Myxoid Pseudotumor Changes Affecting the Distal Ureter Associated With Urothelial Carcinoma In Situ.

Myxoid pseudotumor is a pseudoneoplastic fibroblastic proliferation that has been described in the perinephric and renal sinus fat tissue. It is characterized by the presence of a myxoid matrix, intermingled with the adipocytes, and a hypocellular population of spindle-shaped and stellate cells. We report a myxoid pseudotumor involving the distal ureter, which broadens the spectrum of possible localizations of this lesion around the urinary tract. It occurred in an 80-year-old patient who underwent a nephroureterectomy indicated after an incidental radiological finding of a thickening of the distal left ureter wall which suggested a ureteral neoplasm. He had two voided urine and one ureteroscopic sample cytologies diagnosed as high-grade urothelial carcinoma, as well as a retrograde ureteroscopy ureteral biopsy which was diagnosed as urothelial carcinoma in situ. This emphasizes the problem of the possible misdiagnosis of myxoid pseudotumor as a ureteral infiltrative carcinoma due to the radiological findings being badly interpreted, compounded by the preoperative cytohistologic data on malignancy. A diffuse urothelial carcinoma in situ was seen in our specimen without infiltrative or papillary tumors. This would not support an obstructive pathogenetic mechanism as has been hypothesized for myxoid pseudotumor.

SATB2 as a Marker of the Proximal Nephron: Expression in Nephrogenic Adenoma and Correlation With Other Renal Tubular Markers.

Nephrogenic adenoma (NA) is an infrequent reactive urothelial lesion. The expression of immunohistochemical renal tubular markers has been reported in NA, although a proximal or distal nephron phenotype has not been established. Special AT-rich sequence-binding protein 2 (SATB2) is a marker of a colorectal origin of adenocarcinomas, occasionally reported in renal samples. We have analyzed SATB2 expression in NA, with correlation with other tubular markers, as well as in the normal kidney. Fifty cases of NA were immunostained with PAX8, SATB2, proximal nephron markers [CD10, renal cell carcinoma (RCC) marker, alpha-methylacyl-CoA racemase (AMACR), and CD15], and distal markers (Ksp cadherin, cytokeratin 7, E-cadherin (E-cad), and cytokeratin 19). Ten normal kidney sections were stained with a double method combining SATB2 plus CD10, RCC marker, AMACR, Ksp cadherin, cytokeratin 7, or E-cad. All NA were immunoreactive for PAX8 and 57% for SATB2. Every case was positive for proximal and distal nephron markers: 100% for cytokeratins 7 and 19, 84.1% E-cad +, 81.6% AMACR +, 68.9% Ksp cadherin +, 63% CD15 +, 53.3% CD10 +, and 28.6 % RCC +. In the normal kidney, SATB2 was detected in the straight part of the proximal tubules and the thin descending loops of Henle. NA shows a multiphenotypic pattern with coexpression of both proximal and distal nephron markers, and constant expression of PAX8, cytokeratins 7 and 19. SATB2 is often positive in NA, which should be kept in mind to avoid a possible misdiagnosis of intestinal adenocarcinoma. SATB2 is a marker of the normal proximal nephron.

Clear cell clusters in the kidney: a rare finding that should not be misdiagnosed as renal cell carcinoma.

Clear cytoplasm is a major characteristic feature of most malignant renal neoplasms. Benign clear cells in the renal parenchyma, usually histiocytes, can occasionally be found, but they are infrequently of an epithelial nature. We report histological, immunohistochemical, ultrastructural, and cytogenomic features of clear epithelial cell clusters incidentally found in four kidney specimens. Multiple microscopic clear cell clusters were present in the cortex, often in subcapsular location. They were composed of large epithelial cells with strikingly clear cytoplasm, without nuclear atypia, arranged in solid nests, and some tubules with narrow lumina. Immunohistochemically, they were positive for AE1AE3, PAX 8, EMA, kidney-specific cadherin, cytokeratin 7, E cadherin, and CD117, with focal immunoreactivity for CD10. Carbonic anhydrase IX, vimentin, and markers related to apoptosis and proliferation were negative. Ultrastructurally, the cytoplasms were enlarged and poor in organelles, showing ballooning degeneration. Array comparative genomic hybridization showed no chromosomal gains or losses. Clear cell clusters constitute a rare finding in the kidney and must be differentiated from benign lesions (ectopic adrenal tissue, osmotic tubulopathy, histiocytic clusters, renal adenomas) and renal cell carcinomas. Clear cell clusters appear to be generated from "endocrine-type" atrophic tubules whose cells are enlarged due to intracellular oedema. Immunohistochemistry shows a distal nephron phenotype with a limited expression of a proximal marker, CD10. Coexisting chronic renal disease or ischemic conditions seem to be related to the development of clear cell clusters. Pathological, ultrastructural, and cytogenomic features do not support a preneoplastic nature of this lesion, at least in the cases studied here.

Cadherina E y GATA-3 son útiles para confirmar la presencia de conducto deferente en muestras de vasectomía / E-Cadherine and GATA-3 are useful in the confirmation of the vas deferens in vasectomy specimens

INTRODUCCIÓN Y OBJETIVOS: Con frecuencia los urólogos remiten el tejido resecado durante las vasectomías para estudio anatomopatológico con el fin de confirmar la presencia de conducto deferente. El estudio microscópico es sencillo y se suele hacer con hematoxilina-eosina. En ocasiones, se ve dificultado por artefactos de la muestra y la inmunohistoquímica puede ayudar a reconocer la presencia de deferente. MATERIALES Y MÉTODOS: Hemos investigado la utilidad de la determinación inmunohistoquímica de cadherina E y GATA-3 para confirmar epitelio del deferente en 110 secciones de vasectomías con diferentes artefactos, utilizando anticuerpos monoclonales y técnica de multímero conjugado con peroxidasa; 5 arterias y 5 venas renales fueron controles negativos. RESULTADOS: Con cadherina E se observó tinción de membrana moderada (2,7%) o intensa (97,3%) en el epitelio del deferente en todos los casos: 35 sin artefacto, 7 con epitelio denudado, 56 con epitelio comprimido o distorsionado, 8 con epitelio desprendido y 4 con epitelio desplazado. GATA-3 mostró positividad nuclear moderada (31%) o intensa (69%) en todos los casos, incluyendo los 76 con los artefactos señalados. Las arterias y venas fueron negativas para ambos marcadores en el endotelio, con positividad para GATA-3 en ocasionales linfocitos de la pared. CONCLUSIONES: La inmunohistoquímica puede ayudar a reconocer la presencia de epitelio del deferente en vasectomías artefactadas con positividad de membrana para cadherina E y expresión nuclear de GATA-3. El endotelio vascular, por el contrario, es negativo para ambos marcadores. No se debe malinterpretar como positividad la posible tinción para GATA-3 de linfocitos de la pared

INTRODUCTION AND OBJECTIVES: Urologists often submit the resected tissue from vasectomies for histopathological examination in order to confirm the presence of the vas deferens. Microscopy is simple and based on haematoxylin-eosin staining; however, sample artefacts can sometimes cause confusion and immunohistochemistry can be used to identify the vas deferens. MATERIALS AND METHODS: We investigated the utility of immunohistochemical analysis using E-cadherin and GATA-3 to confirm the presence of vas deferens epithelium in 110 vasectomy sections with different artefacts, using monoclonal antibodies and a multimer conjugated with peroxidase based technique; 5 renal arteries and 5 renal veins were stained as negative controls. RESULTS: Membrane staining was observed for E-cadherin, which was moderate (2.7%) or strong (97.3%) in the vas deferens epithelium in all cases: 35 without artefacts, 7 with denuded epithelium, 56 with compressed/distorted epithelium, 8 with detached epithelium and 4 with displaced epithelium. GATA-3 showed moderate (31%) or strong (69%) nuclear staining in all cases, including the 76 with artefacts. In the control group, arteries and veins were negative for both markers in the endothelium, but GATA-3 occasionally stained lymphocytes in the blood vessel wall. CONCLUSIONS: E-cadherin membrane positivity and GATA-3 nuclear expression are useful for the identification of the vas deferens in vasectomy samples containing artefacts. Vascular endothelium is negative for both markers and any possible GATA-3 staining of the lymphocytes in the blood vessel wall should not be misinterpreted

[E-Cadherine and GATA-3 are useful in the confirmation of the vas deferens in vasectomy specimens]. / Cadherina E y GATA-3 son útiles para confirmar la presencia de conducto deferente en muestras de vasectomía.

INTRODUCTION AND OBJECTIVES: Urologists often submit the resected tissue from vasectomies for histopathological examination in order to confirm the presence of the vas deferens. Microscopy is simple and based on haematoxylin-eosin staining; however, sample artefacts can sometimes cause confusion and immunohistochemistry can be used to identify the vas deferens. MATERIALS AND METHODS: We investigated the utility of immunohistochemical analysis using E-cadherin and GATA-3 to confirm the presence of vas deferens epithelium in 110 vasectomy sections with different artefacts, using monoclonal antibodies and a multimer conjugated with peroxidase based technique; 5 renal arteries and 5 renal veins were stained as negative controls. RESULTS: Membrane staining was observed for E-cadherin, which was moderate (2.7%) or strong (97.3%) in the vas deferens epithelium in all cases: 35 without artefacts, 7 with denuded epithelium, 56 with compressed/distorted epithelium, 8 with detached epithelium and 4 with displaced epithelium. GATA-3 showed moderate (31%) or strong (69%) nuclear staining in all cases, including the 76 with artefacts. In the control group, arteries and veins were negative for both markers in the endothelium, but GATA-3 occasionally stained lymphocytes in the blood vessel wall. CONCLUSIONS: E-cadherin membrane positivity and GATA-3 nuclear expression are useful for the identification of the vas deferens in vasectomy samples containing artefacts. Vascular endothelium is negative for both markers and any possible GATA-3 staining of the lymphocytes in the blood vessel wall should not be misinterpreted.

Nuevos marcadores de inmunohistoquímica para confirmar la presencia de conducto deferente en muestras de vasectomía / New immunohistochemistry markers to determine presence of vas deferens in vasectomy specimen

OBJETIVOS: El estudio anatomopatológico de las muestras de vasectomía para confirmar la presencia de conducto deferente generalmente es sencillo se realiza con tinción rutinaria de hematoxilina-eosina. En aquellos casos con artefacto del epitelio, el uso de técnicas de inmunohistoquímica puede ayudar al diagnóstico y sirve, además para diferenciar deferente de vaso sanguíneo. Hemos investigado la utilidad de CD31, CD34, ERG y PAX8 para estos fines. MATERIAL Y MÉTODOS: Se han estudiado 81 secciones de muestras de vasectomía en las que alguna sección presentaba algún tipo de artefacto en el epitelio. Se realizó inmunohistoquímica con anticuerpos monoclonales para CD31 (clon JC70), CD34 (clon QBEnd/10), ERG (clon EPR3864) y PAX8 (clon MRQ-50) evaluando la tinción en el epitelio deferencial y en el endotelio vascular. RESULTADOS: Histológicamente, el epitelio del conducto deferente aparecía conservado en 18 secciones (22,2%), denudado en 6 (7,4%), con artefacto de compresión o distorsión en 48 secciones (59,3%), desprendidoen 5 (6,2%) y desplazado fuera de la luz del conducto en 4 (4,9%). En la mayoría de las secciones el epitelio del CD presentó positividad citoplasmática para CD31, que fue débil (86,4%) o moderada (9,9%), y expresó intensamente PAX8 en los núcleos, con tinción granular en el epitelio denudado o artefactado. Fueron negativos CD34 y ERG. El endotelio capilar de los vasos de la pared del conducto deferente mostró intensa positividad citoplasmática para CD31 y CD34, y nuclear para ERG, siendo PAX8 negativo. CONCLUSIONES: PAX8 es un anticuerpo útil para confirmar la presencia de conducto deferente en muestras de vasectomía con artefacto. Son negativos CD34 yERG, que, por el contrario, marcan endotelio vascular, presentando ERG la ventaja de que la tinción es nuclear.CD31, marcador endotelial clásico, no es tan específico como se había propuesto puesto que presenta expresión débil en el epitelio del deferente

OBJECTIVES: The pathological examination of vasectomy specimens to confirm the presence of vas deferens is usually simple and is done by routine hematoxylin and eosin staining. Use of immunohistochemical techniques can aid to the diagnosis in those cases with artifacts of the epithelium, and they are also useful to differentiate vas deferens from blood vessel. We have investigated the usefulness of CD31, CD34, ERG and PAX8 for these purposes. MATERIAL AND METHODS: 81 sections from vasectomy specimens in which any section showed some kind of epithelial artifact were analyzed. Immunohistochemistry was performed with monoclonal antibodies for CD31 (clone JC70), CD34 (clone QBEnd/10), ERG (clone EPR3864) and PAX8 (clone MRQ-50). Evaluation of the vas deferens and vascular endothelial staining was done. RESULTS: Histologically, vas deferens epithelium was well-preserved in 18 sections (22.2%), denuded in 6 (7.4%), crushed or distorted in 48 sections (59.3%), detached in 5 (6,2%), and misplaced out of the vas deferens lumen in 4 (4.9%). In most of the sections the epithelium showed weak (86.4%) or moderate (9.9%) CD31 cytoplasmic staining, as well as strong nuclear PAX8 reactivity in all of the sections, exhibiting a granular pattern in the detached or artifacted epithelium. CD34 and ERG were negative in the epithelium. Capillary vessel endothelium in the vas deferens wall showed strong cytoplasmic positivity for CD31 and CD34, as well as nuclear ERG reactivity, being PAX8 negative. CONCLUSIONS: PAX8 is a useful antibody to confirm the presence of vas deferens in artifacted vasectomy specimens. CD34 and ERG are negative in the epithelium, and, otherwise, they are expressed by vascular endothelium, with the advantage of nuclear staining pattern for ERG. CD31, a classic endothelial marker, is not so specific as it had been stated as it shows weak or moderate expression in the vas deferens epithelium

[New immunohistochemistry markers to determine presence of vas deferens in vasectomy specimen.] / Nuevos marcadores de inmunohistoquímica para confirmar la presencia de conducto deferente en muestras de vasectomía.

OBJECTIVES: The pathological examination of vasectomy specimens to confirm the presence of vas deferens is usually simple and is done by routine hematoxylinand eosin staining. Use of immunohistochemical techniques can aid to the diagnosis in those cases with artifacts of the epithelium, and they are also useful to differentiate vas deferens from blood vessel. We have investigated the usefulness of CD31, CD34, ERG and PAX8 for these purposes. MATERIAL AND METHODS: 81 sections from vasectomy specimens in which any section showed some kind of epithelial artifact were analyzed. Immunohistochemistry was performed with monoclonal antibodies for CD31 (clone JC70), CD34 (clone QBEnd/10), ERG (clone EPR3864) and PAX8 (clone MRQ-50). Evaluation of the vas deferens and vascular endothelial staining was done. RESULTS: Histologically, vas deferens epithelium was well-preserved in 18 sections (22.2%), denuded in 6 (7.4%), crushed or distorted in 48 sections (59.3%), detached in 5 (6,2%), and misplaced out of the vas deferens lumen in 4 (4.9%). In most of the sections the epithelium showed weak (86.4%) or moderate (9.9%) CD31 cytoplasmic staining, as well as strong nuclear PAX8 reactivity in all of the sections, exhibiting a granular pattern in the detached or artifacted epithelium. CD34 and ERG were negative in the epithelium. Capillary vessel endothelium in the vas deferens wall showed strong cytoplasmic positivity for CD31 and CD34, as well as nuclear ERG reactivity, being PAX8 negative. CONCLUSIONS: PAX8 is a useful antibody to confirm the presence of vas deferens in artifacted vasectomy specimens. CD34 and ERG are negative in the epithelium,and, otherwise, they are expressed by vascular endothelium, with the advantage of nuclear staining pattern for ERG. CD31, a classic endothelial marker, is not so specific as it had been stated as it shows weak or moderate expression in the vas deferens epithelium.

OBJETIVOS: El estudio anatomopatológico de las muestras de vasectomía para confirmar la presencia de conducto deferente generalmente es sencillo se realiza con tinción rutinaria de hematoxilina-eosina. En aquellos casos con artefacto del epitelio, el uso de técnicas de inmunohistoquímica puede ayudar al diagnóstico y sirve, además para diferenciar deferente de vaso sanguíneo. Hemos investigado la utilidad de CD31, CD34, ERG y PAX8 para estos fines.MATERIAL Y MÉTODOS: Se han estudiado 81 secciones de muestras de vasectomía en las que alguna sección presentaba algún tipo de artefacto en el epitelio. Se realizó inmunohistoquímica con anticuerpos monoclonales para CD31 (clon JC70), CD34 (clon QBEnd/10), ERG (clon EPR3864) y PAX8 (clon MRQ-50) evaluando la tinción en el epitelio deferencial y en el endotelio vascular. RESULTADOS: Histológicamente, el epitelio del conducto deferente aparecía conservado en 18 secciones (22,2%), denudado en 6 (7,4%), con artefacto de compresión o distorsión en 48 secciones (59,3%), desprendidoen 5 (6,2%) y desplazado fuera de la luz del conducto en 4 (4,9%). En la mayoría de las secciones el epitelio del CD presentó positividad citoplasmática para CD31, que fue débil (86,4%) o moderada (9,9%),y expresó intensamente PAX8 en los núcleos, con tinción granular en el epitelio denudado o artefactado. Fueron negativos CD34 y ERG. El endotelio capilar de los vasos de la pared del conducto deferente mostró intensa positividad citoplasmática para CD31 y CD34, y nuclear para ERG, siendo PAX8 negativo. CONCLUSIONES: PAX8 es un anticuerpo útil para confirmar la presencia de conducto deferente en muestras de vasectomía con artefacto. Son negativos CD34 yERG, que, por el contrario, marcan endotelio vascular, presentando ERG la ventaja de que la tinción es nuclear.CD31, marcador endotelial clásico, no es tan específicocomo se había propuesto puesto que presenta expresión débil en el epitelio del deferente.

[Tissue arrays: Two simple and economical methods for manual construction.] / Matrices tisulares: presentación de dos métodos sencillos y económicos de elaboración manual.

OBJECTIVES: Tissue array (TA) technologyis widely used as a method for the in situ investigation oftissue markers in cancer studies. A limitation of this techniqueis the high price of tissue arrayers. We describetwo easy and non-expensive manual methods, that haveproduced small and medium format arrays. MATERIAL AND METHODS: 16 TAs were manuallyconstructed from conventional paraffin blocks using twodifferent techniques. For the first method, a 16G Tru-Cutneedle whose bevel edge had been cut, was used tomake the holes in the donor blocks (80 cases) and thereceptor ones (resulting in 2 TAs each one with 55 casesand two with 25 cases). In the second technique, a 4mm-diameter punch for cutaneous biopsies was appliedto the donor blocks (obtaining 210 cylinders from 108blocks) and to the receptor ones (12 TAs). Hematoxylin-eosin, immunohistochemical and in situ hybridizationstains were performed on sections from these TAs. RESULTS: The tissue loss rate in the sections obtainedfrom the TAs constructed with the first method was26.5%, but as two cylinders were included from eachcase, at least one of them was retained. There was notany loss of tissue in the sections from the TAs constructedwith the second method. The results of all of the stainsperformed were successful. CONCLUSIONS: These two manual methods of elaborationof TAs result rather simple and they are economical.The tissue loss rate is significant in the first methodbut it can be compensated embedding more than onecylinder from each donor block. There was not anyproblem in the sectioning of the TAs constructed with thesecond method.

OBJETIVOS: La tecnología de matricestisulares (MTs) se ha implantado como método de trabajohabitual en la investigación de marcadores tisularesrelacionados con el cáncer. Su inconveniente esla necesidad de contar con un dispositivo especial deprecio elevado. Presentamos dos métodos manuales,económicos, que han sido válidos para construir MTsde pequeño y mediano formato.MATERIAL Y MÉTODOS: Se han elaborado 16 MTs deforma manual a partir de bloques convencionales deparafina, mediante dos técnicas diferentes. En la primerase utilizó una aguja Tru-Cut 16G a la que se cortó el bisel, para realizar los orificios en los bloques donantes(80 casos) y en los receptores (resultando dos MTs de55 casos y dos de 25 casos). Para la segunda técnicase utilizó un dispositivo "punch" para biopsias cutáneas,de 4 mm de diámetro, que se aplicó a los bloques donantes(obteniendo 210 cilindros de 108 bloques) y alos receptores (12 MTs). En las secciones de las MTs obtenidasse realizaron tinciones de hematoxilina-eosina,inmunohistoquímica (IHQ) e hibridación in situ. RESULTADOS: La tasa de pérdida de material en las seccionesobtenidas con el primer método fue del 26,5%,pero al haberse incluído dos cilindros de cada caso, almenos uno de ellos se conservó. En las MTs obtenidascon el método de punch biopsia no hubo pérdidas detejido. Los resultados de todas las tinciones realizadasfueron óptimos. CONCLUSIONES: Estos dos métodos manuales de elaboraciónde MTs resultan relativamente sencillos y soneconómicos. La tasa de pérdida de tejido es sólo significativaen el primero de los métodos pero se puedecompensar incluyendo varios cilindros de cada bloquedonante. En el segundo método no han existido problemasdestacables en la fase de microtomía.

Matrices tisulares: presentación de dos métodos sencillos y económicos de elaboración manual / Tissue arrays: Two simple and economical methods for manual construction

OBJETIVOS: La tecnología de matrices tisulares (MTs) se ha implantado como método de trabajo habitual en la investigación de marcadores tisulares relacionados con el cáncer. Su inconveniente es la necesidad de contar con un dispositivo especial de precio elevado. Presentamos dos métodos manuales, económicos, que han sido válidos para construir MTs de pequeño y mediano formato. MATERIAL Y MÉTODOS: Se han elaborado 16 MTs de forma manual a partir de bloques convencionales de parafina, mediante dos técnicas diferentes. En la primera se utilizó una aguja Tru-Cut 16G a la que se cortó el bisel, para realizar los orificios en los bloques donantes (80 casos) y en los receptores (resultando dos MTs de 55 casos y dos de 25 casos). Para la segunda técnica se utilizó un dispositivo "punch" para biopsias cutáneas, de 4 mm de diámetro, que se aplicó a los bloques donantes (obteniendo 210 cilindros de 108 bloques) y a los receptores (12 MTs). En las secciones de las MTs obtenidas se realizaron tinciones de hematoxilina-eosina, inmunohistoquímica (IHQ) e hibridación in situ. RESULTADOS: La tasa de pérdida de material en las secciones obtenidas con el primer método fue del 26,5%, pero al haberse incluído dos cilindros de cada caso, al menos uno de ellos se conservó. En las MTs obtenidas con el método de punch biopsia no hubo pérdidas de tejido. Los resultados de todas las tinciones realizadas fueron óptimos. CONCLUSIONES: Estos dos métodos manuales de elaboración de MTs resultan relativamente sencillos y son económicos. La tasa de pérdida de tejido es sólo significativa en el primero de los métodos pero se puede compensar incluyendo varios cilindros de cada bloque donante. En el segundo método no han existido problemas destacables en la fase de microtomía

OBJECTIVES: Tissue array (TA) technology is widely used as a method for the in situ investigation of tissue markers in cancer studies. A limitation of this technique is the high price of tissue arrayers. We describe two easy and non-expensive manual methods, that haveproduced small and medium format arrays. MATERIAL AND METHODS: 16 TAs were manually constructed from conventional paraffin blocks using two different techniques. For the first method, a 16G Tru-Cut needle whose bevel edge had been cut, was used to make the holes in the donor blocks (80 cases) and the receptor ones (resulting in 2 TAs each one with 55 cases and two with 25 cases). In the second technique, a 4 mm-diameter punch for cutaneous biopsies was applied to the donor blocks (obtaining 210 cylinders from 108 blocks) and to the receptor ones (12 TAs). Hematoxylin-eosin, immunohistochemical and in situ hybridization stains were performed on sections from these TAs. RESULTS: The tissue loss rate in the sections obtained from the TAs constructed with the first method was 26.5%, but as two cylinders were included from each case, at least one of them was retained. There was not any loss of tissue in the sections from the TAs constructed with the second method. The results of all of the stains performed were successful. CONCLUSIONS: These two manual methods of elaboration of TAs result rather simple and they are economical. The tissue loss rate is significant in the first method but it can be compensated embedding more than one cylinder from each donor block. There was not any problem in the sectioning of the TAs constructed with the second method