Neoplasia papilar de polaridad inversa: un nuevo subtipo de tumor renal de buen pronóstico / Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis

Introducción: La neoplasia papilar renal de polaridad inversa (NPRPI) ha sido recientemente reconocida como una entidad separada de la clasificación tradicional de los carcinomas papilares de células renales por sus peculiares características histopatológicas, inmunofenotípicas y moleculares, y un comportamiento indolente. Material y métodos: En este trabajo aportamos 6 nuevos casos y realizamos una revisión de la literatura publicada al respecto hasta el momento actual, recopilándose un total de 104 casos. Resultados: Nuestros casos de NPRPI corresponden a 5 hombres y una mujer, con edades comprendidas entre los 47 y los 91 años. En 5 casos la NPRPI resultó un hallazgo incidental en piezas de nefrectomía indicada por la presencia de otro tumor renal y en uno la NPRPI fue el motivo de la intervención quirúrgica. Nuestros casos presentan tamaños entre los 2 y los 13mm, y una histología papilar con revestimiento en monocapa de células eosinófilas con núcleos de bajo grado en localización apical. Inmunohistoquímicamente muestran una constante positividad para GATA3 y negatividad para vimentina. Se identificaron mutaciones en KRAS en el 50% de ellos. Tras un seguimiento comprendido entre uno y 60 meses, 5 de los pacientes seguían vivos sin recurrencia o metástasis y uno falleció a causa de un carcinoma urotelial. Conclusiones: Nuestros casos concuerdan con las características clínicas y patológicas descritas en los publicados hasta el momento. Aportamos la primera serie nacional y corroboramos la existencia de unos criterios diagnósticos definidos y constantes que permiten considerar la NPRPI como una entidad propia distintiva. (AU)

Introduction: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior . Material and methods: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. Results: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. Conclusions: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity. (AU)

Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis.

INTRODUCTION: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior. MATERIAL AND METHODS: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. RESULTS: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13 mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. CONCLUSIONS: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity.

Utilidad de GATA-3 como marcador de epitelio seminal en las biopsias de próstata / Usefulness of GATA-3 as a marker of seminal epithelium in prostate biopsies

Objetivos: La presencia incidental de epitelio de la vesícula seminal en las biopsias por aguja de próstata es generalmente reconocible mediante el estudio microscópico de rutina. Sin embargo, en ocasiones, se puede interpretar erróneamente como maligno debido a sus características arquitecturales y citológicas, y la inmunohistoquímica puede ser útil para identificarlo correctamente. Nuestro objetivo ha sido analizar la posible utilidad de GATA-3 como marcador de epitelio seminal. Material y métodos_ Se han estudiado mediante inmunohistoquímica con un anticuerpo monoclonal anti-GATA-3 (clon L50-823) secciones de vesícula seminal procedentes de 20 piezas de prostatectomía, 12 biopsias por aguja de la próstata que contenían tejido de vesícula seminal y 68 biopsias de próstata sin epitelio de vesícula seminal, 36 de las cuales presentaban adenocarcinoma. Resultados: La tinción para GATA-3 fue intensa en las 20 vesículas seminales de las piezas de prostatectomía y en las 12 biopsias por aguja de próstata que contenían epitelio seminal. En las 60 biopsias sin vesícula seminal GATA-3 fue positiva en las células basales de la próstata, e incluso en las células secretoras (57 casos), aunque con menor intensidad en 55 de los casos. Uno de los 36 adenocarcinomas prostáticos fue GATA-3 positivo. Conclusiones: La expresión inmunohistoquímica intensa de GATA-3 en el epitelio de la vesícula seminal puede ayudar a identificarlo en las biopsias prostáticas. Este marcador también es positivo en las células basales de la próstata normal y, con menor intensidad, en las secretoras. Raramente se observa positividad, débil o moderada, en adenocarcinomas prostáticos

Objectives: The incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. Material and methods: Through immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. Results: Staining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. Conclusions: The intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas

Usefulness of GATA-3 as a marker of seminal epithelium in prostate biopsies. / Utilidad de GATA-3 como marcador de epitelio seminal en las biopsias de próstata.

OBJECTIVES: The incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. MATERIAL AND METHODS: Through immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. RESULTS: Staining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. CONCLUSIONS: The intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas.

[Expresion of E-cadherin and catenins in urothelial carcinomas]. / Expresión de cadherina E y cateninas en los carcinomas uroteliales.

OBJECTIVE: We examined the presence of E-cadherin and alpha, beta and gamma catenins detected by immunohistochemistry and correlated with the classic variables: grade, stage and recurrence. MATERIAL AND METHOD: The authors evaluated 37 transitional cell carcinomas. Biopsy specimens included no recurrent transitional cell carcinoma (n=19) and recurrent transitional cell carcinoma (n=18). Association of E-cadherin and alpha, beta and gamma catenins immunoreactivity with tumor grade, clinical stage and tumor recurrence was examined. RESULTS: E-cadherin and gamma catenin expression were related to the clinical stage of the disease, alpha and beta catenins were not correlated with grade, stage and recurrence of disease. CONCLUSIONS: Decreased E cadherin and gamma catenin expression were associated with advanced stage of the disease.

Expresión de cadherina E y cateninas en los carcinomas uroteliales / Expresion of e-cadherin and catenins in urothelial carcinomas

Objetivo: Determinar la correlación entre la expresión de cadherina E y alfa, Beta y gama cateninas detectadas con técnicas de inmunohistoquímica, con las variables pronósticas clásicas del carcinoma urotelial: grado histológico, estadio clínico y recurrencia. Material y métodos: Hemos estudiado la expresión de cadherina E y alfa, Beta y gama cateninas en 37 biopsias de carcinomas transicionales de vejiga. Diecinueve corresponden a carcinomas transicionales de vejiga no recurrentes y 18 a carcinomas transicionales de vejiga recurrentes. Hemos estudiado estadísticamente la asociación de estos marcadores con el estadio clínico, grado histológico y recurrencia del tumor. Resultados: Demostramos una correlación estadísticamente significativa entre la expresión de cadherina E y gama catenina con el estadio clínico del tumor. No demostramos asociación estadística significativa entre la expresión de alfa y Beta catenina con el grado histológico, estadio clínico y recurrencia del tumor. Conclusión: La expresión aberrante de cadherina E y gama catenina parece estar relacionado con la capacidad invasiva de los carcinomas uroteliales

Objetivo: Determinar la correlación entre la expresión de cadherina E y alpha, Beta y Gamma cateninas detectadas con técnicas de inmunohistoquímica, con las variables pronósticas clásicas del carcinoma urotelial: grado histológico, estadio clínico y recurrencia. Material y métodos: Hemos estudiado la expresión de cadherina E y alpha, Beta y Gamma cateninas en 37 biopsias de carcinomas transicionales de vejiga. Diecinueve corresponden a carcinomas transicionales de vejiga no recurrentes y 18 a carcinomas transicionales de vejiga recurrentes. Hemos estudiado estadísticamente la asociación de estos marcadores con el estadio clínico, grado histológico y recurrencia del tumor. Resultados: Demostramos una correlación estadísticamente significativa entre la expresión de cadherina E y gamma catenina con el estadio clínico del tumor. No demostramos asociación estadística significativa entre la expresión de alpha y Beta catenina con el grado histológico, estadio clínico y recurrencia del tumor. Conclusión: La expresión aberrante de cadherina E y Gamma catenina parece estar relacionado con la capacidad invasiva de los carcinomas uroteliales

[Expression of cytokeratin 5 and calretinin in clear-cell renal cell carcinoma]. / Expresión de citoqueratina 5 y calretinina en el carcinoma renal de células claras.

PURPOSE: Cytokeratin 5 (CK5) and calretinin have been useful in different studies as immunohistochemical markers suggestive of mesothelioma, and their expression is analyzed for the histological differential diagnosis with adenocarcinomas, specially when confronting with metastatic tumors of unknown origin. We have analyzed the expression of CK5 and calretinin in clear cell renal cell carcinoma. METHODS: A series of 63 clear cell renal cell carcinomas was studied. 46 of these cases were embedded in two tissue arrays, and a second group, of 17 cases, was constituted by conventional paraffin blocks from high-grade tumors (grade 4 of Fuhrman). Immunohistochemical staining was performed with monoclonal antibodies against CK5 and calretinin, following the labeled sptreptavidin-biotin technique. RESULTS: No positivity for calretinin was observed in any case, while CK5 was focally expressed, in an isolated group of cells, in 1 of the 63 cases (1,59%) which corresponded to a high-grade carcinoma (grade 4 of Fuhrman). CONCLUSIONS: Expression of calretinin was not observed in clear cell renal cell carcinoma and positivity for CK5 occurred only in one case, in a very small proportion of tumor cells. Therefore, in practice, although the positivity for these markers cannot completely exclude renal cell carcinoma, this result is very rare in this tumor and other diagnostic posibilities should be considered.

[Expression of CD10 and renal cell carcinoma marker in clear cell renal cell carcinoma: analysis on tissue arrays]. / Expresión de CD10 y del marcador de carcinoma renal en el carcinoma renal de células claras: análisis en matrices tisulares.

OBJECTIVES: CD10 and renal cell carcinoma (RCC) marker antibodies react against proteins of the epithelium of the renal proximal tubule, being expressed by renal cell carcinomas. The frequence and pattern of expression of both markers are analysed in a series of clear cell renal cell carcinomas. METHOD: Two tissue arrays were used, which were composed of cylinders obtained with a 16G needle from 40 paraffin blocks that corresponded to clear cell renal cell carcinomas. The labeled streptavidin-biotin technique was performed (LSAB2, Dako) using CD10 and RCC monoclonal antibodies (Novocastra), testing different antigen retrieval methods for RCC. Immunoreactivity was evaluated as + (isolated cells or focal staining); ++ (moderate) and +++ (extense). RESULTS: Thirty cases (75%) were positive for CD10: 12 +; 5 ++ and 13 +++. The best antigen retrieval method for RCC was a double enzyme digestion (trypsin + protease). Twenty cases (50%) were positive for RCC: 7 +; 5 ++ and 8 +++. Four cases out of the 20 immunoreactive for RCC were negative for CD10. The 16 remaining cases also expressed CD10. CONCLUSIONS: CD10 and RCC are often expressed by clear cell renal cell carcinomas, and they may be useful markers to suggest a renal origin of carcinomas. RCC is less sensitive than CD10. Staining for both of them is usually focal, and thus sensitivity of these techniques decreases when small samples are investigated, such as tissue arrays. The antigen retrieval method is essential for RCC immunohistochemical detection, obtaining the best results with the use of proteolytic enzymes.

Expresión de Citoqueratina 5 y Calretinina en el carcinoma renal de células claras / Expression of cytokeratin 5 and calretinin in clear cell renal cell carcinoma

Objetivo: La citoqueratina 5 (CK5) y la calretinina se han revelado en numerosos estudios como marcadores inmunohistoquímicos sugestivos de mesotelioma y su análisis se utiliza para el diagnóstico diferencial histológico con adenocarcinomas, especialmente ante metástasis de origen desconocido. En el presente estudio hemos analizado la expresión de CK5 y calretinina en el carcinoma renal de células claras. Métodos: Se estudió un total de 63 casos de carcinoma renal de células claras. De ellos, 46 fueron incluidos en dos matrices tisulares (“tissue arrays”), y un segundo grupo, de 17 casos, estuvo constituido por bloques convencionales de tumores de alto grado (grado 4 de Fuhrman). Se realizaron tinciones inmunohistoquímicas con anticuerpos monoclonales anti CK5 y anti calretinina, mediante el método de estreptavidina marcada con peroxidasa-biotina. Resultados: No se obtuvo positividad en ninguno de los casos para calretinina, mientras que la CK5 se expresó focalmente, en células aisladas, en 1 de los 63 casos (1,59%), que correspondió a un carcinoma de alto grado (grado 4 de Fuhrman). Conclusiones: En el carcinoma renal de células claras no hemos observado expresión de calretinina y la positividad para CK5 ha ocurrido de manera aislada y en un porcentaje muy pequeño de células tumorales. Por tanto, en la práctica si bien la positividad para estos marcadores no excluye de manera absoluta carcinoma de células renales, dicho resultado es muy improbable en este tumor y obliga a considerar otras opciones diagnósticas

Purpose: Cytokeratin 5 (CK5) and calretinin have been useful in different studies as immunohistochemical markers suggestive of mesothelioma, and their expression is analyzed for the histological differential diagnosis with adenocarcinomas, specially when confronting with metastatic tumors of unknown origin. We have analyzed the expression of CK5 and calretinin in clear cell renal cell carcinoma. Methods: A series of 63 clear cell renal cell carcinomas was studied. 46 of these cases were embedded in two tissue arrays, and a second group, of 17 cases, was constituted by conventional paraffin blocks from high-grade tumors (grade 4 of Fuhrman). Immunohistochemical staining was performed with monoclonal antibodies against CK5 and calretinin, following the labeled sptreptavidin-biotin technique. Results: No positivity for calretinin was observed in any case, while CK5 was focally expressed, in an isolated group of cells, in 1 of the 63 cases (1,59%) which corresponded to a high-grade carcinoma (grade 4 of Fuhrman). Conclusions: Expression of calretinin was not observed in clear cell renal cell carcinoma and positivity for CK5 occurred only in one case, in a very small proportion of tumor cells. Therefore, in practice, although the positivity for these markers cannot completely exclude renal cell carcinoma, this result is very rare in this tumor and other diagnostic posibilities should be considered

Expresión de CD10 y del marcador de carcinoma renal en el carcinoma renal de células claras: análisis en matrices tisulares / Expression of CD10 and renal cell carcinoma marker in clear cell renal cell carcinoma: analysis on tissue arrays

Objetivos: Los anticuerpos CD10 y marcador de carcinoma renal (MCR) reaccionan frente a proteínas del epitelio normal del túbulo contorneado proximal, expresándose por tanto en los carcinomas de células renales. Se analizan la frecuencia y el patrón de expresión de ambos marcadores inmunohistoquímicos en una serie de carcinomas renales de células claras. Método: Se han utilizado dos matrices tisulares (“tissue arrays”) constituidas por cilindros obtenidos con aguja 16G de 40 bloques de parafina correspondientes a carcinomas renales de células claras. Se realizó técnica de estreptavidina marcada - biotina (LSAB2, Dako) con anticuerpos monoclonales CD10 y MCR (Novocastra), ensayándose para este último distintos métodos de recuperación antigénica. Se valoró la positividad como + (aislada o muy focal); ++ (moderada) y +++ (extensa). Resultados: Con CD10 fueron positivos 30 casos (75%): 12 +; 5 ++ y 13 +++. Con respecto a MCR, el mejor método de desenmascaramiento antigénico fue un doble tratamiento enzimático (tripsina + proteasa). Se encontró positividad para MCR en 20 casos (50%): 7+; 5 ++ y 8 +++. De los 20 casos positivos para MCR, cuatro habían sido negativos para CD10. Los otros 16 expresaban también CD10. Conclusiones: CD10 y MCR se expresan con frecuencia en los carcinomas renales de células claras, por lo que pueden ser marcadores útiles para sugerir en un carcinoma un origen renal. MCR presenta menor sensibilidad que CD10. Al ser la expresión de ambos habitualmente focal, la sensibilidad de estas técnicas es menor cuando se utilizan muestras pequeñas, como son las matrices tisulares. En la técnica IHQ para MCR resulta crucial el método de desenmascaramiento antigénico, obteniéndose los mejores resultados con el uso de enzimas proteolíticos

Objectives: CD10 and renal cell carcinoma (RCC) marker antibodies react against proteins of the epithelium of the renal proximal tubule, being expressed by renal cell carcinomas. The frequence and pattern of expression of both markers are analysed in a series of clear cell renal cell carcinomas. Method: Two tissue arrays were used, which were composed of cylinders obtained with a 16G needle from 40 paraffin blocks that corresponded to clear cell renal cell carcinomas. The labeled streptavidin-biotin technique was performed (LSAB2, Dako) using CD10 and RCC monoclonal antibodies (Novocastra), testing different antigen retrieval methods for RCC. Immunoreactivity was evaluated as + (isolated cells or focal staining); ++ (moderate) and +++ (extense). Results: Thirty cases (75%) were positive for CD10: 12 +; 5 ++ and 13 +++. The best antigen retrieval method for RCC was a double enzyme digestion (trypsin + protease). Twenty cases (50%) were positive for RCC: 7 +; 5 ++ and 8 +++. Four cases out of the 20 immunoreactive for RCC were negative for CD10. The 16 remaining cases also expressed CD10. Conclusions: CD10 and RCC are often expressed by clear cell renal cell carcinomas, and they may be useful markers to suggest a renal origin of carcinomas. RCC is less sensitive than CD10. Staining for both of them is usually focal, and thus sensitivity of these techniques decreases when small samples are investigated, such as tissue arrays. The antigen retrieval method is essential for RCC immunohistochemical detection, obtaining the best results with the use of proteolytic enzymes