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INTRODUCTION: The aim of this article was to evaluate the effectiveness of the Gleason grade groups (GGG) system on a group of Argentinian patients with prostate cancer (PC) who underwent radical prostatectomy (RP). MATERIAL AND METHODS: We retrospectively studied 262 patients who underwent RP between 1996 and 2014. To determine the performance and validity of the GGG system, a Kaplan-Meier analysis and multivariate analysis with Cox proportional method were performed to evaluate biochemical recurrence, distance metastases and specific cancer mortality. The area under the curve (AUC) was calculated to compare new groups of degrees of the GGG system with the classical scheme of stratification into 3 groups. RESULTS: The median follow-up was 84 months. As the groups ascend, there is less confined organ disease (p <0.001) and greater extraprostatic extension (p <0.001), greater invasion of seminal vesicles (p <0.001) and greater lymph node involvement (p <0.001). The biochemical recurrence-free survival at 5 years was 68%, 55%, 22%, 9%, 0% of the 1-5 groups, respectively. Ten-years cancer-specific survival was 96%, 95%, 78%, 64%, 25% for group 1-5, respectively. In the multivariate analysis, the GGG system is presented as the only independent predictor of biochemical recurrence and specific cancer mortality. The AUC indicates that the GGG system has a higher prognostic discrimination compared to the classic 3-group system (6, 7, ≥8). CONCLUSIONS: The International Society of Urological Pathology (ISUP) GGG system is an independent predictor of biochemical recurrence and mortality from prostate cancer in patients treated with RP. The classification into 5 groups shows greater discrimination in the prognosis than the traditional Gleason classification.

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In pituitary adenomas, early recurrences and resistance to conventional pharmacotherapies are common, but the mechanisms involved are still not understood. The high expression of epidermal growth factor receptor 2 (HER2)/extracellular signal-regulated kinase (ERK1/2) signal observed in human pituitary adenomas, together with the low levels of the antimitogenic transforming growth factor beta receptor 2 (TBR2), encouraged us to evaluate the effect of the specific HER2 inhibition with trastuzumab on experimental pituitary tumor cell growth and its effect on the antiproliferative response to TGFB1. Trastuzumab decreased the pituitary tumor growth as well as the expression of ERK1/2 and the cell cycle regulators CCND1 and CDK4. The HER2/ERK1/2 pathway is an attractive therapeutic target, but its intricate relations with other signaling modulators still need to be unraveled. Thus, we investigated possible cross-talk with TGFB signaling, which has not yet been studied in pituitary tumors. In tumoral GH3 cells, co-incubation with trastuzumab and TGFB1 significantly decreased cell proliferation, an effect accompanied by a reduction in ERK1/2 phosphorylation, an increase of SMAD2/3 activation. In addition, through immunoprecipitation assays, a diminution of SMAD2/3-ERK1/2 and an increase SMAD2/3-TGFBR1 interactions were observed when cells were co-incubated with trastuzumab and TGFB1. These findings indicate that blocking HER2 by trastuzumab inhibited pituitary tumor growth and modulated HER2/ERK1/2 signaling and consequently the anti-mitogenic TGFB1/TBRs/SMADs cascade. The imbalance between HER2 and TGFBRs expression observed in human adenomas and the response to trastuzumab on experimental tumor growth may make the HER2/ERK1/2 pathway an attractive target for future pituitary adenoma therapy.

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INTRODUCTION: The aim of this study was to describe the prognostic impact of microvascular invasion (MVI) in patients with non-metastatic renal cell cancer. MATERIAL AND METHODS: We carried out a retrospective, descriptive and analytical study of patients with non-metastatic renal cell carcinoma who had undergone a radical or partial nephrectomy. Patients were divided according to the presence of MVI. In each group, clinical and pathological characteristics were evaluated. Metastasis-free and cancer-specific survival was evaluated by the Kaplan Meier method. The multivariate analysis was performed with Cox proportional method in order to predict risk factors of metastasis and cancer-specific mortality. RESULTS: A total of 221 patients with a median of 40-month long follow-up were evaluated. Patients with MVI+ were 40 (18%) while those with MVI - were 181 (82%). In the univariate analysis, the presence of MVI had a strong correlation with symptomatic tumors (OR 3.56; p 0.0003), tumor size (OR 12.08; p <0.0001), nuclear grade (OR 6.99; p <0.0001), pathological stage (OR 35.8; p <0.0001), distance metastasis (OR 4.16; p 0.0001), and death by cancer (OR 4.7; p 0.0004). However, in the multivariate analysis it is not presented as an independent predictor of metastasis (HR 0.45; p 0.11) or cancer-specific mortality (HR 0.93; p 0.91). CONCLUSIONS: In our series, MVI is associated with unfavorable tumors characteristics. In spite of this, it does not seem to be an independent predictor for metastasis and death by non-metastatic renal cancer.

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El APE ha derivado en el diagnóstico de CaP en etapas más tempranas de la enfermedad. Por otra parte, existen evidencias de que muchos pacientes son sobretratados. La vigilancia activa tiene como premisa reducir el sobre tratamiento y la morbilidad relacionada con el tratamiento primario. El objetivo de este estudio fue evaluar las características patológicas desfavorables en pacientes sometidos a PR que fueron estratificados pre-operatoriamente de bajo riesgo según 10 modalidades para definir pacientes posibles de seguimiento activo. Realizamos un estudio retrospectivo y analítico de 230 pacientes con diagnóstico de CAP y tratados con PR, realizadas entre 1999 y 2011 en el Centro Urológico Profesor Bengió. Se evaluaron las características clínicas en 10 protocolos de seguimiento activo. Las variables anatomopatológicas evaluadas en la pieza de PR fueron el estadio patológico, SG de la pieza operatoria, la extensión extraprostática (EEP), invasión de vesículas seminales y compromiso de ganglios linfíticos regionales. El informe histopatológico fue realizado por un único uropatólogo (VB).En cada uno de los protocolos se evalúa el índice de recurrencia bioquímica. La población del estudio fue 198 pacientes. La media de edad fue 63 años. La media de APE 12,4/ml. Predominaron los estadíos clínicos T1c (48 por ciento) y T2 (48 por ciento). El índice de concordancia entre el SG de la biopsia y la PR en la serie se observó en 128 pacientes (64,6 por ciento). La extensión extraprostática, invasión de vesículas seminales e invasión ganglionar fue encontrada en 44 (22,2 por ciento), 38 (19,2 por ciento) y 3 (1,5 por ciento) pacientes respectivamente. La presencia de elementos patológicos desfavorables en pacientes candidatos a seguimiento activo oscila entre 12 por ciento y el 32 porciento. En nuestra serie de pacientes tratados con prostatectomía radical, los esquemas de vigilancia activa más estrictos, basados en APE <10ng/ml,...

The PSA has resulted in the diagnosis of prostate cancer in earlier stages of the disease. Moreover, there is evidence that many patients are over-treated. Active surveillance tries to prevent overtreatment and reduce the morbidity associated with primary treatment. The aim of this study was to evaluate the adverse pathologic features in patients who underwent RP and were stratified preoperatively as potential candidate for active surveillance through 10 different protocols. A retrospective study of 230 patients diagnosed with CAP treated with PR, conducted between 1999 and 2011 in the Urological Center Professor Bengio. Clinical characteristics were evaluated in 10 active surveillance protocols. Pathologic variables evaluated in RP specimens were pathological stage, surgical specimen SG, extraprostatic extension (EEP), seminal vesicle invasion and regional lymph nodes. The histopathological report was done by a single uropathologist (VB). In each of the protocols biochemical recurrence rate was evaluated. The study population was 198 patients. The average age was 63. The mean PSA 12.4 / ml. Predominant clinical stages T1c (48 percent) and T2 (48 percent). The concordance rate between the SG biopsy and RP in the series was observed in 128 patients (64.6 percent). Extraprostatic extension, seminal vesicle invasion and lymph node involvement was found in 44 (22.2 percent), 38 (19.2 percent) and 3 (1.5 percent) patients, respectively. The presence of unfavorable pathological elements in candidates for active surveillance patients ranges from 12 percent to 32 percent. In our series of patients treated with radical prostatectomy, stricter schemes of active surveillance based on PSA <10ng/ml, clinical stage T1c-T2a, biopsy Gleason score ¡Ü 6 and minimally invasive biopsy (<2 cylinders and <50 percent involvement) show better agreement with favorable histopathology findings in radical prostatectomy and correspond with greater biochemical recurrence-free survival...

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Estudio de caso: Paciente de sexo femenino de 22 años con diagnóstico de leucemia mieloide aguda (LMA) en mayo de 2013. Presenta una recaída refractaria al tratamiento enenero de 2014. En el transcurso de su internación presenta síndrome febril con lesiones en piel de tipo nódulos y placas infiltradas eritematovioláceas, dolorosas a la palpación en tronco y miembros (fig.1). Se toma biopsia cutánea con diagnósticos presuntivos de leucemide y Sarcoma de Kaposi.

Case Study: Female patient of 22 years with diagnosis acute myeloid leukemia (AML) in May 2013. It presents a relapse refractory to treatment January 2014. During his internment presents feverish syndrome with skin lesions in lymph type and infiltrated erythematous plaques, painful to palpation trunk and limbs (Figure 1). Biopsy is taken with presumptive diagnosis of cutaneous and leucemide Kaposi sarcoma.

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Presentamos el caso de una paciente cuyo diagnóstico anatomo-patológico fue Cistoadenoma seroso micro-quístico multifocal de páncreas, realizamos una revisión de las alternativas diagnósticas y las diferentes propuestas terapéuticas de este infrecuente tumor pancreático.(AU)

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Presentamos el caso de una paciente cuyo diagnóstico anatomo-patológico fue Cistoadenoma seroso micro-quístico multifocal de páncreas, realizamos una revisión de las alternativas diagnósticas y las diferentes propuestas terapéuticas de este infrecuente tumor pancreático.

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El score de Gleason (SG) es un importante predictor de resultados en cáncer de próstata. El SG 7 es un grupo heterogéneo que presenta en las diversas series un riesgo de muerte cáncer específico del 29 por ciento-41 por ciento. La diferenciación de los casos en que el patrón dominante sea 3(3+4) y los casos en donde el patrón dominante sea 4 (4+3) podría representar un factor pronóstico significativo. Objetivos: Evaluar las diferencias clínicas, patológicas y evolutivas de pacientes con prostatectomía radical con score de Gleason 3+4 y 4+3.Materiales y métodos: Se consideraron 73 pacientes con score de Gleason 7 en el espécimen de prostatectomía radical entre 1999 y 2009. Se evaluaron variables clínicas (antígeno prostático específico (APE), estadio clínico y score de Gleason de la biopsia) y patológicas (estadio patológico, Gleason, márgenes quirúrgicos, invasión de vesículas seminales, compromiso ganglionar). Como punto de corte se utilizó la recurrencia bioquímica y la mortalidad cáncer específica. Se consideró fallo bioquímico a la elevación de APE por encima de 0,2 ng/ml con dos ascensos sucesivos. Resultados: En los 73 pacientes, 48 (65,8 por ciento) y 25 (34,2 por ciento) tuvieron score de Gleason 3+4 y 4+3 respectivamente en la pieza operatoria. Esto contrasta con el Gleason de la biopsia previa que sub graduó 54 por ciento para el grupo 3+4 y 32por ciento para el grupo 4+3. Los valores de APE correlacionaron el score de Gleason, siendo el promedio del marcador de 14,4 ng/ml para el grupo 3+4 y 17,7 ng/ml para el grupo 4+3. El grupo de patrón predominante 4 se asoció a mayor estadio patológico, no notándose diferencias significativas en lo referente a márgenes quirúrgicos positivos. La sobre vida libre de recurrencia bioquímica a los 5 años fue de 54,2por ciento en el grupo con patrón predominante 3, con una media al fallo de APE de 14 meses...

The Gleason score (GS) is an important predictor of outcome in prostate cancer. The SG 7 is a heterogeneous group in several series presents a specific cancer death risk of 29 percent-41 percent. The differentiation of cases in which the dominant pattern is 3 (3 +4) and cases where the dominant pattern is 4 (4 +3) could be a significant prognostic factor Objectives: Evaluate the different clinical, pathological and outcome of patients who underwent to radical prostatectomy whit a Gleason score 3+4 and 4+3.Materials and methods: We considered 73 patients with Gleason Score 7 in the specimen of radical prostatectomy between 1999 and 2009. Clinical variables were evaluated (prostate specific antigen (PSA), clinical stage and Gleason score of the biopsy) and pathological (pathological stage, Gleason score, surgical margins, seminal vesicle invasion, lymph node invasion). We used biochemical recurrence and cancer-specific mortality as our end point. Biochemical failure was a PSA rise above0.2 ng/ml with two successive determinations. Results: In the 73 patients, 48 (65.8 percent) and 25 (34.2 percent) had Gleason score 3 +4 and 4 +3, respectively, in the specimen. This contrasts with the previous biopsy Gleason which undergraduate 54 percent for group3+4 and 32 percent for the 4 +3. PSA values correlated the Gleason score, where the average score of 14.4 ng/ml for group 3 +4 and 17.7 ng/ml for group 4 +3. The predominant pattern group 4 was associated with higher pathological stage, no significant differences being noted in terms of positive surgical margins. The biochemical recurrence-free survival at 5 years was 54.2 percent in the group with the predominant pattern 3, with a mean to PSA failure of 14 months. In group 4, the predominant pattern of biochemical recurrence-free survival at 5 years was 16 percent, with a mean to recurrence of 5.8 percent months...

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Los tumores superficiales de vejiga (no músculo-infiltrantes) constituyen un grupo heterogéneo de lesiones de evolución dispar, con marcada tendencia a la recidiva y progresión tumoral, cuya historia natural no puede ser predecida con seguridad en base a un caso individual. Hay evidencias que sugieren que moléculas de adhesión celular, como la E-Caderina (E-Cd) podrýan tener importancia en el desarrollo y progresión del cáncer vesical. En este estudio, se examinaron retrospectivamente 46 pacientes con diagnóstico de tumor superficial de vejiga urinaria, con evaluación, tratamiento y seguimiento estandarizados, con tiempo de observación promedio de 81 meses (tiempo máximo de 130 meses). Los tejidos se fijaron en formol neutro e incluyeron en parafina. Se evaluó la expresión de E-caderina (E-Cd) en el epitelio tumoral mediante sistema de detección inmunohistoquímica a través de sistema Biotina-Estreptavidina-Peroxidasa-DAB. La determinación de expresión de E-Cd por inmunomarcación ermite distinguir dos distintos patrones de expresión: patrón homogéneo, o normal, y heterogéneo o anormal.Se utilizó como método estadístico test de Wald, Odd ratio y test de verosimilitud (p- valor). Para estimación de número de recidivas se ajustó a modelo de regresión Poisson. El tiempo libre de progresión se analizó con modelo de riesgo proporcional deCox. La distribución por sexo fue a predominio masculino (31 casos, 67 %), con promedio de edad de 67,3 años. 67 % de los pacientes tenían factor de riesgo de tabaquismo. El signo clínico dominante fue la hematuria, y la forma macroscópica de presentación predominante fue como tumor único con patrón de crecimiento papilar exofítico. Acorde a la clasificación de OMS, 10 casos fueron categorizados como GI, 27 (58 %) omo G II y 9 casos como G III...(AU)

Superficial bladder tumors (non-muscle infiltrating) are a heterogeneous group of injuries of disparate development, with strong tendency to recurrence and tumor progression, whose natural history can not be predicted with certainty based on an individual case. There is evidence that suggests that cell adhesion molecule, like ECadherin(E-Cd) may play a fundamental role in the development and progression ofbladder cancer. In this study, 46 patients diagnosed with superficial bladder tumor were retrospectivelyreviewed, with standardized evaluation, treatment and follow-up, with an observation average time of 81 months (maximum period of 130 months). The tissues were fixed in neutral formalin and included in paraffin. The expression of E-Cadherin (E-Cd) was evaluated in the epithelial tumor by immunohistochemical detection system via Biotinstreptavidin- Peroxidase-DAB system. The determination of expression of E-Cd by immunohistochemistry allows the distinction between two different patterns of expression: homogeneous or normal pattern, and heterogeneous or abnormal. The statistical method used was Wald test, Odd- ratio test and verisimilitude (p-value). To estimate the number of relapses the Poisson regression model was followed. The progression-free time was analyzed with Cox proportional hazards model. The distribution by sex was a male predominance (31 cases, 67%) with an average age of 67.3 years. 67% of patients had risk factor for smoking. The dominant clinical sign was the hematuria, and the macroscopic form of dominant presentation was a single tumor with exophytic papillary growth pattern. According to the WHO classification, 10 cases wereclassified as GI, 27 (58%) as G II and 9 cases as G III. The abnormal expression of E-Cd of GI versus G III tumors was statistically significant (p = 0.03)...(AU)

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Los tumores superficiales de vejiga (no músculo-infiltrantes) constituyen un grupo heterogéneo de lesiones de evolución dispar, con marcada tendencia a la recidiva y progresión tumoral, cuya historia natural no puede ser predecida con seguridad en base a un caso individual. Hay evidencias que sugieren que moléculas de adhesión celular, como la E-Caderina (E-Cd) podrìan tener importancia en el desarrollo y progresión del cáncer vesical. En este estudio, se examinaron retrospectivamente 46 pacientes con diagnóstico de tumor superficial de vejiga urinaria, con evaluación, tratamiento y seguimiento estandarizados, con tiempo de observación promedio de 81 meses (tiempo máximo de 130 meses). Los tejidos se fijaron en formol neutro e incluyeron en parafina. Se evaluó la expresión de E-caderina (E-Cd) en el epitelio tumoral mediante sistema de detección inmunohistoquímica a través de sistema Biotina-Estreptavidina-Peroxidasa-DAB. La determinación de expresión de E-Cd por inmunomarcación ermite distinguir dos distintos patrones de expresión: patrón homogéneo, o normal, y heterogéneo o anormal.Se utilizó como método estadístico test de Wald, Odd ratio y test de verosimilitud (p- valor). Para estimación de número de recidivas se ajustó a modelo de regresión Poisson. El tiempo libre de progresión se analizó con modelo de riesgo proporcional deCox. La distribución por sexo fue a predominio masculino (31 casos, 67 %), con promedio de edad de 67,3 años. 67 % de los pacientes tenían factor de riesgo de tabaquismo. El signo clínico dominante fue la hematuria, y la forma macroscópica de presentación predominante fue como tumor único con patrón de crecimiento papilar exofítico. Acorde a la clasificación de OMS, 10 casos fueron categorizados como GI, 27 (58 %) omo G II y 9 casos como G III...

Superficial bladder tumors (non-muscle infiltrating) are a heterogeneous group of injuries of disparate development, with strong tendency to recurrence and tumor progression, whose natural history can not be predicted with certainty based on an individual case. There is evidence that suggests that cell adhesion molecule, like ECadherin(E-Cd) may play a fundamental role in the development and progression ofbladder cancer. In this study, 46 patients diagnosed with superficial bladder tumor were retrospectivelyreviewed, with standardized evaluation, treatment and follow-up, with an observation average time of 81 months (maximum period of 130 months). The tissues were fixed in neutral formalin and included in paraffin. The expression of E-Cadherin (E-Cd) was evaluated in the epithelial tumor by immunohistochemical detection system via Biotinstreptavidin- Peroxidase-DAB system. The determination of expression of E-Cd by immunohistochemistry allows the distinction between two different patterns of expression: homogeneous or normal pattern, and heterogeneous or abnormal. The statistical method used was Wald test, Odd- ratio test and verisimilitude (p-value). To estimate the number of relapses the Poisson regression model was followed. The progression-free time was analyzed with Cox proportional hazards model. The distribution by sex was a male predominance (31 cases, 67%) with an average age of 67.3 years. 67% of patients had risk factor for smoking. The dominant clinical sign was the hematuria, and the macroscopic form of dominant presentation was a single tumor with exophytic papillary growth pattern. According to the WHO classification, 10 cases wereclassified as GI, 27 (58%) as G II and 9 cases as G III. The abnormal expression of E-Cd of GI versus G III tumors was statistically significant (p = 0.03)...

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Small cell of undifferenciated tumors are present in almost all organs, and it impose the need of performing a differential diagnosis between undifferenciated tumors with residual differentiation according to the type of organ, and the carcinoma of small cells of neuroendocrine origin. The concept of neuroendocrine differentiation (NED) in the prostatic adenocarcinoma has reached considerable attention due to its prognostic and therapeutic implies. Here it is presented a new neuroendocrine prostatic carcinoma case taking care of its hystopathologic diagnosis and evolution.

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Small cell of undifferenciated tumors are present in almost all organs, and it impose the need of performing a differential diagnosis between undifferenciated tumors with residual differentiation according to the type of organ, and the carcinoma of small cells of neuroendocrine origin. The concept of neuroendocrine differentiation (NED) in the prostatic adenocarcinoma has reached considerable attention due to its prognostic and therapeutic implies. Here it is presented a new neuroendocrine prostatic carcinoma case taking care of its hystopathologic diagnosis and evolution.