Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

Seven percent of renal cell carcinoma (RCC) cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC) and a tubulocystic renal carcinoma (TCRC) in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR) and distal tubule cell (CK19) markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2) of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3) showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression

Sarcoma sinovial monofásico con componente intraneural.: Informe de un caso con expresión inmunohistoquímica del factor de transcripción TLE-1 y presencia de translocación t (X;18) (SYT-SX1)

Synovial sarcoma is a high-grade neoplasm, of uncertain histogenesis, which comprises 5- 10% of all soft tissue sarcomas, and occurs, most frequently in the lower extremities. Intraneural location is extremely rare and it has only been reported in nine cases. The differential diagnosis of an intraneural SS is established with fibrosarcoma and malignant peripheral nerve sheath tumor. Positive immunostaining for cytokeratins and EMA is helpful but may be non-specific. Positive immunostaining for TLE-1 (Transducin-Like Enhancer of split 1) has great sensibility and specificity for the diagnosis of SS. Molecular analysis has a better specificity for diagnosis, because t(X;18)(SYT-SSX ) translocation, may be found in >80% of cases. We report herein, a case of a soft tissue monophasic SS, of a 20 years-old women, which presented a focal intraneural component, affecting the endoneurium of the cyatic nerve. The tumor expressed by immunohistochemistry TTL-1 and molecular analysis identified SYT-SSX1 translocation, allowing exclusion of other possible diagnosis. We review the concept related to the SS cellular origin. Pain, which is a significant clinical feature of SS, the gross relationship to nerve, the intraneural component present in some cases, the histological similarity with nerve sheath tumors, and the presence of calcospherites, unmyelinated fibers and endoneurial-like mucous, support the hypothesis of a possible intraneural origin.El sarcoma sinovial es una neoplasia de alto grado, de histogénesis incierta, que representa el 5-10% de todos los sarcomas blandos, y afecta más frecuentemente las extremidades inferiores. La localización intraneural es extremadamente rara y solamente hay informados nueve casos. El diagnóstico diferencial de los SS intraneurales se establece con fibrosarcoma y con el tumor de vaina nerviosa periférica maligno. La inmunomarcación positiva para las citoqueratinas y el EMA es de ayuda pero puede ser no específica. La inmunomarcación positiva para TLE-1 (Transducin-Like Enhancer of split 1) tiene gran sensibilidad y especificidad para el diagnóstico de los SS. El análisis molecular tiene mejor especificidad para el diagnóstico, porque la translocación t(X;18)(SYT-SSX) se puede encontrar hasta en el 80% de casos. Informamos en este estudio un caso de un SS monofásico de tejidos blandos del muslo, en una mujer de 20 años, que presentó un componente intraneural, afectando el endoneuro del nervio ciático. El tumor expresó por inmunohistoquímica TTL-1 y el análisis molecular identificó la translocación SYT-SSX1, permitiendo la exclusión de otros diagnósticos posibles. Revisamos el concepto relacionado con el origen celular de los SS. El dolor, que es una característica clínica presente en los SS, la relación macroscópica con nervios, el componente intraneural presente en algunos casos, la semejanza histológica con los tumores de la vaina nerviosa periférica, y de la presencia de los calcosferitas, fibras amielínicas y el moco semejante al endoneural, apoyan la hipótesis de un posible origen intraneura

JCPyV T-Antigen Activation of the Anti-Apoptotic Survivin Promoter—Its Role in the Development of Progressive Multifocal Leukoencephalopathy

Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the CNS, resulting from the lytic infection of oligodendrocytes by the human neurotropic polyomavirus JC (JCPyV), typically associated with severe immunocompromised states and, in recent years, with the use of immunotherapies. Apoptosis is a homeostatic mechanism to dispose of senescent or damaged cells, including virally infected cells, triggered in the vast majority of viral infections of the brain. Previously, we showed upregulation of the normally dormant anti-apoptotic protein Survivin in cases of PML, which—in vitro—resulted in protection from apoptosis in JCPyV-infected primary cultures of astrocytes and oligodendrocytes. In the present study, we first demonstrate the absence of apoptotic DNA fragmentation and the lack of caspase activity in 16 cases of PML. We also identified the viral protein large T-Antigen as being responsible for the activation of the Survivin promoter. Chromatin Immunoprecipitation assay shows a direct binding between T-Antigen and the Survivin promoter DNA. Finally, we have identified the specific region of T-Antigen, spanning from amino acids 266 and 688, which binds to Survivin and translocates it to the nucleus, providing evidence of a mechanism that results in the efficient replication of JCPyV and a potential target for novel therapies

México, importador de oftalmoscopios de Alemania

Tesina (medio superior), Centro de Estudios Científicos y Tecnológicos 5 “Benito Juárez”, 2017, 1 archivo pdf, (289 paginas). tesina.ipn.m

México, importador de oftalmoscopios de Alemania

Tesina (medio superior), Centro de Estudios Científicos y Tecnológicos 5 “Benito Juárez”, 2017, 1 archivo pdf, (289 paginas). tesina.ipn.m