Síndrome de leiomiomatose cutânea e uterina múltipla: relato de três casos clínicos / Multiple cutaneous and uterine leiomyomatosis syndrome: report of three clinical cases

A síndrome de Reed ocorre em mulheres com múltiplos leiomiomas cutâneos e leiomiomatose uterina. Relatam-se três casos de pacientes do sexo feminino, acompanhadas em hospital universitário, com pápulas e nódulos eritêmato-acas- tanhados dolorosos em membros superiores e tórax, agravados por frio, pressão e estresse, e associados a miomatose uterina. Foram realizados diversos tratamentos prévios, sem sucesso, tais como: aplicação de corticoterapia e toxina botulínica intralesional, bloqueadores de canais de cálcio, neuromoduladores e analgésicos orais. Foi, então, realizado tratamento cirúrgico, com melhora dos sintomas. O co- nhecimento e o esclarecimento dessa síndrome é fundamental para estabelecer a relação com miomatose uterina e câncer de células renais, para que, então, a partir da lesão de pele, se faça o rastreio das demais neoplasias, diagnóstico precoce e a educação em saúde.

Reed syndrome occurs in women with multiple cutaneous leiomyomas and uterine leiomyomatosis. We report the case of three female patients followed at a university hospital with painful erythematous-brown papules and nodules on the upper limbs and chest, aggravated by cold, pressure, stress, and associated with uterine myoma- tosis. Several previous unsuccessful treatments were performed, such as the applica- tion of corticotherapy and intralesional botulinum toxin, calcium channel blockers, neuromodulators, and analgesics. Surgical treatment was performed with the im- provement of symptoms. Knowledge and clarification of this syndrome are essential to establish a relationship between uterine myomatosis and renal cell neoplasm, so that, after the skin lesion, screening for other neoplasms, early diagnosis, and health education can be carried out.

Presentación clínica de patologías no malignas que simulan leucemia cutis: a propósito de dos casos / Clinical presentation of non-malignant diseases mimicking leukemia cutis: A report of two cases

La infiltración cutánea por células leucémicas conocida como leucemia cutis es una presentación infrecuente de esta patología y constituye un desafío diagnóstico. Los diagnósticos como infecciones, otras patologías neoplásicas con afectación cutánea y los trastornos histiocíticos, entre otros, constituyen los principales diagnósticos diferenciales, ya que configuran un escenario pronóstico y terapéutico diferente. Se presentan dos pacientes que fueron diagnosticados inicialmente como leucemia cutis, cuyo diagnóstico final fue de patologías no malignas.

The infiltration of leukemia cells into the skin, known as leukemia cutis, is a rare presentation of this disease and accounts for a diagnostic challenge. The main differential diagnoses include infections, other neoplastic diseases with skin involvement and histiocytic disorders, among others, as they entail different prognostic and therapeutic approaches. Here we describe two patients who were initially diagnosed with leukemia cutis, whose final diagnosis was of non-malignant diseases.

Reconstrucción palpebral postumorectomía. Presentación de un caso / Lower eyelid reconstruction after lumpectomy. A case report

Algunos pacientes en la tercera edad desarrollan con frecuencia diversas enfermedades, entre ellas se encuentra el cáncer de piel y la predisposición a la aparición de tumores, tanto en los párpados como en la conjuntiva. Entre los tumores epiteliales malignos se destacan: el carcinoma basocelular y el carcinoma epidermoide; con menor frecuencia, el carcinoma de células de Meibomio y el melanoma palpebral, y raramente, el carcinoma de células de Merkel. Por esta causa, se realizó la presentación de un caso clínico que recibió tratamiento en el Servicio de Cirugía Plástica del Hospital Vladimir Ilich Lenin, de Holguín, al cual se le aplicó la técnica de Mustardé por presentar tumor del párpado inferior. El objetivo fue presentar un paciente con reconstrucción palpebral postumorectomía y mostrar su resultado funcional y estético postoperatorio. Este caso evolucionó satisfactoriamente, sin aparición de complicaciones transoperatorias o postoperatorias.

Some elderly patients frequently develop various diseases, including skin cancer as well as a predisposition to the appearance of tumours, both in the eyelids and conjunctiva. Basal cell carcinoma and epidermoid carcinoma stand out among the malignant epithelial lesions; meibomian cell carcinoma and palpebral melanoma which are less common, and Merkel cell carcinoma rarely known. We present a male patient who received treatment in the plastic surgery service at "Vladimir Ilich Lenin" Hospital, in Holguín, to which Mustardé technique was applied for a tumour of the lower eyelid. An eyelid reconstruction was performed after lumpectomy which allowed us to show a postoperative functional and aesthetic result. This case evolved satisfactorily, without the appearance of intraoperative or postoperative complications.

HeberFERON en el tratamiento de pacientes con carcinoma basocelular en zona de alto riesgo / HeberFERON in the Treatment of Patients with Basal Cell Carcinoma on a High-Risk Zone

Introducción: El carcinoma basocelular es un tumor de invasión local de crecimiento; se origina en las células epidérmicas de los folículos pilosos o las células basales de la epidermis, cuando se localizan en zona de alto riesgo en la cara tienen un mayor índice de recurrencia tumoral y de invasión a estructuras adyacentes y subyacentes. Objetivo: Evaluar los resultados de la aplicación del HeberFERON en pacientes con carcinoma basocelular en zona de alto riesgo. Métodos: Se realizó un estudio observacional, descriptivo y prospectivo en pacientes con diagnóstico clínico, dermatoscópico e histopatológico de carcinoma basocelular en zona de alto riesgo, tratados con HeberFERON en la consulta del Policlínico Centro de Sancti Spíritus desde el 12 de enero de 2016 hasta el 25 de marzo de 2022. La muestra quedó conformada por 62 pacientes Las principales variables estudiadas fueron la respuesta al tratamiento y los eventos adversos. Resultados: Predominó el sexo masculino, el área urbana, fototipocutáneo III y la edad mayor de 40 años. La localización más frecuente fue la nasal; el subtipo clínico el nódulo ulcerativo; el histológico, el sólido; el tumor primitivo y menor de 2 cm; la respuesta al tratamiento fue completa en la mayoría de los pacientes. Los eventos adversos más comunes fueron dolor y ardor en el sitio de inyección, edema y eritema perilesional, fiebre y cefalea. Conclusiones: La mayoría de los pacientes tratados con HeberFERON tuvieron una respuesta completa, los eventos adversos fueron los descritos en la literatura por el uso de interferones, sin cambio en la actitud farmacológica(AU)

Introduction: Basal cell carcinoma is a growing and locally invasive tumor; it originates in the epidermal cells of hair follicles or the basal cells of the epidermis. When located in a high-risk facial zone, they present a higher rate of tumor recurrence and invasion to adjacent and underlying structures. Objective: To evaluate the results of HeberFERON application in patients with basal cell carcinoma on a high-risk zone. Methods: An observational, descriptive and prospective study was conducted in patients with a clinical, dermatoscopic and histopathological diagnosis of basal cell carcinoma on a high-risk zone, treated with HeberFERON in the consultation of Policlínico Centro of Sancti Spíritus, from January 12, 2016 to March 25, 2022. The sample was made up of 62 patients. The main variables studied were response to treatment and adverse events. Results: There was a predominance of the male sex, the urban area, skin phototype III and age over 40 years. The most frequent localization was nasal; the clinical subtype, ulcerative nodule; the histological subtype, solid. The response to treatment was complete in most patients. The most common adverse events were pain and burning at the injection site, perilesional erythema and edema, fever and headache. Conclusions: Most patients treated with HeberFERON had a complete response; the adverse events were those described in the literature due to the use of interferons, with no change in pharmacological behavior(AU)

Carcinoma neuroendocrino de la piel: Carcinoma de células de Merkel. Revisión de la Literatura, a propósito de un caso / Neuroendocrine skin carcinoma: Merkel cell carcinoma. Review of literature, about a case

El carcinoma de células de Merkel, también llamado carcinoma neuroendocrino de la piel, es un tipo de cáncer de piel muy poco frecuente que generalmente aparece como un nódulo de color carne o rojo azulado, más frecuentemente en región facial, cabeza y cuello. El carcinoma de células de Merkel se desarrolla principalmente en personas mayores ya que la exposición al sol a largo plazo o un sistema inmunitario débil pueden aumentar el riesgo de desarrollarlo. Las células de Merkel se encuentran en la base de la capa más externa de la piel (epidermis) y están conectadas a las terminaciones nerviosas que son responsables del sentido del tacto. Tiende a crecer rápido y diseminarse a otras partes del cuerpo. Por tanto, las opciones de tratamiento para el carcinoma de células de Merkel dependen de si el cáncer se ha diseminado más allá de la piel

Merkel cell carcinoma, also called neuroendocrine skin of the skin, is a very rare type of skin cancer that generally appears as a bluish meat or red color nodule, more frequently in the facial, head and neck region. Merkel cell carcinoma develops mainly in older people since long -term exposure or a weak immune system can increase the risk of developing it. Merkel cells are at the base of the outermost layer of the skin (epidermis) and are connected to nerve endings that are responsible for the sense of touch. It tends to grow quickly and spread to other parts of the body. Therefore, the treatment options for Merkel cell carcinoma depend on whether cancer has spread beyond the skin

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

Carcinoma metatípico de piel en colgajo cérvico-facial previo. A propósito de un caso / Metatypical carcinoma of the skin in a previous cervicofacial flap. A case report

El carcinoma baso escamoso (CBE) o metatípico, es considerado un subtipo de carcinoma basocelular (CBC). Con frecuencia es infradiagnosticado ya que no posee características clínicas ni histológicas definidas, por lo que se suele diagnosticar erróneamente como un carcinoma basocelular o espinocelular (CEC). En este artículo se presenta el caso de un paciente masculino de 86 años con un CBE que se expresó en un colgajo cérvico-facial previo. Se ha descrito un alto riesgo de recurrencia y metástasis, lo que supone un pronóstico desfavorable para los pacientes. No existen protocolos terapéuticos estandarizados para esta entidad, sin embargo, el manejo es fundamentalmente quirúrgico. No se encontraron en la literatura reportes previos de carcinoma metatípico en injertos autólogos de piel(AU)

Metatypical or basosquamous carcinoma (BSC) is considered a subtype of basal cell carcinoma (BCC). It is often underdiagnosed due to the lack of defined clinical and histological characteristics, leading to misdiagnosis as either BCC or squamous cell carcinoma (SCC). This article presents a case of an 86-year-old male patient with metatypical carcinoma that manifested in a previous cervicofacial flap. There is a high risk of recurrence and metastasis associated with this condition, leading to an unfavorable prognosis for patients. Although there are no standardized therapeutic protocols for this entity, surgical management is the primary approach. No previous reports of metatypical carcinoma in autologous skin grafts were found in the literature(AU)

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.

Clinicopathological and prognostic features of subungual melanoma in situ / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma: results from a retrospective multicenter trial / 医学前沿

Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

Targeted therapeutic strategies for melanoma / 中华医学杂志(英文版)

Melanoma accounts for a small proportion of skin cancers diagnosed each year, but it has a high degree of malignancy and rapid progression, resulting in a short survival period for patients. The incidence of melanoma continues to rise, and now melanoma accounts for 1.7% of cancer diagnoses worldwide and is the fifth most common cancer in the United States. With the development of high-throughput sequencing technologies, the understanding of the pathophysiology of melanoma had also been improved. The most common activating mutations in melanoma cells are BRAF , NRAS , and KIT mutations, which disrupt cell signaling pathways related to tumor proliferation. The progress has led to the emergence of molecularly targeted drugs, which extends the survival of patients with advanced melanoma. A large number of clinical trials have been conducted to confirm that targeted therapy for patients with advanced melanoma can improve progression-free survival and overall survival, and for stage III patients after radical tumor resection targeted therapy can reduce the recurrence of melanoma. Patients who were originally stage III or IV inoperable have the opportunity to achieve tumor radical resection after targeted therapy. This article reviewed the clinical trial data and summarized the clinical benefits and limitations of these therapies.

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

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.

Factores pronósticos de la supervivencia en pacientes con melanoma de piel metastásico, que reciben primera línea de tratamiento con inmunoterapia anti PD-1 o régimen con anti PD-1 y anti CTLA-4, en el Instituto Nacional de Cancerología de Colombia / Prognostic factors for survival in patients with metastatic skin melanoma, receiving first-line treatment with anti-PD-1 or anti-PD-1 and anti-CTLA-4 immunotherapy regimen at the Instituto Nacional de Cancerología (Bogotá, Colombia)

Introducción. En melanoma metastásico, uno de los estándares de tratamiento es la inmunoterapia anti-PD-1 y anti-CTLA-4. El objetivo de esta investigación fue determinar factores pronósticos asociados con la supervivencia de pacientes con melanoma metastásico, con primera línea con inmunoterapia anti-PD-1 o anti-PD-1 y anti-CTLA-4, en el Instituto Nacional de Cancerología de Colombia.Métodos. Se revisaron 63 historias clínicas del Instituto Nacional de Cancerología de enero de 2016 a abril de 2020. Se realizó un análisis de supervivencia con método de Kaplan-Meier, prueba log-rank y regresión de Cox.Resultados. La mayoría de los pacientes fueron mujeres (58,7%); 47,6% tenían subtipo lentiginoso acral, 17,4% BRAF mutado, 20,6% compromiso en SNC, 50,8% recibieron nivolumab, 41,3% pembrolizumab y 7,9% nivolumab + ipilimumab. La mediana de supervivencia libre de progresión fue de 7,3 meses, con una tasa a 1, 2 y 3 años de 38,0%, 22,0% y 12,0% respectivamente; la mediana de supervivencia global fue 12,2 meses con una tasa a 1, 2 y 3 años de 50,0%, 25,0% y 19,0%. Como factor pronóstico protector para SLP se encontró el recibir nivolumab en comparación con pembrolizumab (HR=0,427; IC95% 0,21-0,86) y para SG el estado funcional al diagnóstico (ECOG 2 HR=12,38; IC95% 2,20-69,45).Conclusión. La SLP y SG fueron menores a la de ensayos clínicos aleatorizados en población caucásica, pero similar a la encontrada en estudios que incluyen mayor proporción del subtipo histológico lentiginoso acral, como la nuestra. Se encontraron como factores pronósticos el tipo de inmunoterapia utilizada y el estado funcional al diagnóstico.

Introduction: In metastatic melanoma, one of the standard treatments is anti-PD-1 and anti-CTLA-4 immunotherapy. This research aimed to determine prognostic factors associated with the survival of patients with metastatic melanoma who started first-line treatment with anti-PD-1 or anti-PD-1 and anti-CTLA-4 immunotherapy at the Instituto Nacional de Cancerología (INC) (Bogotá, Colombia).Methods: A total of 63 medical records from the INC were reviewed from January 2016 to April 2020. A survival analysis was performed using the Kaplan-Meier method, log-rank test, and Cox regression.Results: Most patients were women (58.7%); 47.6% had acral lentiginous subtype, 17.4% BRAF-mutated melanoma, 20.6% CNS involvement, 50.8% received nivolumab, 41.3% pembrolizumab, and 7.9% nivolumab + ipilimumab. Median progression-free survival (PFS) was 7.3 months with a rate at 1, 2, and 3 years of 38%, 22%, and 12%, respectively, while median overall survival (OS) was 12.2 months with a rate of 50%, 25%, and 19% at 1, 2, and 3 years, respectively. A protective prognostic factor for PFS was to receive nivolumab compared to pembrolizumab (HR=0.427; CI95% 0.21-0.86), and for OS, functional status at diagnosis (ECOG 2 HR=12.38; CI95% 2.20-69.45).Conclusion: PFS and OS were lower than those of randomized clinical trials in the Caucasian population, but similar to those found in studies that include a higher proportion of the acral lentiginous histological subtype, such as ours. The type of immunotherapy used and functional status at diagnosis were found as prognostic factors

Cirugía micrográfica de Mohs en carcinomas cutáneos: siete años de experiencia en Uruguay / Mohs micrographic surgery in skin cancer: 7 years' experience in uruguay / Cirurgia micrográfica de Mohs em carcinomas cutáneos: 7 anos de experiência no Uruguai

Introducción: la cirugía micrográfica de Mohs es una técnica para la exéresis de cánceres de piel con la ventaja del examen histológico del 100% de los márgenes quirúrgicos, logrando así la tasa de curación más alta con la máxima preservación de tejido sano circundante. Objetivo: realizar una descripción clínico-epidemiológica de 7 años de experiencia en Uruguay. Método: análisis descriptivo de pacientes operados por un mismo cirujano de Mohs registrando datos clínicos, tumorales y quirúrgicos. Resultados: se estudiaron 641 cirugías. 54,9% fueron realizadas en hombres y 45,1% en mujeres. La edad media fue de 69 años. El 68,2% correspondió a carcinoma basocelular y 31,8% a carcinoma espinocelular. El 79,4% se encontraba en cabeza y cuello. El 87,8% de los tumores fueron primarios y un 11,1% recidivas. El tipo más frecuente de cierre fue el cierre simple con 48,7% seguido de los colgajos con un 31,7%. Conclusiones: la cirugía de Mohs es un procedimiento seguro y eficaz, y nuestros resultados coinciden con lo descrito en centros de referencia internacional. Este trabajo describe 7 años de experiencia en Uruguay de la técnica de CMM, siendo el mayor a nivel nacional.

Introduction: Mohs micrographic surgery is a technique for skin cancer exeresis involving the advantage of 100% of surgical margins histological exam, which leads to highest healing rates with the maximum preservation of the surrounding healthy tissue. Objective: to conduct a clinical and epidemiological description of a 7 years' experience in Uruguay. Method: descriptive analysis of patients operated by the same Mohs surgeon who recorded clinical, tumor and surgical data. Results: 641 surgeries were included in the study. 54.9% of surgeries were performed in men and 45.1% in women. Average age was 69 years old. 68.2% of cases corresponded to basal cell carcinoma and 31.8% to squamous cell carcinoma. 79.4% were located in the head and neck, 87.8% of tumors were primary and 11.1% were cases of relapse. The most frequent type of closure was simple in 48.7% of cases, followed by flaps in 31.7%. Conclusions: Mohs surgery is a safe an effective procedure, and the results of the study agree with what is described in international reference centers. The study describes a 7 years' experience in Uruguay of Mohs micrographic surgery, being it the largest research conducted in Uruguay.

Introdução: a cirurgia micrográfica de Mohs é uma técnica de excisão de cânceres de pele com a vantagem do exame histológico de 100% das margens cirúrgicas, alcançando assim a maior taxa de cura com a máxima preservação do tecido saudável circundante. Objetivo: realizar uma descrição clínico-epidemiológica de 7 anos de experiência no Uruguai. Método: análise descritiva de pacientes operados pelo mesmo cirurgião com experiência na técnica de Mohs registrando dados clínicos, tumorais e cirúrgicos. Resultados: foram estudadas 641 cirurgias. 54,9% foram realizados em homens e 45,1% em mulheres. A média de idade foi de 69 anos. 68,2% corresponderam a carcinoma basocelular e 31,8% a carcinoma espinocelular. 79,4% estavam na cabeça e pescoço. 87,8% dos tumores eram primários e 11,1% recidivas. O tipo de fechamento mais frequente foi o fechamento simples (48,7%) seguido do fechamento com retalhos com (31,7%). Conclusões: a cirurgia de Mohs é um procedimento seguro e eficaz, e nossos resultados coincidem com os descritos em centros de referência internacionais. Este trabalho descreve 7 anos de experiência no Uruguai da técnica CMM, sendo a maior a nível nacional.

Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for Photodynamic Therapy of Skin Cancer

Abstract We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.

Cryptic COL1A1-PDGFB fusion in dermatofibrosarcoma protuberans: a clinicopathological and genetic analysis / 中华病理学杂志

Objective: To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans (CC-DFSP). Methods: Three cases of CC-DFSP diagnosed in West China Hospital, Sichuan University, Chengdu, China from January 2021 to September 2021 were studied. Immunohistochemistry for CD34 and other markers, fluorescence in situ hybridization (FISH) for PDGFB, COL1A1-PDGFB and COL1A1, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing were performed. Results: There were three cases of CC-DFSP, including two females and one male. The patients were 29, 44 and 32 years old, respectively. The sites were abdominal wall, caruncle and scapula. Microscopically, they were poorly circumscribed. The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues, typically arranging in a storiform pattern. Immunohistochemically, the neoplastic cells exhibited diffuse CD34 expression, but were negative for S-100, SMA, and Myogenin. Loss of H3K27me3 was not observed in the tumor cells. The Ki-67 index was 10%-15%. The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion, whereas showing unbalanced rearrangement for COL1A1. Case 1 showed a COL1A1 (exon 31)-PDGFB (exon 2) fusion using NGS, which was further validated through RT-PCR and Sanger sequencing. All patients underwent extended surgical resection. Except for case 3 with recurrence 2 years after surgical resection, the other 2 cases showed no recurrence or metastasis during the follow-up. Conclusions: FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection. However, for cases with negative routine FISH screening that were highly suspicious for DFSPs, supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.

Effectiveness of temporal island flap pedicled with perforating branch of zygomatic orbital artery to repair the defects after periocular malignant tumor resection / 中国修复重建外科杂志

OBJECTIVE@#To summarize the effectiveness of the temporal island flap pedicled with the perforating branch of zygomatic orbital artery for repairing defects after periocular malignant tumor resection.@*METHODS@#Between January 2015 and December 2020, 15 patients with periocular malignant tumors were treated. There were 5 males and 10 females with an average age of 62 years (range, 40-75 years). There were 12 cases of basal cell carcinoma and 3 cases of squamous carcinoma. The disease duration ranged from 5 months to 10 years (median, 2 years). The size of tumors ranged from 1.0 cm×0.8 cm to 2.5 cm×1.5 cm, without tarsal plate invasion. After extensive resection of the tumors, the left defects in size of 2.0 cm×1.5 cm to 3.5 cm×2.0 cm were repaired with the temporal island flap pedicled with the perforating branch of zygomatic orbital artery via subcutaneous tunnel. The size of the flaps ranged from 3.0 cm×1.5 cm to 5.0 cm×2.0 cm. The donor sites were separated subcutaneously and sutured directly.@*RESULTS@#All flaps survived after operation and the wounds healed by first intention. The incisions at donor sites healed by first intention. All patients were followed up 6-24 months (median, 11 months). The flaps were not obviously bloated, the texture and color were basically the same as the surrounding normal skin, and the scars at recipient sites were not obviously. There was no complication such as ptosis, ectropion, or incomplete closure of the eyelids and recurrence of tumor during follow-up.@*CONCLUSION@#The temporal island flap pedicled with the perforating branch of zygomatic orbital artery can repair the defects after periorbital malignant tumors resection and has the advantages of reliable blood supply, flexible design, and good morphology and function.

Blue Nevus Hidden within the Nevus of Ota / 中国医学科学杂志(英文版)

A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.

Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively.@*RESULTS@#4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine.@*CONCLUSION@#The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.