Caracterización histológica del melanoma cutáneo en reportes de patología en la ciudad de Cali, 2016-2021 / Histological characterization of cutaneous melanoma in pathology reports in the city of Cali, 2016-2021

Introducción. El melanoma es la proliferación maligna de melanocitos asociado a un comportamiento agresivo. El objetivo de este estudio fue determinar las variables histológicas del melanoma cutáneo. Métodos. Estudio observacional retrospectivo, transversal descriptivo, realizado con reportes de patologías de pacientes con diagnóstico de melanoma cutáneo en un laboratorio de patología en Cali, Colombia, entre 2016-2021. Se incluyeron las variables edad, sexo, localización, subtipo, espesor de Breslow, ulceración, márgenes, mitosis, invasión linfovascular, neurotrofismo, regresión tumoral, nivel de Clark e infiltración tumoral por linfocitos. Resultados. Se obtuvieron 106 reportes y fueron excluidos 54 por duplicación. Se incluyeron 52 registros, la media de edad fue de 61 años, con una mayor frecuencia de mujeres (55,8 %). De los 33 casos donde se especificó el subtipo histológico, el más frecuente fue el de extensión superficial (66,6 %), seguido del acral lentiginoso (18,1 %) y nodular con (15,2 %). La localización más frecuente fue en extremidades (61,5 %). El espesor de Breslow más común fue IV (34,6 %) y el nivel de Clark más frecuente fue IV (34,6 %). La ulceración estuvo en el 40,4 %. El subtipo nodular fue el de presentación más agresiva, donde el 100 % presentaron espesor de Breslow IV. Conclusiones. El subtipo de melanoma más común en nuestra población fue el de extensión superficial; el segundo en frecuencia fue el subtipo acral lentiginoso, que se localizó siempre en extremidades. Más del 50 % de los melanomas tenían espesor de Breslow mayor o igual a III, lo que impacta en el pronóstico.

Background. Melanoma is the malignant proliferation of melanocytes associated with aggressive behavior. The objective of this study was to determine the histological variables of cutaneous melanoma. Methods. Observational, cross-sectional, descriptive, retrospective study carried out with reports of pathologies with a diagnosis of cutaneous melanoma in a pathology laboratory in Cali between 2016-2021. The variables were age, sex, location, subtype, Breslow thickness, ulceration, margins, mitosis, lymphovascular invasion, neurotropism, tumoral regression, Clark level and tumor infiltration by lymphocytes. Results. One hundred and six reports were obtained and 54 were excluded due to duplication. A descriptive analysis was made on the 52 records that were included, the mean age was 61 years, with a higher frequency in women with 55.8%. Of the 33 cases where the histological subtype was specified, the most frequent was superficial extension with 66.6%, followed by acral lentiginous with 18.1% and nodular with 15.2%. The most frequent location was in the extremities (61.5%); the most common Breslow was IV (34.6%), and the most frequent Clark was IV (34.6%). Ulceration was in 40.4%. The nodular subtype was the most aggressive presentation where 100% presented Breslow IV. Conclusions. The most common subtype of melanoma was that of superficial extension. In our population, the second most frequent was the acral lentiginous subtype, which was always located on the extremities. More than 50% of the melanomas had Breslow greater than or equal to III, which affects the prognosis.

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)

Cetoacidosis diabética como debut de diabetes mellitus inmunomediada en paciente en tratamiento con inhibidores de checkpoint / Diabetic ketoacidosis as debut of immune-mediated diabetes mellitus in a patient in treatment with immune checkpoint inhibitors

Los inhibidores de checkpoint (ICP) son anticuerpos usados en inmunoterapia contra el cáncer. Uno de sus blancos de acción es el receptor de muerte celular programada-1 (PD-1), el cual es importante para mantener la tolerancia inmunitaria. Sin embargo, este mecanismo se asocia a riesgo de eventos adversos relacionados a la inmunidad que pueden afectar a múltiples órganos incluyendo el sistema endocrino. Se describe el caso inhabitual de un paciente que a los 18 meses de terapia con ICP debutó con cetoacidosis diabética (CAD).

Immune checkpoint inhibitors consist in antibodies used in immunotherapy against cancer. One of their targets is the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, this mechanism is associated with a risk for immune-related adverse events potentially affecting multiple organs, including the endocrine system. We describe the unusual case of a patient who, after 18 months of treatment with an immune checkpoint inhibitor, debuted with diabetic ketoacidosis

Ultrassonografia de alta frequência e Doppler no diagnóstico, caracterização e seguimento dos tumores cutâneos / High-frequency ultrasonography and Doppler in the diagnosis, characterization and follow-up of skin tumors

A ultrassonografia (US) é uma ferramenta diagnóstica amplamente utilizada na medicina há mais de 50 anos. Na dermatologia, o uso desta técnica vem crescendo, principalmente após o desenvolvimento de dispositivos de maior frequência (acima de 20 MHz), que possibilitaram a avaliação mais detalhada da pele e seus anexos. Apesar da ampla gama de informações que podem ser obtidas através deste exame e da necessidade de métodos não invasivos que auxiliem no diagnóstico, planejamento terapêutico e seguimento dos tumores cutâneos, a falta de uniformidade nos critérios avaliados e parâmetros ultrassonográficos ainda dificulta o uso rotineiro desta técnica de imagem na oncologia cutânea. Objetivos: Descrever as características ultrassonográficas dos tumores cutâneos no modo B e Doppler; comparar com técnicas já estabelecidas, dermatoscopia e histologia; e avaliar características morfológicas no modo B e da vascularização ao Doppler que possam diferenciar nevos e melanomas. Material e métodos: Análise prospectiva de lesões suspeitas de câncer de pele de pacientes provenientes do A.C.Camargo Cancer Center. As lesões foram submetidas à, dermatoscopia, ultrassonografia de alta frequência (USAF) e Doppler para posterior correlação com parâmetros anatomopatológicos. Resultados: Foram incluídas 289 lesões, sendo 105 carcinomas basocelulares (CBC), 35 carcinomas espinocelulares (CEC), 24 melanomas, 2 carcinomas de células de Merkel, 15 tumores malignos mais raros e metástases cutâneas de outros tumores e 108 lesões benignas. Todas as lesões malignas foram visualizadas à US com 24 MHz. As principais características ultrassonográficas dos tumores malignos foram: hipoecogenicidade (98.9%) e ecotextura homogênea (90.6%). A presença de vascularização foi mais frequente nas lesões malignas e este foi o parâmetro mais relevante para diferenciação entre malignas e benignas. Conclusão: A USAF demonstrou ser uma ferramenta bastante útil na avaliação dos tumores cutâneos, apoiando no diagnóstico, estadiamento, avaliação de resposta e seguimento. O diagnóstico diferencial entre os principais tumores cutâneos ainda não é possível utilizandose somente a USAF, sendo, portanto, a correlação com dermatoscopia e histopatologia fundamental para o diagnóstico definitivo. Não foram observadas características ultrassonográficas capazes de diferenciar com segurança nevos de melanomas em nossa amostra.

Ultrasound (US) is a diagnostic tool that has been widely used in medicine for over 50 years. In dermatology, the use of this technology is increasing, mainly after the development of higher frequency devices (above 20 MHz), which allow a more detailed assessment of the skin and its annexes. Despite the wide range of information that can be obtained through this exam and the need for non-invasive methods that help in the diagnosis, therapeutic planning and follow-up of skin tumors, the lack of uniformity in the assessment criteria and ultrasound parameters still hinders the routine use of this imaging technique in cutaneous oncology. Objectives: To describe the sonographic characteristics of cutaneous tumors in B-mode and Doppler and to compare them with dermoscopy and histology; and to evaluate morphological characteristics in B-mode and Doppler ultrasound that allow differentiating nevi and melanomas. Material and methods: Prospective analysis of patients with skin lesions suspicious for cancer from the A.C.Camargo Cancer Center. The lesions were assessed by dermoscopy, high-frequency ultrasound (24 MHz) and Doppler and then correlated with histology. Results: 289 lesions were included, of which 105 were basal cell carcinomas, 35 squamous cell carcinomas, 24 melanomas, 2 Merkel cell carcinomas, 15 less common malignant tumors and cutaneous metastases from other tumors and 108 benign lesions. All malignant lesions were visualized at 24 MHZ ultrasonography. The main sonographic characteristics of malignant tumors were: hypoechogenicity (98.9%) and homogeneous echotexture (90.6%) Vascularization was more frequent in malignant lesions and this was the most relevant parameter for differentiating malignant and benign lesions. Conclusion: High-frequency ultrasound proved to be a very useful tool in the assessment of skin tumors, supporting diagnosis, staging, assessment of therapeutic response and follow-up. It's still not possible differentiate the main skin tumors based only on sonographic criteria, therefore, the correlation with dermoscopy and histology is necessary for the definitive diagnosis. No sonographic features that could reliably differentiate nevi and melanomas were found in our sample

Morphine promotes migration and lung metastasis of mouse melanoma cells

Abstract Background Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Methods Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. Results Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). Conclusion Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

Melanoma metastásico en intestino delgado: causa infrecuente de perforación: reporte de caso / Metastatic melanoma in the small intestine: infrequent cause of perforation: case report / Melanoma metastático em intestino delgado: causa rara de perfuração: relato de caso

El intestino delgado es el sitio de asiento más frecuente del melanoma metastásico. Su diagnóstico es un desafío por cursar asintomático o con síntomas inespecíficos. Son pocos los casos que presentan complicaciones, siendo infrecuente la peritonitis por perforación. El objetivo del trabajo es comunicar el caso clínico de una peritonitis por perforación de una metástasis de melanoma en intestino delgado. Caso clínico: Paciente de sexo masculino de 66 años con diagnóstico de melanoma de cuello y secundario óseo, encefálico y pulmonar, fue intervenido de urgencia por peritonitis aguda por perforación de metástasis en intestino delgado. El estudio histológico confirmó secundarismo de melanoma cutáneo. Conclusión: Sabiendo que el yeyuno íleon es el sitio de asiento más frecuente de las metástasis de melanoma, ante la presencia de síntomas digestivos inespecíficos o anemia se debe sospechar su compromiso y evaluar posibles alternativas terapéuticas.

The small intestine is the most frequent site of metastatic melanoma. However, its diagnosis continues to be a challenge since it is usually asymptomatic or with non-specific symptoms. Few cases result in complications, peritonitis due to perforation being infrequent. The objective of the work is to report a clinical case of peritonitis due to perforation of a melanoma metastasis in the small intestine. Clinical case: A 66-year-old male patient diagnosed with melanoma of the neck and secondary bone, brain and lung melanoma, underwent emergency surgery for acute peritonitis due to perforation of metastasis in the small intestine, which was resected and anastomosed. The histology confirmed the secondary nature of the cutaneous melanoma. Conclusion: Knowing that the jejunum-ileum is the most frequent site of melanoma metastases, in the presence of non-specific digestive symptoms or anemia, its involvement should be suspected and possible therapeutic alternatives should be evaluated.

O intestino delgado é o local mais frequente de melanoma metastático. O diagnóstico é um desafio por ser assintomático ou apresentar sintomas inespecíficos. Há poucos casos que apresentam complicações, sendo pouco frequente a peritonite por perfuração. O objetivo deste trabalho é relatar um caso clínico de peritonite por perfuração de metástase de melanoma no intestino delgado. Caso clínico: Paciente do sexo masculino, 66 anos, diagnosticado com melanoma no pescoço com metástase óssea, cefálica e pulmonar. Foi submetido a cirurgia de emergência por peritonite aguda por perfuração de metástases do intestino delgado. O estudo histológico confirmou melanoma cutâneo. Conclusão: Sabendo que o jejuno e o íleo é o local mais frequente de metástase de melanoma, na presença de sintomas digestivos inespecíficos ou anemia deve-se suspeitar de seu acometimento e avaliar possíveis alternativas terapêuticas.

MAGED4B Promotes Glioma Progression via Inactivation of the TNF-α-induced Apoptotic Pathway by Down-regulating TRIM27 Expression / 神经科学通报·英文版

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.

Research progress in effects of MAGE-A family on gastric cancer / 中南大学学报(医学版)

Gastric cancer (GC) is one of the most common malignant tumors worldwide, and most of the patients are diagnosed at the advanced stage. Most of the treating options are comprehensive treatment, in which immunotherapy plays more and more important role. Melanoma antigen-associated gene-A (MAGE-A) family is a kind of cancer testis antigens. Except in germ cells of testis and trophoblast cells of placenta, MAGE-A family is highly expressed in cancerous tissues and participates in a variety of biological processes, such as cancer cell proliferation, differentiation and metastasis. In addition, cancer testis antigen also possesses good immunogenicity, which can induce humoral and cellular immune responses, is a good target for immunotherapy, and has good application value in the diagnosis, treatment and prognosis of GC. A variety of targeted therapeutic drugs based on MAGE-A are in phase I or II clinical trials, it has good safety and potential clinical application value. With the continuous progress of clinical trials and basic research on MAGE-A targets in GC, it is expected to provide a theoretical basis for clinical transformation and immunotherapy of MAGE-A in the future.

Sinonasal mucosal melanoma: A rare intranasal tumor in an 89-year-old woman

@#Mucosal melanomas are malignant tumors from melanocytes found in epithelium of nasal, oral, reproductive and gastrointestinal mucosa of the body.1,2 As early as 1869, cases of mucosal melanomas have been described as rare and aggressive but insidious in nature.3 The mean age of diagnosis in some studies is 60 - 70 years old,1-7 with early detection proving to be a challenge due to non-specific early stage symptoms.1,4 They generally have poor prognosis, high tumor recurrence and high prevalence of tumor metastasis in around 23 - 50%.4,5 Treatment may involve surgical excision, radiotherapy or chemotherapy.6 However, adequate and appropriate treatment can only be initiated once the diagnosis and staging are established through proper imaging and histopathologic support.4 We present one such case.

Predictive Power of Demographic and Clinicopathological Aspects of Patients with Acral Melanoma: a Single-Center Series Of 394 Cases in Brazil / Poder Preditivo dos Aspectos Demográficos e Clinicopatológicos de Pacientes com Melanoma Acral: uma Série de 394 Casos em um Único Centro no Brasil / Poder Predictivo de Aspectos Demográficos y Clinicopatológicos en Pacientes con Melanoma Acral: una Serie de 394 Casos en un Solo Centro en el Brasil

Introduction: Acral melanoma (AM) is associated with high mortality and poor survival, and its prognosis is worse compared to other melanoma subtypes. Objective: To analyze the predictive power of demographic and clinicopathological aspects in patients with AM. Method: This is a retrospective study with patients diagnosed with AM between January 2001 and December 2015. Demographic and clinicopathological characteristics were collected. The outcome was 5-year overall survival (OS). Kaplan-Meier curves, log rank-test and Cox regression analysis were used. Results: The study identified 394 patients with AM. The 5-year survival rate for patients with AM was found to be 45.6%. The predictive factors of OS included Breslow thickness [hazard ratio (HR): 1.02, 95% confidence interval (CI): 1.01-1.03], ulceration (HR: 4.06, 95%CI: 2.18-7.57) and lymphovascular invasion (LVI) (HR: 2.12, 95%CI:1.12-4.00). Conclusion: The findings highlight the poor prognosis of AM and the predictive power of Breslow thickness, ulceration and LVI

Introdução: O melanoma acral (MA) está associado à alta mortalidade e à baixa sobrevida, e seu prognóstico é pior em comparação com os outros subtipos de melanoma. Objetivo: Analisar o poder preditivo de aspectos demográficos e clinicopatológicos em pacientes com MA. Método: Estudo retrospectivo com pacientes diagnosticados com MA entre janeiro de 2001 e dezembro de 2015. Foram coletadas características demográficas e clinicopatológicas. O desfecho foi a sobrevida global (SG) em cinco anos. Foram utilizados curvas de Kaplan-Meier, teste de log-rank e análise de regressão de Cox. Resultados: Foram identificados 394 pacientes com MA. A taxa de sobrevida em cinco anos para pacientes com MA foi de 45,6%. Os fatores preditivos da SG incluíram espessura de Breslow [hazard ratio (HR): 1,02, intervalo de confiança (IC) de 95%: 1,01-1,03], ulceração (HR: 4,06, IC 95%: 2,18-7,57) e invasão linfovascular (ILV) (HR: 2,12, IC 95%: 1,12-4,00). Conclusão: Tais achados destacam o prognóstico desfavorável do MA e o poder preditivo da espessura de Breslow, ulceração e ILV

Introducción: El melanoma acral (MA) está asociado con una alta mortalidad y una baja supervivencia, y su pronóstico es peor en comparación con los otros subtipos de melanoma. Objetivo: Analizar el poder predictivo de los aspectos demográficos y clinicopatológicos en pacientes con MA. Método: Estudio retrospectivo con pacientes diagnosticados con MA entre enero de 2001 y diciembre de 2015. Se recopilaron características demográficas y clinicopatológicas. El resultado fue la supervivencia global (SG) a los cinco años. Se utilizaron curvas de Kaplan-Meier, prueba de log-rank y análisis de regresión de Cox. Resultados: Se identificaron 394 pacientes con MA. La tasa de supervivencia a cinco años para los pacientes con MA fue del 45.6%. Los factores predictivos de la SG incluyeron el grosor de Breslow [razón de peligro (HR): 1.02, intervalo de confianza del 95% (IC): 1.01-1.03], la ulceración (HR: 4.06, IC del 95%: 2.18-7.57) y la invasión linfovascular (ILV) (HR: 2.12, IC del 95%: 1.12-4.00). Conclusión: Estos hallazgos resaltan el pronóstico desfavorable del MA y el poder predictivo del grosor de Breslow, la ulceración y la ILV

Melanoma Maligno Primário do Colo do Útero: Um Relato de Caso Raro / Primary Malignant Melanoma of the Uterine Cervix: Rare Case Report

O melanoma cervical primário é um diagnóstico raro e frequentemente desafiador, especialmente na presença de lesões amelanóticas, cuja confirmação deve ser feita por métodos imuno-histoquímicos. Apesar do tratamento agressivo, o prognóstico para essa doença costuma ser ruim. Relato do caso: Mulher, 79 anos, com histórico de sangramento vaginal decorrente de uma lesão cervical maligna. Inicialmente, a colposcopia revelou uma lesão ulcerada no exocérvix e a biópsia confirmou ser um tumor maligno. No entanto, após uma histerectomia abdominal radical, o exame histopatológico mostrou tratar-se de uma neoplasia maligna epitelioide, confirmada como um melanoma maligno do colo do útero por meio de exame imuno-histoquímico. A paciente recebeu quimioterapia adjuvante e radioterapia, mas eventualmente apresentou recorrência e veio a óbito. Conclusão: O presente relato avalia uma paciente com um diagnóstico incomum de melanoma cervical que, apesar do tratamento agressivo, teve um desfecho desfavorável. No entanto, uma vigilância cutânea minuciosa deve ser realizada para diagnosticá-lo corretamente como primário.

Primary cervical melanoma is a rare and often challenging diagnosis, particularly in the presence of amelanotic lesions, where confirmation should be made through immunohistochemical methods. Despite aggressive treatment, the prognosis for this disease is typically poor. Case Report: A 79-year-old woman with a history of vaginal bleeding from a malignant cervical lesion. Initially, colposcopy examination revealed an ulcerated lesion of the exocervix, and biopsy confirmed a malignant neoplasm. However, following a radical abdominal hysterectomy, histopathological examination displayed a malignant epithelioid neoplasm, confirmed a malignant melanoma of the cervix through immunohistochemical assays. The patient received adjuvant chemotherapy and radiation therapy, but eventually experienced recurrence and died. Conclusion: The present report assesses a patient with an uncommon diagnosis of cervical melanoma, which, despite aggressive treatment, had an unfavorable outcome. However, thorough skin surveillance should be performed to correctly diagnose it as primary

Mixed-Cell Type Choroidal Melanoma in a Middle-Aged Woman / Melanoma de Coroide do Tipo Misto em uma Mulher de Meia-Idade / Melanoma Coroideo de Tipo Mixto en una Mujer de Mediana Edad

Introduction: Melanomas are malignant neoplasms that occur in various anatomical sites, including the eye. Ocular melanomas account for 5% of all melanomas and are mainly described in Caucasian and older individuals. This study describes the clinical and pathological characteristics of uveal (choroid) melanoma in a Caucasian patient. Case report: A 41-year-old Caucasian female patient, brown eyes, without history of ophthalmological diseases or family history of cancer experienced pain and loss of visual acuity in the left eye. On clinical examination, an increase of ocular pressure was detected. Ultrasound showed a mushroom-like neoformation. Moreover, magnetic resonance imaging showed a mass with spontaneous hypersignal on T1-weighted images, intense gadolinium enhancement, and marked hyposignal on T2-weighted images. The patient was referred to the Oncology Ophthalmology department for enucleation due to suspected uveal melanoma. Anatomopathological analysis revealed a blackened mass in the eyeball. Histologically, the mass comprised spindle cells (50%) and epithelioid cells (50%). A diagnosis of choroidal melanoma was established based on the identification of ophthalmoscopic, imaging, and histological characteristics of the tumor. Conclusion: Choroidal melanomas usually occur in males, clear-eyed, and older individuals. A wide variety of ocular lesions may mimic choroidal melanoma, which should be included in the differential diagnosis of choroidal nevus and peripheral hemorrhages

Introdução: Melanomas são neoplasias malignas que ocorrem em vários sítios anatômicos, incluindo o olho. Os melanomas oculares correspondem a 5% de todos os melanomas e são descritos principalmente em indivíduos caucasianos e idosos. Este estudo descreve as características clinicopatológicas de um caso de melanoma uveal (coroide) em um paciente caucasiano. Relato do caso: Paciente, sexo feminino, 41 anos, caucasiana, olhos castanhos, sem antecedentes de doenças oftalmológicas e sem história familiar de câncer, com queixa de dor e perda da acuidade visual no olho esquerdo. No exame clínico, observou-se aumento da pressão ocular. O ultrassom revelou neoformação com aspecto de cogumelo, e a ressonância magnética, massa com hipersinal espontâneo em T1, intenso realce pelo gadolínio e marcado hipossinal em T2. A paciente foi encaminhada para cirurgia de enucleação em razão da suspeita de melanoma uveal. Foi realizada análise anatomopatológica que evidenciou massa enegrecida no interior do globo ocular. Histologicamente, a massa era constituída por 50% de células fusiformes e 50% de células epitelioides. O diagnóstico de melanoma de coroide baseou-se nas características oftalmoscópicas, imaginológicas e histológicas do tumor. Conclusão: Melanomas de coroide geralmente ocorrem em pacientes do sexo masculino, de olhos claros e idosos. Alerta-se que uma grande variedade de lesões oculares pode se assemelhar ao melanoma de coroide e este deve ser considerado no diagnóstico diferencial de nevo de coroide e hemorragias periféricas

Introducción: Los melanomas son neoplasias malignas que se presentan en varios sitios anatómicos, incluido el ojo. Los melanomas oculares representan el 5% de todos los melanomas y se describen principalmente en individuos caucásicos y de mayor edad. Este estudio describe las características clínicas y patológicas del melanoma uveal (coroides) en un paciente caucásico. Informe del caso: Paciente femenino de 41 años, caucásica, ojos marrones, sin antecedentes de enfermedades oftalmológicas y sin antecedentes familiares de cáncer, que consulta por dolor y pérdida de agudeza visual en el ojo izquierdo. En el examen clínico se observó aumento de la presión ocular. La ecografía mostró una neoformación con aspecto de hongo y la resonancia magnética mostró una masa con hiperseñal espontánea en T1, realce intenso de gadolinio y marcada hiposeñal en T2. La paciente fue remitida para cirugía de enucleación por sospecha de melanoma uveal. Se realizó análisis anatomopatológico, el cual mostró una masa ennegrecida en el interior del globo ocular. Histológicamente, la masa constaba de un 50 % de células fusiformes y un 50 % de células epitelioides. El diagnóstico de melanoma de coroides se basó en las características oftalmoscópicas, imagenológicas e histológicas del tumor. Conclusión: Los melanomas coroideos generalmente ocurren en pacientes masculinos, de ojos claros y de edad avanzada. Se advierte que una amplia variedad de lesiones oculares puede asemejarse al melanoma coroideo, y esto debe incluirse en el diagnóstico diferencial de nevus coroideo y hemorragias periféricas

RITA selectively inhibits proliferation of BAP1-deficient cutaneous melanoma cells in vitro / 南方医科大学学报

OBJECTIVE@#To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion.@*METHODS@#Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting.@*RESULTS@#The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001).@*CONCLUSION@#Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.

Oncologic outcomes of surgical treatments of advanced sinonasal malignancies / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the prognoses of advanced (T3-T4) sinonasal malignancies (SNM). Methods: The clinical data of 229 patients with advanced (T3-4) SNM who underwent surgical treatments in the First Affiliated Hospital of Sun Yat-sen University from 2000 to 2018 were retrospectively analyzed, including 162 males and 67 females, aged (46.8±18.5) years old. Among them, 167 cases received endoscopic surgery alone, 30 cases received assisted incision endoscopic surgery, and 32 cases received open surgery. The Kaplan-Meier method was used to estimate the 3-year and 5-year overall survival (OS) and event-free survival (EFS). Univariate and multivariate Cox regression analyses were performed to explore significant prognostic factors. Results: The 3-year and 5-year OS were respectively 69.7% and 64.0%. The median OS time was 43 months. The 3-year and 5-year EFS were respectively 57.8% and 47.4%. The median EFS time was 34 months. The 5-year OS of the patients with epithelial-derived tumors was better than that of the patients with mesenchymal-derived tumors and malignant melanoma (5-year OS was respectively 72.3%, 47.8% and 30.0%, χ2=36.01, P<0.001). Patients with microscopically margin-negative resection (R0 resection) had the best prognosis, followed by macroscopically margin-negative resection (R1 resection), and debulking surgery was the worst (5-year OS was respectively 78.4%, 55.1% and 37.4%, χ2=24.63, P<0.001). There was no significant difference in 5-year OS between the endoscopic surgery group and the open surgery group (65.8% vs. 53.4%, χ2=2.66, P=0.102). Older patients had worse OS (HR=1.02, P=0.011) and EFS (HR=1.01, P=0.027). Patients receiving adjuvant therapy had a lower risk of death (HR=0.62, P=0.038). Patients with a history of nasal radiotherapy had a higher risk of recurrence (HR=2.48, P=0.002) and a higher risk of death (HR=2.03, P=0.020). Conclusion: For patients with advanced SNM, the efficacy of endoscopic surgery can be comparable to that of open surgery when presence of safe surgical margins, and a treatment plan based on transnasal endoscopic surgery as the main comprehensive treatment is recommended.

Clinicopathological features and prognosis of anorectal melanoma: A report of 68 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological characteristics of anorectal mucosal melanoma (ARMM), and to evaluate the prognostic factors.@*METHODS@#A total of 68 primary ARMM surgical specimens from 2010 to 2018 were retrospectively studied. Slides were reviewed to evaluate pathological features. Slingluff staging method was used for staging.@*RESULTS@#(1) Clinical features: The median age at diagnosis in this group was 61.5 years, with a male-to-female ratio 1 ∶1.62. The most common complaint was blooding (49 cases). For anatomic site, anorectum was the prevalent (66.2%), followed by rectum (20.6%). At the time of diagnosis, 28 cases were stage Ⅰ (localized stage, 41.2%), 25 cases were stage Ⅱ (regional lymph node metastasis, 36.8%), and 15 cases were stage Ⅲ (distant metastasis, 22.1%). Five patients underwent wide local excision, the rest abdominoperineal resection, and 48 patients received adjuvant therapy after surgery. (2) Pathological features: Grossly 88.2% of the tumors were exophytic polypoid masses, with the median tumor size 3.5 cm and the median tumor thickness 1.25 cm. Depth of invasion below lamina muscularis mucosae ranged from 0-5.00 cm (median 1.00 cm). The deepest site of tumor invasion reached muscular layer in 27 cases, and perirectal tissue in 16 cases. Melanin pigmentation was absent or not obvious in 67.6% of the cases. The predominant cytology was epithelioid (45 cases, 66.2%). The rate for ulceration, necrosis, lymphovascular invasion, and perineural invasion was 89.7%, 35.3%, 55.9%, and 30.9%, respectively. The median mitotic count was 18/mm2. The positive rate of S100, HMB-45 and Melan-A were 92.0%, 92.6% and 98.0%, respectively. The median of Ki-67 was 50%. The incidences of mutations within CKIT, BRAF and NRAS genes were 17.0% (9 cases), 3.8% (2 cases) and 9.4% (5 cases), respectively. (3) Prognosis: Survival data were available in 66 patients, with a median follow-up of 17 months and a median survival time of 17.4 months. The 1-year, 2-year and 5-year overall survival rate was 76.8%, 36.8% and 17.2%, respectively. The rate of lymphatic metastasis at diagnosis was 56.3%. Forty-nine patients (84.5%) suffered from distant metastasis, and the most frequent metastatic site was liver. Univariate analysis revealed that tumor size (>3.5 cm), depth of invasion below lamina muscularis mucosae (>1.0 cm), necrosis, lymphovascular invasion, BRAF gene mutation, lack of adjuvant therapy after surgery, deep site of tumor invasion, and high stage at diagnosis were all poor prognostic factors for overall survival. Multivariate model showed that lymphovascular invasion and BRAF gene mutation were independent risk factors for lower overall survival, and high stage at diagnosis showed borderline negative correlation with overall survival.@*CONCLUSION@#The overall prognosis of ARMM is poor, and lymphovascular invasion and BRAF gene mutation are independent factors of poor prognosis. Slingluff staging suggests prognosis effectively, and detailed assessment of pathological features, clear staging and genetic testing should be carried out when possible. Depth of invasion below lamina muscularis mucosae of the tumor might be a better prognostic indicator than tumor thickness.

NETO2 promotes melanoma progression via activation of the Ca2+/CaMKII signaling pathway / 医学前沿

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca2+) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.

Analysis on tumor immune microenvironment and construction of a prognosis model for immune-related skin cutaneous melanoma / 中南大学学报(医学版)

OBJECTIVES@#Malignant melanoma is a highly malignant and heterogeneous skin cancer. Although immunotherapy has improved survival rates, the inhibitory effect of tumor microenvironment has weakened its efficacy. To improve survival and treatment strategies, we need to develop immune-related prognostic models. Based on the analysis of the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Sequence Read Archive (SRA) database, this study aims to establish an immune-related prognosis prediction model, and to evaluate the tumor immune microenvironment by risk score to guide immunotherapy.@*METHODS@#Skin cutaneous melanoma (SKCM) transcriptome sequencing data and corresponding clinical information were obtained from the TCGA database, differentially expressed genes were analyzed, and prognostic models were developed using univariate Cox regression, the LASSO method, and stepwise regression. Differentially expressed genes in prognostic models confirmed by real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Survival analysis was performed by using the Kaplan-Meier method, and the effect of the model was evaluated by time-dependent receiver operating characteristic curve as well as multivariate Cox regression, and the prognostic model was validated by 2 GEO melanoma datasets. Furthermore, correlations between risk score and immune cell infiltration, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) score, immune checkpoint mRNA expression levels, tumor immune cycle, or tumor immune micro-environmental pathways were analyzed. Finally, we performed association analysis for risk score and the efficacy of immunotherapy.@*RESULTS@#We identified 4 genes that were differentially expressed in TCGA-SKCM datasets, which were mainly associated with the tumor immune microenvironment. A prognostic model was also established based on 4 genes. Among 4 genes, the mRNA and protein levels of killer cell lectin like receptor D1 (KLRD1), leukemia inhibitory factor (LIF), and cellular retinoic acid binding protein 2 (CRABP2) genes in melanoma tissues differed significantly from those in normal skin (all P<0.01). The prognostic model was a good predictor of prognosis for patients with SKCM. The patients with high-risk scores had significantly shorter overall survival than those with low-risk scores, and consistent results were achieved in the training cohort and multiple validation cohorts (P<0.001). The risk score was strongly associated with immune cell infiltration, ESTIMATE score, immune checkpoint mRNA expression levels, tumor immune cycle, and tumor immune microenvironmental pathways (P<0.001). The correlation analysis showed that patients with the high-risk scores were in an inhibitory immune microenvironment based on the prognostic model (P<0.01).@*CONCLUSIONS@#The immune-related SKCM prognostic model constructed in this study can effectively predict the prognosis of SKCM patients. Considering its close correlation to the tumor immune microenvironment, the model has some reference value for clinical immunotherapy of SKCM.

Lesiones metastásicas a glándula tiroides. Una serie de casos / Metastatic lesions to the thyroid gland. Case series

Las lesiones metastásicas representan hasta un 3 % de los tumores malignos de la glándula tiroides. La mayoría de los casos se originan de tumores de células renales y de pulmón. El abordaje diagnóstico implica una alta sospecha clínica en pacientes con primarios conocidos, sin embargo, puede ser la manifestación inicial de una enfermedad maligna extensa no diagnosticada hasta en un 20 % a 40 % de los pacientes. La biopsia por aguja fina ha demostrado buen rendimiento para el diagnóstico de los nódulos metastásicos. El pronóstico y la opción del tratamiento quirúrgico dependen del control local del primario y del estado de la enfermedad sistémica asociada, por lo tanto, debe ser individualizado. Por lo general, hasta un 80 % de los pacientes con compromiso de la tiroides tienen enfermedad metastásica multiorgánica, y la intención del tratamiento quirúrgico es con fines paliativos para prevenir las complicaciones derivadas de la extensión local de la enfermedad a las estructuras del tracto aerodigestivo superior en el cuello. Se presenta a continuación, una serie de seis casos de pacientes con lesiones metastásicas a glándula tiroides con primarios en riñón, mama y de melanomas

Metastatic lesions represent up to 3% of malignant tumors of the thyroid gland. Most cases originate from lung and renal cell tumors. The diagnostic approach implies a high clinical suspicion in patients with known primaries, however, it can be the initial manifestation of an extensive undiagnosed malignant disease in up to 20% to 40% of patients. Fine-needle biopsy has shown good performance for the diagnosis of metastatic nodules. The prognosis and the option of surgical treatment depend on the local control of the primary condition and the state of the associated systemic disease, therefore it must be individualized. In general, up to 80% of patients with thyroid involvement have multi-organ metastatic disease and surgical treatment is intended to be palliative to prevent complications resulting from local extension of the disease to structures of the upper aerodigestive tract in the neck. A case series of six patients with metastatic lesions to the thyroid gland with primaries in the kidney, breast and melanomas is presented below

Epidemiología y características anatomoclínicas del melanoma maligno en un instituto oncológico / Epidemiology and clinical features of malignant melanoma. Analysis of 274 cases

BACKGROUND: Malignant melanoma (MM) is the most fatal cutaneous neoplasm. Its incidence is increasing progressively, which cannot be explained only by early diagnosis. Chilean population, due to the geography of the country, has a very varied solar exposure. AIM: To know the incidence of MM in a Chilean population, according to the level of sun exposure and to describe its clinical and histopathological characteristics. MATERIAL AND METHODS: Two hundred seventy-four surgeries for malignant melanoma with histological confirmation, carried out between 2016 and 2018 in an oncological institute were included. RESULTS: The annualized incidence of MM was 13.83 cases per 100,000 people over 15 years of age in the 2016-2018 period. The geographical distribution of the incidence did not have a clear relationship with sun exposure. The most frequent locations of the primary lesions were trunk, head/neck and lower limb. Sixty-one per cent of cases were invasive MM; lesion thickness and presence of ulceration were associated with a higher risk of sentinel node involvement. CONCLUSIONS: No association between the level of sun exposure and the incidence of MM was observed in this study.

Retrospective study of cutaneous neoplasms in horses treated at the Livestock Development Center of the Federal University of Bahia / Estudo retrospectivo das neoplasias cutâneas em equinos atendidos no Centro de Desenvolvimento da Pecuária da Universidade Federal da Bahia

The aim of this study was to determine the prevalence of cutaneous neoplasms in horses treated at the Center for the Development of Livestock at the Federal University of Bahia, as well as to correlate it with the coat color, breed, and age of the animal. For that, the attendance records for the last ten years were reviewed. When evaluating the files, 13 cases of cutaneous tumor in horses confirmed by histopathology and cytology were observed. The most prevalent skin tumors were sarcoid (38.5%), melanoma (23%), and fibrosarcoma (15.4%). Regarding the equine coat color, gray and sorrel horses were the most frequent with 30.7% and 23.1% of cases, respectively. As for the equine breed, the mangalarga marchador was the most prevalent (38.4%). Regarding age, 38.46% of the horses were up to 5 years old, 30.77% of the animals were between 4 and 10 years old, and 30.76% were between 11 and 16 years old. In the end, it can be concluded that sarcoid and melanoma were the most prevalent neoplasms.

Objetivou-se com este trabalho determinar a prevalência de neoplasias cutâneas em equinos atendidos no Centro de Desenvolvimento da Pecuária da Universidade Federal da Bahia, bem como correlaciona-la com a pelagem, raça e idade do animal. Para tanto revisou-se as fichas de atendimento dos últimos dez anos. Ao avaliar as fichas, observou-se 13 casos de tumor cutâneo em equinos confirmado por histopatologia ou citologia. Os tumores cutâneos mais prevalentes foram sarcoide (38,5%), melanoma (23%) e fibrossarcoma (15,4%). Com relação a pelagem, equinos tordilhos e alazões foram os mais frequentes com 30,7% e 23,1% dos casos, respectivamente. Quanto as raças, a mangalarga marchador foi a mais prevalente (38,4%). Em relação a idade, 38,46% dos equinos possuíam até 5 anos de idade, 30,77% dos animais apresentavam idade entre 4 e 10 anos e, 30,76% apresentavam idade entre 11 e 16 anos. Ao fim, pode-se concluir que o sarcoide e o melanoma foram as neoplasias mais prevalentes.