[Anorectal melanoma: Clinical case]. / Melanoma anorrectal: un caso clínico.

Background: Anorectal melanoma (AM) is a rare and aggressive type of tumor, with varied and inconclusive scientific information. Its preoperative diagnosis is challenging due to its rarity and similarity to other anorectal conditions. It represents only 1.3% of melanomas and affects more women than men. Approximately 20-30% of AM cases are amelanotic, complicating endoscopic detection and leading to misdiagnoses. AM is often confused with hemorrhoids, polyps, and rectal cancer in two thirds of patients due to similar symptoms. The causes and risk factors of AM are not well understood, but they are suspected to differ from cutaneous and ocular melanomas. Diagnosis is performed through biopsy and immunohistochemical staining. Colonoscopy helps to characterize the lesions, and histological examination is crucial for definitive diagnosis. Clinical case: 50-year-old woman with rectal bleeding and proctalgia. AM was diagnosed through colonoscopy, and transanal resection with hemorrhoidectomy was performed. Conclusions: Management of AM is complicated by the lack of randomized trials. Resection surgery is the standard treatment, but there is no established protocol. Wide local excision may be an option for limited cases. Further research is needed to improve the management and treatment of AM. Early detection and complete surgical removal are crucial for enhancing survival in these patients.

Introducción: el melanoma anorrectal (MA) es un tipo raro y agresivo de tumor, cuya información científica es variada y poco concluyente. Su diagnóstico preoperatorio es un desafío debido a su rareza y a su similitud con otras afecciones anorrectales. Representa solo el 1.3% de los melanomas y afecta más a mujeres que a hombres. Aproximadamente el 20-30% de los casos de MA son amelanóticos, lo que complica su detección endoscópica y conduce a diagnósticos erróneos. El MA se confunde con hemorroides, pólipos y cáncer de recto en dos tercios de los pacientes debido a síntomas similares. Las causas y factores de riesgo del MA aún no se conocen bien, pero se sospecha que son diferentes de los melanomas cutáneos y oculares. El diagnóstico se realiza mediante biopsia y tinción inmunohistoquímica. La colonoscopía permite caracterizar las lesiones y el examen histológico es crucial para el diagnóstico definitivo. Caso clínico: mujer de 50 años con rectorragia y proctalgia. Se diagnosticó MA mediante colonoscopía y se realizó una resección transanal con hemorroidectomía. Conclusiones: el manejo del MA es complicado por la falta de ensayos aleatorizados. La cirugía de resección es el tratamiento habitual, pero no hay un protocolo establecido. La escisión local amplia puede ser una opción para casos limitados. Se necesita más investigación para mejorar el manejo y tratamiento del MA. La detección temprana y la extirpación quirúrgica completa son cruciales para mejorar la supervivencia en estos pacientes.

Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma.

Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies. Ten canine patients diagnosed by histopathology and confirmed as OMM by immunohistochemistry were enrolled, their prognostic data was assessed, and blood samples were collected for CTC analysis. Results have shown the detection of intact cells in 9/10 patients. ICC has shown 3/9 Melan-A-positive, 3/9 PNL2-positive, and 8/9 S100-positive patients, confirming the importance of opting for a multimarker assay. A significant number of negative-stained CTCs were found, suggesting their high heterogeneity in circulation. Microemboli stained with either PNL2 or S100 were found in a patient with a high isolated cell count and advanced clinical stage. Preliminary statistical analysis shows a significant difference in CTC count between patients with and without lymph node metastasis (p < .05), which may correlate with tumour metastatic potential. However, we recommend further studies with more extensive sampling to confirm this result. This pilot study is the first report of intact CTC detection in canine OMM and the first application of ISET in veterinary medicine, opening new possibilities for liquid biopsy studies in canine OMM and other tumours.

The Expression of PRAME as an Aid for Diagnosis and Evaluation of Histologic Margins of Intraepidermal Cutaneous Melanoma in Xeroderma Pigmentosum Patients.

Xeroderma Pigmentosum (XP) is a genetic disorder characterized by photosensitivity, dyschromia, and high risk of skin cancer. From a clinical and histologic view, it can be difficult to diagnose cutaneous melanoma (CM) in XP patients and to define its resection margins. We aimed to study the role of PRAME (PReferentially Expressed Antigen in MElanoma) in differentiating intraepidermal CM from superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and evaluating the histological margins of CMs. We included XP patients. melanocitic and nonmelanocytic lesions with adjacent skin, and, as control groups, sun-damaged skin from non-XP individuals. Melanocytic lesions with a consensus diagnosis were grouped into CM, SAMPUS, or benign. The selected samples were PRAME-immunoshistochemically stained, and the ratio between immuno-positive cells/mm was recorded, according to Olds and colleagues for intraepidermal lesions. Lezcano and colleagues' method was used for intradermal lesions. Clinical data from XP patients were reviewed. All 9 patients were alive and well at the study closure, even those who developed melanoma metastases. Positive/diffuse PRAME expression was found in 29% (7/24) of intraepidermal CMs and 20% (1/5) SAMPUS samples. All 103 XP control samples and 24 adjacent lesions skin of non-XP patients were PRAME negative. This was a single-center and retrospective study, using a relatively small sample, limiting our conclusions. In XP patients' lesions, PRAME expression could help in the setting of challenging melanocytic tumors and surgical margins evaluation. It is also possible that the method can avoid overdiagnosis and, consequently, more aggressive treatment recommendation in unequivocal CM cases.

BRAF-Mutated Melanoma Journey in Latin America: Expert Recommendations From Diagnosis to Treatment.

OBJECTIVES: • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region. INTRODUCTION: Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region's incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region. METHODS: Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment. RESULTS AND CONCLUSIONS: Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.

Melanoma nodular: um subtipo agressivo / Nodular melanoma: an agressive subtype

Malignant melanoma is considered the most aggressive skin cancer due to its rapid evolution and risk of metastasizing. Early diagnosis and treatment can save the patient's life, and the biological factors of each melanoma subtype must be studied for better patient management. Currently, it is known that nodular subtype melanoma is the most aggressive due to its rapid vertical evolution, with a minor epidermal component but an important dermal component, which increases the risk of lymph node and hematogenous metastasis. Clinical, histopathological, dermoscopic and biological characteristics can help with the diagnosis and subsequent treatment of these patients

Pseudomelanomas at a referral ocular oncology center in Brazil / Pseudomelanomas em um centro de referência em oncologia ocular no Brasil

ABSTRACT Objective: To evaluate the epidemiological, clinical, and imaging profile of lesions that mimic choroidal melanoma. Methods: Retrospective study of medical records of suspected choroidal melanoma lesions referred to the Ocular Oncology Service from the Universidade Federal de São Paulo, from 2014 to 2020. Demographic data, clinical history, and exams were evaluated. Results: A total of 104 patients (mean age: 65.57 ± 13.18; 49.04% female) were referred to our service with suspected choroidal melanoma. Of these, 32 (30.77%) were classified as pseudomelanoma, while 72 (69.23%) had a confirmed diagnosis of choroidal melanoma. Pseudomelanoma cases manifested in older individuals (p < 0.001), with smaller lesions in height (p < 0.001), anteroposterior diameter (p = 0.008), and lateral diameter (p = 0.003) on ultrasound. Pseudomelanoma cases were associated with higher frequencies of vitreous hemorrhage (p = 0.014) and lower rates of the presence of a mass (p = 0.001) and retinal detachment (p < 0.001). The main diagnoses of pseudomelanoma cases were choroidal nevus (40.63%), subretinal hemorrhage (18.75%) and choroidal neovascular membrane (18.75%). Conclusion: Almost one third of the cases referred with suspected choroidal melanoma were pseudomelanomas, which demonstrates that there is still a considerable path to improve the ability of general ophthalmologists to clinically discriminate melanoma from other conditions that can mimic it.

RESUMO Objetivo: Avaliar a frequência e o perfil epidemiológico, clínico e de imagem das lesões que simulam o melanoma de coroide. Métodos: Trata-se de estudo de revisão retrospectiva de prontuários de suspeita de lesões de melanoma de coroide de 2014 a 2020 no Setor de Oncologia Ocular da Universidade Federal de São Paulo. Foram avaliados dados demográficos, dados clínicos e exames complementares. Resultados: Um total de 104 pacientes (média de idade: 65,57 ± 13,18; 49,04% do sexo feminino) foram encaminhados ao nosso serviço com suspeita de melanoma de coroide. Destes, 32 (30,77%) foram classificados como pseudomelanoma, enquanto 72 (69,23%) tiveram diagnóstico confirmado de melanoma de coroide. Os casos de pseudomelanoma manifestaram-se em indivíduos mais velhos (p < 0,001) e apresentaram lesões menores em altura (p < 0,001), diâmetro anteroposterior (p = 0,008) e diâmetro lateral (p = 0,003) na ultrassonografia. Os casos de pseudomelanoma estão associados a maiores frequências de hemorragia vítrea (p = 0,014) e menores taxas de presença de massa (p = 0,001) e descolamento de retina (p < 0,001). Os principais diagnósticos dos casos de pseudomelanoma foram nevo (40,63%), hemorragia sub-retiniana (18,75%) e membrana neovascular coroidal (18,75%). Conclusão: Quase um terço dos casos encaminhados com suspeita de melanoma de coroide foram pseudomelanomas, o que demonstra que ainda há um caminho considerável para melhorar a habilidade do oftalmologista geral em discriminar clinicamente o melanoma de outras condições que o simulam.

Caso infrecuente de melanoma del canal anal / Rare case of melanoma of the anal canal

Introducción: El melanoma anorrectal es un tumor infrecuente que se caracteriza por ser agresivo y de mal pronóstico; constituye el 1 por ciento entre los tumores malignos colorrectales. Es más frecuente en pacientes femeninas de más de 50 años y alcanza un pico máximo en la octava década de la vida. Objetivo: Presentar las características clínicas de una paciente con melanoma del canal anorrectal. Caso clínico: Se estudió a una paciente femenina de 61 años que acudió a consulta de gastroenterología, por presentar constipación de varios meses de evolución, asociada a tenesmo rectal, anorexia, astenia y pérdida de peso de forma rápida y progresiva. Se le diagnosticó un melanoma anorrectal, en estado avanzado de la enfermedad, por lo que tuvo mala evolución. Conclusiones: Con una anamnesis y exploración física minuciosa, asociado al uso de los medios diagnósticos disponibles y un elevado índice de sospecha, se consigue con la paciente, que el estudio y diagnóstico se hicieran con prontitud y con ello imponer tratamiento(AU)

Introduction: Anorectal melanoma is an infrequent tumor characterized by aggressive and poor prognosis; it constitutes 1 percent among colorectal malignancies. It is more frequent in female patients over 50 years of age and reaches a maximum peak in the eighth decade of life. Objective: To present the clinical characteristics of a patient with melanoma of the anorectal canal. Clinical case: A 61-year-old female patient was studied, who came to the gastroenterology department for constipation of several months of evolution, associated with rectal tenesmus, anorexia, asthenia and rapid and progressive weight loss. He was diagnosed with anorectal melanoma, in advanced stage of the disease, for which he had poor evolution. Conclusions: With a thorough anamnesis and physical examination, associated with the use of the available diagnostic means and a high index of suspicion, it is achieved with the patient, that the study and diagnosis were made promptly and thus impose treatment(AU)

Cure rate models for heterogeneous competing causes.

Cure rate models have been widely studied to analyze time-to-event data with a cured fraction of patients. In this type of model, the number of concurrent causes is assumed to be a random variable. However, in practice, it is natural to admit that the distribution of the number of competing causes is different from individual to individual. Our proposal is to assume that the number of competing causes belongs to a class of a finite mixture of competing causes distributions. We assume the number of malignant cells follow a mixture of two power series distributions and suppose that the time to the event of interest follows a Weibull distribution. We consider the proportion of the cured number of competing causes depending on covariates, allowing direct modeling of the cure rate. The proposed model includes several well-known models as special cases and defines many new special models. An expectation-maximization algorithm is proposed for parameter estimation, where the expectation step involves the computation of the expected number of concurrent causes for each individual. A Monte Carlo simulation is performed to assess the behavior of the estimation method. In order to show the potential for the practice of our model, we apply it to the real medical data set from a population-based study of incident cases of cutaneous melanoma diagnosed in the state of São Paulo, Brazil, illustrating that the model proposed can outperform traditional models in terms of model fitting.

Clinical and imaging research in the diagnosis of anorectal melanoma with surgical outcome: a case report and literature review

Objective: This study aims to report the case of a 69-year-old female patient with a diagnosis of anorectal melanoma (AM) established by immunohistochemistry. Methods: Clinical case report, a descriptive and qualitative study. Results: The patient had a nodular and ulcerative lesion in the anal region, the imaging exams revealed an expansive lesion that affected the rectum and the vaginal wall. The chosen course of treatment was initial surgical intervention, the surgery and postoperative course progressed without complications, and the anatomopathological examination confirmed the diagnosis of invasive malignant melanoma of the distal rectum of anorectal transition. The anatomopathological examination confirmed the diagnosis of invasive malignant melanoma located in the distal rectum of the anorectal transition. Immunohistochemistry analysis showed infiltrative melanoma with microsatellites, as well as peri and intratumoral lymphocytic infiltrate, angiolymphatic invasion, and perineural invasion. The surgical resection margins, ovaries, posterior vaginal wall, and parametrium showed no signs of neoplastic involvement. Following the surgery, the patient began immunotherapy, which she is still undergoing. Conclusions: The survival rate of AM can be improved through various diagnostic and therapeutic modalities. However, further exploration of this topic through clinical studies is necessary to enhance both diagnosis and treatment. (AU)

Clinical Outcomes and Prognostic Factors of Patients With Early Malignant Melanoma in One Latin American Country: Results of the Epidemiological Registry of Malignant Melanoma in Colombia Study.

To describe the population with early malignant melanoma, we performed a cohort study on the basis of the Epidemiological Registry of Malignant Melanoma in Colombia-Asociacion Colombiana de Hematologia y Oncologia. From January 2011 until December 2021, 759 patients were included; the average age was 66 years, 57% were women, acral lentiginous histology was found in 27.8% of patients, and the median follow-up was 36.5 months. The prognostic factors for overall survival in our population are Eastern Cooperative Oncology Group 3-4 (hazard ratio [HR], 13.8), stage III (HR, 5.07), received radiotherapy (HR, 3.38), ulceration on histology (HR, 2.68), chronic sun exposure (HR, 2.3), low income (HR, 2.04), previous local surgery (HR, 0.27), and have received adjuvant treatment (HR, 0.41).

The association between skin cancer and HIV infection.

Background People affected by Human Immunodeficiency Virus (HIV), are burdened by a higher risk of developing malignancies including non-melanoma skin cancer (NMSC) and melanoma skin cancer. Objective To evaluate the association of HIV with melanoma and NMSC at a University Hospital. Methods This is a cross-sectional retrospective study of HIV-infected and a matched comparison group, analyzing the associations between skin cancer and HIV infection. Results Compared to the HIV-uninfected, HIV-infected had 80% association with skin cancer (CI 95%: 1.3-2.4, P = 0.001) The risk was 45-fold higher by patients" age (CI 95%: 3.3-15.9: P = 0.001). When adjusted for patient age, sex and race, the risk was 6.4 fold ligher of having cancer if compared to the others (CI 95%: 49-84, P = 0.001). Melanoma was not found in HIV-infected. Conclusion With this study, we have demonstrated that HIV-infected patients have an increased risk of BCC and SCC. Preventive dermatologic management is pivotal in the care of immunosuppressed patients. These patients must undergo the dermatological examination annually and should receive extensive counseling regarding sun avoidance, use of sunscreens,and sun-protective clothing.

Focal melanocytic lesions of the oral mucosa: An epidemiological and morphological study.

OBJECTIVE: This study aimed to analyse the clinical and histopathological characteristics of focal oral melanocytic lesions in a Brazilian reference service in Oral and Maxillofacial Pathology. MATERIALS AND METHODS: A cross-sectional study was conducted over an 18-year period. Demographic data and clinical features were collected from the archives, and all biopsy specimens diagnosed as oral melanocytic lesions were retrieved and reviewed. RESULTS: We identified 339 melanocytic lesions. Of these, 191 were melanotic macules, 112 melanocytic nevi, 14 mucosal lentigo simplex, 12 melanomas, 9 solar lentigos, and 1 melanoacanthoma. Lesions occurred mostly in white-skinned (74.2%) women (65.2%). The main reported clinical aspect was the macule (67.4%), and the most affected site was the lip vermilion (25.4%), followed by the palate (22.9%). Melanomas were larger in size and were observed in older patients with an overall shorter time of onset. The most frequent subtypes of melanocytic nevi were intramucosal (44.6%), compound (24.1%), and blue nevus (20.5%). They showed a heterogeneous architectural pattern with the presence of the three cell types. CONCLUSION: The most frequent lesions are melanotic macule and nevus, especially the intramucosal subtype. Patients are usually white-skinned women presenting a small, long-lasting, macular lesion on the lip vermilion or palate.

Did COVID-19 lockdown delay actually worsen melanoma prognosis?

BACKGROUND: The COVID-19 lockdown possibly meant a delay in the diagnosis and treatment of melanoma and therefore, worsening its prognosis. This unique situation of diagnosis deferral is an exceptional opportunity to investigate melanoma biology. OBJECTIVES: To evaluate the immediate and mid-term impact of diagnosis delay on melanoma. METHODS: A retrospective observational study of melanoma diagnosed between March 14th 2019 and March 13th 2021. We compared the characteristics of melanomas diagnosed during the first 6-month period after the lockdown instauration and a second period after recovery of normal activity with the same periods of the previous year, respectively. RESULTS: A total of 119 melanomas were diagnosed. There were no differences in age, sex, incidence, location, presence of ulceration or mitoses, and in situ/invasive melanoma rate (p>0.05). After the recovery of the normal activity, Breslow thickness increased in comparison with the previous year (2.4 vs 1.9mm, p<0.05) resulting in a significant upstaging according to the AJCC 8th ed. (p<0.05). STUDY LIMITATIONS: The main limitation is that this is a single-center study. CONCLUSIONS: The COVID-19 lockdown implied a diagnosis delay leading to a mid-term increase in Breslow thickness and an upstaging of invasive melanomas. However, the detection deferral did not result in a higher progression of in situ to invasive melanoma, in our sample.

Supratentorial meningeal melanocytoma mimicking meningioma: case report and literature review.

Introduction: Primary melanocytic tumors originating from CNS melanocytes are rare, with a low incidence of 0.7 cases per 10 million annually. This study focuses on primary leptomeningeal melanocytomas, emphasizing their epidemiology, clinical characteristics, and diagnostic challenges. Despite their infrequency, these tumors warrant attention due to their unique features and potential for local recurrence. Case Report: A 32-year-old female presented with syncope and seizures, leading to the discovery of two left-sided supratentorial lesions initially misidentified as convexity meningiomas. Detailed imaging suggested meningioma-like features, but intraoperative findings revealed unexpected hyperpigmented lesions. Histopathological examination, supported by immunohistochemistry, confirmed primary leptomeningeal melanocytoma. The surgical approach and subsequent management are discussed. Discussion: The discussion emphasizes challenges in diagnosing primary leptomeningeal melanocytomas. Treatment debates, especially regarding adjuvant radiotherapy, are explored. Recurrence risks stress the importance of vigilant follow-up, advocating for complete surgical resection as the primary approach. The rarity of supratentorial cases adds complexity to diagnosis, necessitating a multidisciplinary approach. Insights from this case contribute to understanding and managing primary leptomeningeal melanocytomas, addressing challenges in differentiation from more common tumors and prompting ongoing research for refined diagnostics and optimized treatments. Conclusion: This study contributes insights into primary leptomeningeal melanocytomas, highlighting their rarity in supratentorial regions. The case underscores the importance of a multidisciplinary approach, incorporating clinical, radiological, and histopathological expertise for accurate diagnosis and tailored management. Ongoing research is crucial to refine treatment strategies, enhance prognostic precision, and improve outcomes for individuals with this uncommon CNS neoplasm.

Choroidal melanoma tumor profile and treatment pattern for newly diagnosed patients at a reference public hospital in Sao Paulo, Brazil.

BACKGROUND: Choroid, ciliary body, and iris melanomas are often grouped as uveal melanoma, the most common intraocular primary malignancy. The purpose of the current study was to analyze the tumor profile of newly diagnosed cases of choroidal melanoma at a reference center in Sao Paulo, Brazil, and to investigate the frequency of eyes treated by enucleation that could have been treated with brachytherapy if available in the service. METHODS: Medical records of patients referred to our service with initial diagnostic hypothesis of choroidal melanoma from July 2014 to June 2020 were analysed on demographics, diagnosis confirmation, tumor measurement by ultrasonography and established treatment. Data were evaluated on clinical and demographic characteristics as age, sex, affected eye, ultrasound parameters, and treatment management of patients with clinically diagnosed choroidal melanoma. Among the patients submitted to enucleation, we investigated how many could have been selected to receive brachytherapy. RESULTS: From the 102 patients referred with the choroidal melanoma diagnosis hypothesis, 70 (68.62%) were confirmed. Mean measurements from the tumors in millimetres were: 9.19 ± 3.69 at height and 12.97 ± 3.09 by 13.30 ± 3.30 at basal. A total of 48 cases (68.57%) were enucleated, 8 (11.43%) were treated by brachytherapy in a different service, and 14 patients (20.00%) returned for enucleation at their original referral center. Out of the 48 patients enucleated, 26 (54.17%) could have been selected to brachytherapy treatment. CONCLUSIONS: The results indicate a late diagnosis of choroidal melanoma cases referred to our service. Most enucleated cases could have been treated with brachytherapy if it was broadly available at the national public health insurance. Further public health political efforts should focus on early diagnosis and better quality of life post-treatment for oncologic patients.