[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

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)

Angiomixolipoma: una variante de lipoma / Angiomyxolipoma: a variant of lipoma

Presentamos un caso de angiomixolipoma en el tejido subcutáneo de la espalda superior en un varón de 50 años. En el examen clínico, la lesión se observa móvil y ligeramente dolorosa. La muestra patológica es redondeada, bien circunscrita, blanda y con una superficie pardo amarillenta y gelatinosa. Histológicamente la lesión consiste en tejido adiposo y estroma mixoide que contiene numerosos vasos sanguíneos de pequeño y mediano tamaño.Ésta es una variante poco frecuente de lipoma, que fue descrita por primera vez en 1996 en la zona de cuerda espermática. La consideramos un híbrido entre angiolipoma y lipoma de células fusiformes. La lesión debería distinguierse del liposarcoma mixoide por razones terapeúticas y pronósticas (AU)

Susceptibility to apoptosis measured by MYC, BCL-2, and BAX expression in arterioles and capillaries of adult spontaneously hypertensive rats.

Hypertension results in microvascular rarefaction or disappearance of microvessels. In the present study, we investigated the pathogenic role of apoptosis in hypertension-induced rarefaction of heart arterioles and capillaries of spontaneously hypertensive rats (SHR). Experiments were performed on hearts from 6-week-old, 16-week-old, and 30-week-old SHR (n = 30 rats) (SHR6, SHR16, SHR30). We used as controls 6-week-old, 16-week-old, and 30-week-old normotensive rats (WKY) (n = 30 rats) (WKY6, WKY16, WKY30). We analyzed the expression of c-myc, bcl-2, and bax and in situ end-labeling DNA fragmentation in vascular smooth muscle cells of arterioles and endothelial cells of arterioles and capillaries. Endothelial cells of capillaries and endothelial and smooth muscle cells of arterioles of hypertensive animals (SHR) express more Bax protein and Myc protein than their respective normotensive controls by margins that were statistically significant. The SHR30 group expressed the lowest levels of Bcl-2 protein by a margin that was statistically significantly different from WKY30. We did not find evidence of apoptosis in arterioles or capillaries on the basis of in situ end-labeling. However, our results indicated that alterations in the expression of members of the Bcl-2 family of proteins and Myc protein occurred in smooth muscle cells and endothelial cells of arterioles and capillaries of SHR. In conclusion, although evidence of apoptosis in arterioles and capillaries was not found by in situ end-labeling, our findings suggest that in hypertension they may have a higher susceptibility to apoptosis, and therefore rarefaction may be a consequence of apoptosis.

Intraabdominal desmoplastic small round cell tumor with EWS/ERG fusion transcript.

This report describes an intraabdominal small cell tumor in a 37-year-old woman, with clinical, topographic, and morphologic features highly suggestive of the desmoplastic small round cell tumor. Immunohistochemical analysis revealed a polyphenotypic profile consistent with this tumor--positivity for keratin, epithelial membrane antigen, neuron-specific enolase, vimentin, and desmin--but, in addition, a strong membranous immunoreactivity for CD99 (MIC2 protein). Reverse transcription polymerase chain reaction revealed a EWS/ERG fusion transcript characteristic of the Ewing's sarcoma/peripheral primitive neuroectodermal tumor group of tumors, rather than the EWS/WT1 chimeric transcript typical of the desmoplastic small round cell tumor. This is the third report of a hybrid tumor with features of the desmoplastic small round cell tumor and Ewing's sarcoma/peripheral primitive neuroectodermal tumor, and the first one with the EWS/ERG fusion gene. Our case shows the existence of some overlap between these two groups of tumors, which are considered to be histogenetically different, and the need for further studies of molecular characterization of small cell tumors, especially in those with atypical morphologic or immunohistochemical features.

[Lymphatic metastases of osteosarcomas]. / Metástasis ganglionares de osteosarcomas.

Osteosarcoma lymph node metastasis are uncommon. This paper shows two patients having osteoblastic osteosarcoma with loco-regional lymph node involvement. In the first case two inguinal and pelvic adenomegalies were found to have tumor metastasis two years and a half after initial diagnosis in a control radiological study. Currently the patient is alive three months after the lymphadenectomy. In the second case, several inguinal high density tumoral nodules were identified during the workup of primary tumor.

Serum markers of collagen type I metabolism in spontaneously hypertensive rats: relation to myocardial fibrosis.

BACKGROUND: The assay of serum peptides of extracellular collagen synthesis and degradation could provide an indirect estimate of the rate of fibrillar turnover. This study was designed to investigate whether serum peptides of collagen type I synthesis and degradation are altered in spontaneously hypertensive rats (SHR) with left ventricular hypertrophy and whether these serum collagen-derived peptides are related to myocardial fibrosis. METHODS AND RESULTS: We measured serum levels of carboxyterminal propeptide of procollagen type I (PIP) as a marker of collagen I synthesis and serum levels of the pyridinoline crosslinked telopeptide domain of collagen type I (CITP) as a marker of fibrillar collagen I degradation in ten 36-week-old normotensive Wistar-Kyoto (WKY) rats, ten 36-week-old SHR, and ten 16-week-old SHR treated with the angiotensin-converting enzyme inhibitor quinapril (10 mg /kg body wt per day, orally) for 20 weeks. PIP and CITP were determined by specific radioimmunoassays. Histomorphometric and immunohistochemical studies of the left ventricle were performed in all rats. In untreated SHR compared with WKY rats, we found a more extensive interstitial and perivascular fibrosis, an increased (P<.01) collagen volume fraction, a more marked deposition of collagen type I, an increased (P<.01) serum concentration of PIP, and a similar serum concentration of CITP. In quinapril-treated SHR compared with untreated SHR, we found an absence of left ventricular hypertrophy, a marked decrease of fibrosis, a lower (P<.01) collagen volume fraction, a diminished deposition of collagen type I, a decreased (P<.01) concentration of PIP, and a similar concentration of CITP. A direct correlation was found between the collagen volume fraction and serum PIP (r=.753, P<.05) in untreated SHR. CONCLUSIONS: These results suggest that tissue metabolism of collagen type I is abnormal in SHR and can be normalized by treatment with quinapril. On the basis of our findings, we propose that serum PIP may be a marker of collagen type I-dependent myocardial fibrosis in rats with genetic hypertension.

Histological outcome of chronic hepatitis C treated with a 12-month course of lymphoblastoid alfa interferon.

To assess the effect of long-term alfa interferon therapy (12 months) on liver histology of chronic hepatitis C, we studied 61 treated patients, and compared their outcome with 28 untreated cases followed as controls. A liver biopsy was taken from all patients, before (month 0) and after the completion of the treatment or the control period (month 12). A third liver specimen taken at month 24 was available in 29 treated cases. Liver biopsies were blindly graded following Knodell's method. In 33 out of the 61 treated patients (54.1%), aminotransferase levels became normal shortly after starting therapy and remained within normal values until the end of treatment (sustained response). Nine (27%) sustained responders relapsed after interferon discontinuation, while the remaining 24 (73%) continued with normal aminotransferase values during follow-up (16.8 +/- 9.9 months). All histological parameters, except fibrosis, improved significantly after 12 months of therapy (periportal necrosis, month 0: 2.7 +/- 1.0, month 12: 1.6 +/- 1.1, p < 0.0001; lobular damage, month 0: 2.5 +/- 1.1, month 12: 1.4 +/- 0.9, p < 0.0001; portal inflammation, month 0: 3.6 +/- 0.5, month 12: 3.0 +/- 0.9, p < 0.0001). Histological improvement was especially marked in patients who did not relapse, although those who relapsed and partial responders also improved. Overall histological diagnoses improved in most patients. A sustained response to interferon was predicted by high periportal and lobular scores, and by a low fibrosis score on the pretreatment liver biopsy. At 24 months, histological improvement persisted in patients without posttreatment relapse, while liver inflammation had returned to pretreatment levels in the remaining cases.

Cystadenofibroma of fallopian tube.

We present two cases of cystadenofibroma of the fallopian tube in 2 patients of 49 and 32 years, respectively. The first tumor was a chance finding in a hysterosalpingo-oophorectomy because of multiple leiomyomas. The second tumor appeared in a pregnant woman; the tumor was considered in an echographic study as an ectopic pregnancy. This tumor was a borderline cystadenofibroma. The second case is the first report of cystadenofibroma of the fallopian tube associated with pregnancy.

Liver cell injury (bodies similar to Lafora's) in alcoholics treated with disulfiram (Antabuse).

Inclusions, structurally similar to Lafora's bodies, are described in the liver cells of three chronic alcoholic patients who stopped drinking after disulfiram treatment. The inclusions were strongly positive with PAS and methenamine silver stains. Shikata stain for HBsAg was negative. On electron microscopy the inclusions are not membrane-bound and contain glycogen beta-granules, secondary lysosomes containing lamellar structures, lipid droplets and filaments; the SER was almost completely lost. In the patient least affected, the cells bearing inclusions were predominantly periportal in location, as is usual in Lafora's disease. In the two other patients the change involved the whole lobule. The possibility of an induced carbohydrate metabolic disorder, which could be due to the disulfiram, a drug that interferes with the activity of several hepatic enzymes is discussed. The presence of appearances suggestive of SER breakdown could also be interpreted as a manifestation of 'disuse atrophy' due to alcohol withdrawal.