Topographical and Chronological Analysis of Thin Cutaneous Melanoma's Progressions: A Multicentric Study.

A great portion of cutaneous melanoma's diagnoses nowadays is attributed to thin tumors with up to 1 mm in Breslow thickness (hereafter thin CMs), which occasionally metastasize. The objective of this study was to identify thin CM's metastatic patterns from a topographical and chronological standpoint. A total of 204 cases of metastatic thin CMs from five specialized centers were included in the study, and corresponding data were collected (clinical, epidemiological, histopathological information of primary tumor and the number, anatomical site, and time intervals of their progressions). First progressions occurred locally, in regional lymph nodes, and in a distant site in 24%, 15% and 61% of cases, respectively, with a median time to first progression of 3.10 years (IQR: 1.09-5.24). The median elapsed time between the first and second progression and between the second and third progression was 0.82 (IQR: 0.34-1.97) and 0.49 (IQR: 0.21-2.30) years, respectively, while the median survival time was about 4 years since first progression. Furthermore, the sequences of locations and time intervals of the progressions were associated with the clinicopathological and demographic features of the primary tumors along with the features of the preceding progressions. In conclusion, the findings of this study describe the natural history of thin CMs, thus highlighting the necessity to identify subgroups of thin CMs at a higher risk for metastasis and contributing to the optimization of the management and follow-up of thin CM patients.

A prognostic nomogram for the cancer-specific survival of white patients with invasive melanoma at BANS sites based on the Surveillance, Epidemiology, and End Results database.

Objective: The purpose of this study was to develop a comprehensive nomogram for the cancer-specific survival (CSS) of white patients with invasive melanoma at back, posterior arm, posterior neck, and posterior scalp (BANS) sites and to determine the validity of the nomogram by comparing it with the conventional American Joint Committee on Cancer (AJCC) staging system. Methods: This study analyzed the patients with invasive melanoma in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divide the patients into training and validation cohorts at a ratio of 7:3. Multivariable Cox regression was used to identify predictive variables. The new survival nomogram was compared with the AJCC prognosis model using the concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), net reclassification index (NRI), integrated discrimination index (IDI), calibration plotting, and decision-curve analysis (DCA). Results: A novel nomogram was established to determine the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma. According to the nomogram, the Age at Diagnosis had the greatest influence on CSS in invasive melanoma, followed by Bone Metastasis, AJCC, Stage, Liver Metastasis, Histologic Subtype, Brain Metastasis, Ulceration, and Primary Site. The nomogram had a higher C-index than the AJCC staging system in both the training (0.850 versus 0.799) and validation (0.829 versus 0.783) cohorts. Calibration plotting demonstrated that the model had good calibration ability. The nomogram outperformed the AJCC staging system in terms of AUC, NRI, IDI, and DCA. Conclusion: This was the first study to develop and evaluate a comprehensive nomogram for the CSS of white patients with invasive melanoma at BANS sites using the SEER database. The novel nomogram can assist clinical staff in predicting the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma more accurately than can the AJCC staging system.

Management of Advanced Invasive Melanoma: New Strategies.

The incidence of cutaneous melanoma (CM) is increasing. CM is defined as melanoma in situ when limited within the epidermis and invasive when atypical melanocytes progressively invade the dermis. Treatment of CM is challenging. On one hand, melanoma in situ does not require further treatment except for a limited secondary excision with reduced margins to minimize the risk of local recurrences; on the other, invasive melanoma requires a personalized approach based on tumor staging. Consequently, an association of surgical and medical treatments is often necessary for invasive forms of the disease. In this scenario, new knowledge on melanoma pathogenesis has led to the development of safe and effective treatments, and several drugs are currently under investigation. However, extensive knowledge is required to offer patients a tailored-tail approach. The aim of our article was to review current literature to provide an overview of treatment options for invasive melanoma, highlighting strategical approaches that can be used in patients with these forms of disease.

Outcomes of invasive melanoma of the head and neck treated with Mohs micrographic surgery - A multicenter study.

BACKGROUND: There are no randomized controlled trials to guide surgical margins for invasive head and neck (H&N) melanoma using conventional excision. Mohs micrographic surgery (MMS) has shown improved local recurrence rates and survival for invasive H&N melanomas. OBJECTIVE: Determine local recurrence (LR), nodal recurrence, and distant recurrence rates, and disease specific survival for invasive melanoma of the H&N treated with MMS. METHODS: A retrospective multicenter study of 785 cases of invasive H&N melanoma treated with MMS using frozen sections with melanoma antigen recognized by T-cells 1 immunohistochemical staining was performed to evaluate long-term outcomes over 12-years. RESULTS: 785 melanomas (thickness: 0.3 mm-8.5 mm) were treated with MMS. LR, nodal recurrence, and distant recurrence rates were 0.51% (4/785), 1.0% (8/785), and 1.1% (9/785) respectively. For T1, T2, T3, and T4 tumors LR was 0.16% (1/636), 1.18% (1/85), 2.22% (1/45), and 5.26% (1/19), respectively. Five and 10-year disease specific survival were 96.8% (95% CI 95.0% to 98.5%) and 93.4% (95% CI 88.5% to 98.3%). LIMITATIONS: A nonrandomized retrospective study. CONCLUSION: MMS achieves significant improvements in LR compared to a meta-analysis of historical cohorts of patients treated with conventional excision. MMS should be considered an important surgical option for invasive H&N melanoma.

Staged melanoma excision requires larger margins for tumor clearance and results in low rates of recurrence.

There is controversy regarding the optimal surgical modality and ideal recommended margins for treating melanoma in situ (MIS) and invasive melanoma (IM). Although wide local excision is recommended, staged excision offers excellent margin control and low recurrence rates. In this manuscript, we reviewed a 10-year experience of staged excisions for the treatment of MIS and IM. A retrospective review was performed of 130 MIS and 32 IM cases treated with staged excision from April 2012 to April 2022. Staged excision was performed on the head and neck in 102 (79%) MIS and 23 (72%) IM cases. Approximately 10% of cases required surgical margins above the current recommendations (11 (9%) MIS and 6 (19%) IM). Twenty-three (19%) MIS and 7 (22%) IM cases required more than one excision to obtain clearance. Recurrence rates among MIS and IM were 0.0% and 0.6%, respectively. Upstaging occurred in 5 (4%) MIS and 7 (22%) IM cases. Complex repairs were performed on 82 (63%) MIS and 17 (53%) IM cases. Our findings revealed that staged excision provides effective margin control and low recurrence rates. Approximately 10% of patients required margins greater than the current recommendations, leading to larger defects and more complex repairs.

Mohs Micrographic Surgery for Melanoma: Evidence, Controversy, and a Critical Review of Excisional Margin Guidelines.

Evidence supports the safety of Mohs micrographic surgery for melanoma. Because of its potential benefits to the patient in terms of very low-recurrence rates and same-day histologic confirmation of tumor removal with reconstruction of tumor-free margins of potentially smaller wounds, it should be one of the treatment options considered. The informed consent process for the patient should not be complete without a discussion of the attributes of Mohs surgery for melanoma.

Segmenting Skin Biopsy Images with Coarse and Sparse Annotations using U-Net.

The number of melanoma diagnoses has increased dramatically over the past three decades, outpacing almost all other cancers. Nearly 1 in 4 skin biopsies is of melanocytic lesions, highlighting the clinical and public health importance of correct diagnosis. Deep learning image analysis methods may improve and complement current diagnostic and prognostic capabilities. The histologic evaluation of melanocytic lesions, including melanoma and its precursors, involves determining whether the melanocytic population involves the epidermis, dermis, or both. Semantic segmentation of clinically important structures in skin biopsies is a crucial step towards an accurate diagnosis. While training a segmentation model requires ground-truth labels, annotation of large images is a labor-intensive task. This issue becomes especially pronounced in a medical image dataset in which expert annotation is the gold standard. In this paper, we propose a two-stage segmentation pipeline using coarse and sparse annotations on a small region of the whole slide image as the training set. Segmentation results on whole slide images show promising performance for the proposed pipeline.

Early detection of melanoma in specialised primary care practice in Australia.

BACKGROUND: Primary care skin cancer clinics facilitate early treatment of melanoma in Australia. We investigated the clinical and histopathological features of melanomas diagnosed and treated in an established clinic in Brisbane. METHODS: Retrospective audit of medical records of patients diagnosed with in situ or invasive primary cutaneous melanoma in a primary care clinic specializing in skin cancer, 2000-2017. Demographic and clinical data were standardly extracted by a medically-trained investigator. We used descriptive analyses to assess characteristics of patients and melanomas, and examine surgical management according to tumour thickness. RESULTS: Of 380 patients (median age 57 years; 57 % male) newly diagnosed with 497 histologically-confirmed primary cutaneous melanomas, 369 were in situ and 128 invasive. Of the 369 in situ melanomas, 143 (39 %) were on the trunk and 87 (24 %) on the head and neck; 247 (67 %) were diagnosed by shave biopsy; and 141 (38 %) referred for wide local excision (WLE). Of the 128 invasive melanomas, only 21 (16 %) had thickness ≥ 0.8 mm and these occurred more often on head and neck than thin invasive melanomas (p = 0.02). The majority of invasive melanomas were diagnosed by excision biopsy, and WLE was carried out in a median of 3 days (melanomas ≥ 0.8 mm) and 2 days (<0.8 mm). The doctor detected the majority of in situ (83 %) and thin invasive (73 %) melanomas during surveillance, compared with 48 % of thicker invasive melanomas ≥ 0.8 mm (p < 0.001). CONCLUSION: In Australia, specialised primary care practice plays a major role in detection and treatment of early primary melanoma.

Non-surgical management of primary invasive melanoma.

Surgical excision is standard-of-care for primary invasive melanoma, but best care can be unclear for patients who are surgically high-risk or for whom resection may be excessively morbid. Alternatives to surgical excision have emerged for treatment of metastatic melanoma but have not yet been explored for primary invasive melanoma. Two elderly patients with primary invasive melanoma with many medical co-morbidities who were not surgical candidates were determined to be appropriate candidates for an intralesional IL-2 based regimen. Herein we report their clinical and histological outcome. An intralesional-based regimen (intralesional IL-2, topical imiquimod cream 5%, and tretinoin cream 0.1% under occlusion to the treatment site) was administered over the course of six to seven weeks, followed by two weeks of topical-only therapy. A complete response was seen after eight to nine weeks of treating invasive melanomas that were ≥1.85 mm and 5.5 mm thick. For patients with primary invasive melanoma on high morbidity sites and patients who are poor surgical candidates, a neoadjuvant intralesional IL-2-based approach may be a reasonable alternative. The two cases presented here suggest that alternative intralesional-based treatment modalities may minimize the size of the excision site and can be associated with complete histological clearance of invasive melanoma.

Long-term outcomes of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities.

BACKGROUND: Microscopic evaluation of the entire surgical margin during excision of cutaneous malignancies results in the highest rates of complete excision and lowest rates of true local scar recurrence. Few studies demonstrate the outcomes of Mohs micrographic surgery specifically for invasive melanoma of the trunk and proximal portion of the extremities. OBJECTIVE: To evaluate the long-term efficacy of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities, including true local scar recurrence rate, distant recurrence-free survival, and disease-specific survival. METHODS: Prospectively collected study of 1416 cases of invasive melanoma of the trunk and proximal portion of the extremities was performed to evaluate long-term outcomes. RESULTS: True local scar recurrences occurred in our cohort at a rate of 0.14% (2/1416), after a mean follow-up period of 75 months and were not associated with tumor depth. The rate of satellite/in-transit recurrences and the disease-specific survival stratified by tumor thickness were superior to historical control values. LIMITATIONS: We used a nonrandomized, single institution, retrospective design. CONCLUSIONS: Mohs micrographic surgery of primary cutaneous invasive melanoma on the trunk and proximal portion of the extremities resulted in local control of 99.86% of tumors and an overall disease-specific death rate superior to that of wide local excision.

Internal Pathology Review of Invasive Melanoma: An Academic Institution Experience.

BACKGROUND: Prior studies of internal pathology review (IPR) for melanoma have shown that changes in the pathology analysis are common. How these changes impact clinical management of melanoma or how the margin status reports may modify has not been evaluated. Our goal was to determine what changes to staging and surgical management occurred after IPR of newly diagnosed melanomas and to determine how the final surgical pathology report may correlate with the IPR. METHODS: A retrospective study was conducted from 2014 to 2016 of newly diagnosed invasive melanomas referred to a single National Comprehensive Cancer Network tertiary care center. RESULTS: A total of 370 cases met inclusion criteria. The most common feature changed after internal review was mitotic rate, in 155 (41.7%) patients, followed by Breslow depth in 99 (26.9%) patients. Tumor staging was changed in 45 (12.2%) patients. The most common change was a T1a lesion being upgraded to a T1b lesion. These tumor staging changes lead to 38 (10.3%) overall staging differences. A biopsy's deep margin status was changed in 27 (7.3%) patients. Outside hospital reports lacked information about deep margin status in 71 (19.2%) of specimens. Based on the National Comprehensive Cancer Network guidelines, 22 (5.9%) patients had changes in their sentinel lymph node biopsy recommendations and one of these patients had a positive node found on pathology. Of those patients who had changes in the T-stage, 16 (4.3%) of them also had changes in the recommended wide local excision radial margin. CONCLUSIONS: IPR of invasive melanoma leads to both changes in staging and the surgical management of melanoma and should remain an important component of care of melanoma patients at a tertiary referral center.

Residual Tumor on Wide Excisional Margins After Treatment of Invasive Melanoma.

BACKGROUND/AIM: The surgical management of invasive melanoma has been debated for many years and recommended excisional margins have been established. We aimed to describe the factors and survival related to the presence of residual tumor in patients with invasive melanoma lymph nodes negative. PATIENTS AND METHODS: We performed a retrospective study by querying the National Cancer Database from 2004 to 2015. Associations were tested using a multivariate analysis. Overall survival was compared using the Kaplan-Meier method. RESULTS: A total of 26,440 patients met the inclusion criteria. For Breslow depth groups ≤1 mm and >2 mm, older age and location in the head and neck were factors associated to residual tumor in margins (p<0.05), whereas only location in the head and neck was associated to residual tumor for patients with Breslow depth between 1.01-2.00 mm (p<0.05). CONCLUSION: Knowledge of the factors associated with the residual tumor will help establish a patient-centered management and decrease the recurrence of disease.

Wide Excisional Surgery in Invasive Melanoma Treatment: Factors Driving Non-compliance With National Guidelines.

BACKGROUND/AIM: Margin size during wide excisional surgery for invasive melanoma treatment have been established by national guidelines. This study identified factors associated with wider than recommended excisional margins and its impact on survival. PATIENTS AND METHODS: The National Cancer Database was queried to identify patients with primary invasive melanoma. Statistical analysis was performed using univariate and multivariate analysis. Overall survival was compared using Kaplan-Meier method. RESULTS: A total of 26,440 patients were included in the analysis. Melanomas located on the trunk were more likely to be treated using wider than recommended excisional margins for certain Breslow depth groups (p<0.05), while the opposite was true for those being treated in an academic/research program (p<0.05). The practice of taking wider than recommended margins was not associated with improved survival. CONCLUSION: Tumor location and facility type influence non-compliance with the National Comprehensive Cancer Network guidelines. Lack of survival benefit in patients with wider excisional margins seems to support guideline recommendations.

Pathologists' agreement on treatment suggestions for melanocytic skin lesions.

BACKGROUND: Although treatment guidelines exist for melanoma in situ and invasive melanoma, guidelines for other melanocytic skin lesions do not exist. OBJECTIVE: To examine pathologists' treatment suggestions for a broad spectrum of melanocytic skin lesions and compare them with existing guidelines. METHODS: Pathologists (N = 187) completed a survey and then provided diagnoses and treatment suggestions for 240 melanocytic skin lesions. Physician characteristics associated with treatment suggestions were evaluated with multivariable modeling. RESULTS: Treatment suggestions were concordant with National Comprehensive Cancer Network guidelines for the majority of cases interpreted as melanoma in situ (73%) and invasive melanoma (86%). Greater variability of treatment suggestions was seen for other lesion types without existing treatment guidelines. Characteristics associated with provision of treatment suggestions discordant with National Comprehensive Cancer Network guidelines were low caseloads (invasive melanoma), lack of fellowship training or board certification (melanoma in situ), and more than 10 years of experience (invasive melanoma and melanoma in situ). LIMITATIONS: Pathologists could not perform immunohistochemical staining or other diagnostic tests; only 1 glass side was provided per biopsy case. CONCLUSIONS: Pathologists' treatment suggestions vary significantly for melanocytic lesions, with lower variability for lesion types with national guidelines. Results suggest the need for standardization of treatment guidelines for all melanocytic lesion types.

Think before you shave: Factors influencing choice of biopsy technique for invasive melanoma and effect on definitive management.

BACKGROUND/OBJECTIVE: Partial biopsies are sometimes used for melanoma diagnosis with anticipated time and cost savings compared to excisional biopsy. However, their impact on subsequent melanoma management is unknown. Determine factors related to choice of partial over excisional biopsy to diagnose invasive melanoma and examine the effect of partial biopsies on definitive melanoma management. METHOD: Retrospective repeated cross-sectional population-based study through the Victorian Cancer Registry of diagnosed melanomas in 2005, 2010 and 2015. A random sample of 400 patients per year, stratified by tumour thickness, was selected. RESULTS: A total of 1200 patients had 833 excisional and 337 partial biopsies. Omission of suspected diagnosis on pathology requests affected 46% (532/1151) of all diagnostic biopsies. Diagnostic suspicion did not influence preference for partial over excisional biopsy [Odds Ratio (OR) 1.2, 95%CI 0.8-1.7; P = 0.40]. The partial:excisional biopsy usage ratio was higher in patients aged > 50 years than patients aged <50 years [relative risk ratios (RRR) 1.5; 95%CI 1.0 to 2.2; P = 0.03]. In 34% and 17% of tumours diagnosed with punch and shave, respectively, three procedures were required for definitive excision instead of two, compared with 5% of excisional biopsies When partial biopsy was used, patients were at greater risk of requiring three-staged excisions when controlled for age, anatomical site, melanoma subtype and thickness (RRR 6.7; 95%CI 4.4-10.1; P < 0.001). CONCLUSION: Diagnostic suspicion does not appear to be a major factor influencing choice of biopsy technique. Using partial biopsy to diagnose melanoma often leads to an extra procedure for definitive treatment compared with excisional biopsy.

Melanoma vaginal. Reporte de un caso / Vaginal melanoma. A case report

Resumen: ANTECEDENTES: El melanoma vaginal es una alteración excepcional, por lo que el diagnóstico se establece en etapas avanzadas de la enfermedad. El pronóstico a corto plazo es malo y no existen factores de riesgo identificados hasta la fecha. CASO CLINICO: Paciente de 77 años, acudió a consulta por sangrado transvaginal fétido, de dos meses de evolución. Durante la colposcopia se observó una tumoración en la cara lateral izquierda de la vagina, que se extendía hasta su tercio inferior; la cara anterior estaba hiperpigmentada y friable. De acuerdo con el reporte de citología y la biopsia se estableció el diagnóstico de melanoma invasor. La concentración de marcadores tumorales fue positiva para HMB-45, Ki-67 (20%), MART-1 (Melan-1) y PS-100. La paciente fue enviada al servicio de Oncología para estadificación y tratamiento de la enfermedad. CONCLUSIONES: La identificación de una tumoración hiperpigmentada en la exploración ginecológica, además de la biopsia dirigida complementada con estudio de inmunohistoquímica, es sugerente de melanoma vaginal. Las pacientes con este tipo de lesión deben atenderse por un equipo médico multidisciplinario.

Abstract: BACKGROUND: Vaginal melanoma is an exceptional alteration, for which the diagnosis is established in advanced stages of the disease. The short-term prognosis is poor and there are no identified risk factors to date. CLINICAL CASE: 77-year-old patient, who came to the clinic for fetid transvaginal bleeding, two months old. During colposcopy, a tumor was observed on the left lateral aspect of the vagina, which extended to its lower third; the anterior face was hyperpigmented and friable. Based on the cytology report and biopsy, the diagnosis of invasive melanoma was established. The concentration of tumor markers was positive for HMB-45, Ki 67 (20%), MART-1 (Melan-1) and PS-100. The patient was sent to the Oncology service for staging and treatment of the disease. CONCLUSIONS: The identification of a hyperpigmented tumor on gynecological examination, in addition to a directed biopsy, complemented by an immunohistochemical study, is suggestive of vaginal melanoma. Patients with this type of injury should be cared for by a multidisciplinary medical team.

Clinical and pathologic factors associated with subclinical spread of invasive melanoma.

BACKGROUND: Indications to treat invasive melanoma with Mohs micrographic surgery (MMS) or analogous techniques with exhaustive microscopic margin assessment have not been defined. OBJECTIVE: Identify clinical and histologic factors associated with subclinical spread of invasive melanoma. METHODS: This retrospective, cross-sectional study evaluated 216 invasive melanomas treated with MMS and melanoma antigen recognized by T cells 1 immunostaining. Logistic regression models were used to correlate clinicopathologic risk factors with subclinical spread and construct a count prediction model. RESULTS: Risk factors associated with subclinical spread by multivariate analysis included tumor localization on the head and neck (OR 3.28, 95% confidence interval [CI] 1.16-9.32), history of previous treatment (OR 4.18, 95% CI 1.42-12.32), age ≥65 (OR 4.45, 95% CI 1.29-15.39), and ≥1 mitoses/mm2 (OR 2.63, 95% CI 1.01-6.83). Tumor thickness and histologic subtype were not associated with subclinical spread. The probability of subclinical spread increased per number of risk factors, ranging from 9.22% (95% CI 2.57%-15.86%) with 1 factor to 80.32% (95% CI 68.13%-92.51%) with 5 factors. LIMITATIONS: This study was conducted at a single academic institution with a small study population using a retrospective study design that was subject to potential referral bias. CONCLUSION: Clinical and histologic factors identify invasive melanomas that are at increased risk for subclinical spread and might benefit from MMS or analogous techniques prior to reconstruction.

Risk of subsequent melanoma after melanoma in situ and invasive melanoma: a population-based study from 1973 to 2011.

BACKGROUND: Patients with melanoma in situ are at an increased risk of subsequent melanoma compared with the general population, but the risk of subsequent melanoma after initial melanoma in situ versus after initial invasive melanoma is not known. OBJECTIVE: We sought to compare the risk of subsequent melanoma in the cohort whose first cancer was melanoma in situ to the risk in the cohort whose first cancer was invasive melanoma. METHODS: In this cohort study, we identified individuals whose first cancer was either melanoma in situ or invasive melanoma from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2011 and used Cox proportional hazards models for comparison. RESULTS: Compared with the invasive melanoma cohort, the melanoma in situ cohort was more likely to develop subsequent melanoma of any stage after 2 years, subsequent invasive melanoma after 10 years, and subsequent melanoma in situ at all the time points (P < .001, P = .003, P < .001, respectively). LIMITATIONS: Underreporting of melanomas, particularly melanoma in situ cases, and missing cases of subsequent melanomas as a result of patient migration from the SEER registry areas could affect results. CONCLUSION: Given the increased long-term risk of subsequent melanoma in the melanoma in situ cohort, the patients with melanoma in situ diagnosis may benefit from a long-term surveillance for subsequent melanomas.