Teratoma quístico maduro con transformación maligna: serie de casos / Cystic teratoma with malignant transformation: Series of cases

Resumen OBJETIVO: Describir las características clínicas e histopatológicas de los casos de teratoma maduro con transformación maligna, su tratamiento y supervivencia. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y observacional efectuado entre enero de 2014 y diciembre de 2018 en un servicio de oncología ginecológica. Parámetros de estudio: etapa patológica del tumor, concentraciones de Ca 125, supervivencia y tratamiento. El tamaño de la muestra no permitió aplicar pruebas estadísticas. RESULTADOS: Se estudiaron 147 pacientes con diagnóstico de teratoma maduro, de éstos 4 experimentaron transformación maligna a carcinoma epidermoide y se descartaron 18 por información incompleta. El estudio histopatológico transoperatorio identificó malignidad en 3 de los 4 tumores de ovario. No se practicaron cirugías conservadoras de la fertilidad porque en ninguno de los casos fue necesaria. En 3 de los 4 teratomas maduros con transformación maligna se indicó esquema de quimioterapia coadyuvante. Todas las pacientes permanecen vivas y sin recaída hasta el momento. CONCLUSIONES: El estudio histopatológico transoperatorio es indispensable en todas las lesiones de ovario, incluso las de aspecto quístico. El tratamiento quirúrgico cuidadoso de los tumores malignos de ovario evita su ruptura y cambio en el pronóstico y tratamiento de las pacientes. El tratamiento quirúrgico y médico de una neoplasia poco frecuente, como el teratoma maduro con transformación maligna, mejora la supervivencia y evita subtratamientos o sobretratamientos.

Abstract OBJECTIVE: Describe the clinical and histopathological characteristics of cases of mature teratoma with malignant transformation, its treatment and survival. MATERIALS AND METHODS: Retrospective, cross-sectional and observational study conducted between January 2014 and December 2018 in a gynecological oncology service. Study parameters: pathological stage of the tumor, concentrations of Ca 125, survival and treatment. The sample size did not allow statistical tests to be applied. RESULTS: 147 patients with a diagnosis of mature teratoma were studied of these 4 underwent malignant transformation to squamous cell carcinoma and 18 were ruled out due to incomplete information. The transoperative histopathological study identified 3 of the 4 ovarian tumors as malignant. Fertility conservative surgeries were not performed because in none of the cases was it necessary. In 3 of the 4 mature teratomas with malignant transformation, adjuvant chemotherapy scheme was indicated. All patients remain alive and have no relapse so far. CONCLUSIONS: The histopathological transoperatory study is absolutely necessary for an ovarian tumor, even in cystic ovarian tumors. Carefully management of ovarian tumors is very important, we should prevent a rupture of the malignant tumor because this changes the surgical stage and the prognosis. The surgical and medical treatment of infrequent tumor-like mature teratoma with malignant transformation improves survival and avoid sub treatments or overtreatment.

Micrometástasis ganglionares en pacientes con cáncer ginecológico. Serie de casos y revisión de la bibliografía / Nodal micrometastasis in gynecological cancer patients. Case series and literature review

Resumen OBJETIVO: Identificar micrometástasis ganglionares en neoplasias malignas ginecológicas, y las características histopatológicas y clínicas asociadas con los hallazgos. MATERIALES Y MÉTODOS: Estudio observacional, descriptivo y retrospectivo efectuado en pacientes con uno o más ganglios con micrometástasis identificados en cirugías primarias etapificadoras por cáncer de endometrio, ovario o cervicouterino, linfadenectomía sistemática o ganglio centinela, atendidas en el Hospital de Ginecoobstetricia Dr. Luis Castelazo Ayala, de enero de 2014 a diciembre de 2018. Criterios de exclusión: ausencia micrometástasis ganglionares. Criterios de eliminación: información incompleta en el expediente clínico, sin seguimiento y falta de evidencia patológica de micrometástasis ganglionar. Variables de estudio: identificación de ganglios con micrometástasis, diagnóstico de cáncer ginecológico por tratamiento quirúrgico y tasa de supervivencia. Para la revisión bibliográfica se consultó la base de datos de PubMed, con MeSH o palabras clave: "micrometástasis ganglionares" y "cáncer de ovario"; "cáncer de endometrio", "cáncer cervicouterino" y "cáncer ginecológico con micrometástasis". RESULTADOS: Se registraron 11 casos de micrometástasis ganglionares, de un total de 433 con cáncer de ovario, endometrio o cervicouterino. No se aplicaron pruebas estadísticas por lo limitado de la muestra. En todos los casos se identificó, mínimo, un ganglio con micrometástasis, con ganglio centinela o linfadenectomía sistemática. Todas las pacientes recibieron tratamiento coadyuvante. CONCLUSIONES: Es importante efectuar la identificación de micrometástasis en linfadenectomías sistemáticas mediante la tinción con hematoxilina-eosina (es la metodología más accesible y económica para el sistema público de salud de México) o búsqueda de ganglio centinela, con la finalidad de determinar la frecuencia en población mexicana y establecer la etapa patológica real de la enfermedad.

Abstract OBJECTIVE: To identify lymph node micrometastases in malignant gynecological neoplasms and their histopathological and clinical characteristics associated with the findings. MATERIALS AND METHODS: Observational, descriptive and retrospective study performed in patients with one or more lymph nodes with micrometastases in primary stage surgery for endometrial, ovarian or cervical cancer, systematic lymphadenectomy or sentinel node, attended at the Hospital de Ginecoobstetricia 4 Dr. Luis Castelazo Ayala, from January 2014 to December 2018. Exclusion criteria: no ganglion micrometastases. Elimination criteria: incomplete information in the clinical file, without follow-up and lack of pathological evidence of lymph node micrometastasis. The variables to be considered were: identification of lymph nodes with micrometastases, diagnosis of gynecological cancer by surgical treatment and survival rate. For the literature review, the PubMed database was consulted, with key words such as "ganglionic micrometastases" and "ovarian cancer", "endometrial cancer", "cervical cancer" and "gynecological cancer with micrometastasis". RESULTS: There were 11 cases of lymph node micrometastases, of a total of 433 with ovarian, endometrial or cervical cancer. No statistical tests were applied because of the limited sample. In all cases, a lymph node with micrometastasis, with a sentinel lymph node or systematic lymphadenectomy was identified. All patients received coadjuvant treatment. CONCLUSIONS: It is important to identify micrometastases in systematic lymphadenectomy by staining with haematoxylin-eosin (the most accessible and economical methodology for the public health system in Mexico) or sentinel lymph node search, in order to determine the frequency in the Mexican population and establish the actual pathological stage of the disease.

Resección ganglionar retroperitoneal en el cáncer ginecológico: utilidad como biomarcador predictivo / Retroperitoneal nodal dissection in gynecological cancer: utility as a predictive biomarker

Resumen Antecedentes: La linfadenectomía retroperitoneal y pélvica es parte del proceso quirúrgico de etapificación del cáncer de endometrio y ovario. La asignación de etapa y tratamiento de pacientes con cáncer cervicouterino es clínica; con radioterapia y quimioterapia concomitante, sin conocer factores pronósticos de la enfermedad local, ni el estado de la enfermedad ganglionar pélvica y retroperitoneal. En cáncer ginecológico la evaluación sistemática patológica de los ganglios retroperitoneales es decisiva para asignar la etapa (en ovario y endometrio), pero en el cáncer de cuello uterino tiene menos aprobación en las guías de tratamiento internacionales y existen menos estudios sólidos que estén a favor de la linfadenectomía etapificadora. Objetivo: Revisar el tema y demostrar la pertinencia y ventajas de la estadificación ganglionar retroperitoneal en las distintas neoplasias malignas ginecológicas. Método: Se revisó la bibliografía en la base de datos PubMed con búsqueda de palabras clave: linfadenectomía en cáncer ginecológico y metástasis ganglionares retroperitoneales en cáncer ginecológico. Resultados: Se localizaron 71 artículos con información de las variables de estudio. Al momento de su análisis sólo se incluyeron documentos con información de estudios con asignación al azar, y con información que incluyera al cáncer de endometrio, ovario o cuello uterino, abarcó 31 artículos para su análisis. Conclusiones: Además de la revisión de artículos se presenta una propuesta para evaluar las metástasis retroperitoneales y su utilidad futura como biomarcador. Con la bibliografía expuesta y nuestra propuesta de evaluación ganglionar retroperitoneal se favorece la estadificación del cáncer ginecológico (endometrio, ovario y cuello uterino).

Abstract Background: Retroperitoneal and pelvic lymphadenectomy is part of the surgical process staging of endometrial and ovarian cancer. The stage assignment and treatment of patients with cervical cancer is clinical; with radiotherapy and chemotherapy concomitant, without knowing prognostic factors of the local disease, neither status of pelvic and retroperitoneal lymph node disease. In gynecological cancer the systematic pathological evaluation of the retroperitoneal ganglia is decisive for stablished the stage (in ovarian and endometrial) but in cervical cancer has less approval in international treatment guidelines and there are fewer studies solids that are in favor of staging lymphadenectomy. Objective: To review the topic and demonstrate the relevance and advantages of staging retroperitoneal ganglionar in the different gynecological malignancies. Method: The bibliography was revised in the PubMed database with search of key words: lymphadenectomy in gynecological cancer and lymph node metastases retroperitoneal in gynecological cancer. Results: 71 articles were finded with information on the study variables. At the time of its analysis only documents with study information were included randomized, and with information that included endometrial cancer, ovary or cervix, covered 31 articles for analysis. Conclusions: In addition to the review of articles, a proposal is presented to evaluate retroperitoneal metastases and their future usefulness as a biomarker. With the exposed literature and our proposed retroperitoneal lymph node evaluation is it favors the staging of gynecological cancer (endometrium, ovary and cervix).

[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism]. / Interacción de las vías de señalización intracelulares participantes en la proliferación celular: potencial blanco de intervencionismo terapéutico.

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined.

[Tissue regeneration strategies: cells, biochemical inductors, bionanomaterials and bioconstructions. Clinical and surgical achievements]. / Estrategias para la regeneración de tejidos: células, inductores bioquímicos, bionanomateriales y bioconstrucciones. Alcances clínico-quirúrgicos.

Regenerative medicine is a medical multidisciplinary area with the aim of morphologic and functional restoration of tissues or organs in order to re-establish normal function. The main bases of regenerative medicine are the use of autologous stem or progenitor cells and the ex vivo construction of physical-mechanical tissue structuring organization, which with stem cells may form bioartificial organs. Another eventual strategy is in vivo stem or progenitor cell stimulation for proliferation. Tissue engineering entirely combines the use of cells, biochemical and physicochemical factors, nanomaterials and bioengineering methods to improve or replace biological functions of tissues and organs. The progressive understanding of the proliferation and differentiation of the process of stem cells and their in vitro manipulation has been the launching platform for the field of regenerative medicine. In this review we describe the main strategies used for regenerative medicine in tissue regeneration along with the main obtained clinicalsurgical benefits.

La medicina regenerativa es una área multidisciplinaria destinada a la recuperación morfológica y funcional de tejidos y órganos severamente lesionados. Los principales recursos que emplea la medicina regenerativa son: células madre o troncales autólogas, y moldes estructurales de soporte físico-mecánico tisular construidos ex vivo, que pueden formar órganos bioartificiales; otra posibilidad es la estimulación de células madre in vivo para su proliferación. La ingeniería tisular combina, integralmente, el uso de células, factores bioquímicos y físicos, nanomateriales y métodos de bioingeniería para mejorar o remplazar las funciones biológicas de tejidos y órganos. El entendimiento progresivo de los procesos de proliferación y diferenciación celulares, y la manipulación in vitro de las células madre, ha sido la plataforma del desarrollo de la medicina regenerativa. En esta revisión se describen las diferentes estrategias que utiliza la medicina regenerativa en la regeneración de tejidos, y los principales beneficios clínico-quirúrgicos conseguidos con su aplicación.

[Targeted epigenetic therapy of cancer. Achievements and perspectives]. / Terapia epigenética en el cáncer. Logros y perspectivas.

In this review, we provide an overview of the physiological and pathophysiological epigenetic changes of normal cells and cancer cells, and emphasize the achievements and the perspectives of cancer epigenetic therapy. Cancer epigenetic alterations correspond foremost to hypermethylation of tumor suppressor genes promotors, global DNA hypomethylation, and overexpression and activity of histone deacetylases. The purpose of epigenetic therapy is to revert the epigenetic alterations in cancer cells and obtain the "normal epigenome" restoration. Epigenetic targets in cancer therapy have focused on HDACs and DNMTs inhibition. The azacitidine and the decitabine, the vorinostat and the romidepsin were approved by US-FDA for treatment of myelodysplastic syndrome, and cutaneous T-cell lymphoma, respectively. Epigenetic and epigenomic changes in single or multiple genes have showed potential impact in cancer as early detection, prognosis and predictive marks. The epigenetic revolution has arrived for biology. The significant progress in epigenetic studies have allowed us, to understand new looks in the physiology and pathophysiology of embryonic development, cancer and other chronic diseases. Specific molecular epigenetic alterations in different cancer types, give us new strategies to design improved cancer therapy. The challenge for epigenetic investigators is design more specific epidrugs with lesser side effects.

[Non-classical cellular and molecular deficits in cancer development]. / Alteraciones celulares y moleculares no clásicas en el desarrollo del cáncer.

A wide number of genetic and epigenetic changes are required to drive normal cells towards malignancy. These changes participate in oncogenic intracellular pathways that allow tumor cells proliferation and dissemination. Hanahan and Weinberg' in their seminal paper "The hallmarks of cancer" described the classic cell hallmarks acquired in cancer development and progression: self-sufficiency in growth signals, insensitivity to anti-growth signals, evading apoptosis, limitless replication potential, sustained angiogenesis, tissue invasion and metastasis. This review covers other recently described biological characteristics associated with the emergence of cancer. Some of the main non-classical hallmarks of cancer that are broadly accepted include: genetic instability, evasion of cell senescence, epigenetic alterations of cancer related-genes, RNA interference alterations in the expression of cancer related-genes, changes in glucose and glutamine metabolism, participation of cancer stem cells in cellular proliferation, stromal cell participation in the tumor's micro-environment, and changes in antigenic presentation and immunosuppression due to cytokines in the tumor's micro-environment. The identification of molecular biomarkers of classical and non classical tumor processes in a specific tumor will allow a better understanding of its pathophysiology. It will also permit the design of ad-hoc therapeutic strategies.

[Alterations in cancer cell signaling pathways].

Transitions from normal cell to neoplastic malignant cell type require multiple alterations in cell signalling pathways. Transduction and transmission of these signalling pathways are dependent on integrated molecular circuits. A paramount aspect in cancer development is the concept that the cell loses its ability to detect and respond to extracellular signals and frequently develops autocrine signals for overcoming normal physiological controls. Therefore, we analyzed the current concepts of general principles in physiological and some oncogenic cell signalling pathway patterns. We carried out a documentary review of 29 scientific items in which we identified intracellular signalling pathway systems in each cell so complex due to the high number of participants and the multiple differences among specific cell types. The knowledge and identification of general principles regarding the whole physiological cell signaling pathway patterns help us to understand the oncogenic signaling pathways. Identification of these pathways in any tumor can be used as prognosis or predictor biomarkers in the patient's outcome or as target in clinical therapeutic trials.

Alteraciones en los señalamientos intracelulares en el cáncer / Alterations in cancer cell signaling pathways

La transición de una célula normal a una célula maligna implica diferentes alteraciones de sus vías de señalización intracelular. La transducción y transmisión de estos señalamientos intracelulares depende de circuitos moleculares. Un aspecto central del cáncer es el concepto de que las células pierden su capacidad para detectar y responder de forma adecuada a los señalamientos extracelulares y que frecuentemente desarrollan señalamientos autocrinos para superar los controles normales. El objetivo de esta investigación fue analizar los principios generales de las vías de señalamiento celulares fisiológicas y sus principales alteraciones en algunos modelos de células neoplásicas, para lo cual se realiza una revisión documental de 29 artículos recientes. Las redes de señalización intracelular en cada célula son muy complejas debido al gran número de vías participantes y a las múltiples diferencias de ellas en los tipos celulares específicos. El entendimiento e identificación de los principios generales comunes en la mayoría de las vías de señalamiento intracelulares normales, facilitará la comprensión de las vías de señalamiento oncogénicas. La identificación del patrón de las vías de señalamiento oncogénicas en cada tumor, podría servir como marcador pronóstico o predictivo en la evolución clínica del paciente o como blanco en protocolos de intervensionismo terapéutico molecular.

Transitions from normal cell to neoplastic malignant cell type require multiple alterations in cell signalling pathways. Transduction and transmission of these signalling pathways are dependent on integrated molecular circuits. A paramount aspect in cancer development is the concept that the cell loses its ability to detect and respond to extracellular signals and frequently develops autocrine signals for overcoming normal physiological controls. Therefore, we analyzed the current concepts of general principles in physiological and some oncogenic cell signalling pathway patterns. We carried out a documentary review of 29 scientific items in which we identified intracellular signalling pathway systems in each cell so complex due to the high number of participants and the multiple differences among specific cell types. The knowledge and identification of general principles regarding the whole physiological cell signaling pathway patterns help us to understand the oncogenic signaling pathways. Identification of these pathways in any tumor can be used as prognosis or predictor biomarkers in the patient's outcome or as target in clinical therapeutic trials.

[Molecular therapeutics in patients with cancer unresponsive to conventional treatments]. / Terapias moleculares dirigidas en los pacientes con cáncer: logros y perspectivas.

Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of molecularly target-therapeutic (MTT) strategies. Cancer is a complex process due to accumulation of multiple mutations and alterations in the genoma. Tumor cells seem to rely heavily on the continued deregulation of one or more signaling pathways. Complete identification on cell signaling deregulations have provided greater understanding on the biology that underlies most cancers. High-throughput technologies in genomics and proteomics can help to detect the response in vitro and in vivo of targeted MTT effects. Cancer MTT are drugs blocking specific oncogenes or oncogenic signaling pathways and can secondary block off the growth and spreading involved in carcinogenesis and tumor progression. In this paper we revised concepts of oncogene addiction, oncogenic pathways signature and commented the high-tech technologies related to their study. Also we revised the favorable clinical results using new MTT strategies for hard-to-treat cancers in the last year, and the limitations and perspectives to achieve more effective targeted cancer therapy results. Identification of a progressive number of molecularly targeted oncogenes and their corresponding blocking agents will give cancer MTT strategies great potential for development in the next years. Novel biologic endpoints and innovative clinical designs are also required to the successful application of the therapies.

[Renal cell carcinoma with colon metastases: an infrequent site for metastases]. / Cáncer de riñón con metástasis a colon. Un sitio poco frecuente de metástasis.

BACKGROUND: Renal cell carcinoma (RCC) represents approximately 3% of malignant tumors in adults and occurs in a M:F ratio of 1.5:1.0. Although in most cases it occurs in persons 50 to 70 years of age, there are also reports in children. Clear cell carcinoma is the most frequent histological type, and 30% of renal carcinomas have metastasized at the time of diagnosis. The objective of the present study is to report colon metastasis of clear cell carcinoma that required surgery and chemotherapy. CLINICAL CASE: We report the case of a 60-year-old male with a history of metastatic RCC. His treatment consisted of cytoreductive radical nephrectomy and interferon because of pulmonary disease. He was followed-up for 8 years. Nevertheless, he presented with hematochezia and underwent colonoscopy where a splenic flexure tumor was demonstrated. Biopsy reported a clear cell tumor. We performed a left hemicolectomy. Pathology report was clear cell carcinoma with involvement of the colon from the mucosa to serosa. The patient again received interferon. Currently, there is no evidence of tumor activity and the patient is being followed-up. CONCLUSIONS: RCC metastases are most frequent in lung, liver, and bone and less frequent in brain, skin, and soft tissue. Metachromic metastases are identified in the first to second year after nephrectomy in most cases. Survival of patients who present metastasis <1 year after nephrectomy is 33 months vs. patients who present metastasis after 1 year from nephrectomy (55 months). Metastatic clear cell carcinoma requires surgery and immunotherapy. Surgery is the first step for disease control and metastatecomies are indicated in localized disease or when one organ is affected and surgically accessible.

Terapias moleculares dirigidas en los pacientes con cáncer: logros y perspectivas / Molecular therapeutics in patients with cancer unresponsive to conventional treatments

Los avances recientes en la patogénesis molecular del cáncer han permitido descubrir y desarrollar estrategias basadas en la utilización de moléculas con actividad biológica específicas o terapias moleculares dirigidas (TMD). El cáncer es un proceso complejo debido a la acumulación de mutaciones y alteraciones en el genoma. Las células tumorales parecen depender de una continua desregulación de una o varias vías de señalamiento intracelular. El conocimiento integral de estas vías logrará descifrar la biología de trasfondo de la mayoría de los cánceres. Las tecnologías de punta en genómica y proteómica pueden ayudar a identificar la respuesta in vitro e in vivo del intervensionismo de las TMD, las cuales comprenden agentes que bloqueando los oncogenes o las vías oncogénicas de señalamientos, pueden secundariamente detener la carcinogénesis y la progresión tumoral. Revisamos los conceptos de adicción oncogénica, de rúbrica de la vía oncogénica, algunas tecnologías, los resultados obtenidos con TMD en pacientes con cáncer que no responde a tratamiento convencional, y las limitaciones y perspectivas de esta nueva estrategia. Potencialmente, la TMD conseguirá mayor desarrollo a través de identificar un número progresivo de oncogenes blanco-moleculares y sus correspondientes agentes bloqueadores. Se requiere mejorar los criterios de diseño, ejecución y valoración clínicos en la aplicación de protocolos con terapias moleculares dirigidas.

Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of molecularly target-therapeutic (MTT) strategies. Cancer is a complex process due to accumulation of multiple mutations and alterations in the genoma. Tumor cells seem to rely heavily on the continued deregulation of one or more signaling pathways. Complete identification on cell signaling deregulations have provided greater understanding on the biology that underlies most cancers. High-throughput technologies in genomics and proteomics can help to detect the response in vitro and in vivo of targeted MTT effects. Cancer MTT are drugs blocking specific oncogenes or oncogenic signaling pathways and can secondary block off the growth and spreading involved in carcinogenesis and tumor progression. In this paper we revised concepts of oncogene addiction, oncogenic pathways signature and commented the high-tech technologies related to their study. Also we revised the favorable clinical results using new MTT strategies for hard-to-treat cancers in the last year, and the limitations and perspectives to achieve more effective targeted cancer therapy results. Identification of a progressive number of molecularly targeted oncogenes and their corresponding blocking agents will give cancer MTT strategies great potential for development in the next years. Novel biologic endpoints and innovative clinical designs are also required to the successful application of the therapies.

Cáncer de riñón con metástasis a colon: un sitio poco frecuente de metástasis / Renal cell carcinoma with colon metastases: an infrequent site for metastases

BACKGROUND: Renal cell carcinoma (RCC) represents approximately 3% of malignant tumors in adults and occurs in a M:F ratio of 1.5:1.0. Although in most cases it occurs in persons 50 to 70 years of age, there are also reports in children. Clear cell carcinoma is the most frequent histological type, and 30% of renal carcinomas have metastasized at the time of diagnosis. The objective of the present study is to report colon metastasis of clear cell carcinoma that required surgery and chemotherapy. CLINICAL CASE: We report the case of a 60-year-old male with a history of metastatic RCC. His treatment consisted of cytoreductive radical nephrectomy and interferon because of pulmonary disease. He was followed-up for 8 years. Nevertheless, he presented with hematochezia and underwent colonoscopy where a splenic flexure tumor was demonstrated. Biopsy reported a clear cell tumor. We performed a left hemicolectomy. Pathology report was clear cell carcinoma with involvement of the colon from the mucosa to serosa. The patient again received interferon. Currently, there is no evidence of tumor activity and the patient is being followed-up. CONCLUSIONS: RCC metastases are most frequent in lung, liver, and bone and less frequent in brain, skin, and soft tissue. Metachromic metastases are identified in the first to second year after nephrectomy in most cases. Survival of patients who present metastasis <1 year after nephrectomy is 33 months vs. patients who present metastasis after 1 year from nephrectomy (55 months). Metastatic clear cell carcinoma requires surgery and immunotherapy. Surgery is the first step for disease control and metastatecomies are indicated in localized disease or when one organ is affected and surgically accessible.