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.

Quimioprospecção de cianobactérias brasileiras utilizando metabolômica e ensaios biológicos / Chemoprospecting of Brazilian cyanobacteria using metabolomics and biological assays

Os produtos naturais são uma importante fonte de moléculas com aplicações terapêuticas e biotecnológicas. No entanto, a complexidade inerente às matrizes biológicas e as crescentes taxas de redescoberta de moléculas impõem desafios para a busca por novos compostos bioativos. A exploração de novos espécimes da biodiversidade e a aplicação de ferramentas computacionais são imperativos para a identificação de novas entidades químicas promissoras. Foi proposto catalisar o processo de prospecção química para demonstrar o potencial das cianobactérias brasileiras como fonte de novas moléculas bioativas. Nove linhagens de cianobactérias de água doce/terrestres foram cultivadas, extraídas e fracionadas. Extratos e frações foram testados quanto ao potencial citotóxico contra o microcrustáceo Artemia salina, antiproliferativo contra linhagens celulares de melanoma humano e contra promastigotas de Leishmania (L.) amazonensis. As amostras foram analisadas em paralelo via UPLC-HRMS/MS. Foi criada uma rede molecular através da plataforma GNPS. A desreplicação contou também com o suporte da plataforma DAFdiscovery, ferramenta que, através da fusão de informações dos dados de LC-MS/MS com os metadados contendo informações obtidas dos bioensaios, elenca quais as features se correlacionam com a atividade biológica. A anotação seguida de busca em base de dados foi realizada com auxílio do software SIRIUS. Quatro linhagens de cianobactérias foram selecionadas seguindo essa abordagem devido ao seu potencial ineditismo químico e bioatividade, sendo elas Brasilonema octagenarum, Anagnostidinema amphibium, Nostoc sp. e Komarekiella atlântica

Natural products are an important source of molecules with therapeutic and biotechnological applications. However, the inherent complexity of biological matrices and the increasing rediscovery rates challenge the search for new bioactive compounds. Exploring new specimens of biodiversity and applying computational tools are imperative for identifying promising new chemical entities. In this study, we proposed to catalyze the chemical prospecting process to demonstrate the potential of Brazilian cyanobacteria as a source of new bioactive molecules. Nine strains of freshwater cyanobacteria were cultivated, extracted, and fractionated. Extracts and fractions were tested for cytotoxic potential against the microcrustacean Artemia salina, antiproliferative against human melanoma cell lines, and Leishmania (L.) amazonensis promastigotes. Samples were analyzed in parallel via UPLCHRMS/MS. A molecular network was created using the GNPS platform. Dereplication was guided by DAFdiscovery, a computational tool that, through the fusion of information from LC-MS/MS data with metadata containing information obtained from bioassays, indexed which features correlate with biological activity. Annotation followed by a database search was performed using the SIRIUS software. Brasilonema octagenarum, Anagnostidinema amphibium, Nostoc sp., and Komarekiella atlântica were selected following this approach due to their potential chemical novelty and bioactivity

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.

Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studie

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)

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)

The in vitro cytotoxicity against human melanoma cells, tyrosinase inhibition and antioxidant activity of Grewia tenax leaves extracts / La citotoxicidad in vitro contra las células de melanoma humano, inhibición de la tirosinasa y actividad antioxidante de los extractos de hojas de Grewia tenax

Grewia tenax (Forssk.) Fiori (Malvaceae) grows in the Arabian Peninsula and is used for several medicinal purposes. To characterize the dermatological bioactivities of G. tenax in terms of its antimelanoma, antityrosinase and antioxidant activities. Cytotoxicity was assessed by cell proliferation and mitochondrial viability assays. Ability to inhibit mushroom tyrosinase and scavenge free radicals were evaluated by an enzymatic and DPPH scavenging microtiter assay, respectively. Phytochemical analyses were carried out using TLC, HPLC-UV and NMR. The chloroform extract shown significant cytotoxic activity in terms of mitochondrial viability (43 ± 14 µg/mL). We identified lupeol and b-sitosterol as the main active components for the tyrosinase inhibitory activity of the hexane extract. Scavenging activity of the DPPH· radical was confined to the water extract. Extracts from this plant have the potential to be used as a base in the development of cosmeceutical products intended to whiten skin or to combat radical-induced physiopathological processes.

Grewia tenax (Forssk.) Fiori (Malvaceae) crece en la Península Arábiga y se utiliza con varios fines medicinales. Para caracterizar las bioactividades dermatológicas de G. tenax en cuanto a sus actividades antimelanoma, antitirosinasa y antioxidante; la citotoxicidad se evaluó mediante ensayos de proliferación celular y viabilidad mitocondrial. La capacidad para inhibir la tirosinasa de hongo y eliminar los radicales libres se evaluó mediante un ensayo de microtitulación enzimático y de eliminación de DPPH, respectivamente. Los análisis fitoquímicos se realizaron mediante TLC, HPLC-UV y NMR. El extracto de cloroformo mostró una actividad citotóxica significativa en términos de viabilidad mitocondrial (43 ± 14 µg/mL). Identificamos lupeol y b-sitosterol como los principales componentes activos para la actividad inhibitoria de tirosinasa del extracto de hexano. La actividad depuradora del radical DPPH· se limitó al extracto acuoso. Los extractos de esta planta tienen potencial para ser utilizados como base en el desarrollo de productos cosmecéuticos destinados a blanquear la piel o combatir procesos fisiopatológicos inducidos por radicales.

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

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

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.

ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization

BACKGROUND: Melanoma is one of the most aggressive and deadliest skin tumor. Cholesterol content in melanoma cells is elevated, and a portion of it accumulates into lipid rafts. Therefore, the plasma membrane cholesterol and its lateral organization might be directly linked with tumor development. ATP Binding Cassette A1 (ABCA1) transporter modulates physico-chemical properties of the plasma membrane by modifying cholesterol distribution. Several studies linked the activity of the transporter with a different outcome of tumor progression depending on which type. However, no direct link between human melanoma progression and ABCA1 activity has been reported yet. METHODS: An immunohistochemical study on the ABCA1 level in 110 patients-derived melanoma tumors was performed to investigate the potential association of the transporter with melanoma stage of progression and prognosis. Furthermore, proliferation, migration and invasion assays, extracellular-matrix degradation assay, immunochemistry on proteins involved in migration processes and a combination of biophysical microscopy analysis of the plasma membrane organization of Hs294T human melanoma wild type, control (scrambled), ABCA1 Knockout ( ABCA1 KO) and ABCA1 chemically inactivated cells were used to study the impact of ABCA1 activity on human melanoma metastasis processes. RESULTS: The immunohistochemical analysis of clinical samples showed that high level of ABCA1 transporter in human melanoma is associated with a poor prognosis. Depletion or inhibition ofABCA1 impacts invasion capacities of aggressive melanoma cells. Loss of ABCA1 activity partially prevented cellular motility by affecting active focal adhesions formation via blocking clustering of phosphorylated focal adhesion kinases and active integrin ß3. Moreover, ABCA1 activity regulated the lateral organization of the plasma membrane in melanoma cells. Disrupting this organization, by increasing the content of cholesterol, also blocked active focal adhesion formation. CONCLUSION: Human melanoma cells reorganize their plasma membrane cholesterol content and organization via ABCA1 activity to promote motility processes and aggressiveness potential. Therefore, ABCA1 may contribute to tumor progression and poor prognosis, suggesting ABCA1 to be a potential metastatic marker in melanoma.

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

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

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

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

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.

Ganglio centinela positivo en melanoma: factores predictivos y resultados del vaciamiento ganglionar / Positive sentinel lymph node in melanoma: predictive factors and results of completion lymph node dissection

RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.

ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.

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.

Aspectos clínicos do câncer durante o período gestacional: desafios diagnósticos e terapêuticos / Clinical aspects of cancer during the gestational period: diagnostic and therapeutic challenges

O câncer é uma das maiores causas de morte em mulheres na idade reprodutiva e ocorre em aproximadamente 0,05% a 0,1% das gestações. Os cânceres ginecológicos, de mama, tireoide e hematológicos são os mais comuns na gravidez. O obstetra é o principal médico para investigar sintomas que podem estar relacionados à malignidade. O diagnóstico pode ser dificultado devido à sobreposição de sintomas da gravidez, como náusea, vômitos, aumento do útero e das mamas, dor abdominal, além da limitação para uso de exames de imagem e alterações comuns em exames laboratoriais. O risco e o benefício do diagnóstico e o tratamento para o bem-estar materno e fetal devem ser avaliados com cuidado pelos profissionais envolvidos. Este artigo tem como objetivo realizar uma revisão sobre quando suspeitar e como investigar os principais cânceres na gestação.(AU)

Cancer is the major cause of death in women on reproductive age and occurs in approximately 0.05% to 0.1% of pregnancies. Gynecological, breast, thyroid and hema- tological cancers are the most common in pregnancy. The obstetrician is the primary physician to investigate symptoms that may be related to malignancy. The diagnosis can be difficult due to the overlap of pregnancy symptoms, such as nausea, vomiting, enlargement of the uterus and breasts, abdominal pain, in addition to the limitation for the use of imaging tests and common changes in laboratory tests. The risk and be- nefit of diagnosis and treatment for maternal and fetal well-being should be carefully assessed by the professionals involved. This article aims to conduct a review on when to suspect and how to investigate the main cancers in pregnancy.(AU)