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.

Long-term vemurafenib therapy in advanced melanoma patients: cutaneous toxicity and prognostic implications.

BACKGROUND: The introduction of targeted therapies for the treatment of BRAF-mutated metastatic melanoma was associated with different cutaneous adverse events (AEs). OBJECTIVES: To describe the type, frequency and severity of cutaneous AEs related to vemurafenib; to understand the association between AEs and vemurafenib efficacy in terms of median overall survival (OS) and median progression-free survival (PFS); to identify molecular characteristics of long-term responders. METHODS: This observational, retrospective, monocentric study included all consecutive patients with unresectable stage III or stage IV melanoma and BRAF V600E mutation that started treatment with vemurafenib between May 2012 and May 2014. RESULTS: 62 patients with a median age of 56 years (range 26-82) were enrolled and received vemurafenib for a median period of 7.9 months (range 0.8-63.7). Among them, 45 patients presented at least one skin AE, 12 reduced the dosage due to cutaneous toxicity, and only one firstly reduced and after stopped the therapy. No specific molecular biomarkers were detected in long-term survivors. CONCLUSIONS: Among long-term survivors, skin AEs seem to be less frequent and less severe. Results on multivariable analysis revealed that the presence of at least one G2 toxicity is a protective factor considering PFS, but not in terms of OS.

Neoplastic and inflammatory skin disorders and serum levels of polychlorinated biphenyls in a population living in a highly polluted area.

BACKGROUND: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions. OBJECTIVES: To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders. MATERIALS & METHODS: Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases. RESULTS: No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error. CONCLUSION: Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy.

Panniculitis and vitiligo-like lesions have been recently identified as rare cutaneous side effects of the combination of BRAF and MEK inhibitors, a standard of care in metastatic and locally advanced BRAF V600 mutated melanoma. An immune-mediated mechanism has been advocated in the pathogenesis of these skin lesions. Herein we retrospectively reviewed our institutional experience with the aim to explore the association between the occurrence of panniculitis and vitiligo-like lesions during combination therapy with dabrafenib (D) and trametinib (T) and outcome of advanced melanoma patients. Among 52 consecutive BRAF V600 mutated melanoma patients submitted to DT in our center, 12 (23%) developed immune related skin lesions (IRSLs): 8 panniculitis and 4 vitiligo. Patients with IRSLs diagnosis obtained a better disease response (83% versus 25%) (p = 0.001) than their counterpart and had a longer progression free survival and overall survival. The association of IRSLs and lower risk of disease progression (HR 0.19; CI 95% 0.04-0.90; p = 0.043) was confirmed after adjusting for major prognostic factors in multivariate analysis. IRSLs might represent an easy predictive surrogate marker for treatment response and favourable outcome in melanoma patients submitted to DT combination therapy.

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.

Melanoma density and relationship with the distribution of melanocytic naevi in an Italian population: a GIPMe study--the Italian multidisciplinary group on melanoma.

The most frequent site for melanoma is the back in men and the lower limbs in women, where intermittent sun exposure has been reported to be an environmental agent, although studies on age-specific incidence have suggested that melanoma in chronically sun-exposed areas, such as the face, increases with age. To identify the preferential development of melanoma in chronically or intermittently sun-exposed areas and the relationship between body site distribution and parameters such as sex, age, distribution of melanocytic naevi, atypical naevi and actinic keratoses, a prospective epidemiological multicentre study was carried out on all the consecutive melanoma cases diagnosed in a 2-year period from 27 Italian GIPMe centres (GIPMe: the Italian Multidisciplinary Group on Melanoma). Both the relative density of melanoma (RDM), defined as the ratio between observed and expected melanoma for a specific body site, and the average nevi density were identified. The most common melanoma site was the back, a factor that was not affected by either age or sex, even if men had higher density values. Statistically significant higher RDM values were observed in women aged more than 50 years for leg lesions and in the anterior thighs for young women (<50 years), whereas the lowest values were observed in the posterior thighs in women of any age. Facial RDM was statistically significantly higher than expected in both male and female patients more than 50 years of age. Melanoma was associated with a significantly higher atypical naevi density only for the back, chest and thighs. Indeed, facial melanoma was related to the presence of more than four actinic keratoses and not naevi density. To the best of our knowledge, the RDM method was applied for the first time together with naevus density calculation to obtain these data, which strongly substantiate the 'divergent pathway' hypothesis for the development of melanoma, but not find a direct correlation between melanoma and nevi for each anatomical site.

Recurrent melanocytic nevi and melanomas in dermoscopy: results of a multicenter study of the International Dermoscopy Society.

IMPORTANCE Differentiating recurrent nevi from recurrent melanoma is challenging. OBJECTIVE To determine dermoscopic features to differentiate recurrent nevi from melanomas. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of 15 pigmented lesion clinics from 12 countries; 98 recurrent nevi (61.3%) and 62 recurrent melanomas (38.8%) were collected from January to December 2011. MAIN OUTCOMES AND MEASURES Scoring the dermoscopic features, patterns, and colors in correlation with the histopathologic findings. RESULTS In univariate analysis, radial lines, symmetry, and centrifugal growth pattern were significantly more common dermoscopically in recurrent nevi; in contrast, circles, especially if on the head and neck area, eccentric hyperpigmentation at the periphery, a chaotic and noncontinuous growth pattern, and pigmentation beyond the scar's edge were significantly more common in recurrent melanomas. Patients with recurrent melanomas were significantly older than patients with recurrent nevi (mean [SD] age, 63.1 [17.5] years vs 30.2 [12.4] years) (P<.001), and there was a significantly longer time interval between the first procedure and the second treatment (median time interval, 25 vs 8 months) (P<.001). In a multivariate analysis, pigmentation beyond the scar's edge (P=.002), age (P<.001), and anatomic site (P=.002) were significantly and independently associated with the diagnosis of recurrent melanoma in dermoscopy. CONCLUSIONS AND RELEVANCE Dermoscopically, pigmentation beyond the scar's edge is the strongest clue for melanoma. Dermoscopy is helpful in evaluating recurrent lesions, but final interpretation requires taking into account the patient age, anatomic site, time to recurrence, growth pattern, and, if available, the histopathologic findings of the first excision.

Pigmentation of axillary sentinel nodes from extensive skin tattoo mimics metastatic melanoma: case report.

BACKGROUND: The relationship between the occurrence of skin diseases and skin tattoos remains unclear. Dermatologic disorders have been reported to occur in about 2% of cases. In addition, tattoo pigment can migrate to the regional lymph nodes through the lymphatic vessels and subsequently mimic metastatic disease from melanoma. METHODS: A 23-year-old Caucasian man presented with a pigmented lesion on the left scapular region, which had slowly enlarged over time. The patient exhibited an extensive tattoo on the left upper arm, left shoulder, and part of the upper back. His medical history was unremarkable. The pigmented lesion was excised. Histology confirmed malignant melanoma. Ultrasound examination of the abdomen, neck, and inguinal and axillary lymph nodes and a total body computed tomography scan showed no sign of disease. A re-excision with 2-cm margins and sentinel lymph node biopsy (SLNB) were performed. Two grossly enlarged, black sentinel lymph nodes (SLNs) highly suggestive of melanoma metastases were removed. RESULTS: No evidence of melanoma metastasis was found in any of the sampled tissues. Large amounts of pigment were present within the subcapsular space and sinusoid areas of the two clinically suspicious lymph nodes. Immunohistochemical analysis was negative. CONCLUSIONS: Sentinel lymph node biopsy is widely performed in cutaneous melanoma. Histologic confirmation of any enlarged, pigmented SLN is essential prior to radical surgery, especially when pigmented SLNs are found near a tattoo. Tattoo pigments may deposit in the regional lymph nodes and may clinically mimic metastatic disease. A history of tattooing should be considered in all melanoma patients eligible for SLNB. In a finding of darkly pigmented nodes during SLNB, radical lymphadenectomy should be withheld until immunohistologic confirmation of metastasis in the SLN is obtained.

Dermoscopic, histological and immunohistochemical evaluation of cancerous features in acquired melanocytic nevi that have been repeatedly exposed to UVA or UVB.

Previous studies have reported that repeated solar and artificial UVB (280-320 nm) and UVA (320-400 nm) exposures can modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes in AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least three AMN on the trunk were enrolled in the present study and randomized into two groups to receive equally effective doses of narrow-band (NB)-UVB or UVA1. Three exposures per week were delivered for a total of 4 weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and underwent histological and immunohistochemical assessment of melanocyte/melanogenesis-related proteins (MART-1, tyrosinase, HMB-45), cell cycle activation markers (Ki-67, topoisomerase IIalpha, p53, Cdk2) and transcription factors (microphthalmia-associated transcription factor, STAT3). Nevi that were exposed to NB-UVB or UVA1 also showed statistically significant increase in size and changes in their dermoscopic features, including overall darkening, increased pigment network expression, formation of branched streaks, and increased number and size of brown globules and dots. AMN that had been covered with opaque tape or sunscreen did not show changes in size or dermoscopic features following UVA1 or NB-UVB exposure. Histological and immunohistochemical analysis did not show any significant change in exposed AMN in comparison with AMN shielded with an opaque adhesive tape or covered with the sunscreen.

Cutaneous melanoma in patients in treatment with biological therapy: review of the literature and case report.

Herein we report a case of a melanoma arising in a patient receiving adalimumab and methotrexate for rheumatoid arthritis. A limited number of studies reported melanoma growth in patients undergoing treatment with biologics. This case report with a brief review of literature suggests that patients under treatment with biologics should be counseled to identify new pigmented lesions or changes in preexisting nevi. Clinicians' collaboration will facilitate recognition and timely diagnosis of early melanoma. If there is any doubt, excision for histological evaluation should be considered. Pending new studies, careful observation is encouraged.

Important risk factors in melanoma from the Dermato-Oncologic Unit of Brescia, Italy.

One of the most significant risk factors for melanoma is a positive family history of the disease. It is estimated that approximately 10 percent of melanoma cases report a first-or second-degree relative with melanoma. We reported the experience of the Dermato-Oncologic Unit of Brescia, Italy.