Tumor neuroectodérmico maligno del tracto gastrointestinal: a propósito de un caso / Malignant neuroectodermal tumor of the gastrointestinal tract: case report

El tumor neuroectodérmico maligno del tracto gastrointestinal es una neoplasia rara con pocos casos reportados en la literatura, especialmente en América Latina. Descrito por primera vez en 2003, se trata de una entidad sin tratamiento estandarizado y de pobre pronóstico. Se presenta el caso de una paciente de 22 años de edad que acude a la consulta por dolor abdominal, anemia y masa abdominal palpable. Luego de estudios pertinentes se decide la conducta resectiva y el posterior tratamiento oncológico. (AU)

Malignant gastrointestinal neuroectodermal tumor (GNET), formerly known as clear cell sarcoma of the gastrointestinal tract, is an extremely rare tumor of mesenchymal origin, which presents great microscopic and molecular similarity to clear cell sarcoma found in other parts of the body, such as tendons and aponeurosis. It is characterized by its rapid evolution, high recurrence rate and frequent diagnosis as metastatic disease.1,2 (AU)

MiR-15b-5p Promotes Growth and Metastasis of Renal Clear Cell Carcinoma / MiR-15b-5p Promueve el Crecimiento y la Metástasis del Carcinoma Renal de Células Claras

SUMMARY: We investigated the expression and clinical significance of miR-15b-5p in clear cell renal cell carcinoma (RCC) through bioinformatics analysis and experimental verification. The differentially expressed miRNAs were screened in the GEO database. Venn diagram showed that there were 5 up-regulated miRNAs (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p, and has-miR-193a-3p) and only 1 down-regulated miRNA (has-miR-532-3p) that were commonly expressed between GSE189331 and GSE16441 datasets. This was further confirmed in TCGA. Further analysis showed that the has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p, and has-miR-15b-5p were closely related to tumor invasion, distant metastasis and survival probability. The expression of miR-15b-5p in ccRCC tissues was significantly higher than that in adjacent normal kidney tissues (P0.05). Following inhibition of miR-15b-5p expression, RCC cells had attenuated proliferation, increased apoptosis, and attenuated migration and invasion. has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC. miR-15b-5p is highly expressed in cancer tissues of ccRCC patients. It may promote proliferation, inhibit apoptosis and enhance cell migration and invasion of RCC cells. The has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, and has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC.

Investigamos la expresión y la importancia clínica de miR-15b-5p en el carcinoma de células renales (CCR) de células claras mediante análisis bioinformático y verificación experimental. Los miARN expresados diferencialmente se examinaron en la base de datos GEO. El diagrama de Venn mostró que había 5 miARN regulados positivamente (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p y has-miR-193a-3p). ) y solo 1 miARN regulado negativamente (has-miR-532-3p) que se expresaron comúnmente entre los conjuntos de datos GSE189331 y GSE16441. Esto fue confirmado aún más en TCGA. Un análisis más detallado mostró que has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p y has-miR-15b-5p estaban estrechamente relacionados con la invasión tumoral, la metástasis a distancia y la probabilidad de supervivencia. La expresión de miR-15b-5p en tejidos ccRCC fue significativamente mayor que la de los tejidos renales normales adyacentes (P 0,05). Tras la inhibición de la expresión de miR-15b-5p, las células RCC tuvieron una proliferación atenuada, un aumento de la apoptosis y una migración e invasión atenuadas. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC. miR-15b-5p se expresa altamente en tejidos cancerosos de pacientes con ccRCC. Puede promover la proliferación, inhibir la apoptosis y mejorar la migración celular y la invasión de células RCC. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E y has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC.

Acantoma de células claras. Estudio clínico de 70 pacientes / Clear Cell Acanthoma: A Series of 70 Cases

Antecedentes y objetivo El acantoma de células claras (ACC) es una lesión poco frecuente caracterizada histológicamente por la presencia de acantosis epidérmica a expensas de queratinocitos de citoplasma claro. Aunque se han descrito muchos casos clínicos de forma individual, se han publicado pocas series de pacientes con ACC. Nuestro objetivo fue analizar las características clínicas del ACC en nuestra población. Material y métodos Estudio retrospectivo de los pacientes con ACC diagnosticados en el Hospital Universitario de Bellvitge en Barcelona, España, entre 1995-2021. Se revisaron las historias clínicas para obtener los siguientes datos: edad, sexo, localización, número de lesiones, diámetro, tiempo de evolución, características clínicas de los tumores, diagnóstico clínico de sospecha y el tratamiento realizado Resultados Setenta pacientes con ACC fueron incluidos en el estudio (30 mujeres y 40 varones, edad media 62 años, DE 13). La mediana del tiempo de evolución fue de dos años, rango intercuartílico (RIQ) 4 y la del diámetro 6 mm, RIQ 5. Una paciente presentó lesiones múltiples. Las lesiones se localizaron en las extremidades inferiores en 57 pacientes (81%), en la cara posterior del tronco en ocho (11%), la cara anterior del tronco en cuatro (5%) y en las extremidades superiores en uno (1%). Se planteó el diagnóstico clínico de ACC en 40% de los pacientes atendidos por dermatólogos. Conclusiones El aspecto clínico característico del ACC es el de una lesión cupuliforme eritematosa con punteado vascular y collarete epidérmico. La proporción de ACC diagnosticados clínicamente ha mejorado respecto a series antiguas, quizás por un mayor conocimiento clínico de la entidad y un mayor uso de la dermatoscopia (AU)

Background and objective Clear cell acanthoma (CCA) is an uncommon lesion histologically characterized by the presence of epidermal acanthosis with keratinocytes containing clear cytoplasm. Although many single cases of CCA have been described, few case series have been published. The aim of this study was to describe the clinical characteristics of CCA in our practice setting. Material and methods Retrospective study of patients diagnosed with CCA at Hospital Universitario de Bellvitge in Barcelona, Spain, between 1995 and 2021. We conducted a chart review to record age, sex, number and location of lesions, diameter, time since onset, clinical characteristics, suspected clinical diagnosis, and treatment. Results Seventy patients (30 women and 40 men) with a mean (SD) age of 62 (13) years were diagnosed with CCA during the study period. Median (interquartile range) time since onset was 2 (4) years and median lesion diameter was 6 (5) mm. One woman had multiple lesions. Lesions were located on the lower extremities in 57 patients (81%), the posterior aspect of the trunk in 8 (11%), the anterior aspect of the trunk in 4 (5%), and the upper extremities in 1 (1%). CCA was clinically suspected in 40% of patients seen by dermatologists. Conclusions CCA presents as an erythematous, dome-shaped lesion with pinpoint vessels and an epidermal collarette. The accuracy of clinical diagnosis has improved relative to earlier series, possibly due to a better clinical understanding of this lesion and a greater use of dermoscopy (AU)

[Translated article] Clear Cell Acanthoma: A Series of 70 Cases / Acantoma de células claras. Estudio clínico de 70 pacientes

Background and objective Clear cell acanthoma (CCA) is an uncommon lesion histologically characterized by the presence of epidermal acanthosis with keratinocytes containing clear cytoplasm. Although many single cases of CCA have been described, few case series have been published. The aim of this study was to describe the clinical characteristics of CCA in our practice setting. Material and methods Retrospective study of patients diagnosed with CCA at Hospital Universitario de Bellvitge in Barcelona, Spain, between 1995 and 2021. We conducted a chart review to record age, sex, number and location of lesions, diameter, time since onset, clinical characteristics, suspected clinical diagnosis, and treatment. Results Seventy patients (30 women and 40 men) with a mean (SD) age of 62 (13) years were diagnosed with CCA during the study period. Median (interquartile range) time since onset was 2 (4) years and median lesion diameter was 6 (5)mm. One woman had multiple lesions. Lesions were located on the lower extremities in 57 patients (81%), the posterior aspect of the trunk in 8 (11%), the anterior aspect of the trunk in 4 (5%), and the upper extremities in 1 (1%). CCA was clinically suspected in 40% of patients seen by dermatologists. Conclusions CCA presents as an erythematous, dome-shaped lesion with pinpoint vessels and an epidermal collarette. The accuracy of clinical diagnosis has improved relative to earlier series, possibly due to a better clinical understanding of this lesion and a greater use of dermoscopy (AU)

Antecedentes y objetivo El acantoma de células claras (ACC) es una lesión poco frecuente caracterizada histológicamente por la presencia de acantosis epidérmica a expensas de queratinocitos de citoplasma claro. Aunque se han descrito muchos casos clínicos de forma individual, se han publicado pocas series de pacientes con ACC. Nuestro objetivo fue analizar las características clínicas del ACC en nuestra población. Material y métodos Estudio retrospectivo de los pacientes con ACC diagnosticados en el Hospital Universitario de Bellvitge en Barcelona, España, entre 1995-2021. Se revisaron las historias clínicas para obtener los siguientes datos: edad, sexo, localización, número de lesiones, diámetro, tiempo de evolución, características clínicas de los tumores, diagnóstico clínico de sospecha y tratamiento realizado. Resultados Setenta pacientes con ACC fueron incluidos en el estudio (30 mujeres y 40 varones, edad media: 62 años, DE: 13). La mediana del tiempo de evolución fue de 2 años, rango intercuartílico (RIQ): 4 y la del diámetro 6mm, RIQ: 5. Una paciente presentó lesiones múltiples. Las lesiones se localizaron en las extremidades inferiores en 57 pacientes (81%), en la cara posterior del tronco en 8 pacientes (11%), la cara anterior del tronco en 4 pacientes (5%) y en las extremidades superiores en un paciente (1%). Se planteó el diagnóstico clínico de ACC en el 40% de los pacientes atendidos por dermatólogos. Conclusiones El aspecto clínico característico del ACC es el de una lesión cupuliforme eritematosa con punteado vascular y collarete epidérmico. La proporción de ACC diagnosticados clínicamente ha mejorado respecto a series antiguas, quizás por un mayor conocimiento clínico de la entidad y un mayor uso de la dermatoscopia (AU)

Clear Cell Acanthoma: A Series of 70 Cases. / Acantoma de células claras. Estudio clínico de 70 pacientes.

BACKGROUND AND OBJECTIVE: Clear cell acanthoma (CCA) is an uncommon lesion histologically characterized by the presence of epidermal acanthosis with keratinocytes containing clear cytoplasm. Although many single cases of CCA have been described, few case series have been published. The aim of this study was to describe the clinical characteristics of CCA in our practice setting. MATERIAL AND METHODS: Retrospective study of patients diagnosed with CCA at Hospital Universitario de Bellvitge in Barcelona, Spain, between 1995 and 2021. We conducted a chart review to record age, sex, number and location of lesions, diameter, time since onset, clinical characteristics, suspected clinical diagnosis, and treatment. RESULTS: Seventy patients (30 women and 40 men) with a mean (SD) age of 62 (13) years were diagnosed with CCA during the study period. Median (interquartile range) time since onset was 2 (4) years and median lesion diameter was 6 (5) mm. One woman had multiple lesions. Lesions were located on the lower extremities in 57 patients (81%), the posterior aspect of the trunk in 8 (11%), the anterior aspect of the trunk in 4 (5%), and the upper extremities in 1 (1%). CCA was clinically suspected in 40% of patients seen by dermatologists. CONCLUSIONS: CCA presents as an erythematous, dome-shaped lesion with pinpoint vessels and an epidermal collarette. The accuracy of clinical diagnosis has improved relative to earlier series, possibly due to a better clinical understanding of this lesion and a greater use of dermoscopy.

Metástasis de cáncer de células claras renal en cuerdas vocales. Reporte de un caso / Metastasis of renal clear cell carcinoma in vocal cords. A Case report

Introducción: Las metástasis a distancia de tumores primarios a cuerdas vocales son poco frecuentes. Las metástasis a laringe con mayor frecuencia corresponden a melanomas y carcinomas, afectando principalmente a la región supraglótica. Las metástasis a cabeza y cuello de los carcinomas de células renales (CCR) tienen una incidencia de 14-16%. Se presenta el caso de un paciente con metástasis de carcinoma de células claras renal a cuerdas vocales, cuya importancia recae en que es un caso poco frecuente y no existen reportes similares en el país. Paciente masculino, 57 años, con disfonía de 3 meses de evolución. Nasofibroscopía evidencia lesión polipoídea en cuerda vocal y ventrículo izquierdo. Se realiza microcirugía laríngea, enviando muestra a biopsia diferida, resultando lesión metastásica de CCR células claras. Evaluado por nefrología, se pesquisa tumor renal izquierdo sugerente de CCR. Las metástasis de neoplasias remotas a laringe son infrecuentes. Se considera al CCR el tercero en frecuencia respecto a neoplasias infraclaviculares. Éstas se pueden presentar hasta 10 años después del tratamiento del primario. Se recomienda seguimiento a largo plazo y énfasis a nuevos síntomas en región de cabeza y cuello, teniendo en consideración antecedente de CCR en pacientes con disfonía y lesiones polipoídeas en cuerdas vocales.

Introduction: The metastasis of distant site primary tumors to the vocal cords is infrequent. The most frequent source of metastasis to the larynx is melanomas and carcinomas, mainly affecting the supraglottic region. The metastasis to the head and neck of renal cell carcinomas (RCC) has an incidence of 14-16%. To present a case of metastasis of clear renal cell carcinoma to the vocal cords, since it is very infrequent, and there are no similar reports in the country. A male patient, 57 years old, presenting dysphonia for a duration of 3 months. Nasofibroscopy showed a polypoid lesion in the left vocal cord and ventricle. Larynx microsurgery was performed, and a sample was sent for biopsy, which reported a metastatic lesion of RCC clear cells. When assessed by nephrology, a left renal tumor is found, suggesting RCC. The metastasis of distant site neoplasias are infrequent. RCC is considered the third in frequency concerning to infraclavicular neoplasias. These can present up to 10 years after the treatment of the primary. Long term follow-up is recommended, and an emphasis on new symptoms in the head and neck region, considering the history of RCC in patients with dysphonia and polypoid lesions in vocal cords.

PEComa pulmonar / PEComa of the lung

Resumen Los tumores de células claras "de azúcar" (CCTL) son lesiones benignas muy infrecuentes. Forman parte de un grupo de neoplasias mesenquimales denominadas PEComas que se originan de las células epiteloides perivasculares. Por su rico estroma vascular, suelen tener avidez por los distintos tipos de contrastes utilizados en los estudios de diagnóstico por imágenes, simulando lesiones de estirpe maligna. Presentamos el caso de un paciente de 66 años con hallazgo de un nódulo pulmonar durante la estadificación oncológica por adenocarcinoma de próstata al que se le realizó una segmentectomía pulmonar anatómica. El resultado definitivo de anatomía patológica fue tumor de células epiteloides perivasculares (PEComa pulmonar o tumor de células claras "de azúcar").

Abstract Clear cell ''sugar'' tumor of the lung is a rare benign tumor arising from perivascular epithelioid cells (PECs). They belong to a group of mesenchymal neoplasms called PEComas. Although widely presumed as benign, due to their rich vascular stroma they are usually avid for the different types of contrast agents used in imaging studies, mimicking a malignant lesion. We report the case of a 66-year-old man in whom a solitary pul monary nodule was discovered during oncological staging for an adenocarcinoma of the prostate who underwent an anatomical pulmonary segmentectomy. The final pathology result was a perivascular epithelioid cell tumor (pulmonary PEComa or clear "sugar" cell tumor).

Tumor neuroectodérmico maligno del tracto gastrointestinal: Reporte de 2 casos y revisión de la literatura / Malignant gastrointestinal neuroectodermal tumor: A report of 2 cases and a review of the literature

El tumor neuroectodérmico maligno del tracto gastrointestinal (GNET) es una neoplasia maligna sumamente rara, descrita por primera vez por Zambrano et al. en 2003 como tumor similar al sarcoma de células claras del tracto gastrointestinal, pues a diferencia del sarcoma de células claras posee células gigantes osteoclásticas y positividad difusa e intensa para S-100 con ausencia inmunohistoquímica y ultraestructural de diferenciación melanocítica. La presente publicación busca aportar los 2 primeros casos de GNET reportados en nuestro país, Perú, y América Latina. Reportamos 2 casos de GNET, en paciente mujer y en varón, ambos en la sexta década de la vida, cuyos casos llegaron a nuestra institución para reevaluación diagnóstica. Uno de los casos continuó tratamiento en nuestro instituto con evolución desfavorable. El conocimiento de su existencia y criterios diagnósticos por los patólogos es necesario para evitar confundirla y maldiagnosticarla con alguna otra neoplasia gastrointestinal no epitelial.(AU)

Malignant gastrointestinal neuroectodermal tumour (GNET) is an extremely rare neoplasm first described by Zambrano in 2003 as clear cell sarcoma like tumor of the gastrointestinal tract. In contrast to clear cell sarcoma, it has giant osteoclast cells and shows diffuse and intense positivity for S-100 with no immunohistochemical or ultrastructural melanocyte differentiation. We present the first cases of GNET reported in South America, occurring in Peru. Two cases of GNET, one in a female and one in a male, both between 60 and 70 years of age, were referred to our hospital for reevaluation. One underwent further treatment in our centre, but with an unfavourable evolution. Pathologists should be aware of the diagnostic criteria for GNET in order to avoid misdiagnosis due to confusion with other non-epithelial gastrointestinal neoplasms.(AU)

[Malignant gastrointestinal neuroectodermal tumor: A report of 2 cases and a review of the literature]. / Tumor neuroectodérmico maligno del tracto gastrointestinal: Reporte de 2 casos y revisión de la literatura.

Malignant gastrointestinal neuroectodermal tumour (GNET) is an extremely rare neoplasm first described by Zambrano in 2003 as clear cell sarcoma like tumor of the gastrointestinal tract. In contrast to clear cell sarcoma, it has giant osteoclast cells and shows diffuse and intense positivity for S-100 with no immunohistochemical or ultrastructural melanocyte differentiation. We present the first cases of GNET reported in South America, occurring in Peru. Two cases of GNET, one in a female and one in a male, both between 60 and 70 years of age, were referred to our hospital for reevaluation. One underwent further treatment in our centre, but with an unfavourable evolution. Pathologists should be aware of the diagnostic criteria for GNET in order to avoid misdiagnosis due to confusion with other non-epithelial gastrointestinal neoplasms.

[Lung clear cell tumor «sugar tumor¼. Unusual diagnostic neoplasm]. / Tumor de células claras «sugar tumor¼ pulmonar. Neoplasia de diagnóstico inusual.

Clear Cell «sugar tumor¼ of the lung is a rare nosological entity of which around 60 cases have been published in the scientific literature. Considered to be of mesenchymal origin, it presents a typical histochemical - immunohistochemical profile, positive PAS and melanic markers, which allows it to be differentiated from other more frequent neoplasms with worse prognosis. We present the case of a 56-year-old man with a clear cell lung tumor. Radiological, macro-microscopic and histochemistry - immunohistochemical characterization, as well as a brief review of the literature.

Hidradenoma nodular maligno / Malignant Nodular Hidradenoma

Introducción: El hidradenoma nodular maligno es un tumor maligno de glándula sudorípara ecrinas, poco común, considerada una lesión de diferenciación anexial ecrinas, que generalmente surge de nuevo, aunque se han descrito unos pocos casos surgidos sobre un hidradenoma nodular. Es decir, representa la contrapartida maligna del hidradenoma nodular. Objetivo: Dar a conocer la presentación de un caso, dada la inusual aparición de esta entidad, con revisión de los criterios para su diagnóstico. Caso clínico: Se informa el caso de un hombre de 74 años de edad con una neo formación en la región parietal derecha del cuero cabelludo. Conclusiones: Debemos pensar en un hidradenoma nodular maligno ante un tumor solitario, firme o fluctuante, infrecuente en el cuero cabelludo, con curso agresivo, recurrencias y metástasis ganglionares y confirmar su diagnóstico con el estudio inmunohistoquímico(AU)

Introduction: Malignant nodular hidradenoma is a rare malignant eccrine sweat gland tumor considered a lesion of eccrine adnexal differentiation, which usually arises again, although a few arising cases on nodular hidradenoma have been described. In other words, it represents the malignant counterpart of nodular hidradenoma. Objective: To report a case, given the unusual occurrence of this entity, with a review of the criteria for its diagnosis. Case report: We report the case of a 74-year-old man with a neoformation in the right parietal region of the scalp. Conclusions: We should consider a malignant nodular hidradenoma when faced with a solitary, firm or fluctuant tumor, rare in the scalp, with aggressive evolution, recurrences and lymph node metastasis, and confirm its diagnosis with immunohistochemical study(AU)

Análise do perfil de mRNAs diferencialmente traduzidos no carcinoma renal de células claras / Analysis of differentially translated mRNA profile in clear cell renal cell carcinoma

O carcinoma renal de células claras (CRCC) é o tipo de neoplasia renal com maior incidência, cerca de 80%. A maioria dos casos são curados após cirurgia, porém, cerca de um terço dos pacientes apresentam recidiva da doença com metástase à distância. O tratamento para este tumor evoluiu muito nas últimas duas décadas, entretanto, pacientes metastáticos ainda apresentam baixas taxas de resposta aos tratamentos devido a resistência adquirida pelo tumor para escapar da terapia alvo. Identificar os mecanismos moleculares associados à carcinogênese do CRCC é essencial para entender as características tumorais que estão associadas a progressão da doença e resistência aos tratamentos. Entre as alterações mais frequentes no CRCC está a perda do gene VHL, um supressor tumoral e principal regulador da resposta à hipóxia. VHL tem dois principais alvos, o fator induzido por hipóxia 1α (HIF-1α) e o fator induzido por hipóxia α (HIF-2α). Em normóxia, VHL é responsável pela degradação das subunidades de HIF. Em hipóxia, VHL deixa de reconhecer e marcar HIF-1α e HIF-2α para degradação e, uma vez estabilizadas, ativam vias de sinalização associadas a sobrevivência celular. As informações sobre alterações encontradas em tumores normalmente são estudadas a partir do sequenciamento da população total de mRNAs, oferecendo uma visão do transcriptoma. Nossa abordagem metodológica coleta e analisa apenas a população de mRNAs ativamente traduzidos, oferecendo uma visão mais próxima da expressão proteica final. A via de mTOR regula o início da tradução de mRNAs e está frequentemente mutada em CRCC. A hipóxia afeta a expressão de genes tanto via transcrição quanto via tradução. Alterações no controle traducional em CRCC afetam a expressão gênica contribuindo para a formação do tumor e progressão da doença. Assim, nosso objetivo principal foi identificar o perfil de genes diferencialmente traduzidos dependendo do status de VHL e da via de mTOR. Para isso utilizamos um modelo celular de CRCC deficiente em VHL e sua contraparte onde VHL foi restituído. Realizamos o perfil polissomal em modelos celulares de CRCC para separar e coletar a população de mRNAs ativamente traduzidos que foram posteriormente sequenciados. Nossos dados mostraram perfis distintos de tradução entre as células VHL- deficientes e VHL-proficientes. Além disso, após a inibição de mTOR, ambas as células também apresentaram respostas diferentes ao tratamento. Além disso, observamos alterações na resposta imune e aumento do ciclo celular na ausência de VHL, que podem contribuir para a progressão tumoral. Em modelo com tecido tumoral congelado, nossos resultados parciais indicam que alterações na tradução global podem interferir principalmente no estadiamento clínico de pacientes com CRCC. Por fim, também analisamos a expressão de HIF-2α, um dos alvos de VHL, em tecidos de pacientes com CRCC. Nossos resultados mostram que HIF-2α pode ser utilizado na estratificação de pacientes com maior risco de recidiva, dependendo do estadiamento clínico.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal neoplasia with 80% of incidence. Most cases are cured after surgery, however, one third of all patients will have disease recurrence with distant metastasis. ccRCC treatment had evolved in the past two decades, however, metastatic patients still have low response rates due to tumor resistance. The identification of molecular mechanisms associated with ccRCC carcinogenesis is essential to understand the characteristics associated with disease progression and treatment resistance. The most frequent alteration in ccRCC is the loss of VHL gene, a tumor suppressor and the main regulator in response to hypoxia. VHL has two main target, hypoxia-induced factor 1 α (HIF-1 α) and hypoxia-induced factor α (HIF-2 α). In normoxic conditions, VHL can lead HIF subunits to degradation. In hypoxia, HIF-1α and HIF-2α stabilize and activate cell survival associated signaling pathways. Studies about tumor alterations usually provides a view of the transcriptome. Our approach is based on the actively translated mRNAs collection and analysis, which provides a closer view from protein expression. mTOR pathway regulates translation initiation and is frequently mutated in ccRCC. Hypoxia affects gene expression in both transcriptional and translational regulation. Alteration in translational control in ccRCC affect gene expression which contributes to tumor progression. Our main objective was to identify the differentially translated gene profile depending on VHL status and mTOR pathway activation. To assess this, we used a VHL-deficient and a VHL-proficient ccRCC cell line. We used the polysome profiling technique to separate and collect the population of mRNAs actively translated that were subsequently sequenced. Our data showed distinct translation profiles between VHL-deficient and VHL-proficient cells. In addition, after mTOR inhibition, both cells showed different responses to treatment. We observed changes in immune response and increased cell cycle pathways in VHL deficient cells, which may contribute to tumor progression. In tumor tissue, our polysome profiling analysis indicate that changes in global translation may interfere in clinical staging of ccRCC patients. Finally, we analyzed the expression of HIF-2α, a VHL target, in ccRCC patient's tissues. Our results showed that HIF-2α can distinct patients at higher recurrence risk depending on clinical staging.

Clear cell chondrosarcoma of the proximal tibia - case report

ABSTRACT Introduction: Clear cell chondrosarcomas are a rare type of low-grade chondrosarcoma. Unlike conventional chondrosarcomas, these tumors occur mainly in the epiphyses of long bones, especially in the proximal femur and proximal humerus. Given their lytic characteristics with a cystic appearance, they can be mistaken for bone cysts and diagnosed late. Diagnosis must be made based on histopa-thology and immunohistochemistry. Likewise, negativity for cytokeratins and anti-endomysial antibodies are tools to rule out the differential diagnosis of metastasis. The treatment of this low-grade chondral lesion is surgical, either with intralesional management or complete resection. Case presentation: This is the case of a 46-year-old woman who consulted the orthopedic oncology service of a quaternary care institution due to medial knee pain at the level of the proximal tibia for 8 months. Diagnostic imaging studies showed a cystic lesion in the lateral tibial plateau; a biopsy of the lesion was performed, and clear cell chondrosarcoma was diagnosed based on histopathology and immunohistochemistry. Surgical management included tumor-free resection margins and reconstruction of the bone defect with a structural allograft of the proximal tibia. The patient progressed satisfactorily. Conclusions: This was the case of a patient with a subtype of low-grade chondrosarcoma that is rare in incidence and location, who was diagnosed based on immunohistochemistry and treated surgically to achieve a successful limb salvage.

RESUMEN Introducción. El condrosarcoma de células claras es un subtipo de tumor poco frecuente del grupo de los condrosarcomas de bajo grado. A diferencia de los condrosarcomas convencionales, estos tumores se presentan principalmente en epífisis de huesos largos. Dadas sus características líticas de aspecto quístico, pueden confundirse con quistes óseos, por lo que su diagnóstico debe hacerse por histopatología e inmunohistoquímica mediante biopsia. Igualmente, la negatividad para citoqueratinas y anticuerpos antiendomisio es una herramienta para descartar el diagnóstico diferencial de metástasis. Su tratamiento es quirúrgico, bien sea con manejo intralesional o resección completa con márgenes libres. Presentación del caso. Mujer de 46 años quien consultó al servicio de ortopedia oncológica de una institución de IV nivel de atención por un cuadro clínico de 8 meses de evolución consistente en dolor en la cara medial de la rodilla izquierda a nivel de la tibia proximaluna. Se practicaron imágenes diagnósticas que mostraron una lesión quística en el platillo tibial lateral; se ordenó biopsia de la lesión, y mediante histopatología e inmunohistoquímica se diagnosticó condrosarcoma de células claras. Se realizó un manejo quirúrgico con resección de la lesión con márgenes libres y una reconstrucción del defecto óseo con un aloinjerto estructural de tibia proximal, con lo cual se obtuvo una evolución satisfactoria. Conclusiones. Se presenta el caso de una paciente con un subtipo de condrosarcoma de bajo grado infrecuente en su presentación y localización, quien fue diagnosticada mediante inmunohistoquímica y tratada quirúrgicamente para lograr un salvamento exitoso de su extremidad.

Lesión granulomatosa en encía insertada-metástasis de carcinoma renal de células claras. Presentación de caso / Granulomatous Lesion in Inserted Gum-Metastasis of Renal Clear Cell Carcinoma. Case Presentation

Resumen: A nivel mundial el carcinoma renal constituye el 3% de todas las formas de cáncer en el cuerpo humano. Su comportamiento biológico es variable dependiendo de la biología de cada individuo; tiende a realizar metástasis a sitios contiguos como glándulas suprarrenales, hígado, pulmón, hueso, ganglios linfáticos sin embargo la presentación a distancia en cavidad bucal es poco frecuente más aún en encía insertada. Las lesiones granulomatosas del periodonto incluyen granulomas piógenos, granulomas de células gigantes entre otros. El objetivo principal de este caso clínico es describir las características clínicas e histopatológicas de las metástasis a cavidad bucal como lesiones granulomatosas. Se presenta el caso de una paciente femenina de 60 años de edad con antecedente de carcinoma renal de células papilares en riñón derecho tratado mediante nefrectomía en el año 2017, en el año 2019 presenta metástasis a pulmón izquierdo y a cavidad bucal. En la actualidad se encuentra bajo protocolo de tratamiento para metástasis de células claras renales.

Abstract: Worldwide, renal carcinoma constitutes 3% of all forms of cancer in the human body. Its biological behavior is variable depending on the biology of each individual; it tends to metastasize to contiguous sites such as adrenal glands, liver, lung, bone, lymph nodes, however, remote presentation in the oral cavity is less frequent, even in inserted gums. Granulomatous lesions of the periodontium include pyogenic granulomas, giant cell granulomas among others. The main objective of this clinical case is to describe the clinical and histopathological characteristics of oral cavity metastases as granulomatous lesions. The case of a 60-year-old female patient with a history of renal cell papillary carcinoma in the right kidney treated by nephrectomy in 2017 is presented, in 2019 she presented metastases to the left lung and oral cavity. It is currently under treatment protocol for renal clear cell metastases.

[Expression of Hemeoxygenase-1 and clear cell renal cell carcinoma aggressiveness.] / Expresión de Hemo Oxigenasa-1 y agresividad del carcinoma renal de células claras.

OBJECTIVE: Hemoxigenase 1 (HO-1) is an enzyme that has anti-apoptotic and proliferative effects on tumor cells. However, there is little epidemiological and clinical evidence on the role of HO-1 in urologic tumors. OBJECTIVE: To determine if there is correlation between the expression of HO-1 and the histological characteristics, evolution, Disease Free Survival (DFS) and cancer mortality in Clear Cell Renal Cell Carcinoma (cRCC). MATERIALS AND METHODS: A retrospective study including 34 patients (9 women and 25 men) with cRCC from the "Servicio de Urología del Policlínico Neuquén" (Argentina) throughout 2003-2008. The expression of HO-1 by Immunohistochemistry (IHC) was determined. The statistical analysis was performed using the Student'sT test and Pearson correlation coefficient (p≤0.05). RESULTS: HO-1 was expressed in the epithelial cells of the tubules from normal kidney tissue and in the cytoplasmof cRCC tumor cells. There were no differences in the HO-1 expression related to the gender, age, tumorsize, stage of disease and 5 years DFS. High FuhrmancRCC had a greater expression of HO-1 compared with low Fuhrman cRCC (p≤0.05). The score of immunostaining for HO-1 was greater in those tumors located in the mesorrenal area, which coincidentally presented a more advanced stage of the disease. CONCLUSIONS: Over expression of HO-1 in tumors located in the interpolar zone and with high Furhman grade suggest that HO-1 could be a good adjunctive marker for the aggressiveness of the cRCC.

OBJETIVO: Hemoxigenasa 1 (HO-1) es una enzima que tiene efectos antiapoptóticos y proliferativos en células tumorales. Sin embargo, existe poca evidencia epidemiológica y clínica sobre el rol de la HO-1 en los tumores urológicos. Objetivo: determinar si existe correlación entre la expresión de HO-1 y las características histológicas, evolución, Sobrevida Libre de Enfermedad (SLE) y mortalidad por cáncer en Carcinomas Renales de Células Claras (cRCC). MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo en 34 pacientes (9 mujeres y 25 hombres) con cRCC del Servicio de Urología del Policlínico Neuquén, reclutados entre los años 2003 y 2008. Se determinó la expresión de HO-1 por Inmunohistoquímica (IHQ). El análisis estadístico se realizó mediante la prueba T de Student y Coeficiente de correlación de Pearson (p<0,05). RESULTADOS: HO-1 se expresó en el epitelio de los túbulos del tejido renal normal y en el citoplasma de las células tumorales de cRCC. No se observaron diferencias en la expresión de HO-1 según género, edad, tamaño tumoral, estadio de la enfermedad y SLE a los 5 años. Los tumores con Fuhrman alto presentaron una mayor expresión de HO-1 que los Furhman bajo (p≤0,05). El score de inmunotinción de HO-1 fue mayor en los tumores localizados en la zona interpolar, que coincidentemente presentaban un estadio más avanzado de la enfermedad. CONCLUSIONES: La sobreexpresión de HO-1 en tumores localizados en la zona interpolar y con grado de Furhman alto sugieren que HO-1 podría ser un buen marcador complementario de la agresividad del cRCC.

Clear cell renal cell carcinoma with osseous metaplasia: Two extremely rare cases and review of the literature. / Carcinoma de células renales de células claras con metaplasia ósea: dos casos extremadamente raros y revisión de la literatura.

OBJECTIVE: Renal cell carcinoma is constantly associated with calcification, but ossification is extremely scarce. METHOD: We retrospectively analyzed two cases with clear cell renal cell carcinoma with osseous metaplasia. RESULTS: We criticized the oldest case of woman whose a 32x31mm irregular renal mass with calcifications and we also mentioned about a diffusely calcified mass of 90 mm of a 68-year-old male patient. The histopathological examinations of both were reported as clear cell carcinoma with metaplastic bone formation. CONCLUSION: Although there are no definitive data on prognosis and follow-up due to the low number of cases; this entity usually occurs with early stage disease and a favorable prognosis as in our cases. While the prognostic importance of osseous metaplasia existence in renal cell carcinoma is controversial, such that can safely be managed with nephron sparing surgery in appropriate cases. As the number of cases and follow-up periods increased; more definitive information will be obtained.

OBJETIVO: El carcinoma de células renales se asocia constantemente con la calcificación, pero la osificación es extremadamente escasa. MÉTODO: Analizamos retrospectivamente dos casos del carcinoma de células renales de células claras con metaplasia ósea. RESULTADOS: Criticamos el caso más antiguo de una mujer cuya masa renal irregular era de 32x31 mm con calcificaciones y también mencionamos una masa calcificada de forma difusa de 90 mm de un paciente masculino de 68 años. Los exámenes histopatológicos de ambos demostraron que se trataba del carcinoma de células claras con formación de hueso metaplásico. CONCLUSIÓN: Aunque, debido al bajo número de casos, no hay datos definitivos sobre el pronóstico y el seguimiento; esta entidad generalmente ocurre en un estadio temprano de la enfermedad con un pronóstico favorable como en nuestros casos. Si bien la importancia pronóstica de la existencia de metaplasia ósea en el carcinoma de células renales es controvertida, puede manejarse de manera segura con cirugía conservadora de nefronas en los casos apropiados. Dado el hecho de que se aumentó el número de casos y períodos de seguimiento, se obtendrá más información definitiva.

Analysis of the nuclear expression of pSer727-STAT3 as a prognostic factor in patients with clear cell renal carcinoma. / Análisis de la expresión nuclear de pSer727-STAT3 como factor pronóstico en pacientes con carcinoma renal de células claras.

INTRODUCTION: Currently, clear cell renal carcinoma (CCRCC) has no prognostic markers. STAT3 protein (Signal Transducer and Activator of Transcription 3) is involved in the carcinogenesis of CCRCC. Its activation is produced by phosphorylation of the serine 727 residue, translocating to the nucleus where it is involved in carcinogenesis and tumor progression. The primary objective of the study was to evaluate cancer-specific survival rates in a series of 166 patients with CCRCC, and its subsequent correlation with the expression of pSer727-STAT3 as a prognostic marker of CCRCC. MATERIAL AND METHODS: We conducted a retrospective study on 166 patients with CCRCC undergoing partial or radical nephrectomy between 2000 and 2010. A tumor tissue microarray was constructed for immunohistochemical analysis of pSer727-STAT3 expression. The main variable of the study was cancer-specific survival. RESULTS: Patients were classified according to the UICC risk groups as follows: low in 78 patients (47%), intermediate in 52 (31.3%) and high 36 (21.7%); 11 patients (6.7%) were diagnosed with metastatic disease. During a mean follow-up of 97.2 months (1-208), 37 patients (22.3%) developed local and/or distant recurrence. Cancer-specific and overall mortality rates were 28.3% and 67.5%, respectively. The mean expression of pSer727-STAT3 was 92.9 (95% CI: 84.6-101.1) without showing any relationship with risk groups or other prognostic factors. In a Cox logistic regression analysis, pSer727-STAT3 did not behave as an independent predictor of cancer-specific mortality. However, in high-risk and metastatic patients, cancer-specific survival was significantly higher when the expression of pSer727-STAT3 was lower than 110, HR: 5.4 (96% CI: 1.8-16.4) and HR: 2.3 (95% CI: 1.1-4.6) respectively, P<.001. CONCLUSIONS: pSer727-STAT3 is not a survival marker in patients with CCRCC. However, it is a cancer-specific survival marker in high-risk patients, even in metastatic patients undergoing treatment with antiangiogenic agents.

Sarcoma de Células Claras en pierna de mujer de 28 años / Clear cell sarcoma on 28 years old woman leg

Los tumores de partes blandas son tumores que se presentan en adultos, aproximadamente a los 60 años. De estos tumores los sarcomas son poco frecuentes y tienen preferencia en las extremidades y muchas veces invaden estructuras músculo aponeuróticas cercanas, y poca invasión vascular o nerviosa lo que las hace de fácil acceso con poca morbilidad para su biopsia. El diagnóstico de los tumores de partes blandas se basa en el estudio histológico de anatomía patológica y, a veces se debe asociar a estudios de citogenética para poder tener un diagnóstico específico. El tratamiento principal es quirúrgico y puede llegar estar asociado a terapia adyuvante.

Soft tissue tumors are tumors that occur in adult's age, at about 60 age. Of these tumors, sarcomas are rare and have preference in the extremities, and often invade nearby muscle-fascia structures, and little vascular or nerve invasion, making them easily accessible with little morbidity for biopsy. The diagnosis of soft tissue tumors is based on the histological study of pathological anatomy and, sometimes, it must be associated with cytogenetic studies in order to have specific diagnosis. The main treatment is surgical and may end up being associated with adjuvant therapy.

[Pancreatic metastasis of primary kidney cancer: A presentation of a serie of clinical cases and revision of the literature.] / Metástasis pancreáticas de tumor primario renal: presentacion de una serie de casos y revisión de la literatura.

OBJECTIVE: Kidney cancer is around 2-3% of malignant tumours in adults. It has an important tendency to metastasize, being the most affected organs lungs, liver,brain, bone and adrenal glands. The pancreas is a rare site of kidney metastasis, with an incidence of 1-2.8%. The aim of this paper is to analyze the clinical diagnosis, treatment and prognosis of the pancreatic metastasis secondary to kidney cancer. METHOD: We present a retrospective descriptive analysis of 6 cases of pancreatic metastasis of primary kidney cancer diagnosed at Cruces University Hospital since 2011.We describe the cases individually also making a global analysis of the pathology and literature review. RESULTS: Two of the patients had pancreatic and extrapancreatic metastatic lesions, being treated systemic treatment without adjacent surgery. They showed an overall worse prognosis. The rest of the patients had only pancreatic disease,rational for surgical removal of all masses without need of further adjuvant treatment. The results after surgery were encouraging, with longer overall survival, progression free survival and better quality of life. CONCLUSIONS: Pancreatic metastases of kidney cancer are very rare and they can appear several years after nephrectomy. Patients with history of kidney cancer should be followed for long term after surgery. When metastases are limited to the pancreas, radical surgery has longer overall survival, progression free survival and better quality of life outcomes.

OBJETIVO: El cáncer renal constituye el 2-3% de los tumores malignos del adulto y tiene una gran tendenciaa metastatizar, siendo el pulmón, hígado, cerebro, hueso y suprarrenales los órganos diana más frecuentes. Sin embargo, también puede afectar a otros órganos más inusuales,como el páncreas, con una incidencia de 1-2,8%.El objetivo de este trabajo es analizar la presentación, tratamiento y pronóstico de las metástasis pancreáticas de cáncer renal.MÉTODO: Se realiza un análisis descriptivo retrospectivo de 6 casos de metástasis pancreáticas de tumor primario renal diagnosticados en el Hospital Universitario Cruces desde 2011. Se presentan los casos individualmente, se realiza un análisis global y revisión de la literatura. RESULTADO: En dos pacientes se objetivaron lesiones pancreáticas y extrapancreáticas, por lo que se decidió tratamiento sistémico, presentando estos pacientes un pronóstico peor. En el resto de los pacientes no se objetivó enfermedad extrapancreática, por lo que las lesiones pancreáticas se trataron quirúrgicamente, obteniendo una mejoría importante en la supervivencia, tiempo libre de enfermedad y calidad de vida, sin necesidad de tratamiento adyuvante. CONCLUSIONES: Las metástasis pancreáticas de cáncer renal son raras y pueden aparecer muchos años después de la nefrectomía, por lo que debería realizarse seguimiento a largo plazo en los pacientes con antecedentes de tumor renal. Cuando la enfermedad metastásica está limitada al páncreas, la cirugía radical mejora la supervivencia y calidad de vida de los pacientes.