503 negative SLN patients (22.7%); the first metastatic site was regional in 64% and distant in 36% of these cases. Thirty-nine patients had nodal metastases in the SLN basin as first site of progression. High-risk melanomas ( P = 0.001) and elderly patients ( P = 0.0005) had an increased probability of progression. Women with a higher median age and lower limbs primary melanoma developed mainly regional skin metastases, while an increased probability of distant metastases was demonstrated in patients with primary on the trunk and axillary SLN ( P = 0.003, P = 0.001 respectively). Age at diagnosis, Breslow thickness and regression showed a prognostic relevance in univariate and multivariate analyses on disease-free survival and overall survival. Conclusions Even if SLN status remains the most important prognostic factor for melanoma patients, progressive disease after a negative SLNB is a relatively frequent event. However, in our opinion, only a part of negative SLNB patients with metastatic spreading should be considered as false negative (7.75%). [ABSTRACT FROM AUTHOR]

Abstract: Objective: Completion Lymph Node Dissection (CLND) is the current standard of practice for patients with a positive Sentinel Lymph Node Biopsy (SLNB). Significant morbidity is associated to CLND, so we tried to evaluate which prognostic variables could predict NSLN invasion in SLN-positive patients and their impact on the overall survival (OS). Methods: A retrospective chart review of 603 patients that had undergone SLNB for melanoma between 2000 and 2009 at our department was done. 100 SLN were positive at the histopathological analysis of SLN. Demographic variables, primary melanoma, SLN pathologic features and results of CLND were analysed. Multivariate logistic regression and OS analyses were carried out to test the prognostic relevance of clinico-pathologic variables on CLND results and disease course. Results: Breslow thickness, ulceration and micro/macrometastatic pattern of SLN invasion carried a significantly independent higher likelihood of NSLN involvement; Starz classification did not maintain a statistical significance in multivariate analysis. Only one patient (4.3%) without adverse prognostic factors showed NSLN involvement, which was found in 33.3% of patients with one and 55.9% with two or more adverse parameters (p = 0.0001). OS analyses confirmed the prognostic significance of these factors. Conclusion: Waiting for the results of Multicenter Selective Lymphadenectomy Trial II, our study suggests a clinically useful and easily applicable means of identifying patients with an unfavourable disease course. The presence of one or more adverse factors identifies patients in whom CLND is mandatory to include thereafter in a more strict follow-up program. Moreover, the finding of no adverse prognostic indicators associated to the presence of significant co-morbidities and/or elderly age, could be useful in identifying patients not to treat by CLND. [Copyright &y& Elsevier]

Background Systemic sclerosis (SSc) and morphoea are connective tissue diseases characterized by fibrosis of the skin. Although to date their pathogenesis has not been clearly defined, it is thought that autoimmunity may play a role in the development of the skin lesions observed in both these diseases. As regulatory T cells (Tregs) play a key role in the modulation of immune responses, it has recently been suggested that Treg impairment may lead to the development of autoimmune diseases. Objectives To investigate the presence of Tregs and their immunomodulatory cytokines, transforming growth factor (TGF)-β and interleukin (IL)-10, in patients with SSc and morphoea. Patients/methods Fifteen patients with SSc and 15 with morphoea were enrolled. Immunohistochemistry was applied to identify FoxP3+ (forkhead/winged helix transcription factor) Tregs, TGF-β+ cells and IL-10+ cells in the skin, cytofluorometry to detect CD4+CD25+FoxP3+ Tregs in the blood, and enzyme-linked immunosorbent assays to analyse TGF-β and IL-10 serum levels. Results Fewer FoxP3+ Tregs and TGF-β + and IL-10+ cells were found in the skin of patients with scleroderma than in controls. Similarly, there were reduced TGF-β and IL-10 serum levels and fewer circulating CD4+CD25brightFoxP3+ cells in patients with SSc or morphoea, than in controls. Conclusions The quantitative reduction of Tregs, together with that of TGF-β and IL-10 serum levels, may be responsible for the loss of tolerance observed in both SSc and morphoea. [ABSTRACT FROM AUTHOR]

Background Primary cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphomas where the tumour population emerges within a multiple subclone pattern. Mycosis fungoides (MF) and Sézary syndrome (SS) are characterized by the expansion of clonal CD4+/CD45RO+ memory T cells. Lymphomatoid papulosis (LyP) is a chronic, lymphoproliferative disorder included in the CD30+ primary CTCL spectrum. Several studies have suggested a role of viral infection for super-antigenic activation of T lymphocytes; however, evidence of their association with CTCLs is still lacking. Human herpesvirus (HHV) 7 is a CD4+ T-lymphotropic herpesvirus; its restricted cellular tropism and the ability to induce cytokine production in infected cells could make it an important pathogenic cofactor in lymphoproliferative disorders. Objectives To investigate the presence of HHV7 DNA on CTCL and healthy skin donors (HD). Methods We used quantitative real time polymerase chain reaction to evaluate the potential pathogenic role of HHV7. Results Twenty-seven of 84 (32·1%) HD were positive for HHV7 DNA. Twenty-one of 148 (14·2%) patients with CTCLs were positive for HHV7 DNA: nine of 39 (23·1%) SS, six of 14 (42·9%) CD30+ CTCLs and six of 24 (25·0%) LyP, and HHV7 DNA was negative in all 71 patients with MF. Conclusions These results seem to exclude a pathogenic role of HHV7 in CTCLs, suggesting the possibility of skin as a latency site. [ABSTRACT FROM AUTHOR]

Examines the efficacy of systematic polychemotherapy in the treatment of primary cutaneous B-cell lymphomas (CBCL) or T-cell lymphomas (CTCL). Account on the objective and complete response rates; Comparison between the relapse rate for leg and trunk lesions.

A letter to the editor is presented in response to the article about a study which reveals that serum interleukin-13 levels are increased in patients suffering from Stevens-Johnson syndrome or toxic epidermal necrolysis but not in those with erythema multiforme.

Background Lymphatic drainage to multiple basins (MLBD) is frequently observed in patients with primary melanoma located in the trunk. Conflicting data regarding the prognostic impact of MLBD are reported. Objective and methods We reviewed our case series of 352 patients with trunk melanoma to evaluate the pattern of basin drainage and to analyse whether different basin drainages may have different significance in negative sentinel lymph node (SLN) patients. The presence of single/multiple basin drainage, the status of SLN, the presence of melanoma regression, Breslow thickness, ulceration and type of melanoma were recorded for each patients and correlated to Disease Free Survival (DFS) and Overall Survival (OS). Results MLBD occurred in 77 patients (21.9%) and single basin lymphatic drainage (SLBD) occurred in 275 patients (79.1%). The presence of metastases in SLN was not significantly different in patients with MLBD compared to those with SLBD (26% vs. 19.6%). No differences in OS and DFS were found in SLBD/MLBD independently from SLN status. However DFS was higher in patients with MLBD and negative SLN ( P = 0.0001), in addition, in patients with negative SLN and SLBD disease recurrence was 19% while was only 7% in patients with negative SLN obtained from MLBD ( P = 0.03). Multivariate analysis showed that Breslow thickness <2 mm, MLBD pattern and regression of melanoma were favourable variables for DFS of patients with negative SLN. Conclusions An accurate study of the drainage basin and of all the SLNs obtained from MLBD is recommended because of the impact in prognosis of melanoma of the trunk. [ABSTRACT FROM AUTHOR]