Cystic nephroma (CN) and mixed epithelial and stromal tumor (MEST) are rare benign renal neoplasms that have overlapping clinical and morphologic features, including predominance in middle-aged women, variably cystic architecture, eosinophilic cells, and hobnail cells lining the cysts and ovarian-type stroma. The aim of this study was to analyze and compare the histologic features and immunohistochemical profile of these tumors. We studied 34 cases from 5 large academic institutions. Twenty tumors were diagnosed as CNs, 18 in women and 2 in men, their age ranged from 24 to 63 (mean 48; median 50) years. Fourteen tumors were diagnosed as MESTs, all in women, their age ranged from 26 to 84 (mean 52; median 51) years. Histologically, all tumors were well-circumscribed except for one MEST. The stromal/epithelial ratio was approximately 2.3 in MESTs versus 0.3 in CNs; cellular ovarian-type stroma composed 45% of the stroma in MESTs and 12% of the stroma of CNs. Stromal hyalinization was prominent in both. Five MESTs showed stromal luteinization. In the epithelial component, the relative amount of large cysts, medium to small cysts, and phyllodes-type glands was: 65%/25%/10% in CNs versus 25%/40%/35% in MESTs. The epithelial component ranged from flat to cuboidal to hobnail cells in both types of tumors. No significant atypia of either component was seen, although the epithelial cells showed reactive changes. Immunohistochemical stains for estrogen receptors and progesterone receptors showed 62% and 85% positivity in the stromal component of MESTs versus 19% and 40% in CNs. CD10 positivity was seen in 77% of MESTs versus 50% of CNs, calretinin was seen in 69% of MESTs versus 41% of CNs, and inhibin in 42% of MESTs versus 36% of CNs, although the staining was focal. Follow-up in both categories of tumors (mean 3.2 y, median 3 y for CNs and mean 2.5 y, median of 2 y for MESTs) showed no evidence of recurrence or metastases in keeping with their benign nature. This study highlights the remarkable similarity between CN and MEST in sex predilection, age distribution, and morphologic attributes of both the epithelial and stromal components and immunohistochemical profile albeit with variation in individual categories with higher prevalence of stromal to epithelial ratio, prominent ovarian stroma, smaller cysts with phyllodes glands pattern and stromal luteinization being more common in MEST; and large cysts, thin septae and low stromal to epithelial ratio in CN. The presence of ovarian-type stroma and müllerian related immunohistochemical markers raises the possibility that these tumors may originate from müllerian remnants misplaced during embryogenesis. On the basis of detailed morphologic analysis of this series of CN and MEST, we propose a unifying term of "renal epithelial and stromal tumor" (REST) to encompass the spectrum of findings observed in these tumors at least until new molecular studies can prove or disprove this challenging hypothesis.

Mucinous tubular and spindle cell carcinoma, a rare, recently described distinctive subtype of renal cell carcinoma, may have some morphologic similarities to the more common papillary renal cell carcinoma, particularly the basophilic (type 1) tumors with prominent solid growth pattern. Tumor circumscription, compact tubular architecture, focal papillations, mucin production and foam cells (features seen in both papillary renal cell carcinoma and mucinous tubular and spindle cell carcinoma), as well as spindle cell morphology, have resulted in some cases sent to us in consultation with a question of possible sarcomatoid papillary renal cell carcinoma. In this study, tissue microarrays with triplicate samples each from 27 mucinous tubular and spindle cell carcinomas and 20 papillary renal cell carcinomas were created to simulate experience in renal biopsy specimens. From immunohistochemistry (IHC) data, published in the contemporary literature, a panel consisting of alpha-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), epithelial membrane antigen (EMA), renal cell carcinoma marker (RCC Ma), CD10, high molecular weight cytokeratin (HMWK), and c-kit was designed to test its utility in differential diagnosis. The immunoreactivity in mucinous tubular and spindle cell carcinoma was AMACR 93%, CK7 81%, EMA 95%, RCC Ma 7%, CD10 15%, HMWK 15%, and c-kit 5% and in papillary renal cell carcinoma was AMACR 95%, CK7 65%, EMA 88%, RCC Ma 25%, CD10 80%, HWMK 15%, and c-kit 18%. This largest study to date on IHC of mucinous tubular and spindle cell carcinoma dispels the specificity of AMACR for papillary renal cell carcinoma among the RCC subtypes. The histogenesis of mucinous tubular and spindle cell carcinoma from the distal nephron continues to be debatable, as our study showed the expression of the proximal convoluted tubule-related marker AMACR among these tumors. Thus, in tumors with predominant compact tubular growth and focal papillary architectures, careful attention to the presence of a low-grade spindle cell population may be helpful in the distinction of mucinous tubular and spindle cell carcinoma, as the key immunohistochemical stains for papillary renal cell carcinoma are also expressed in this subtype of renal cell carcinoma.

In this study, we used imaging and proteomics to identify the presence of virus-associated cellular proteins that may play a role in respiratory syncytial virus (RSV) maturation. Fluorescence microscopy of virus-infected cells revealed the presence of virus-induced cytoplasmic inclusion bodies and mature virus particles, the latter appearing as virus filaments. In situ electron tomography suggested that the virus filaments were complex structures that were able to package multiple copies of the virus genome. The virus particles were purified, and the protein content was analyzed by one-dimensional nano-LC MS/ MS. In addition to all the major virus structural proteins, 25 cellular proteins were also detected, including proteins associated with the cortical actin network, energy pathways, and heat shock proteins (HSP70, HSC70, and HSP90). Representative actin-associated proteins, HSC70, and HSP90 were selected for further biological validation. The presence of ␤-actin, filamin-1, cofilin-1, HSC70, and HSP90 in the virus preparation was confirmed by immunoblotting using relevant antibodies. Immunofluorescence microscopy of infected cells stained with antibodies against relevant virus and cellular proteins confirmed the presence of these cellular proteins in the virus filaments and inclusion bodies. The relevance of HSP90 to virus infection was examined using the specific inhibitors 17-N-Allylamino-17-demethoxygeldanamycin. Although virus protein expression was largely unaffected by these drugs, we noted that the formation of virus particles was inhibited, and virus transmission was impaired, suggesting an important role for HSP90 in virus maturation. This study highlights the utility of proteomics in facilitating both our understanding of the role that cellular proteins play during RSV maturation and, by extrapolation, the identification of new potential targets for antiviral therapy. Molecular & Cellular Proteomics 9:1829 -1848, 2010. Respiratory syncytial virus (RSV)1 belongs to the paramyxovirus group of viruses, and it is the most important respiratory virus causing lower respiratory tract infection in young children and neonates. The mature RSV particle comprises a ribonucleoparticle (RNP) core formed by the interaction between the viral genomic RNA (vRNA), the nucleocapsid (N) protein (42 kDa), the phospho (P) protein (35 kDa), and the large (L) protein (250 kDa). The RNP core is visualized by electron microscopy as a strand of repeating N protein subunits that form a herringbone-like structure of ϳ10 -20 nm in diameter (1). Although the minimal functional polymerase activity requires an association between the N, P, and L proteins and the virus genome vRNA (2-4), additional viral proteins called the M2-1 protein (22 kDa), M2-2 protein, and M protein (28 kDa) regulate the activity of the polymerase (5-8). The virus is surrounded by a lipid envelope that is formed from the host cell during the budding process in which the three virus membrane proteins are inserted. The G protein (90 kDa) mediates attachment of...

Core needle biopsies of breast carcinomas provide diagnostic, prognostic, and predictive information before neoadjuvant therapy. Possible intratumoral heterogeneity of biomarker expression questions the validity of core needle biopsy interpretation in small biopsy specimens. Using tissue microarray (TMA) technology, we studied intratumoral heterogeneity of 7 immunomarkers. Five TMAs were constructed from 44 breast carcinomas and 5 normal breast tissues, each represented by 1-mm cores in triplicate from each of 3 foci. TMAs were immunostained for monoclonal estrogen receptor (ER), monoclonal progesterone receptor (PR), polyclonal human epidermal growth factor receptor 2 (HER2), monoclonal E-cadherin (E-cad), monoclonal epidermal growth factor receptor (EGFR), monoclonal p53, and monoclonal MIB-1. Expression was quantified visually by light microscopy and by image cytometry as intensity, percentage of cells positive, and score. Using intraclass correlation coefficient, heterogeneity in the expression of the immunomarkers within subjects was compared with the overall variance. Intratumoral heterogeneity was seen with 5 immunomarkers: ER, PR, HER2, p53, and MIB-1. E-cad and EGFR failed to show intratumoral heterogeneity. Intratumoral heterogeneity in ER, PR, HER2, p53, and MIB-1 indicates their problematic interpretation in small biopsy specimens as indicative of the status of the entire tumor. A negative result does not exclude the expression of these markers in the remainder of the tumor. E-cad (positive in ductal carcinomas) and EGFR lacked heterogeneity.

Digital Rocks Portal (DRP, https://www.digitalrocksportal.org) organizes and preserves imaged datasets and experimental measurements of porous materials in subsurface, and beyond, with the mission to connect them to simulation and analysis, as well as educate the research community. We have over 150 projects represented in more than 200 publications, and an active community that reuses the data, most recently in multiple machine learning applications for automating image analysis as well as the prediction of transport. Such automation is crucial for performing formation evaluation tasks in near-real time. We present benchmark datasets that have played a role in recent machine learning prediction successes in the field. We further discuss the vision for further research advances, educational materials, as well as growth and sustainability plan of this digital rock physics community resource. In particular, we are in the process of expanding into a broader repository of engineered porous materials, specifically those for energy storage and the portal will transition to Digital Porous Media (DPM) in near future.