Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma.

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies.

Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management. METHODS: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up. RESULTS: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient's comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards. CONCLUSION: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil.

Local therapy in advanced melanoma after immune checkpoint inhibitors aiming to achieve complete response.

Background and Objectives: New scenarios for local therapy have arisen after starting immune checkpoint inhibitors (ICIs) to treat advanced melanoma (AM). The aim of this study is to examine the role of local therapies with curative intention for patients with AM that have been on ICI. Methods: This was a single institution, retrospective analysis of unresectable stage III or IV melanoma patients on treatment with anti-PD1 ± anti-CTLA-4 who underwent local therapy with curative intention with no other remaining sites of disease (NRD). Results: Of the 170 patients treated with ICI, 19 (11.2%) met the criteria of curative intention. The median time on ICI before local therapy was 16.6 months (range: 0.92-43.2). At the time of the local treatment, the disease was controlled in 16 (84.25%) and progressing in 3 patients (15.75%); 14 patients (73.7%) treated a single lesion and 5 (26.3%) treated 2 to 3 lesions. In a median follow-up of 17 months (range: 1.51-38.2) after the local therapy and 9.8 months after the last ICI cycle (range: 0.56-31), only 2 (10.5%) out of 19 patients relapsed. Conclusions: Patients with AM on treatment with ICI were able to achieve NRD after local treatment and may benefit from long-term disease control without systemic treatment.

Multiple Primary Melanoma: A Five-Year Prospective Single-Center Follow-Up Study of Two MC1R R/R Genotype Carriers.

BACKGROUND: Multiple primary melanoma (MPM) is a diagnostic challenge even with ancillary imaging technologies available to dermatologists. In selected patients' phenotypes, the use of imaging approaches can help better understand lesion characteristics, and aid in early diagnosis and management. METHODS: Under a 5-year prospective single-center follow-up, 58 s primary melanomas (SPMs) were diagnosed in two first-degree relatives, with fair skin color, red hair, green eyes, and personal history of one previous melanoma each. Patients' behavior and descriptive demographic data were collected from medical records. The information on the first two primary melanomas (PMs) were retrieved from pathology reports. The characteristics of 60 melanomas were collected from medical records, video dermoscopy software, and pathology reports. Reflectance confocal microscopy (RCM) was performed prior to excision of 22 randomly selected melanomas. RESULTS: From February 2018 to May 2023, two patients underwent a pooled total of 214 excisional biopsies of suspect lesions, resulting in a combined benign versus malignant treatment ratio (NNT) of 2.0:1.0. The number of moles excised for each melanoma diagnosed (NNE) was 1.7:1.0 and 6.9:1.0 for the female and male patient respectively. The in-situ melanoma/invasive melanoma ratio (IIR) demonstrated a higher proportion of in-situ melanomas for both patients. From June 2018 to May 2023, a total of 58 SPMs were detected by the combination of total body skin exam (TBSE), total body skin photography (TBSP), digital dermoscopy (DD), and sequential digital dermoscopy imaging (SDDI) via comparative approach. The younger patient had her PM one month prior to the second and third cutaneous melanomas (CMs), characterizing a case of synchronous primary CM. The male older relative had a total of 7 nonsynchronous melanomas. CONCLUSIONS: This CM cohort is composed of 83.3% in-situ melanoma and 16.7% invasive melanoma. Both patients had a higher percentage of SPM with clinical nevus-like morphology (84.5%), global dermoscopic pattern of asymmetric multiple component (60.3%) and located on the lower limbs (46.6%). When RCM was performed prior to excision, 81% of SPM had features suggestive of malignancy. As well, invasive melanomas were more frequent in the lower limbs (40%). In the multivariate model, for the two high-risk patients studied, the chance of a not associated with nevus ("de novo") invasive SPM diagnosis is 25 times greater than the chance of a diagnosis of a nevus-associated invasive SPM.

Role of Annexin A1 Secreted by Neutrophils in Melanoma Metastasis.

Annexin A1 (AnxA1) is highly secreted by neutrophils and binds to formyl peptide receptors (FPRs) to trigger anti-inflammatory effects and efferocytosis. AnxA1 is also expressed in the tumor microenvironment, being mainly attributed to cancer cells. As recruited neutrophils are player cells at the tumor sites, the role of neutrophil-derived AnxA1 in lung melanoma metastasis was investigated here. Melanoma cells and neutrophils expressing AnxA1 were detected in biopsies from primary melanoma patients, which also presented higher levels of serum AnxA1 and augmented neutrophil-lymphocyte ratio (NLR) in the blood. Lung melanoma metastatic mice (C57BL/6; i.v. injected B16F10 cells) showed neutrophilia, elevated AnxA1 serum levels, and higher labeling for AnxA1 in neutrophils than in tumor cells at the lungs with metastasis. Peritoneal neutrophils collected from naïve mice were co-cultured with B16F10 cells or employed to obtain neutrophil-conditioned medium (NCM; 18 h incubation). B16F10 cells co-cultured with neutrophils or with NCM presented higher invasion, which was abolished if B16F10 cells were previously incubated with FPR antagonists or co-cultured with AnxA1 knockout (AnxA1-/-) neutrophils. The depletion of peripheral neutrophils during lung melanoma metastasis development (anti-Gr1; i.p. every 48 h for 21 days) reduced the number of metastases and AnxA1 serum levels in mice. Our findings show that AnxA1 secreted by neutrophils favors melanoma metastasis evolution via FPR pathways, addressing AnxA1 as a potential biomarker for the detection or progression of melanoma.

Terapia a laser de baixa potência no manejo da cicatrização de feridas cutâneas / Low-level laser therapy in the management of skin wound healing

Introdução: O reparo tecidual e a cicatrização de feridas cutâneas são processos complexos que envolvem uma série de eventos dinâmicos, incluindo coagulação, inflamação, formação de tecido de granulação, contração da ferida e remodelação tecidual. A necessidade de cuidar de pacientes com dificuldades na cicatrização de feridas é um desafio crescente e requer estratégias inovadoras. Uma abordagem que se destaca no tratamento dessas lesões é a laserterapia de baixa potência. Este estudo tem como objetivo demonstrar a aplicabilidade e os resultados de um protocolo de laserterapia de baixa potência no manejo da cicatrização de feridas cutâneas. Métodos: Trata-se de estudo retrospectivo de revisão de casos relatando o uso de laser no tratamento de feridas cutâneas em um centro único. Resultados: Avaliamos os resultados do uso de laserterapia de baixa potência e relatamos cinco casos de pacientes com feridas cutânea que não apresentaram melhora com o tratamento convencional. As lesões eram localizadas em sítios diversos, com lesão no tronco, membro superior e membro inferior. Os cinco casos apresentaram uma boa resposta com a terapia a laser, evoluindo com a cicatrização das feridas em um curto período de tempo, com período médio de cicatrização de 48 dias. Conclusão: Conclui-se que a laserterapia de baixa potência quando aplicada sobre feridas cutâneas sugere uma ação benéfica, promissora e tem um potencial para aumentar as opções terapêuticas disponíveis para o cirurgião, porém, como relatamos um número de cinco casos, há necessidade de mais estudos para verificar a eficiência do laser em feridas.

Introduction: Tissue repair and skin wound healing are complex processes that involve a series of dynamic events, including coagulation, inflammation, granulation tissue formation, wound contraction and tissue remodeling. The need to care for patients with difficulties in wound healing is a growing challenge and requires innovative strategies. One approach that stands out in the treatment of these injuries is low-power laser therapy. This study aims to demonstrate the applicability and results of a low-power laser therapy protocol in the management of skin wound healing. Methods: This is a retrospective case review study reporting the use of laser in the treatment of skin wounds in a single center. Results: We evaluated the results of the implementation of this low-power laser therapy protocol and reported five cases of patients with skin wounds that did not improve with conventional treatment. The lesions were located in different places, with lesions on the trunk, upper limb and lower limb. The five cases showed a good response to laser therapy, evolving with wound healing in a short period of time, with an average healing time of 48 days. Conclusion: It is concluded that low power laser therapy when applied to skin wounds suggests a beneficial, promising action and has the potential to increase the therapeutic options available to the surgeon, however as we report a number of five cases, further studies are needed for check laser efficiency on wounds.

Manejo de defeitos complexos do couro cabeludo após excisão de tumores malignos / Management of complex scalp defects after excision of malignant tumors

Introdução: A reconstrução do couro cabeludo após a ressecção oncológica continua sendo um desafio para o cirurgião, especialmente considerando a incidência crescente de câncer de pele entre pacientes idosos. A matriz dérmica (MD) é um grupo heterogêneo de materiais de cobertura de feridas que auxiliam no fechamento da ferida e substituem algumas das funções da pele, temporária ou permanentemente. Pacientes com maior risco cirúrgico podem se beneficiar do uso de MD, que ajuda a gerar uma nova derme, oferecendo grandes melhorias na cobertura de defeitos complexos e extensos. Métodos: É um trabalho retrospectivo com análise de prontuário e relato de dois casos de pacientes do A.C.Camargo Cancer Center-SP, Brasil. Resultados: Relatamos dois casos de defeitos complexos e extensos de couro cabeludo em um centro único usando MD associada a enxerto cutâneo e terapia de pressão negativa (TPN) na cirurgia reconstrutiva após ressecção de neoplasia maligna da pele com resultados funcionais e estético satisfatório. Conclusões: As lesões extensas do couro cabeludo são um desafio na prática clínica e um tratamento multidisciplinar é fundamental. Os resultados obtidos indicam que a MD associada com a enxertia de pele parcial e com a TPN tem enorme potencial para aumentar as opções terapêuticas disponíveis para o cirurgião e possivelmente beneficiando os pacientes, especialmente aqueles que não têm condições clínicas para uma cirurgia extensa de cobertura com retalho microcirúrgico.

Introduction: Scalp reconstruction after cancer resection remains a challenge for surgeons, especially considering the increasing incidence of skin cancer among elderly patients. Dermal matrix (DM) is a heterogeneous group of wound covering materials that aid in wound closure and replace some of the skins functions, either temporarily or permanently. Patients at higher surgical risk can benefit from the use of DM, which help to generate a new dermis, offering great improvements in coverage of complex and extensive defects Methods: It is a retrospective study with analysis of medical records and report of two cases of patients at the A.C.Camargo Cancer Center-SP, Brazil. Results: We report two cases of complex and extensive scalp defects at a single center using DM associated with skin grafting and negative pressure therapy (NPT) in reconstructive surgery after resection of malignant skin neoplasm with satisfactory functional and esthetic results. Conclusions: Extensive lesions of the scalp are a challenge in clinical practice and a multidisciplinary treatment is essential. The results obtained indicate that DM associated with partial skin grafting and NPT have enormous potential to increase the therapeutic options available to the surgeon and possibly benefit patients, especially those who do not have the clinical conditions for extensive coverage surgery with microsurgical flap.

Intraoperative assessment of surgical margins using ‟en face" frozen sections in the management of cutaneous carcinomas

Abstract Background: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative ‟en face" freezing technique evaluates all peripheral and deep margins. Objective: To report the results of the ‟en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. Methods: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. Results: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative ‟en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. Study limitations: Not having a minimum follow-up time of 5 years for all patients. Conclusion: The ‟en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Intraoperative assessment of surgical margins using "en face" frozen sections in the management of cutaneous carcinomas.

BACKGROUND: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative "en face" freezing technique evaluates all peripheral and deep margins. OBJECTIVE: To report the results of the "en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. METHODS: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. RESULTS: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative "en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. STUDY LIMITATIONS: Not having a minimum follow-up time of 5 years for all patients. CONCLUSION: The "en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.

Agreement Between Optoelectronic Volumetry and Circumferential Girth Measurements to Diagnose Lymphedema in Patients Submitted to Axillary Radical Lymphadenectomy for Treatment of Cutaneous Melanoma.

Background: To assess the agreement between indirect and optoelectronic volumetries to diagnose lymphedema based on arm volume difference in patients with axillary lymph node dissection (ALND) for cutaneous melanoma. Methods and Results: Patients were assessed by circumferential girth measurements (truncated cone formula) to determine the upper limb volumes (indirect volumetry) and by optoelectronic volumetry (Perometer®) of affected and control limbs. A diagnosis of lymphedema on each measuring method was defined as an absolute volume difference >200 mL or a relative volume >10%. Forty-six patients with ALND were included. There were no significant differences between the volume means or the mean absolute or relative differences measured by each method. Good correlation was observed between the volume of upper limbs for both the left (r = 0.998) and right (r = 0.985) arms. As for the diagnosis of lymphedema, an absolute volume difference >200 mL determined a prevalence of 28% (13/46) of lymphedema by indirect volumetry and 35% (16/46) by optoelectronics volumetry. The crude diagnostic agreement was 93% with a kappa = 85% (agreement adjusted by chance) between methods. If a 10% increase in the relative volume difference between the arms was used as the diagnostic criterion, prevalence was 20% (9/46) and 22% (10/46), respectively. Conclusion: There is good agreement between perometry and circumferential girth measurements when classifying patients as having a difference between arm volumes >200 mL or 10%, the most frequently used cutoffs to diagnose lymphedema.

How does the mitotic index impact patients with T1 melanoma? Comparison between the 7th and 8th edition of the American Joint Committee on Cancer melanoma staging system

Abstract Background: The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. Objectives: To evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. Material and methods: This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. Results: Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). Study limitation: Unicentric study. Conclusion: The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.

Primary cutaneous melanoma of the scalp: Patterns of clinical, histological and epidemiological characteristics in Brazil.

BACKGROUND/OBJECTIVES: Scalp melanoma is a subgroup of melanomas on the head and neck, historically associated with worst prognosis. Knowledge of the usual presentation of scalp melanoma can help to understand the reasons for the poor outcomes of treatment. This is the first publication to describe the clinical, histopathological and epidemiological profile of patients with scalp melanoma in a Latin American population. METHODS: A cross-sectional study was performed of all primary cutaneous melanoma seen by the A.C.Camargo Cancer Center between 2008 and 2018, using an electronic health records to access clinical and pathology data. RESULTS: When compared to trunk and limbs, increasing age is expected for patients with scalp melanoma (10.865; CI (95%) = [8.303; 13.427]). Regarding risk of invasion, scalp melanomas have a higher chance to be invasive than in situ (OR = 1.783; CI (95%) = [1.196; 2.657]) and present with higher Breslow thickness (OR = 3.005; CI (95%) = [2.507; 3.601]). Scalp site was significantly associated with male sex (OR = 3.750; CI (95%) = [2.533; 5.554]), perineural invasion (OR = 13.739; CI (95%) = [5.919; 31.895]), ulceration (OR = 2.311; CI (95%) = [1.488; 3.588]), and mitosis (OR = 2.366; CI (95%) = [1.701; 3.292]), when compared to trunk and limbs melanoma. CONCLUSION: In the present study, head and neck melanomas represented 14.9% of all melanomas, a frequency slightly lower than that described in the literature and the mean age of melanoma on the scalp found was lower than that reported in the literature. These results could be explained by the demographic characteristics of Brazil, which has a population with a lower life expectancy compared to the European and North American population. Scalp melanomas occurred in older men, were diagnosed with greater Breslow thickness and were associated with the presence of perineural invasion, mitosis and ulceration.

Sentinel Node Status is the Most Important Prognostic Information for Clinical Stage IIB and IIC Melanoma Patients.

BACKGROUND: Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario. METHODS: This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS. RESULTS: From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73 months (95% CI 21.38-50.08, SE 7.32) and median MSS of 66.4 months (95% CI 29.76-103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS). CONCLUSIONS: SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.

Demographic, Clinical, and Pathologic Features of Patients With Cutaneous Melanoma: Final Analysis of the Brazilian Melanoma Group Database.

PURPOSE: National epidemiologic data on melanoma are scarce in Brazil. The current work presents final demographic, clinical, and pathologic results from the Brazilian Melanoma Group database to detail how patients with melanoma present at diagnosis. METHODS: The online database includes patients diagnosed between 1982 and 2015 and evaluated at their centers of origin between 2001 and 2016. The primary objective was to describe the demographic, clinical, and pathologic characteristics of the patients, and secondary objectives were to investigate the association between clinical and pathologic variables of interest. RESULTS: A total of 1,596 patients were included. Median age was 52 years, 57% were women, and the majority were identified as white. Invasive melanoma was diagnosed in 1,297 patients, mostly localized, whereas 299 (19%) had in situ disease (TisN0M0). Only 165 patients had initial lymph node involvement. Fitzpatrick skin types I or II were slightly more frequent with in situ melanoma (73%) than with invasive disease (67%; P = .054). The median Breslow thickness was 0.95 mm, Clark levels 2 and 3 comprised nearly 70% of cases, and ulceration was present in 18% of patients. The mitotic rate was significantly associated with the presence of ulceration and both vascular and perineural invasion but not with margin positivity, whereas histologic regression was associated with both intratumoral and peritumoral inflammatory infiltrates. CONCLUSION: Despite the limitations of an observational, registry-based study, the current results provide a general profile of patients with cutaneous melanoma in Brazil at the time of diagnosis.

A nomogram to identify high-risk melanoma patients with a negative sentinel lymph node biopsy.

BACKGROUND: Melanoma patients with negative nodes after sentinel lymph node biopsy are a heterogeneous group. Current guidelines fail to adequately stratify surveillance and treatment for this group. Also, there is scarce data on adjuvant treatments for these patients. OBJECTIVE: To create a nomogram including clinical and pathologic characteristics capable of evaluating the risk for recurrence of primary melanoma patients with negative sentinel lymph node biopsies (SLNBs). METHODS: We used a retrospective cohort of patients who underwent SLNB during 2000-2015 at a single institution. RESULTS: Our cohort comprised 1213 patients. Among these patients, 967 (79.7%) had a negative SLNB, and mean follow-up was 59.67 months. There were 133 recurrences (13.8%); 45 (33.8%) presented with nodal recurrence, and 35 (26.3%) recurred where a SLNB was performed. Breslow thickness, ulceration, and microsatellitosis were found to be predictive of risk for recurrence at 1, 2, 5, and 10 years. LIMITATION: Single center analysis. CONCLUSION: We created a predictive nomogram for melanoma patients with negative SLNBs. This nomogram is easy to use and identifies high-risk patients who should have more strict surveillance and be considered for adjuvant treatment.

Validation of a Nomogram for Non-sentinel Node Positivity in Melanoma Patients, and Its Clinical Implications: A Brazilian-Dutch Study.

BACKGROUND: Non-sentinel node (NSN) positivity impacts the prognosis of melanoma patients; however, the benefits of completion lymph node dissection in patients with positive sentinel nodes (SNs) are limited. OBJECTIVE: We aimed to present a predictive nomogram for NSN positivity in melanoma patients with a positive SN biopsy. METHODS: This retrospective analysis from patients who underwent SN biopsy in a Brazilian institution from 2000 to 2015 was used for the construction and internal validation of the nomogram. This nomogram was then externally validated in a cohort of Dutch patients. RESULTS: The Brazilian cohort comprised 1213 patients, with a mean follow-up of 5.11 years. Breslow thickness (odds ratio [OR] 1.170, 95% confidence interval [CI] 1.043-1.314]; p = 0.008), number of positive SNs (OR 1.092, 95% CI 1.034-1.153; p = 0.001), and largest diameter of the metastatic deposit (OR 3.217, 95% CI 1.551-6.674; p = 0.002) were statistically significant for NSN positivity. Internal validation was performed using a bootstrapping technique. A good performance was observed (Brier score 0.097) and an excellent power of discrimination was achieved (area under the curve [AUC] 0.822). The nomogram was then applied to the Dutch cohort, and its overall performance (Brier score 0.085), calibration (Hosmer-Lemeshow goodness-of-fit test; p = 0.198), and discriminatory power (AUC 0.752, 95% CI 0.615-0.890) were all adequate. CONCLUSIONS: We presented a nomogram for assessing NSN probability that should not only be used for surgical considerations but also for risk stratification and clinical decisions. Internal validation has shown that this is an adequate model, while external validation increases the model's reliability and suggests that it can be globally incorporated.

Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience.

Diphencyprone has been reported as a local immunotherapy for cutaneous melanoma metastases. We aim to report cases of melanoma patients treated with diphencyprone in a single Brazilian institution and highlight their outcomes. Since 2012, we have treated 16 melanoma patients with cutaneous metastases with topical diphencyprone. To date, we have had 37.5% of complete response, 25% of partial responses, and 31.25% patients without any response. Treatment was well tolerated and local toxicity was easily controlled. We believe topical diphencyprone is a feasible treatment that can be another option for treating melanoma patients, especially in cases of in-transit or extensive disease.