Adult type granulosa cell tumor in adult testis: report of a case and review of the literature

Granulosa cell tumors can be classified into juvenile and adult types and more commonly occur in ovaries. Adult testicular granulosa cell tumors are extremely rare and only 29 cases of adult type have previously been reported. We report here a 28-year old Caucasian man with a left testicular adult type granulosa cell tumor. The tumor measured 2.6×2.6×2.5 cm and was mitotically active (10/10 HPF). Immunohistochemical stains showed the tumor diffusely positive for inhibin and vimentin, and negative for epithelial membrane antigen, cytokeratins, synaptophysin, HMB-45, OCT-4, placental-like alkaline phosphatase and lymphoid markers. The reported granulosa cell tumors in adult testis were briefly reviewed

Cardiac Epithelioid PEComa: Report of Two Cases and Review of the Literature

Cardiac PEComa is very rare. We reported two cases of epithelioid PEComas, one in an adult and one in a 2-year-old child. Both tumors were composed of sheets of epithelioid cells with coagulation necrosis. In addition, the adult case showed marked nuclear atypia and high mitotic activity with atypical mitosis and the pediatric case showed unusual clear cell features. Immunohistochemically, both tumors were positive for HMB-45 and SMA and negative for S100 and cytokeratin. Electron microscopy was performed in the pediatric case and showed premelanosomes. The adult patient developed extensive metastasis indicating malignant behavior. Prior to the two cases, only 5 other cases of cardiac PEComa were reported and the literatures are reviewed

Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes

SummaryNegative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor α (PPARα), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes

Adult urinary bladder tumors with rabdomyosarcomatous differentiation: Clinical, pathological and immunohistochemical studies

Adult rhabdomyosarcoma (RMS) in the urinary bladder is rare, and is the subject of case reports and small series. It consists of sheets of small round blue cells with high nuclear cytoplasmic ratio, brisk mitosis and apoptosis. In this study, we reported one case of pure rhabdomyosarcoma and two cases of urothelial carcinomas with extensive rhabdomyosarcomatous differentiation. In addition, their immunohistochemical profile was compared to that of small cell carcinoma of the bladder. Our study showed that sufficient sampling was critical for the diagnosis of urothelial carcinoma with extensive rhabdomyosarcomatous differentiation. As adult RMS in the bladder and urothelial carcinoma with rhabdomyosarcomatous differentiation shared morphological features with small cell carcinoma of the bladder, appropriate immunohistochemical stains were necessary in the differential diagnosis. We showed both rhabdomyosarcoma and rhabdomyosarcomatous areas of the urothelial carcinoma were positive for myogenin, negative for cytokeratin and chromogranin stains. In contrast, small cell carcinoma was positive for cytokeratin, and 7 out of 9 cases were also positive for chromogranin. Both rhabdomyosarcoma and small cell carcinoma could be positive for synaptophysin, a potential pitfall to avoid. In addition, all of the tumors with rhabdomyosarcomatous differentiation were negative for FKHR rearrangement

Transcription factor SEF: Purification and functional characterization

Cytokine-induced transcription of the serum amyloid A3 (SAA3) gene promoter requires a transcriptional enhancer that contains three functional elements: two C/EBP-binding sites and a third site that interacts with a constitutively expressed transcription factor, SAA3 enhancer factor (SEF). Deletion or site-specific mutations in the SEF-binding site drastically reduced SAA3 promoter activity, strongly suggesting that SEF is important in SAA3 promoter function. To further elucidate its role in the regulation of the SAA3 gene, we purified SEF from HeLa cell nuclear extracts to near homogeneity by using conventional liquid chromatography and DNA-affinity chromatography. Ultraviolet cross-linking and Southwestern experiments indicated that SEF consisted of a single polypeptide with an apparent molecular mass of 65 kDa. Protein sequencing, oligonucleotide competition and antibody supershift experiments identified SEF as transcription factor LBP-1c/CP2/LSF. Cotransfection of SEF expression plasmid with SAA3-luciferase reporter resulted in 3- to 5-fold activation of SAA3 promoter. Interestingly, when SEF-transfected cells were treated with either conditioned medium (CM) or interleukin (IL) 1, the SAA3 promoter was synergistically activated in a dose-dependent manner. Furthermore, when SEF-binding site was mutated, the response of SAA3 promoter to IL-1 or CM stimulation was abolished or drastically decreased, suggesting that SEF may functionally cooperate with an IL-1-inducible transcription factor. Indeed, our functional studies showed that NFκB is a key transcription factor that mediates the IL-1-induced expression of SAA3 gene, and that SEF can synergize with NFκBp65 to activate SAA3 promoter. By coimmunoprecipitation experiments, we found that SEF could specifically interact with NFκBp65, and that the association of these two factors was enhanced upon IL-1 and CM stimulation. This suggests that the molecular basis for the functional synergy between SEF and NFκB may be due to the ability of SEF to physically interact with NPκB. In addition to its interaction with SEF, NFκB-dependent activation also requires the weak κB site in the C element and its interaction with C/EBP. Besides its role in regulating SAA3 gene expression, we provide evidence that SEF could also bind in a sequence-specific manner to the promoters of α2-macroglobulin, Aα fibrinogen, and 6–16 genes and to an intronic enhancer of the human Wilm\u27s tumor 1 gene, suggesting a functional role in the regulation of these genes. By coimmunoprecipitation experiments, we determined that SEF could specifically associate with both Stat3 and Stat2 upon cytokine stimulation. To examine the functional roles of such interactions, we evaluated the effects of SEF on the transcriptional regulation of two reporter genes: Aα fibrinogen and 6–16, which are IL-6- and interferon-α-responsive, respectively. Our results showed that cotransfection of SEF expression plasmid can activate the expression of Aα fibrinogen gene and 6–16 gene. Moreover, SEF can dramatically enhance the interferon-α-induced expression of 6–16 gene and IL-6-induced expression of Aα fibrinogen gene, suggesting that SEF may functionally cooperate with ISGF3 and Stat3 to mediate interferon-α and IL-6 signaling. Our findings that SEF can interact with multiple cytokine-inducible transcription factors to mediate the expression of target genes open a new avenue of investigation of cooperative transcriptional regulation of gene expression, and should further our understanding of differential gene expression in response to a specific stimulus. In summary, our data provide evidence that SEF can mediate the signaling of different cytokines by interacting with various cytokine-inducible transcription factors

Clear Cell Papillary Renal Cell Carcinoma in the Bilateral Native Kidneys after 2 Years of Renal Transplantation: Report of a Case and Review of the Literature

Renal transplantation increases the probability of malignant tumors by about 2–4-fold overall with a much higher rate for renal epithelial malignancy. Renal tumors in renal transplant recipients are commonly conventional clear cell or papillary renal cell carcinoma. Clear cell papillary renal cell carcinoma is a recently described unique renal epithelial neoplasm with scant eosinophilic or moderate amount of clear cytoplasm and pyknotic small nuclei oriented commonly toward the apical surfaces. No such tumor has been reported in renal transplant recipients. In this paper, we describe a clear cell papillary renal cell carcinoma involving bilateral native kidneys in a patient who had received a renal transplant 2 years earlier. Clear cell papillary renal cell carcinoma commonly presents with low pathologic stage and lower Fuhrman grade and is clinically indolent. Additional cases are needed to evaluate the clinical behavior of this type of tumor in renal transplant recipients

Expression of parafibromin in clear cell papillary renal cell carcinoma.

Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal cell neoplasm. In this study, we investigated the expression of parafibromin, CK7, and RCC marker (RCC-Ma) in this tumor by immunohistochemistry in a group of CCPRCC. Twenty cases of CCPRCC were stained for parafibromin and showed diffuse and strong nuclear positivity for this marker. In addition the cases of CCPRCC were stained for CK7 and RCC-Ma, respectively, and the majority of tumors were positive for cytoplasmic staining of CK7 and negative for RCC-Ma. This unique staining pattern can be useful in the differential diagnosis from conventional clear cell renal cell carcinomas, which have a higher positivity rate for RCC-Ma, but largely negative for CK7 and parafibromin, and papillary renal cell carcinomas, which are usually positive for CK7 and RCC-Ma but are largely negative for parafibromin

Primary retroperitoneal mature cystic teratoma with focal enteric type adenocarcinoma in a post-partum woman: report of a case with literature review

Teratomas are characterized by containing tissue from all three germinal cell layers. Occasionally, somatic type malignancies develop within a mature cystic teratoma. We reported here a rare case of enteric type adenocarcinoma, with associated dysplastic epithelial precursor lesion, arising within a mature cystic teratoma in the retroperitoneum of a 30-year-old woman status post vaginal delivery 11 weeks earlier. The mass is 17.5 cm and cystic. A polypoid mass component measuring 4.7x4.2x2.5 cm was located inside the cystic component. Microscopically, the majority of the specimen was a mature cystic teratoma with all three germinal cell layers. The polypoid mass component was an adenocarcinoma with an adjacent dysplastic epithelial precursor lesion. The adenocarcinoma was diffusely positive for CK20 and CDX-2, and focally positive for CD7, indicating enteric differentiation. A brief review of retroperitoneal mature cystic teratomas with associated somatic type malignancy was performed

Microstructure, Properties, and Numerical Simulation of Semi-Solid Aluminum Alloy under Planetary Stirring Process

In order to solve the problem of insufficient convective heat transfer of uniaxial stirred melt, the temperature field and shear rate of melt under planetary stirring were studied based on CFD simulation. The microstructure and properties of this technology were also experimentally studied. The results show that compared with the uniaxial stirring semi-solid technology, the convective heat transfer ability of aluminum alloy, semi-solid slurry in planetary stirring mode is stronger. In addition, its temperature field can be reduced to the semi-solid range faster and more evenly, which is conducive to a large number of nucleation and improves the nucleation rate. The temperature difference of the whole melt is small, so the preferred direction growth and uniform growth of dendrites are avoided, and the morphology is improved. Properly increasing the revolution and rotation speed of the stirring shaft can refine the grains of semi-solid aluminum alloy parts, improve the grain morphology, and improve the tensile strength. The planetary stirring semi-solid process is very suitable for rheological high-pressure casting