Efficacy of electrochemotherapy for eruptive legs keratoacanthomas.

Generalized eruptive keratoacanthoma, is considered a serious condition because the eruptions are diffuse, persistent, and recurrent. Constant pruritus, visceral neoplasms, and unsatisfactory response to treatment are ominous prognostic factors. Even if skin cancers are usually well controlled with surgical and/or radiotherapic approaches, there are some cases in which these two techniques are not effective. With respect to surgery, radiotherapy and other standard treatments, ECT acts rapidly on multiple lesions with limited side effects and no functional impairment; moreover, repeated sessions can be performed to achieve or maintain the clinical response. We report a case of generalized eruptive keratoacanthomas in which electrochemotherapy was effective in inducing local regression of skin lesions. A 72-year-old woman with eruptive and painful keratoacanthomas for 3 months on both the lower limbs in which the conventional treatments could not be cosmetically acceptable. One session of electrochemotherapy with bleomycin sulfate was then performed on all isolated skin lesions. The treatment was well tolerated and led to a rapid clinical regression of the treated lesions. Use of ECT should be considered as an excellent alternative to current therapies in treatment of painful eruptive keratoacanthomas with a significant improvement of quality of life.

Sentinel Lymph Node Biopsy in Thick-Melanoma Patients (N=350): What is Its Prognostic Role?

BACKGROUND: Sentinel lymph node biopsy (SLNB) is currently recommended for patients with intermediate-thickness melanomas (T2-T3). Historically, T4 melanoma patients have not been considered good candidates for SLNB because of the high risk of distant progression. However, some authors suggest that T4 melanoma patients could be considered as a heterogeneous group that could benefit from SLNB. METHODS: We retrospectively analyzed 350 patients with thick (>4 mm) melanomas between 1999 and 2011. Patients were stratified into three groups depending on the results of SLNB: (1) 94 SLNB-negative; (2) 84 SLNB-positive; and (3) 172 SLNB not performed (observation group). The associations of clinical-pathologic features with the result of SLNB, disease-free interval (DFI), and disease-specific survival (DSS) were analyzed. RESULTS: Multivariate analyses confirmed a better prognosis for SLN-negative patients compared with patients in the observation group (DSS hazard ratio [HR] 0.62, p = 0.03; DFI HR 0.47, p < 0.001). The observation group was shown to have the same prognosis as the positive-sentinel lymph node group, when adjusted for principal confounders in the model. CONCLUSIONS: We confirmed that thick-melanoma patients are a heterogeneous group with different prognosis. In our experience, SLNB allowed for an appropriate stratification of patients in different survival groups. On the basis of our results, we strongly recommend the routine execution of SLNB in cases of primary melanoma thicker than 4 mm.

Favourable prognostic role of regression of primary melanoma in AJCC stage I-II patients.

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.

Melanoma relapse over a pacemaker pocket: case report and integrated management strategies.

We report the first related case of a metastasis from melanoma appeared on a pacemaker device pocket. The stadiation exams showed that this is the only localization of the pathology. The integrated management from both cardiologic and dermatologic surgery was described. It was composed by two interventions, a first time for the implant of a new device contralaterally, and later by the surgical intervention, with exeresis of the lesion, radical lymph node dissection of the axilla and plastic reconstruction. The previous pacemaker implant may hypothetically create a favourable environment for metastatic cells ingrowth. This could be explained by a chronic inflammatory reaction and capsule formation around the device as previously reported, or by a blockage of lymphatic drainage in this specific site.

Relevance of multiple basin drainage and primary histologic regression in prognosis of trunk melanoma patients with negative sentinel lymph nodes.

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.

An ultrasonography-cytology protocol for the diagnostic management of regional nodes in a subset of patients with Merkel cell carcinoma of the skin.

BACKGROUND: The status of regional lymph nodes (LNs) is one of the most consistent predictors of survival in Merkel cell carcinoma (MCC). In cases of clinically localized disease, current practice involves sentinel lymph node (SLN) assessment. OBJECTIVES: To propose ultrasonography (US) followed by fine needle aspiration cytology (FNAC) and immunohistochemistry as a useful diagnostic tool in the pre-surgical management of patients with MCC. METHODS: US of LNs was performed in 75 patients with MCC (22 with stage III tumours; 53 with stage I-II). In patients with US suspected disease, US coupled with FNAC of the LN was performed. Smears were examined by routine cytological staining supplemented with immunohistochemical staining for cytokeratin 20. All patients underwent surgical removal of regional LNs. RESULTS: In all 22 patients with stage III tumours, US was indicative of tumour deposits and FNAC confirmed metastases to LNs. In 11 of 53 patients with localized MCC without clinical evidence of nodal disease, US revealed enlarged, equivocal nodes where FNAC was performed. Ten LNs were cytologically positive for metastases, and one was negative. Upon histological examination, the FNAC-negative case showed a metastasis 5 mm in diameter. In all the other 42 cases with no clinical or US evidence of LN involvement, only SLN biopsy was performed and in six cases small metastatic foci were detected. Ultimately, of the 53 stage I-II MCC, 17 had positive LN involvement. In 10 cases (59%) metastases were detected by FNAC, and in seven cases, were detected by SLN biopsy. CONCLUSIONS: In a selected subset (∼20%) of patients with MCC with clinically localized disease, US followed by FNAC in the suspect LN is a valid alternative to the classical protocol of SLN histological examination.

Melanoma in patients younger than 20 years.

AIM: Melanoma is rare in children and uncommon in adolescents. Clinical and prognostic factors can differ from adult population. There is often a delay in diagnosis and the therapeutic management is not unequivocally established. The aim of this study was to review our monocentric case series to establish the characteristics of the population and the possible different behaviour of the malignancy compared to adults. METHODS: From 1975 to 2011 we selected 36 out of 43 patients with a diagnosis of melanoma before the age of 20. We reported a female predominance, the most common site of primary lesions for both sexes were the lower extremities and according to adulthood population the most common histotype was Superficial Spreading Melanoma. RESULTS: None of our patients presented distant metastasis at diagnosis, but 29.4% showed a progression, and the 17.6% died during the follow-up. A significant difference based on gender was found at the multivariate analysis on Disease free survival as well as Breslow thickness, but only Breslow thickness was the only parameter that maintained a role on survival at multivariate analysis when corrected for gender and age. We performed the sentinel lymph node biopsy in 3 patients and they all resulted negative. CONCLUSION: Despite our small case series we observed some important differences of melanoma in children compared to adults. It remains difficult to establish the prognostic factors in younger melanoma patients. Similar to adults, the detection of melanoma in an early phase of development, with a low Breslow thickness, is the most important prognostic factor.

Disease progression in melanoma patients with negative sentinel lymph node: does false-negative specimens entirely account for this phenomenon?

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%).

Clinico-pathologic features of primary melanoma and sentinel lymph node predictive for non-sentinel lymph node involvement and overall survival in melanoma patients: a single centre observational cohort study.

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.