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JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease in immunocompromised patients. Inherited and acquired T cell deficiencies are associated with PML. The incidence of PML is increasing with the introduction of new immunomodulatory agents, several of which target T cells or B cells. PML patients often carry mutations in the JCPyV VP1 capsid protein, which confer resistance to neutralizing VP1 antibodies (Ab). Polyomaviruses (PyV) are tightly species-specific; the absence of tractable animal models has handicapped understanding PyV pathogenesis. Using mouse polyomavirus (MuPyV), we found that T cell deficiency during persistent infection, in the setting of monospecific VP1 Ab, was required for outgrowth of VP1 Ab-escape viral variants. CD4 T cells were primarily responsible for limiting polyomavirus infection in the kidney, a major reservoir of persistent infection by both JCPyV and MuPyV, and checking emergence of these mutant viruses. T cells also provided a second line of defense by controlling the outgrowth of VP1 mutant viruses that evaded Ab neutralization. A virus with two capsid mutations, one conferring Ab-escape yet impaired infectivity and a second compensatory mutation, yielded a highly neurovirulent variant. These findings link T cell deficiency and evolution of Ab-escape polyomavirus VP1 variants with neuropathogenicity.

The Bethesda system for reporting thyroid cytopathology was proposed to provide a clinically relevant framework for interpretations to improve interobserver agreement. Limited data is available regarding the level of interobserver agreement between groups of cytotechnologists (CTs) and cytopathologists (CPs) examining the same thyroid fine needle aspirate (FNA) samples.Retrospective review of 1,229 thyroid FNAs from 976 patients between 03/2010 and 08/2012 was performed. FNAs received preliminary evaluation by a CT followed by final interpretation by a CP. We calculated Cohen's Kappa coefficient to measure agreement between CTs and CPs, and analyzed levels of discrepancy using delta analysis.Overall Kappa between CTs and CPs was 0.79 (95%CI: 0.76-0.83). Kappa values were higher for the nondiagnostic (0.89), benign (0.83), and malignant (0.91) categories than for other categories. Overall Kappa did not show a trend over time, and inversely correlated with the percentage of intermediate grade lesions (coefficient of -0.8; P0.01). CTs overcalled more cases (n = 71) than undercalled (n = 29) (P0.001), as compared to CPs, with a Δ1 ratio of 2.2 and Δ2 ratio of 3.5. Most two-level discrepancies were related to follicular lesions (19/21) (P = 0.0002). Differences in sample adequacy assessment occurred in 2% of cases.Overall, there was a high level of interpretative agreement between CTs and CPs, which remained stable over time, including judgments regarding specimen adequacy. Agreement was most robust for the benign and malignant categories. Our data supports the current practice of allowing CTs to perform on-site adequacy evaluation of thyroid FNAs.

Introduction For cytologic specimens, the vast majority of immunocytochemical studies (ICC) are performed on non-gynecologic specimens for diagnostic purposes, and they can be performed on unstained or previously stained direct smears. Although the ThinPrep® processor (TPP) has been approved for the preparation of non-gynecologic specimens, there is scant literature describing the utility of ICC methodology on cytology specimens fixed and processed by this method. Materials and Methods Forty-one fresh specimens were obtained from the surgical gross room and aspirated or scraped to collect cells for thin layer (TL) and direct smears (DS). Specimens included a variety of neoplastic and nonneoplastic samples that were either Papanicolaou (P) stained or unstained (US). One group of US TL slides was subjected to antigen retrieval (AR). Staining was graded semiquantitatively. Each sample acted as its own control. Antibodies (abs) included: CAM5.2, AE1/3, K903, vimentin, MSA, desmin, s-100, HMB45, PSA, PAP, chromogranin, NSE, insulin, synaptophysin, pCEA, mCEA, mCEAD14, LCA, L26, UCHL-1, OPD-4, thyroglobulin, GCDFP, ER/PR, laminin, collagen IV, PLAP, HCG, CD68, HAM56, and MAC387. Results Semiquantitative staining overall results comparisons: TLP 〉 DSP TLP 〈 DSP TLP = DSP TLUS &rang DSUS 11/25 (44%) 6/25 (24%) 8/25 (32%) 9/24 (38%) TLUS 〈 DSUS TLUS = DSUS 3/24 (12%) 12/24 (50%) TLP Vs. TLUS TLP 〉 TLUS TLP 〈 TLUS TLP = TLUS 8/41 (20%) 9/41 (22%) 24/41 (58%) There were five false-negative results, 2 with TL and 3 with DS, and 1 false-positive TL. Discussion Immunocytochemistry performed on the ThinPrep® Processor showed equal or greater intensity and distribution of proper staining when compared to direct smears with the following advantages: (1) cleaner background, easier to interpret; (2) less abs required in a smaller area; (3) IPX can be done on Papanicolaou-stained thin layer slides; (4) thin layer slides can be modified for multiple abs tests; (5) additional thin layer slides can be prepared for ICC bases on needs. No significant differences of immunostaining were seen when comparing thin layer Papanicolaou-stained and unstained slides. Antigen retrieval offered no advantage in this study. Diagn. Cytopathol. 1997;17:388–392. © 1997 Wiley-Liss, Inc.

An 8-mo-old female transgenic adenocarcinoma of the mouse prostate (C57BL/6-Tg(TRAMP)8247Ng/J) mouse presented with abdominal distention, lethargy, and serosanguineous vaginal discharge. A large primary renal tumor with metastases to lung and liver was present at necropsy. The tumor was composed of poorly differentiated and crowded epithelial cells forming ducts, acini, and cribriform patterns, with comedonecrosis and frequent bizarre mitoses. Immunohistochemistry revealed that neoplastic cells expressed nuclear SV40 T antigen, confirming aberrant expression of the transgene. In addition, cells were positive for pancytokeratin and negative for synaptophysin and estrogen and progesterone receptors. This report details the first transgene-induced tumor in a female TRAMP mouse.