Similar local recurrence and survival in patients with T1 radial growth phase melanoma on head and neck treated with 5 or 10 mm margins: A retrospective study.

BACKGROUND: Melanoma guidelines recommend surgical excision with 10 mm margins for T1 melanomas (invasive melanomas with Breslow thickness ≤1 mm), including those in radial growth phase, which are without metastatic potential; however, such margins may be problematic on head-and-neck. OBJECTIVE: We compared outcomes of wide (10 mm margins) versus narrow (5 mm margins) excisions in patients with radial growth phase T1 melanoma on head-and-neck including face. METHODS: We retrospectively examined 610 consecutive patients excised with wide versus narrow margins, from 2001 to 2018, at six European centres. In all cases, radial growth phase, and clear margins with 5 or 10 mm of clearance, were ascertained histologically. Multivariable models investigated associations of margins and other factors with overall survival and local recurrence. RESULTS: Three hundred and sixteen (51.8%) patients received wide excision, 219 (69.3%) with primary wound closure, 97 (30.7%) with reconstruction; 294 (48.2%) patients received narrow excision, 264 (89.8%) with primary wound closure, 30 (10.2%) with reconstruction (p < 0.001). Median follow-ups were 88 months (wide) and 187 months (narrow) (inter-quartile ranges 43-133 and 79-206, respectively). Ten-year overall survival (95% confidence interval) was 96.7% (94.2%-99.3%) in wide and 98.2% (96.4%-100%) in narrow patients. Ten-year local recurrence incidence was 6.4% (4.1%-10.1%) in wide and 7.8% (5.3%-11.6%) in narrow groups. Lentigo maligna melanoma subtype appeared associated with increased risk of local recurrence in narrow versus wide patients (15.0% vs. 7.5%; p = 0.190). CONCLUSIONS: Narrower excision margins for T1 radial growth phase melanoma are not associated with worse overall survival (hazard ratio 0.97, p = 0.996) or increased local recurrence (subdistribution hazard ratio: 0.87; p = 0.751) compared to wider margins, and may be safely applied to such lesions, although caution may be required in the presence of lentigo maligna melanoma.

The role of sentinel lymph node status performed in melanoma patients with local recurrence or in transit metastasis.

BACKGROUND: Sentinel Node Biopsy (SNB) is routinely performed for primary melanoma, but its role in the treatment of Local Recurrence (LR) and In-Transit metastasis (IT) is controversial. This study aims to assess the role of SNB in melanoma patients who developed first loco-regional recurrence. METHODS: A series of consecutive melanoma patients who received SNB for a first IT or LR at the National Cancer Institute of Milan, Italy, from 2000 to 2015 were selected from a prospective database. Clinicopathological characteristics were analyzed. RESULTS: Seventy-two patients met selection criteria. Forty-three patients (59.7%) received SNB for LR and 29 (40.3%) for IT. The average interval between treatment of primitive melanoma and first recurrence diagnosis was 19 months (interquartile range: 6.9-49.0). SN identification rate was 97.2%. SN positivity was detected in 26 (37.1%) patients. The SN-positive ratein melanoma patients who had LR or IT was significantly higher than reported for primary tumours. Of patients with nodal involvement 17 had LR and 9 IT lesions. Disease Free Survival (DFS) was slightly higher in SN negative patients, in the absence of statistically significant differences. Overall Survival (OS) analysis showed similar values in the two groups. CONCLUSION: Since DFS and OS do not show significant differences between SN negative and positive patients, our data do not give clear indications about performing SNB in case of first LR or IT. However, we suggest submitting patients with LR to this procedure to obtain a more accurate staging and eventually candidate these patients to adjuvant treatment.

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

BACKGROUND: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. PATIENTS AND METHODS: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. RESULTS: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. CONCLUSIONS: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.

Pembrolizumab in the treatment of advanced/metastatic melanoma: a single-center institution experience.

Pembrolizumab is an anti-programmed cell death-1 monoclonal antibody, currently representing the first-line treatment for advanced melanoma. Apart from registration trials, there is a paucity of data on its effectiveness and safety in a real-world setting. We retrospectively analyzed patients with metastatic melanoma treated at our institution in the context of an Expanded Access Program. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Overall, 42 melanoma patients were treated. BRAF status was wild type in 30 (71%) patients and mutated in 12 (29%). Twelve (29%) patients received pembrolizumab as the II line treatment, the other 30 (71%) as at least III line treatment. One (2%) patient experienced complete response, six (14%) partial response, and seven (17%) stable disease; 39 (93%) patients had disease progression. Median progression-free survival and overall survival were 2.4 (range: 0.2-46.5) and 5.5 months (range: 0.2-47.1), respectively. Results of the multivariate analysis showed that performance status [hazard ratio (HR): 7.10; 95% confidence interval (CI): 2.73-18.4; P<0.001] and the number of previous therapeutic lines (HR: 1.84; 95% CI: 1.08-3.13; P=0.025) influenced progression-free survival. Similarly, performance status (HR: 6.14; 95% CI: 2.44-15.4; P<0.001) and the number of previous lines (HR: 2.04; 95% CI: 1.17-3.56; P=0.012) influenced overall survival. Fourteen (33%) patients reported immune-related adverse events. Three (7%) patients discontinued treatment due to immune-related adverse events onset. At present eight (19%) patients are still alive and one patient is still on treatment. Despite the limitations related to the size and characteristics of this report, our experience confirms the use of pembrolizumab for advanced melanoma in a real-life setting.

Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience.

PURPOSE: Combination therapy with dabrafenib and trametinib is safer and more effective than BRAF inhibitor-based monotherapy for metastatic melanoma. METHODS: We retrospectively analyzed BRAF-mutated metastatic melanoma patients treated at our institution with daily oral dabrafenib 300 mg and trametinib 2 mg from November 2013 to April 2016. This clinical record included both untreated and previously treated stage IV melanomas. Physical examination and laboratory examinations were performed monthly and disease re-evaluations were performed every 3 months. RESULTS: A total of 48 patients (24 male, 24 female) with BRAF-mutated metastatic melanoma received dabrafenib and trametinib; median age was 48 years (range 23-75). Median follow-up was 362.5 days (range 72-879). Best overall response rate consisted of 6.2% (3 patients) complete response, 64.6% (31) partial response, and 25% (12) stable disease; median time to best response was 11 weeks (range 5.7-125.5). Progression of disease was seen in 19 patients (39.6%), with median time to progression (TTP) of 26 weeks (range 8-54). A total of 15 patients (31.2%) died due to progression of disease. Median progression-free survival and median overall survival were not reached. To date, 30 patients (62.5%) are still under treatment. A total of 27 (56.2%) patients had at least one adverse event (AE); grade 3-4 AEs were seen in 4 cases (8.3%). The main toxicities were fever (25%), skin rash (14.6%), arthralgias (10.4%), and aspartate aminotransferase/alanine aminotransferase increase (8.3%). Treatment dose was reduced in 7 subjects (14.6%), with only one case of discontinuation due to AE. CONCLUSIONS: Our data, using combined targeted therapy, are in line with the scientific literature in terms of both safety and effectiveness in a real-life setting.

Prediction of survival in patients with thin melanoma: results from a multi-institution study.

PURPOSE: Cutaneous melanoma incidence is increasing. Most new cases are thin (≤ 1 mm) with favorable prognoses, but survival is nonetheless variable. Our aim was to investigate new prognostic factors and construct a nomogram for predicting survival in individual patients. PATIENTS AND METHODS: Data from 2,243 patients with thin melanoma were retrieved from prospectively maintained databases at six centers. Kaplan-Meier survival and crude cumulative incidences of recurrence were estimated, and competing risks were taken into account. Multivariable Cox regression was used to investigate survival predictors. RESULTS: Median follow-up was 124 months (interquartile range, 106 to 157 months); 12-year overall survival was 85.3% (95% CI, 83.4% to 87.2%). Median times to local, regional, and distant recurrence were 79, 78, and 107 months, respectively. Relapse was significantly related to age, Breslow thickness, mitotic rate (MR), ulceration, lymphovascular invasion (LVI), and regression; incidence was lower and subgroup differences were less marked for distant metastasis than for regional relapse. The worst prognosis categories were age older than 60 years, Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, presence of LVI, and regression ≥ 50%. Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, and LVI (all P = .001) were significantly associated with sentinel node positivity. Age, MR, ulceration, LVI, regression, and sentinel node status were independent predictors of survival and were used to construct a nomogram to predict 12-year overall survival. The nomogram was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.88). CONCLUSION: Our findings suggest including LVI and regression as new prognostic factors in the melanoma staging system. The nomogram appears useful for risk stratification in clinical management and for recruiting patients to clinical trials.

Accuracy and prognostic value of sentinel lymph node biopsy in head and neck melanomas.

BACKGROUND: Debate remains around the accuracy and prognostic implications of sentinel lymph node biopsy (SLNB) for melanoma arising in the head and neck (HN) areas because several analyses have shown discordances between clinically predicted lymphatic drainage pathways and those identified by lymphoscintigraphy. This study assesses the accuracy and prognostic value of SLNB in this critical anatomic region. METHODS: Retrospective review of a prospectively collected melanoma database identified 331 patients with HN melanomas from January 2000 to December 2012. Primary end points included SLNB result, time to recurrence, site of recurrence, and survival. Multivariate models were constructed for analyses. RESULTS: A sentinel lymph node (SLN) was identified in all 331 patients. There were 59 patients with a positive SLN (17.8%) with a recurrence rate of 88.1% compared with 22.4% in SLN-negative patients (P < 0.0001). The 5-y overall survival was 91.2% for SLN-negative patients and 48.7% for SLN-positive patients (P < 0.0001). Patients with scalp melanoma had thicker lesions and an elevated risk of SLN positivity, recurrence, and death compared with those with other sites. Among the 272 SLN-negative patients, four patients developed regional nodal disease in the same basin and had undergone a previous SLNB procedure for a false-omission rate of 1.45%. Risks for false-negative SLN occurrences included thick and scalp melanomas. Multivariate analysis on prognostic factors affecting relapse-free survival showed positive SLNB status to be the most prognostic clinicopathologic predictor of recurrence (hazard ratio, 20.56; P < 0.0001). CONCLUSIONS: SLNB for patients with HN melanomas is an accurate procedure and has prognostic value.

The use of polytetrafluoroethylene to facilitate the vascular access in recurrent melanoma to limbs.

INTRODUCTION: Melanoma with recurrent loco-regional metastases to limbs often makes difficult a second surgical approach because of the adhesions affecting the vascular access. Our aim was to evaluate whether the placement of a polytetrafluoroethylene (PTFE) membrane around vessels might facilitate a surgical re-approach. PRESENTATION OF CASE: We reported a case of a 64-year-old male with a melanoma on the left foot who developed in transit metastases after LND. While performing the inguinopelvic LND we coated the iliac vessels with PTFE patch to facilitate the vascular access in case of re-intervention for a ILP. In the second surgical approach we made a cutaneous incision in the left iliac region and we proceeded through the subcutaneous tissue until detection of iliac vessels, more clearly visible because of the PTFE patch fixed around vascular walls to minimize adhesions. We removed the PTFE coating and easily performed arteriotomy and venotomy for the completion of the ILP. DISCUSSION: This case report seems to demonstrate the efficacy of a PTFE membrane applied in a patient around iliac vessels during inguinopelvic dissection, to reduce adhesion density. In fact this membrane provided a barrier to adhesions of the iliac vessels, decreasing the risk of vascular injury thereby facilitating a subsequent vascular access. Re-coating of the iliac vessels with PTFE could be preparatory to a better identification of the vascular structures in cases of a surgical re-approach. CONCLUSION: The use of PTFE effectively simplifies the second approach to vessels in event of a melanoma metastasizing to limbs.

Small nodular melanoma: the beginning of a life-threatening lesion. A clinical study on 11 cases.

AIMS AND BACKGROUND: Because of its high thickness, nodular melanoma often bears a poor prognosis. Thus, an earlier diagnosis of this type of lesion while it is still thin would be an important step in secondary prevention. The principal aim of the present study was to better define the initial clinical features of nodular melanoma to allow an early diagnosis. A secondary aim was to establish the prognosis of this type of lesion. METHODS: We retrospectively studied and illustrated the clinical features of 11 small (< or = 6 mm maximum diameter) cutaneous nodular melanomas seen and treated during a 10-year period. Prognostic characteristics of the various lesions were also described. RESULTS: The results of the study help to describe a small nodular melanoma as a dark and/or pink/red raised lesion, which may be evenly or unevenly colored, with well-defined borders, that often appears de novo. A correct clinical diagnosis was made in 7 of the cases. During a median follow-up of 6 years, none of the patients had local or distant relapses. CONCLUSIONS: Detection of small nodular melanoma is feasible by accurate visual inspection, provided that physicians are aware of this type of lesion and maintain the index of suspicion at a high level to bring about curative surgery.

Metamorphosis of melanoma. Trends in size and thickness of cutaneous melanoma over one decade at the Istituto Nazionale Tumori, Milan.

AIMS AND BACKGROUND: Messages about the description of the clinical features of cutaneous melanoma (CM) have remained unchanged since 1985, when the ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) rule for melanoma detection was formulated. Given the significant shift to the diagnosis of earlier-stage CMs over the past decades, it is reasonable to think that also the clinical aspects of the disease might have changed. The aim of this study was to examine trends in the presentation of CM over the last decade at our Institution, focusing on two characteristics of the disease: size and thickness. METHODS: A retrospective study was conducted including 1,603 primary invasive CMs seen and treated at the Unit for Melanoma Detection at our Institute between January 1997 and December 2006. RESULTS: The results showed a trend towards smaller CMs, with a difference of 3 mm in median size from the beginning to the end of the period. Detection of small (< or =6 mm) CMs increased at a rate of about 1.5% per year, with a current ratio of 25% with respect to all CMs. Thickness remained substantially unchanged over time. CONCLUSIONS: Physicians must be aware that the characteristics of melanoma have undergone a metamorphosis over the years and the ABCD signs cannot be relied on for adequate sensitivity to further the early detection of CM.

Basal cell carcinomas of the areola-nipple complex: case reports and review of the literature.

Two white men 57 and 39 years old, and a 47-year-old white woman were seen with slowly developing papulo-nodular lesions of the areola-nipple complex. None of the patients presented with regional lymphadenopathy, history of trauma, or relevant sun-exposure. After excison of the mass, the histologic diagnosis of basal cell carcinoma was made. At two years of follow-up, no recurrence was evident. The low incidence of basal cell carcinoma in this particular site allows us to consider the areola-nipple complex location as unusual. Moreover, literature reports do not suggest that these BCCs have an increased potential for malignancy. The treatment options depend on the extension of the tumor and on the possible involvement of the areola-nipple complex and mammary tissue.

Factors of delay in the diagnosis of melanoma.

Delay in the diagnosis of melanoma was defined as the interval in months from the patient's report of first noticing a suspected lesion to the date of the removal of a histologically confirmed melanoma. 216 patients were included in our study. Total delay was subdivided in three components: patient, medical and referral delay. The major component of delay is due to the patient and the most important cause of it was lack of concern. Lesions in men were detected more frequently by family members, while in women melanomas tended to be self-detected. Nodular melanoma had lower delay but higher thickness. Amelanotic melanomas had a higher delay principally due to the physicians. A significative positive correlation between Breslow thickness and patient delay was observed. The visibility of the tumor and the educational or socio-economic status did not seem to improve early diagnosis. The observation about the shorter delays in thicker tumors lead us to think that educational campaigns should be more focused on recognition of changing or growing lesions than other signs of the ABCD rule and that nodular melanomas are quite different from superficial spreading melanomas.