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.

Application of CRISPR-Cas9 to interrogate novel gene functions in cutaneous melanoma

Melanoma accounts for 3% of skin neoplasms and is the leading cause of death from skin disorders worldwide. The high mortality rate associated with this disease stems from the high capacity of melanoma patients to develop metastases and treatment relapse with inhibitors of the MAPK signaling pathway (such as BRAF inhibitors), commonly used in melanoma therapy. Thus, the investigation of genes involved in the mechanisms of melanoma development is essential for new and more effective therapeutic strategies. Hence, we describe in this thesis two projects involving the genes SIN3B and IRF4 as possible biomarkers for cutaneous melanoma. Initially, through bioinformatics analyses performed by our group, an upregulation of SIN3B was found in metastatic melanomas. This result together with the understanding of SIN3B role in regulating gene expression and oncogenic transformation, prompted us to describe in this thesis some mechanisms by which SIN3B may influence melanoma development. We then sought to characterize the gene function using SIN3B-deleted cells, generated by the CRISPR-Cas9 methodology. Initially, we observed increased SIN3B expression in BRAF-mutant metastatic melanomas, where we noted that the long splicing variant of the gene (NM_001297595.1) was effectively prevalent in melanomas. Subsequently, we designed gRNAs between the exons 2 and 3 of the human SIN3B gene and engineered three knockout clones and three control clones (containing empty lentiCRISPRv2 plasmid) from different melanoma cell lines (SKMEL28, A2058, and A375). Through functional analyses, it was observed that the absence of the gene did not interfere in the proliferation of tumor cells; however, it led to a decrease in invasive properties. These results were verified by Boyden chamber assays and transcriptome analysis (total RNA sequencing of deleted cells), where a decrease in migration and motility pathways was observed. Additionally, a screening of synthetically lethal genes with SIN3B was performed with a genome wide CRISPR library. These results showed that USP7 and STK11 genes, which belong to the FoxO signaling pathway, were essential in SIN3B-depleted melanoma cells. Finally, through a collaborative project with the Wellcome Trust Sanger Institute, previous large-scale sequencing analyses demonstrated that deletion of the IRF4 gene was lethal for melanoma cells. Accordingly, we performed IRF4 silencing in vitro and noticed that the lack of IRF4 promotes cell death and apoptosis, independently of MYC and MITF, known in the literature to be downstream targets of this gene. Therefore, these data suggest that IRF4 plays a vital role in melanoma cell survival. Taken together, both works herein described in this thesis demonstrate how CRISPR-Cas9 can be applied to study the functions and mechanisms of genes involved in melanoma progression, collectively helping in the development of more effective therapeutic strategies for this tumor

O melanoma representa 3% dos tipos de neoplasias cutâneas e é a maior causa das mortes por distúrbios de pele no mundo. A alta taxa de mortalidade associada à essa doença advém da alta capacidade de pacientes com melanoma desenvolverem metástases, e apresentarem recidiva após tratamento com inibidores da via de sinalização MAPK (como da proteína BRAF), comumente utilizados no tratamento de pacientes metastáticos. Assim, a investigação de genes envolvidos nos mecanismos de desenvolvimento do melanoma é primordial para novas estratégias terapêuticas mais efetivas. Dessa forma, descrevemos no presente trabalho dois projetos envolvendo os genes SIN3B e IRF4 como possíveis biomarcadores para melanoma cutâneo. Em análises prévias de bioinformática realizados pelo nosso grupo, SIN3B foi identificado tendo maior expressão em melanomas metastáticos. Além disso, diversos estudos mostraram que o gene está envolvido na regulação da expressão gênica e transformação oncogênica. Dessa forma, descrevemos nessa tese alguns mecanismos pelos quais SIN3B pode influenciar no desenvolvimento do melanoma, através da caracterização funcional de células SIN3B-deletadas pela metodologia CRISPR-Cas9. Inicialmente, observamos aumento na expressão de SIN3B em melanomas metastáticos BRAF-mutados, onde notamos que a variante de splicing longa do gene (NM_001297595.1), era efetivamente prevalente em melanomas. Assim, desenhamos sequências de RNA guias entre os éxons 2 e 3 do gene SIN3B humano e, obtivemos três clones knockout e outros três clones controle (contendo plasmídeo vazio) em diferentes linhagens de melanoma (SKMEL28, A2058 e A375), para caracterização funcional. Observou-se que a ausência do gene não interferiu na proliferação das células tumorais, contudo, acarretou na diminuição de processos invasivos. Esses resultados foram averiguados através de ensaios em câmara de Boyden e análises de transcriptoma (sequenciamento de RNA total das células deletadas), onde notou-se diminuição das vias de migração e motilidade. Adicionalmente, um rastreamento de genes sinteticamente letais com SIN3B foi realizado com uma biblioteca de CRISPR capaz de silenciar todo o genoma. Esses resultados mostraram que os genes USP7 e STK11, ambos pertencentes à via de sinalização de FoxO, são essenciais nas células SIN3B deletadas. Por fim, através de um projeto colaborativo com o Wellcome Trust Sanger Institute, análises prévias de sequenciamento de larga escala demonstraram que a deleção do gene IRF4 era letal para células de melanoma. Dessa forma, realizamos o silenciamento de IRF4 in vitro e notamos que a ausência do gene promove morte celular e apoptose, independentemente de MYC e MITF, conhecidos na literatura por serem alvos downstream do gene. Portanto, esses dados sugerem que IRF4 tem um papel importante na sobrevivência de células de melanoma. Em conjunto, ambos trabalhos descritos nessa tese, demonstram como a metodologia CRISPR-Cas9 pode auxiliar no entendimento de processos importantes para a malignidade do melanoma e contribuir para estratégias terapêuticas mais efetivas para esse tumor

Large basal cell carcinoma defect closure on the lateral cheek using multiple advancement flaps / Cierre de defecto por carcinoma de células basales en la mejilla lateral usando múltiples flaps de avance

Basal cell carcinoma (BCC) is the most common type of nonmelanoma skin cancer (NMSC). It grows slowly and very rarely metastasizes but can cause substantial morbidity due to its tendency to relapse and locally invasive nature, especially when located on the face. Excision surgery is still the gold standard treatment for primary BCC and is usually followed by reconstruction procedure. Skin flap techniques vary widely, one of which is flap advancement technique. The main benefit of flap advancement technique is the ability to hide the excision line, thus resulting in an aesthetically sound outcome. We report a case of 72-year-old female with hyperpigmented plaque brownish lump on the left lateral cheek. A diagnosis of igmented basal cell carcinoma had been confirmed through histopathological examination. The patient was treated with wide excision surgery and the defectwas closed by multiple advancement flaps. Follow-up after three months showed excellent cosmetic and functional outcome.

El carcinoma basocelular (CBC) es el tipo más común de cáncer de piel no melanoma. Crece lentamente y rara vez hace metástasis, pero puede causar una morbilidad sustancial debido a su ubicación en la cara, tendencia a la recidiva y su comportamiento invasivo local. La cirugía de escisión sigue siendo el tratamiento estándar de oro para el CBC primario y generalmente se acompañan de procedimientos reconstructivos. Las técnicas de flap varían ampliamente, una de las cuales es la técnica de avance del colgajo. El principal beneficio de la técnica de avance es la capacidad de ocultar la línea de escisión y, por lo tanto, se obtiene un resultado más estético. En este artículo reportamos el caso de una mujer de 72 años con placa hiperpigmentada y abultada en su mejilla lateral izquierda. Se había confirmado un diagnóstico de carcinoma de células basales pigmentadas mediante un examen histopatológico. El paciente fue tratado con una amplia cirugía de escisión y el defecto fue cerrado por múltiples colgajos de avance. El seguimiento después de tres meses mostró un excelente resultado cosmético y funcional.

Carcinoma epidermoide metastásico asociado a epidermólisis ampollosa distrófica / Metastasic squamous cell carcinoma in dystrophic epidermolysis bullosa

Caso clínico: femenino de 18 años con diagnóstico de epidermolisis ampollosa distrófica (EAD) quién desarrolló una neoformación nodular sobre una úlcera crónica. Se diagnosticó carcinoma epidermoide (CE) invasor al que se realizó resección. Sin embargo, 5 meses después del tratamiento quirúrgico presentó metástasis a ganglios, pulmón e hígado con desenlace fatal. Comentarios: el CE es la causa más importante de muerte en pacientes con EAD. Suele ser agresivo y metastásico. Se recomienda una vigilancia cada 3 a 6 meses para realizar diagnóstico y tratamiento oportunos (AU)

Case report: 18-year-old female patient with dystrophic epidermolysis bullosa (DEB) who developed a tumor over a chronic ulcer. She was diagnosed with invasive squamous cell carcinoma (SCC) and underwent surgical resection. However, 5 months later she presented metastases to the lymph nodes, lung and liver with a fatal outcome. Comments: SCC is the most important cause of death in patients with DEB. It is usually aggressive and metastatic. Surveillance every 3 to 6 months is recommended for prompt diagnosis and treatment (AU)

Dermal regeneration template: a new option for the repair of a large surgical defect after mohs surgery in epidermolysis bullosa

La epidermólisis ampollar es un raro trastorno hereditario caracterizado por fragilidad cutánea, formación de ampollas mucocutáneas recurrentes luego de un traumatismo mínimo y cicatrización deficiente de heridas. Además, algunas variantes se han asociado con la aparición de carcinomas espinocelulares. Presentamos el caso clínico de un paciente con epidermólisis ampollar, que presentó un extenso carcinoma espinocelular localizado en cara posterior de brazo. Este fue tratado con cirugía micrográfica de Mohs y el defecto quirúrgico resultante fue reparado aplicando una matriz de regeneración dérmica sobre la herida durante un mes. Posteriormente continuamos con curaciones y ungüento antibiótico sobre la herida dos veces al día, completando la cicatrización con un excelente resultado cosmético y funcional. Enfatizamos en el carácter novedoso de esta opción terapéutica y en su utilidad en pacientes con epidermólisis ampollar.

Epidermolysis bullosa is a rare hereditary disorder characterized by skin fragility, recurrent mucocutaneous blisters following minimal trauma, and compromised wound healing. Moreover, some variants have been associated with squamous cell carcinoma. Following, we present the clinical case of a patient with epidermolysis bullosa, who presented a large squamous cell carcinoma of the arm. It was resected using Mohs micrographic surgery, and the final defect was repaired by applying a dermal regeneration template over the wound for a month. After this period, we continued using cures and antibiotic ointment over the wound twice a day, and healing was completed with excellent cosmetic and functional results. We emphasize the novelty of this therapeutic option, and its usefulness in patients with epidermolysis bullosa.

Lepromatous leprosy, melanoma, and basal cell carcinoma: clinical-histopathologic association

Abstract Cutaneous neoplasms frequently occur in leprosy, but there are few reports of the coexistence of leprosy and basal cell carcinoma in the same lesion. This case reports a 49-year-old male with an ulcerated plaque on the right lateral nasal wall, bright papules on the sternal region, and a blackened plaque on the right temporal region. The nasal and temporal lesions were diagnosed by histopathology as basal cell carcinoma and melanoma, respectively. The sternal lesions were excised with the repair of the "dog ear" which histopathological examination showed macrophages in the dermis parasitized with acid-fast bacilli, confirming the diagnosis of lepromatous leprosy with Fite-Faraco staining. This case report highlights the importance of referring the dog-ear specimen for histopathologic analysis.

Sarcoma de Kaposi epidémico en África Subsahariana / Epidemic Kaposi sarcoma in Sub-Saharan Africa

El sarcoma de Kaposi se ha convertido en uno de los tumores más prevalentes en África tras la epidemia de VIH, que afecta de una manera similar a hombres y mujeres. El retraso diagnóstico y el limitado acceso a tratamiento antirretroviral o quimioterapia condicionan el pronóstico de los pacientes que lo padecen. En este artículo se realiza una revisión sobre la referida enfermedad, con el objetivo de describir sus aspectos más relevantes en los últimos años en África, como son su epidemiología, caractéristicas clínicas y opciones terapéuticas existentes. Este tumor es provocado por la infección por virus herpes humano tipo 8, que resulta más prevalente en las zonas rurales del continente africano. Se postula la transmisión a través de la saliva como la vía más importante de contagio en África. La inmunodepresión que causa el VIH favorece el efecto oncogénico del virus. La forma epidémica de SK se manifiesta inicialmente como lesiones hiperpigmentadas o violáceas en la piel, que pueden extenderse a linfáticos o mucosas y a nivel sistémico, principalmente a pulmón o aparato digestivo. El síndrome de reconstitución inmune sistémica puede complicar la evolución del paciente. El inicio temprano de la terapia antirretroviral resulta imprescindible. Además, el pronóstico de los pacientes mejora con la suma de tratamiento quimioterápico con doxorrubicina, vincristina, etopóxido o bleomicina principalmente(AU)

Kaposi sarcoma (KS) has become one of the most prevalent tumors in Africa after the HIV epidemic. KS affects both men and women. Diagnostic delay and limited access to antiretroviral treatment or chemotherapy have an impact on the prognosis of KS patients. A review was conducted about KS with the purpose of describing its most outstanding characteristics in recent years in Africa, such as its epidemiology, clinical features, and existing therapeutic options. This tumor is caused by infection with human herpesvirus 8, which is more prevalent in rural areas of the African continent. Transmission via saliva was found to be the most important transmission route in Africa. HIV-related immunosuppression fosters the oncogenic effect of the virus. The epidemic form of KS initially presents as hyperpigmented or violet-colored skin lesions which may extend to lymph nodes or mucosae, or systemically, mainly to the lungs or the digestive tract. Systemic immune reconstitution syndrome may complicate the patient's evolution. Early start of antiretroviral therapy is indispensable. Additionally, prognosis improves with chemotherapy with doxorubicin, vincristine, etoposide or bleomycin, mainly(AU)

Avaliação pré e pós-operatória do efeito da cirurgia reparadora na qualidade de vida e da autoestima do paciente: um estudo prospectivo envolvendo 52 pacientes / Pre- and postoperative evaluation of the effect of reconstructive surgery on patient quality of life and self-esteem: a prospective study of 52 patients

Introdução: As lesões de pele benignas e malignas podem afetar a qualidade de vida (QV) e a autoestima dos pacientes, tendo a cirurgia plástica reparadora im-portante papel nesses indivíduos. O objetivo é estudar o efeito da cirurgia plástica reparadora sobre a QV e a autoestima de pacientes. Métodos: Foi realizado um estudo quase-experimental (antes e de-pois). A QV foi medida pelo questioná-rio SF-36. Para a medida da autoestima, foi utilizada a escala de autoestima de Rosemberg. Alterações nos escores de ambos os instrumentos foram medidas antes e após o procedimento cirúrgico e a significância estatística da diferença foi avaliada pelo teste t. A proporção de indivíduos com aumento de escore de QV e autoestima, segundo as categorias de variáveis sociodemográficas, caracte-rísticas da lesão ou da doença, classifica-ção do tratamento cirúrgico e eventos estressantes, foi medida, e a significância estatística foi avaliada pelo teste do Qui-quadrado. Resultados: Foram entrevis-tados 52 pacientes. Após a intervenção cirúrgica, houve melhora significativa no escore de QV na maioria dos domínios de SF-36 (aspectos emocionais, físicos, sociais, dor, estado geral de saúde e saú-de mental) e melhora na escala de autoes-tima de Rosemberg. Os fatores associa-dos a maior probabilidade de melhora na QV e autoestima após a cirurgia foram idade igual ou superior a 60 anos, cor de pele branca, maior escolaridade, ocorrên-cia de evento estressante e tipo maligno de neoplasia. Conclusões: A cirurgia reparadora teve um impacto positivo em vários domínios de QV e autoestima, mostrando outras melhorias na saúde do paciente, além dos benefícios clínicos.

Introduction: Benign and malignant skin lesions can affect patients' quality of life and self-esteem; thus, reconstructive plastic surgery is important for these individuals. The objective is to assess the effect of reconstructive plastic surgery on the quality of life (QoL) and self-esteem in patients with benign or malignant skin lesions. Methods: This quasi-experimental "prepost study" measured QoL using the 36-Item Short Form Health Survey (SF-36) questionnaire. For the measure of self-esteem, the Rosenberg Self-Esteem Scale was used. The changes in scores of both instruments were measured before and after surgery, and the statistical significance of the difference was evaluated using a paired sample t test. The proportion of individuals with an increased QoL score and self-esteem according to sociodemographic variables, lesion or disease characteristics, surgical treatment classification, and stressful events was measured, whereas the statistical significance was assessed using the chi-square test. Results: Fifty-two patients were interviewed. After the surgical intervention, significant improvement in QoL score in most SF-36 domains (emotional, physical, social, pain, general health, and mental health aspects) and improvement in the Rosenberg Self-Esteem Scale score were noted. The factors associated with a higher probability of improvements in QoL and self-esteem after surgery were age ≥60 years, white skin color, higher education level, occurrence of a stressful event, and malignant neoplasia. Conclusions: Reconstructive surgery positively affected several domains of QoL and self-esteem, showing other improvements in patient health beyond its technical and clinical benefits.

Retalho nasogeniano de interpolação na reconstrução da asa nasal após ressecção de tumores cutâneos / Nasolabial interpolation flap for nasal alar reconstruction after skin tumor resection

Introdução: O nariz é sede frequente de neoplasias cutâneas. Pela importância estético-funcional, a reconstrução do nariz, em especial da asa nasal, é um desafio. O objetivo é descrever o retalho nasogeniano de interpolação na reconstrução da asa nasal após ressecção de tumores cutâneos. Métodos: Pacientes com tumores de pele não melanoma de asa nasal, sem comprometimento dos sulcos alar ou supra-alar, foram submetidos à reconstrução com retalho nasogeniano de interpolação associado a enxerto de cartilagem conchal. Detalhes do planejamento cirúrgico e da sequência operatória, assim como a análise dos resultados, são demonstrados. Resultados: No tratamento de tumores de pele localizados na asa nasal, deve-se buscar resultados sob o ponto de vista oncológico e estético. Assim, a preservação da estrutura tridimensional e das características cutâneas da asa nasal deve ser objetivada. Conclusão: O retalho nasogeniano de interpolação mostrou-se eficaz na reconstrução da asa nasal, apesar da necessidade de dois tempos cirúrgicos.

Introduction: The nose is a common site for skin neoplasms. Due to its functional and esthetic importance, nasal reconstruction, mainly that of the nose ala, is challenging. The objective is to describe the nasolabial interpolation flap for nasal alar reconstruction after skin tumor resection. Methods: Patients with nonmelanoma skin tumors on the nasal ala without involvement of the alar and supra-alar sulcus underwent reconstruction with a nasolabial interpolation flap associated with conchal cartilage grafting. Details of the surgical planning and operative sequence and an analysis of the results are presented. Results: In the treatment of skin tumors on the nasal ala, results from the oncological and esthetic point of view should be sought, i.e., maintenance of the threedimensional structure and cutaneous features should be intended. Conclusion: Use of the nasolabial interpolation flap was effective for nasal alar reconstruction despite the need for two surgeries.

Hemangioma de crecimiento mínimo o detenido con lipoatrofia: presentación de un caso clínico / Hemangioma with minimal or arrested growth

Los hemangiomas de la infancia (HI) son tumo-res vasculares que presentan un patrón evolutivo característico. Existe un subgrupo de HI que pre-senta un tipo de crecimiento distinto denominados hemangiomas de la infancia con crecimiento míni-mo o detenido (HI-CMD). En estos, el componen-te proliferativo no supera el 25% de la superficie total; además, afecta a niños de al menos dos meses de edad en la consulta inicial o a niños menores de dicha edad en los que se realiza un seguimiento mayor a 2 meses. Los HI- CMD con lipoatrofia son una variante poco frecuente de HI de la cual exis-ten escasos reportes en la literatura. El objetivo de nuestro trabajo es presentar un caso de HI-CMD con lipoatrofia en una lactante. Los HI-CMD presentan un desafío diagnóstico ya que deben ser reconocidos precozmente y diferencia-dos de otras lesiones vasculares.

Infantile hemangiomas (IH) are vascular tumors that present a characteristic evolutive pattern. There is a subgroup of hemangiomas that pre-sents a different type of growth called infantile hemangiomas with minimal or arrested growth (IH-MAG). In these, the proliferative component does not exceed 25% of the total surface; it also affects children of at least two months of age in the initial consultation or children under that age in which a follow-up of more than 2 months is carried out. IH-MAG with lipoatrophy is a rare variant of IH of which there are few reports in the literature.The aim of our report is to present a case of IH-MAG with lipoatrophy in an infant. IH-MAGs present a diagnostic challenge since they must be recognized early, and differentiated from other vascular lesions.

Multifocal oral melanoacanthoma associated with Addison's disease and hyperthyroidism: a case report

SUMMARY Oral melanoacanthoma is a mucocutaneous, pigmented, rare, benign, and probably reactive lesion. This paper reports for the first time in the literature a case of multifocal oral melanoacanthoma in a patient diagnosed with Addison's disease and concomitant Graves' disease with hyperthyroidism. The patient presented with oral pigmented lesions, which were hypothesized to be mucosal pigmentation associated with Addison's disease. Due to their unusual clinical pattern, these oral lesions were biopsied and diagnosed as oral melanoacanthoma on histopathology and immunohistochemistry for HMB-45. At the moment of this report, the patient was being treated for her systemic conditions, but the lesions had not regressed. Reactive hyperpigmentation of the skin and mucous membranes may be found in Addison's disease and hyperthyroidism. This case reinforces the hypothesis of a reactive nature for oral melanoacanthoma and highlights the need for investigation of endocrine disorders in patients with multifocal oral melanoacanthoma.

Neoplasias de origen sebáceo asociadas a Síndrome de Muir-Torre. A propósito de un caso / Sebaceous neoplasias associated to Muir-Torre syndrome. A propos of a case

El Síndrome de Muir-Torre (SMT) descrito desde 1967, es una genodermatosis con herencia autosómica dominante y penetrancia variable, caracterizada por la presencia de neoplasias cutáneas de origen sebáceo manifestado en áreas seborreicas, como la cara y cuero cabelludo. Los adenomas son los tumores sebáceos más frecuentes. Se han descrito también hiperplasias, neoformaciones sebáceas quísticas, epiteliomas o carcinoma. Los mismos pueden presentarse de manera aislada o múltiple; en conjunto con al menos una neoplasia visceral maligna. Entre las descritas con frecuencia están las gastrointestinales. Se pueden asociar a otras neoplasias, como las renales, las de endometrio, útero y de laringe. El diagnóstico clínico está dado por la presencia y asociación de un tumor visceral primario y otro de origen sebáceo. El tratamiento de esta entidad se basa en la exéresis de los tumores y el seguimiento especializado según el sistema afectado. Se presentó el caso de un hombre de 62 años de edad, cuya afección cutánea demostró múltiples lesiones de origen sebáceo de siete años de evolución por lo que se le realizaron complementarios para identificar entidades asociadas (AU).

The Muir-Torre syndrome, described since 1967, is a genodermatosis with dominant autosomal inheritance and variable penetrance, characterized by the presence of sebaceous skin neoplasias manifested in seborrheic areas as the face and scalp. Adenomas are the most frequent sebaceous tumors. Hyperplasia, cystic sebaceous neoformations, epitheliomas or carcinomas have been also described. They could appear in an isolated or multiple way, in all with at least one malignant visceral neoplasia. The gastrointestinal ones are among those frequently described. They might be associated to other neoplasias, as the renal ones, or the ones of the endometrium, the uterus and the larynx. The clinical diagnosis is given by the presence and association of one primary visceral tumor and another of sebaceous origin. The treatment of this entity is based on the tumors resection and the specialized follow-up according to the affected system. The case of a man, aged 62 years, is presented; his cutaneous condition showed multiple sebaceous lesions of seven years of evolution. Complementary exams were carried out for identifying associated lesions (AU).

Reconstrucción facial con colgajo libre lateral del brazo / Facial reconstruction with free lateral arm flap

ResumenLas lesiones faciales malignas complejas o muy extensas, tratadas mediante resección quirúrgica, a menudo constituyen un reto para el cirujano plástico, debido a la gran exposición social del sitio, así como la escasa oferta de tejido para la reconstrucción del defecto cutáneo residual. En estos casos es imperativa la obtención de márgenes libres de malignidad; en segundo lugar, intentar recuperar la funcionalidad del área quirúrgica, y por último, buscar resultados estéticos favorables. Cuando sea posible, la ausencia de cobertura cutánea debe ser restaurada con tejido de similar grosor, color y textura, para lo cual el cirujano debe evaluar cuidadosamente el tamaño del defecto, la localización, las capas de tejido involucradas, la relación con estructuras aledañas y la cantidad de tejido donador disponible, con el fin de conseguir el mejor resultado final. Para deformidades de gran extensión que involucran múltiples capas de tejido, el concepto del triángulo reconstructivo de Mathes y Nahai, puede brindar mejores resultados, dándole opción al cirujano de escoger entre transposición de colgajos locoregionales, colgajos libres o expansión tisular. Los colgajos libres pueden satisfacer mejor las necesidades de forma y función facial, y permiten una considerable oferta de tejido con adecuada vascularidad, similitud de color, textura y grosor. A continuación se presenta el caso clínico de un paciente masculino de 21 años con el diagnóstico de carcinoma basocelular de mejilla derecha recidivante, quien fue sometido a resección completa y reconstrucción del defecto mediante transferencia libre de un colgajo lateral del brazo derecho, con excelentes resultados anatómicos y funcionales.

AbstractComplex or very extensive malignant facial lesions that are treated by surgical resection are often challenging for the plastic surgeon because of the large social exposure of the site as well as for the limited supply of tissue for reconstruction of the residual skin defect. In these cases it is imperative to first obtain free margins from malignancy, secondly try to recover the functionality of the surgical area and finally seek for favorable aesthetic results. Whenever possible, the facial defect should be restored with tissue of similar thickness, color and texture, for which the surgeon should carefully evaluate the size of the defect, location, tissue layers involved, the relationship with surrounding structures and the available donor tissue, in order to obtain the best final result. For large deformities involving multiple layers of tissue, the Mathes and Nahai concept of the reconstructive triangle can provide better outcomes, giving the surgeon a choice among transposition of locoregional flaps, free flaps, or tissue expansion. Free flaps can better satisfy the need of facial contour and function, they allow a considerable supply of tissue with adequate vascularity, similarity of color, texture and thickness. The authors present a clinical case of a 21-year-old male patient with the diagnosis of recurrent basal cell carcinoma of the right cheek who underwentcomplete resection and reconstruction of the facial defect with a free right lateral arm flap with excellent anatomical and functional results.

Giant congenital melanocytic nevi: 40 years of experience with the serial excision technique

Abstract: Although giant congenital melanocytic nevus is a rare lesion, it causes significant deformity and carries a risk of malignant degeneration. Different surgical techniques for the lesion removal are described, including serial resection, resection with skin grafting, and resection and coverage with expanded skin flap (skin expanders). The aim of this study is to report the author's 40 years of experience with cases requiring at least 4 serial excisions to complete the treatment. Serial resection is an effective, safe, and simple technique that requires a lot of patience. Treatment often results in a single linear scar, requires no donor sites, nor large flaps. It is not subject to potencial complications of expanders and avoid aesthetic deformities depending on the location.

Diffuse cutaneous melanosis: rare complication of metastatic melanoma

Abstract Diffuse cutaneous melanosis is a rare complication of metastatic melanoma related to a worse prognosis. There are few cases reported in the literature. Its pathogenesis has not been completely elucidated, although studies have suggested certain mechanisms for its occurrence. It is clinically manifested as a blue-gray discoloration of the skin and mucous membranes in a cephalo caudal progression and usually associated with melanuria. Skin and mucosa histopathology reveals only the presence of melanophages in the dermis, mainly perivascular, and free interstitial melanin. We report the case of a 68-year-old male with metastatic melanoma, diffuse hyperpigmentation of the skin and melanuria.

Dermatofibrosarcoma protuberans: série de 27 casos consecutivos / Dermatofibrosarcoma protuberans: a single series of 27 consecutive cases

INTRODUÇÃO: A dermatofibrosarcoma protuberans (DFSP) é um tumor maligno de baixo grau de partes moles caracterizado por infiltração local agressiva e propenso a recidiva local. Este estudo retrospectivo analisou resultados clínicos, taxas de recidiva e sobrevida após tratamento cirúrgico de DFSP. MÉTODOS: Pacientes submetidos a cirurgia para erradicação completa do tumor, e subsequente seguimento por exame clínico e vigilância ultrassonográfica de locais primários do tumor e linfonodos correspondentes para detectar recidiva local ou distante. A cirurgia, invariavelmente, incluiu grande excisão do tumor, seguida por procedimentos de reconstrução diferente como enxerto de pele em 23 casos (85%), retalho local em 2 pacientes (7.4%), retalho livre em 1 caso (4%), enquanto a principal sutura foi realizada apenas em um caso (4%). RESULTADOS: Foi necessária segunda cirurgia em 9 casos (33%) para atingir margens livres mínimas de 2-3 cm. Outros tratamentos cirúrgicos foram utilizados, como cirurgia micrográfica de Mohs, ou terapias adjuvantes, como radioterapia e quimioterapia. Em nossa série de pacientes o intervalo livre de recidiva variou de 1 a 10 anos, com média de 6 anos. A recidiva local ocorreu em 3 pacientes (11%), e necessitou de outras excisões cirúrgicas extensas. Um total de 27 pacientes não desenvolveu metástase distante durante o seguimento. CONCLUSÃO: A excisão extensa é efetiva para disponibilizar local confiável para controlar a doença, porém somente se limitadas por margens livres de 2-3 cm e confirmadas por patologista. A vigilância clinica e ultrassonografia durante o seguimento permite identificação precoce de eventuais recidivas locais e envolvimento de linfonodos.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade malignant tumor of soft tissues characterized by aggressive local infiltration and propensity for local recurrence. This retrospective study analyzed clinical outcomes, recurrence and survival rates after surgical treatment of DFSP. METHODS: Patients underwent surgery to complete eradicate tumor, and subsequently a close follow-up by clinical examination and ultrasounds surveillance of primary tumor site and corresponding lymph nodes, to detect local or distant recurrence. Surgery invariably included wide excision of tumor, followed by different reconstructive procedures as skin grafting in 23 cases (85%), local flap in 2 patients (7.4%), free flap in 1 case (4%), while primary closure was performed only in one case (4%). RESULTS: Second surgery was needed in 9 cases (33%) to achieve minimum free-margins of 2-3cm. Other surgical treatments like Mohs Micrographic Surgery, or adjuvant therapies, like radio- or chemotherapy were not used. Free-recurrence lapse among this series of patients varied from 1 to 10 years, with a medium period of 6 years. Local recurrence occurred in 3 patients (11%), and required a further extended surgical excision. A total of 27 patients did not develop distance metastasis during the follow-up. CONCLUSION: Extended excision is effective to provide a reliable local control of disease, but only if free margins limiting 2-3 cm is confirmed by pathologist. Clinical and ultrasound surveillance during close follow-up provide early detection of eventual local recurrence and of lymph nodes involvement.

Neurofibromatosis: part 2 – clinical management / Neurofibromatoses: parte 2 – manejo clínico

Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH). NF shares some features such as the genetic origin of the neural tumors and cutaneous manifestations, and affects nearly 80 thousand Brazilians. Increasing scientific knowledge on NF has allowed better clinical management and reduced rate of complications and morbidity, resulting in higher quality of life for NF patients. Most medical doctors are able to perform NF diagnosis, but the wide range of clinical manifestations and the inability to predict the onset or severity of new features, consequences, or complications make NF management a real clinical challenge, requiring the support of different specialists for proper treatment and genetic counseling, especially in NF2 and SCH. The present text suggests guidelines for the clinical management of NF, with emphasis on NF1.

A primeira parte desta diretriz abordou o diagnóstico diferencial das neurofibromatoses (NF): neurofibromatose do tipo 1 (NF1), neurofibromatose do tipo 2 (NF2) e schwannomatose (SCH). As NF compartilham algumas características, como a origem neural dos tumores e sinais cutâneos, e afetam cerca de 80 mil brasileiros. O aumento do conhecimento científico sobre as NF tem permitido melhor manejo clínico e redução da morbidade das complicações, resultando em melhor qualidade de vida para os pacientes com NF. A maioria dos médicos é capaz de realizar o diagnóstico das NF, mas a variedade de manifestações clínicas e a dificuldade de se prever o surgimento e a gravidade de complicações, torna o manejo da NF um desafio para o clínico e envolve diferentes especialistas para o tratamento adequado e aconselhamento genético, especialmente a NF2 e a SCH. O presente texto sugere algumas orientações para o acompanhamento dos portadores de NF, com ênfase na NF1.

Evaluation of cardiovascular disease risk factors in patients with mycosis fungoides

BACKGROUND: Mycosis fungoides, the most common subtype of cutaneous T-cell lymphoma, is more common in patients aged 45-55. OBJECTIVE: Cardiovascular risk factors have been investigated in several skin diseases. However, the relation between cardiovascular diseases and mycosis fungoides remains unclear. Therefore, the aim of this study was to assess cardiovascular risk factors in patients with mycosis fungoides. METHODS: 32 patients with mycosis fungoides and 26 healthy controls were enrolled in the study. Glucose, total cholesterol, high-density lipoprotein cholesterol, triglyceride, homocystein, high sensitivity C-reactive protein, low-density lipoprotein – cholesterol, were measured in the sera of patients. RESULTS: Patients had significantly higher high-sensitivity C-reactive protein, homocysteine, low-density lipoprotein - cholesterol, total cholesterol (p= 0.032) (p< 0.001) (p= 0.001) (p< 0.001). There was a positive correlation between the levels of homo-cysteine and total cholesterol (p= 0.001, r = +0.431). Additionally, a significantly positive correlation was found between the levels of high-sensitivity C-reactive protein and low-density lipoprotein - cholesterol (p= 0.014, r = +0.320) in patient group. CONCLUSIONS: Patients with mycosis fungoides had significantly higher levels of total-cholesterol, low-density lipoprotein -cholesterol, homocysteine and high-sensitivity C-reactive protein than healthy subjects. The present study has demonstrated an increased rate of cardiovascular risk in patients with mycosis fungoides. Even though the etiology of these associations is elusive, dermatologists should be sensitized to investigate metabolic derangements in patients with mycosis fungoides, in order to lessen mortality and comorbidity with a multidisciplinary approach. .