[Renal cell carcinoma with sarcomatoid and rhabdoid features: a clinico-pathological series of 74 cases]. / Carcinomas renales con rasgos sarcomatoides y rabdoides: estudio clínico-patológico de 74 casos.

Objetives. Our aim is to analyze and compare the clinico-pathological features in renal cell carcinomas (RCC) with sarcomatoid and rhaboid phenotype. MATERIAL AND METHODS: We reviewed consecutive patients with nephrectomy RCC from January 1988 to January 2015. The subtyping of the RCC followed the recommendations of the College of American Pathologists. Cases with at least 1% of sarcomatoid and/or rhabdoid change were selected. They were classified as sarcomatoid or rhabdoid according with the predominant morphology, considering the global frecuency of both phenotypes as dedifferentiated component. The following variables were collected: sex, age, symptoms and existence of metastases at diagnosis, parameters listed in the protocol of renal carcinoma of the American College of Pathologists, pattern of tumor growth, perineural invasion, percentage of both tumor necrosis and characteristics of the inflammatory infiltrate. They were described by mean / median or percentage, and compared with Student-t / Mann-Whitney U or ? 2 / Fisher, depending on the sample characteristics. RESULTS: From 1,258 RCC, we identified 45 RCC with sarcomatoid predominance (3,6%) and twenty-nine with rhabdoid predominance (2,3%). RCC with sarcomatoid features showed a higher dedifferentiated component and perineural invasion (27.5 vs. 13.5%, p=0.003 and 28.9 vs. 3.4%, p=0.006, respectively) than RCC with rhabdoid features, while the former showed a higher proportion of neutrophilic inflammation (44.8 vs. 22.2%, p=0.04) and arose more frequently over high grade RCC (55.9 vs. 90.5%, p<0,001). CONCLUSIONS: There was overlapping of the clinico-pathological features of RCC with sarcomatoid and rhaboid phenotype, except for the dedifferentiated component, perineural invasion and neutrophilic inflammation. This close relationship could be explained by a common underlying mechanism, the epithelial-mesenchymal transition, with a double morphological expression that, if confirmed, could lead to selecting patients that would benefit from follow-up or treatment depending on their molecular characteristics.

Carcinomas renales con rasgos sarcomatoides y rabdoides: estudio clínico-patológico de 74 casos / Renal cell carcinoma with sarcomatoid and rhabdoid features: a clinico-pathological series of 74 cases

Fundamento: Nuestro objetivo fue comparar las variables clínico-patológicas de los carcinomas renales (CCR) con fenotipos sarcomatoide y rabdoide. Material y métodos: Se revisaron 1.258 CCR de pacientes consecutivos nefrectomizados entre 1988 y 2015, y se seleccionaron aquellos con ≥1% de cambio sarcomatoide y/o rabdoide. Se clasificaron como sarcomatoide o rabdoide según el fenotipo predominante, considerándose componente desdiferenciado la suma del porcentaje de ambos. Se recopilaron: sexo y edad de los pacientes, síntomas y existencia de metástasis al diagnóstico, parámetros del protocolo de CCR del Colegio Americano de Patólogos, patrón de crecimiento tumoral, invasión perineural, porcentaje de necrosis tumoral y características del infiltrado inflamatorio. Se describieron mediante la media/mediana o el porcentaje y se compararon mediante t de Student/U de Mann-Whitney o χ2/F de Fisher. Resultados: Se identificaron 45 CCR con predominio sarcomatoide (3,6%) y 29 con rabdoide (2,3%); los primeros mostraron mayor componente indiferenciado e invasión perineural respecto a los CCR con rasgos rabdoides (27,5 vs. 13,5%; p=0,003 y 28,9 vs. 3,4%, p=0,006, respectivamente), mientras que estos mostraron doble frecuencia de inflamación neutrofílica (44,8 vs. 22,2%, p=0,04) y surgieron más frecuentemente sobre un CCR de alto grado (55,9 vs. 90,5%, p<0,001). Conclusiones: Los CCR con fenotipos sarcomatoide y rabdoide compartieron características clínico-patológicas, excepto para componente desdiferenciado, invasión perineural, inflamación neutrofílica y origen en CCR de alto grado. Esta similitud sugiere la presencia de un mecanismo común, la transición epitelio-mesénquima, con una expresión morfológica doble que, de confirmarse, podría suponer la posibilidad de seleccionar pacientes para tratamiento o seguimiento a partir de sus características moleculares

Objetives. Our aim is to analyze and compare the clinico-pathological features in renal cell carcinomas (RCC) with sarcomatoidand rhaboid phenotype. Material and methods: We reviewed 1,258 RCC from consecutive patients with nephrectomy from 1988 to 2015, and those with ≥1% of sarcomatoid and/or rhabdoid change were selected. They were classified as sarcomatoid or rhabdoid according with the predominant morphology, considering the global frecuency of both phenotypes as dedifferentiated component. The following variables were collected: sex, age, symptoms and existence of metastases at diagnosis, parameters listed in the protocol of renal carcinoma of the American College of Pathologists, pattern of tumor growth, perineural invasion, percentage of both tumor necrosis and characteristics of the inflammatory infiltrate. They were described by mean/median or percentage, and compared with Student-t/Mann-Whitney U or χ2/Fisher). Results: We identified 45 RCC with sarcomatoid predominance (3,6%) and twenty-nine with rhabdoid predominance (2,3%); the first one showed a higher dedifferentiated component and perineural invasion (27.5 vs. 13.5%, p=0.003 and 28.9 vs. 3.4%, p=0.006, respectively), while the former showed a higher proportion of neutrophilic inflammation (44.8 vs. 22.2%, p=0.04) and arose more frequently over high grade RCC (55.9 vs. 90.5%, p<0,001). Conclusions: There was overlapping of the clinico-pathological features of RCC with sarcomatoid and rhaboid phenotype, except for dedifferentiated component, perineural invasion and neutrophilic inflammation. This close relationship could be explained by a common underlying mechanism, the epithelial-mesenchymal transition, with a double morphological expression that, if confirmed, could lead to selecting patients that would benefit from follow-up or treatment depending on their molecular characteristics

Adenoma nefrogénico prostático. A propósito de un caso / Prostatic nephrogenic adenoma. A case report

No disponible

Identification of TNF-alpha and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array.

BACKGROUND: Several drugs are available to treat metastatic renal-cell carcinoma (MRCC), and predictive markers to identify the most adequate treatment for each patient are needed. Our objective was to identify potential predictive markers of sunitinib activity in MRCC. METHODS: We collected sequential serum samples from 31 patients treated with sunitinib. Sera of six patients with extreme phenotypes of either marked responses or clear progressions were analysed with a Human Cytokine Array which evaluates 174 cytokines before and after treatment. Variations in cytokine signal intensity were compared between both groups and the most relevant cytokines were assessed by ELISA in all the patients. RESULTS: Twenty-seven of the 174 cytokines varied significantly between both groups. Five of them (TNF-alpha, MMP-9, ICAM-1, BDNF and SDF-1) were assessed by ELISA in 21 evaluable patients. TNF-alpha and MMP-9 baseline levels were significantly increased in non-responders and significantly associated with reduced overall survival and time-to-progression, respectively. The area under the ROC curves for TNF-alpha and MMP-9 as predictive markers of sunitinib activity were 0.83 and 0.77. CONCLUSION: Baseline levels of TNF-alpha and MMP-9 warrant further study as predictive markers of sunitinib activity in MRCC. Selection of patients with extreme phenotypes seems a valid method to identify potential predictive factors of response.

Quiste del cuarto arco branquial en la membrana tirohioidea: un difícil diagnóstico diferencial con el laringocele mixto / Four branchial cyst within the thyrohyoid membrane: a difficult differential diagnosis with mixed laryngocele

Se presenta el caso de una paciente de 62 años con una masa laterocervical derecha y en el repliegue aritenoepiglótico que provocaba disfonía. En el estudio de tomografía computarizada (TC) se detectóuna lesión quística unilocular de contenido homogéneo y bordes bien defi nidos. Atravesaba la membrana tirohioidea, por lo que se sospechó que correspondía a un laringocele mixto. Tras la cirugía, al no demostrarse la comunicación con el ventrículo laríngeo, se dio eldiagnóstico fi nal de quiste branquial. Se discute la etiopatogenia, las manifestaciones clínicas, radiológicas e histológicas para abordar eldiagnóstico diferencial entre el laringocele mixto y los quistes derivados de las hendiduras branquiales, principalmente de la segunda y de la cuarta. Los hallazgos radiológicos e histológicos de estas dos entidades pueden ser superponibles en algunos casos, por lo que sólo el hallazgo o la ausencia de comunicación de la lesión con el ventrículo laríngeo despeja la duda diagnóstica

We present a case of a 62-year-old female patient with a right laterocervical mass and an enlarged arytenoepiglottic fold, that caused voice disturbances. Computed tomography of the neck depicted an unilocularand homogeneous well-defi ned cyst located in the right parapharyngeal space that extended through the thyrohyoid membrane. It was initially diagnosed of mixed laryngocele. During surgical resection, no connexionbetween the lesion and laryngeal ventricle was detected, so the fi nal diagnosis was branchial cyst. We discuss the pathogenicity and clinical, radiological and histological fi ndings that facilitate differential diagnosis between mixed laryngocele and branchial cysts, mainly those derived from the second and fourth clefts. The radiological and histological findings in both lesions may be similar, so only the communication withthe larynx, or its absence, can solve diagnostic doubts. course

[Fourth branchial cyst within the thyrohyoid membrane: a difficult differential diagnosis with mixed laryngocele]. / Quiste del cuarto arco branquial en la membrana tirohioidea: un difícil diagnóstico diferencial con el laringocele mixto.

We present a case of a 62-year-old female patient with a right latero-cervical mass and an enlarged arytenoepiglottic fold, that caused voice disturbances. Computed tomography of the neck depicted an unilocular and homogeneous well-defined cyst located in the right parapharyngeal space that extended through the thyrohyoid membrane. It was initially diagnosed of mixed laryngocele. During surgical resection, no connexion between the lesion and laryngeal ventricle was detected, so the final diagnosis was branchial cyst. We discuss the pathogenicity and clinical, radiological and histological findings that facilitate differential diagnosis between mixed laryngocele and branchial cysts, mainly those derived from the second and fourth clefts. The radiological and histological findings in both lesions may be similar, so only the communication with the larynx, or its absence, can solve diagnostic doubts, course.

[Salivary gland choristoma (hamartoma) of the middle ear: a case report]. / Cas clinique : choristome de glande salivaire au niveau de l'oreille moyenne.

OBJECTIVE: Middle ear salivary gland choristoma are extremly rare. We report a case, describe the clinical management and review the literature. CLINICAL CASE: A 12 year old boy presented with unilateral conductive hearing loss associated with a large inferior retraction pocket on otoscopy. CT scan demonstrated a large mass in the left middle ear cavity. The incus was absent and the stapes was partially eroded. Middle ear exploration demonstrated an 8 mm yellow/red mass in the region of the fallopian canal. This mass was comptly removed and histopathology confirmed salivary gland choristoma. CONCLUSION: These lesions result from an abnormal development of the second branchial arch. It is important to consider these lesions as part of the differential diagnosis for any unilateral hearing loss associated with a middle ear mass in children.

[Molecular biology of follicular thyroid carcinoma (II). Clinical applications]. / Biología molecular del carcinoma de tiroides de estirpe folicular (II). Aplicaciones clínicas.

The great advance of molecular medicine over the last few years gives us an attractive vision of the new possibilities in diagnosis and therapeutics of thyroid cancer and helps us to understand its biological behaviour. The clinical application of the growing understanding of gene alterations involved in thyroidal oncogenesis is becoming a reality. Such knowledge might contribute to greater diagnostic accuracy, by helping us characterise malignant or benign cells, predict tumour outcome or state its origin. Likewise it might be useful to know the response to conventional therapies or the future implications of pharmacogenetics. In addition molecular medicine applications ought to be considered in determining the prognosis of spontaneous and familiar carcinomas. Such information can significantly improve current clinical-pathologic prognostic methods.

PTEN protein expression correlates with PTEN gene molecular changes but not with VEGF expression in astrocytomas.

PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression in astrocytomas when similar areas are considered.

Apoptotic cell death and genetic control in graft coronary artery disease in heart transplant.

AIM: Apoptosis is a type of programmed cell death whereby, immunologic, genetic and biochemical mechanisms are involved in its control. On the other hand, graft coronary artery disease is the most important restrictive factor for the long-term survival of heart transplantation. The purpose of this study is to analyse both apoptotic cell lesions in transplanted patients that present coronary artery disease. METHODS: From August 1984 until December 1996, 148 heart transplants were carried out in the Clínica Universitaria de Navarra. In 102 patients, annual coronary angiography was performed, reaching a diagnosis of coronary artery disease in 30 patients. Study of apoptotic cell death was done in the tissue of endomyocardial biopsies on all patients by means of the TUNEL technique. Procedures of immunohistochemistry with antibodies antic-myc, p53 and bcl-2 were carried out and results were compared with a control group of 30 patients with homogeneous characteristics. RESULTS: All patients with coronary artery disease showed apoptotic cardiomyocytes, 13 patients to a mild degree, 14 to a moderate degree and 3 to a severe degree, while in the control group apoptosis was found only to a mild degree in 8 patients, obtaining a very significant statistical difference (p<0.0001). The expression of analysed oncoproteins was null in the 2 groups. CONCLUSION: Myocardial apoptosis is a constant finding in transplanted patients with coronary artery disease. We have not seen any correlation between the apoptotic process and genetic mechanisms.

Utilización de células madre en terapia regenerativa Cardíaca / No disponible

La posibilidad de utilizar células madre en el tratamiento de diversas enfermedades humanas como la diabetes, la enfermedad de Parkinson, la cardiopatía isquémica constituye uno de los retos mas importantes de la medicina moderna. Sin embargo, antes de que los resultados de los estudios con células madre se traduzcan clínicamente existen múltiples problemas que deben ser resueltos. A continuación trataremos de exponer algunos conceptos relacionados con las células madre y su potencial, centrándonos principalmente en las células madre adultas tal como han sido recientemente descritas por el grupo de Catherine Verfaillie. Además presentaremos resultados de alguno de los primeros estudios clínicos realizados con células madre adultas como forma de terapia regenerativa cardíaca. En dichos trabajos se han empleado células madre de músculo (células satélite) autólogas en pacientes con infarto de miocardio, inyectándose directamente dichas células en la periferia de la cicatriz secundaria al infarto (AU)

One of the most important challenges in modern medicine is the use of stem cells for the treatment of human disease such as diabetes, Parkinson´s disease or isquemic cardiomyopathy. A number of problems need to be solved before stem cells can be applied clinically. In this paper we will review some concepts related to the potential of stem cells, focusing on adult stem cells as they have recently been described by the group of Catherine Verfaillie. We will also present our initial clinical results using adult stem cells for cardiac regenerative therapy. In the studies mentioned above, autologous muscle stem cells (satelite cells) were infused directly in the periphery of the scar tissue of the infarct. We describe the technique for ex vivo expansion and purification of muscle stem cells (AU)

Biología molecular del carcinoma de tiroides de estirpe folicular. Bases moleculares en la oncogénesis tiroidea / No disponible

Existen datos que nos permiten afirmar que probablemente, en gran parte de los casos, no existe una solución de continuidad entre las diferentes neoplasias tiroideas de estirpe folicular. Cabe pensar que el proceso evolutivo comienza con una serie de alteraciones moleculares que condicionan la aparición del adenoma folicular (AF). Cambios posteriores propiciarán el desarrollo de un carcinoma folicular (CF). La aparición del carcinoma papilar (CP) tiene probablemente un itinerario similar sin que esté demostrado que tenga su origen en AF. Ulteriores cambios genéticos, tanto en el CP como en el CF encaminarán hacia la indiferenciación celular y con ello el desarrollo del carcinoma indiferenciado (CI). Esta sucesión de alteraciones moleculares condiciona un empeoramiento en el pronóstico de la neoplasia tiroidea. Por ello, las neoplasias tiroideas constituyen un excelente modelo para el estudio de la cronología de los cambios moleculares que condicionan la evolución desde la benignidad a la malignidad. Se ha comprobado que en algunas neoplasias de tiroides existe inestabilidad genética que favorece dichos cambios moleculares. Como fenómeno inicial es frecuente observar alteraciones en los protooncogenes mientras que las mutaciones en los genes supresores de tumor suelen ser un evento tardío. La aparición de agresividad o invasividad de la neoplasia también se puede investigar mediante el estudio de cambios moleculares. La aplicación clínica de dichos hallazgos comienza a ser una realidad, lo que facilitará la precisión diagnóstica y con ello una terapéutica más eficaz (AU)

According to current data, it seems probable that there is no interruption in the evolution of different follicular thyroid neoplasm. Probably transforming events responsible for the transition from normal to tumor cells start with molecular changes that determine the appearance of follicular adenoma. Later changes propitiate the development of follicular cancer. It is likely that the generation of papillary carcinoma follows a different pathway without passing through a previous phase of follicular adenoma. Subsequently, genetic changes render the cell prone to a failure to differentiate, culminating in the development of anaplastic cancer. Those incidental molecular changes result in a dramatic worsening in the prognosis of thyroid cancer. Research into thyroid tumors is likely to be instructive in view of the spectrum they span, from benign adenomas to poorly differentiated carcinomas. It has been proven that molecular alterations in thyroid tumor cells are predisposed by genome instability. Usually changes of protooncogenes represent an early event whereas mutations of suppressant genes are usually a late phenomenon. The onset of aggressive or invasive behavior may be studied, and perhaps can be predicted in the future, by molecular changes. The clinical application of the growing understanding of gene alterations involved in thyroidal oncogenesis is becoming a reality. Such knowledge might contribute, in the near future, to greater diagnostic accuracy and effective treatment for thyroid malignancies (AU)

Valor diagnóstico de la proteína WT-1 como marcador inmunohistoquímico / Diagnostic value of the WT-1 protein as an inmunohistochemical marker

No disponible

Immunocytochemistry in the differential diagnosis of serous effusions: a comparative evaluation of eight monoclonal antibodies in Papanicolaou stained smears.

BACKGROUND: The distinction between pleural mesothelioma (MS), reactive mesothelium (RM), and adenocarcinoma (AC) in serous effusions continues as a diagnostic problem in pathology. Immunohistochemistry can help, especially in surgical samples, but the optimum panel of antibodies has yet to be reported. The application of these antibodies to serous effusions has displayed variable results. The aim of this study was to evaluate the usefulness of eight monoclonal antibodies in the differential diagnosis of MS, RM, and AC in serous effusions. METHODS: A total of 44 cytologic specimens of serous effusions (26 pleural, 15 peritoneal, and 3 pericardial) from 30 ACs, 3 MSs, and 11 RMs, previously stained with Papanicolaou stain, were selected retrospectively from our files and stained with HBME-1, thrombomodulin, calretinin, MOC-31, Ber-EP4, E-cadherin, CEA, and CD-15. The immunoreactions were evaluated independently by two pathologists. A stepwise logistic regression analysis was applied to the data to select an appropriate panel of antibodies. RESULTS: Statistical significance was found with HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15, when comparing both AC versus MS, and AC versus any type of mesothelial proliferation (MS or RM). Using HBME-1, 80% of ACs were negative whereas all three MSs reacted strongly with P = 0.003. A P = 0.02 was reached with thrombomodulin with 76.5% of ACs showing no immunoreactivity. Ber-EP4 and MOC-31 displayed good results with a P < 0.001 and 0.01, respectively. CD-15 reached a P = 0.034. No differences were found using the other antibodies. Ten ACs, all 3 MSs, and 10 RMs were double immunostained with HBME-1 and/or MOC-31 and Ber-EP4 successfully. CONCLUSIONS: Immunohistochemical studies performed on Papanicolaou stained cytologic smears proved to be useful in the differentiation between metastatic AC and mesothelial proliferation. HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15 were the most useful. In selected cases, it appeared that double immunostaining aided the differential diagnosis. Cancer (Cancer Cytopathol)

Carcinoma plasmocitoide de células transicionales de la vejiga urinaria / Plasmacytoid transitional cell carcinoma of the urinary bladder: A case report and review of the literature

Presentamos el caso de un varón de 63 años con una variante plasmocitoide de carcinoma de células transicionales de vejiga urinaria. Debutó clínicamente con disuria y hematuria. En la cistoscopia se observó una lesión ulcerada en la pared de la vejiga que se biopsió. Tras el diagnóstico se realizó una cistectomía. El estudio histopatológico mostró un crecimiento difuso de células tumorales que asemejaban células plasmáticas. El diagnóstico diferencial se estableció entre un linfoma, melanoma y plasmocitoma. Las células neoplásicas mostraron inmunorreactividad frente a citoqueratinas, siendo negativo el estudio frente a S100 y marcadores de células linfoides y plasmáticas. En la literatura únicamente se recogen dos casos de esta variante tumoral, con datos clínicos y morfológicos semejantes a los que presentamos. La confirmación de la naturaleza epitelial de las células neoplásicas es la clave para el diagnóstico (AU)

Papel de la cirugía en el tratamiento del linfomagástrico primario / Surgery´s role in management of primary gastric lymphoma

El Linfoma Gástrico Primario es una entidad patológica cuyo manejo óptimo está en discusión. Se estudian retrospectivamente 23 pacientes tratados en nuestro Centro por Linfoma Gástrico entre 1976 y 1998 con resección quirúrgica como terapia principal. En diez pacientes la cirugía fue el único tratamiento realizado, en el resto se asoció quimio y/o radioterapia según criterio del oncólogo-hematólogo responsable. No hubo diferencias en cuanto a morbimortalidad entre los diferentes tratamientos. Se analizan las características clínicas e histológicas y la evolución de los pacientes. Ninguno de los pacientes ha fallecido a consecuencia del linfoma, no habiéndose presentado tampoco ningún caso de recurrencia local ni a distancia. Opinamos que la cirugía es una opción válida en el tratamiento del Linfoma Gástrico Primario. La asociación de tratamientos complementarios dependerá del estadio definitivo, las características histológicas del tumor y la posibilidad de realizar o no una resección radical (AU)

Mast cells in chronic rejection of human renal allografts.

An increased number of mast cells (MCs) is found in renal specimens of patients with diseases associated with persistent chronic inflammation. MCs proliferation is partly dependent on the presence of T lymphocytes. Both chronic inflammation and T-lymphocytes are essential in the development of chronic rejection (CR), and probably for the infiltration of MCs. MC-derived products such as heparin, histamine, and serine proteases may be responsible for endothelial proliferation and excess collagen production by fibroblasts. In this study, a quantitative evaluation of the MCs infiltration in kidney allografts with CR is performed. The extent of renal fibrosis was analysed in samples stained with Masson's trichrome. To evaluate the potential relationship between MCs and fibrosis in CR we analysed 30 kidneys with CR (25 from nephrectomies and 5 from autopsies). Ten transplanted kidneys obtained from patients died by causes not related with rejection were used as controls. CR was graded according to the Banff schema, which assesses the degree of vasculopathy, tubular atrophy, interstitial fibrosis and transplantation glomerulopathy. Giemsa-stained sections and immunohistochemistry using anti-MC tryptase and c-kit monoclonal antibodies were used to detect MCs. The mean number of MCs per 20 high-power fields (HPF) in the transplanted kidney with CR was 101.8+/-15.3 in the renal cortex and 46.60+/-6.52 in the medulla. MCs were significantly more numerous in CR with respect to normal kidneys, both in the cortex (P<0.01; Mann-Whitney U test) and in the medulla (P<0.01; Mann-Whitney U test). There was a positive correlation between the number of MCs and extent of fibrosis (P<0.01; Kruskal-Wallis one-way anova test) and tubular atrophy (P<0.01). These results suggest that MCs may play a role in the process of development of interstitial fibrosis in CR.

Prognostic impact of P53 status in Ewing sarcoma.

BACKGROUND: Disease stage at the time of diagnosis and response to therapy are the main prognostic factors for patients with Ewing sarcoma or peripheral neuroectodermal tumor (ES/PNET). The primary genetic alteration in ES/PNET, the fusion of the EWS gene with FLI1 or ERG, is diagnostically highly specific for these tumors, and molecular variation in the structure of the EWS-FLI1 fusion gene also is of prognostic significance. In contrast, secondary genetic alterations, such as P53 alterations, are relatively uncommon in ES/PNET, and their prognostic impact has not been extensively studied. METHODS: Prechemotherapy, paraffin embedded, nondecalcified, primary tumor material in a well-characterized series of 55 patients with ES/PNET with defined EWS-FLI1 fusion transcripts (32 patients with type 1 and 23 patients with other types) was studied retrospectively by immunohistochemical techniques for cell cycle regulators and proliferative markers, such as P53, P21(WAF1), and Ki-67, as well as by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique for apoptosis. Nuclear P53 expression in > 20% of tumor cells was scored as aberrant overexpression. Histologic response to neoadjuvant chemotherapy was assessed. RESULTS: Aberrant P53 expression (in > 20% of tumor cells) was present in 6 patients (11%) but showed no statistically significant correlation with disease stage, tumor size, proliferation rate (Ki-67), apoptotic rate (TUNEL), or EWS-FLI1 fusion type. By univariate analysis, the P53 > 20% group showed a significantly poorer overall survival among patients with localized disease (n = 43 patients) (P = 0.001) and in the entire study group (P = 0.01). In multivariate Cox analyses of overall survival, P53 > 20% was the strongest negative factor among prognostic factors available at the time of diagnosis (P = 0.001; relative risk [RR] = 9) and when chemotherapy response was included in the analysis (P53 > 20%: P = 0.01; RR = 10). CONCLUSIONS: P53 alteration appears to define a small clinical subset of patients with ES/PNET with a markedly poor outcome. The current observations warrant a systematic prospective study with comprehensive P53 mutation analysis. [See related article on pages 793-9, this issue.]

Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology.

BACKGROUND: The histopathological spectrum and role of hepatitis viruses in cases of hypertransaminasaemia of unknown aetiology have not been correctly analysed in a sufficiently large number of patients. METHODS: We studied 1075 consecutive patients referred for liver biopsy because of elevation of alanine aminotransferase (ALT) levels for more than six months. From this population we selected those cases in whom the aetiology could not be defined from clinical, biochemical, and serological data obtained before biopsy. In these patients liver biopsies were reviewed, and hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA were assayed in serum by polymerase chain reaction (PCR). Serum hepatitis G virus (HGV)-RNA was determined by PCR in 74 patients. RESULTS: Of 1075 patients studied, the cause of the increased serum ALT levels remained elusive after appropriate testing in 109 patients (10.1%). Liver biopsies from these patients showed non-specific changes in 32.7% of cases, non-alcoholic steatohepatitis (NASH) in 15.8%, and chronic hepatitis or cirrhosis in 51.5%. HBV-DNA and/or HCV-RNA was detected more frequently in cryptogenic liver disease than in healthy blood donors (26.7% v 3.4%; p<0.001). HGV-RNA was found in only one patient. The proportion of cases with detectable HBV-DNA or HCV-RNA was 14.3% in patients with non-specific changes or NASH, 30.7% in patients with chronic hepatitis, and 61.5% in patients with cirrhosis. Cirrhosis was found more frequently in patients with positive HBV-DNA and/or HCV-RNA in serum than in those who tested negatively (p=0.005). CONCLUSIONS: In our series, patients in whom biochemical and serological data did not determine the aetiology of the disease represented 10% of all cases referred for liver biopsy for persistent elevation of serum transaminases. Approximately 50% of patients had chronic hepatitis or cirrhosis and the remainder had NASH or non-specific changes. Occult viral infections were found in a high proportion of cases in the first group and in a low percentage of patients in the second.