Establishing an Anal Neoplasia Screening Service for a Unique HIV Positive Patient Population in a Small City: Lessons Learned

Mortality from human papillomavirus (HPV) mediated squamous carcinoma of the uterine cervix has dramatically decreased in recent decades as a result of broad scale population screening for early detection of cervical cancer precursors. Concomitantly, deaths associated with HPV related carcinomas of the anus have oppositely trended upward. At this time, there are no national guidelines for anal screening. We herein report our experience with establishing an anal cytology screening program for HIV infected patients in a small city. The HIV positive population studied is unique in that 75% of patients had undetectable viral loads by PCR with average CD4+ cell/uL counts of 550. In addition 40% are adult females. 45% of patients in this relatively healthy HIV+ population were discovered to have atypical squamous cells or worse on entry into screening, and 20% of patients were ultimately shown on high resolution anoscopic biopsy histology to harbor high grade squamous intraepithelial lesions (AIN 2/3). Meaningful small scale anal cytology screening programs are possible with clinical and anoscopic collaborations. It seems possible that this simple and inexpensive test may prevent morbidity and mortality from HPV mediated anal carcinoma

Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Background: Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).Methods: In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.Results: Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm3, CI = 0.40-0.97).Conclusions: In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women.</p

Ursinus College Alumni Journal, August 1963

The President writes • The uses and limitations of words • Commencement 1963 • 3,032 pledge $509,081; 2,809 contribute$192,568 • Loyalty Fund committee reorganized • Joseph J. Lynch, college steward • A description of the new dining hall • Chemistry changes • NSF grants for bio profs • Teaching awards • Pilot project: Physics chemistry mathematics • The not-so-ugly American • Best track season in Ursinus history • Double your dollars • Things are looking up • Preliminary thoughts on wills • Reading, writing, and Mazurkiewicz • The augmented Roman alphabet • Edwin C. Myers, \u2764 and Frederic W. Yocum, Jr. \u2764 • Eugene J. Bradford, \u2736 • Robert A. Petersen, \u2760 • Sue Harman, \u2765 • Results of the 1963 Loyalty Fund campaign • The leaders • Contributors to the 1963 Loyalty Fund • Ursinus alumni at Methacton High School • Class notes • Weddings • Births • Necrology • Our role as alumnihttps://digitalcommons.ursinus.edu/alumnijournal/1077/thumbnail.jp

Exploring constituency-level estimates for the 2017 British general election

Most opinion polls conducted during British general election campaigns report on each party’s estimated national vote share. Although of considerable interest, these data do not put the spotlight on the marginal seats, the constituencies targeted by the parties for intensive canvassing; these are where the contest for a majority in the House of Commons is won and lost. There have been some polls covering those constituencies as a whole, but very few of individual constituencies so there was very little reporting of the outcome for each party in those individual constituencies. That changed with the 2017 general election, when three analysts published estimates on the internet of each party’s vote share separately for each constituency and with those data predicted which party would win each seat. This paper explores the veracity of those estimates, finding that although in general terms they accurately represented the relative position of each constituency in the share of each party’s votes, nevertheless their estimates of which marginal seats would be won by each were not as accurate. The implications of such polls, especially as their predictive ability is improved, is discussed

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study)

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types

Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm(3), CI = 0.40-0.97).In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women

Ancillary alpha-methylacyl coa racemase immunocytochemistry in the diagnosis of adenocarcinoma of the prostate in urinary cytology: a case report

Alpha-methylacyl-coA racemase (AMACR) was recently shown to be a sensitive immunohistochemical marker for substantiating a diagnosis of adenocarcinoma of the prostate. Its applicability to exfoliative urinary cytology has not been investigated before. Case The patient was a 77-year-old male with a history of persistent intermittent hematuria who was evaluated with urine cytology. Cytopathologic studies were interpreted to demonstrate \u93atypical urothelial cells.\u94 The patient was evaluated with computed tomography, which demonstrated new left hydroureter and hydronephrosis. He underwent cystoscopy, which showed an abnormal left hemitrigone with the left ureteral orifice obscured by an infiltrative mass. This area was biopsied, and histologic studies of the tissue chips demonstrated underlying prostatic adenocarcinoma directly invading the urothelium. We used AMACR immunoreactivity on a retrospectively studied, catheterized urine slide to confirm the diagnosis. Conclusion: This case suggests that combined cytomorphology and immunocytochemisty for AMACR may allow an accurate identification of cells of prostatic adenocarcinoma when cytomorphologic studies or the clinical history raises the differential diagnosis of prostate cancer presenting with exfoliation of malignant cells into the urin

Small Cell Carcinoma of the Uterine Cervix in a Pregnant Patient Diagnosed with Liquid Based Cytology and Cell Block Immunocytochemistry

Definitive cytomorphologic diagnosis of small cell carcinoma of the uterine cervix is possible but can be challenging in routine cervicovaginal cancer screening specimens. Several small series of reported cases of cervical small cell carcinoma have shown this uncommon malignancy to represent fewer than 2% of all invasive cervical cancers. This tumor type is associated with poor prognosis and rapid disease progression and can develop to an advanced stage in the interval between screening visits. Only rare case reports of small cell carcinoma arising in gravid cervices are known. In the current case a 29-year-old, gravida 6, para 2, pregnant (10-week gestation) female presented with postcoital bleeding. A definitive diagnosis of small cell carcinoma of the cervix was made possible by liquid based Pap testing with ancillary cell block preparation allowing for immunocytochemical characterization of the lesional cell population

Desmoplastic Small Round Cell Tumor, a “Floating Island” Pattern in Pleural Fluid Cytology: A Case Report and Review of the Literature

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive sarcoma with characteristic clinical and pathologic features. It typically involves pelvic and abdominal organs of young male patients, and patients usually present at advanced stage with poor prognosis. A few reports are available describing the cytopathologic features of DSRCT in serous effusions, with the majority of published cases depicting undifferentiated small blue cells that need to be distinguished from other small blue cell tumors. We report an interesting case of DSRCT involving a pleural effusion with a “floating island” pattern that has been described in hepatocellular carcinoma, renal cell carcinoma, and adrenal cortical carcinoma. In our case, the epithelioid tumor cells form cohesive aggregates surrounded by a single layer of spindle cells, mimicking the “endothelial wrapping” in other tumors with “floating island” patterns. We demonstrate, by ancillary testing, that these peripheral spindle cells are tapered/flattened DSRCT cells, in contrast to endothelial wrapping cells, as seen in other tumors with this unique cytomorphology. To our knowledge, this is the first case report describing DSRCT showing a “floating island” pattern that needs to be differentiated from metastatic hepatocellular carcinoma, renal cell carcinoma, and adrenal cortical carcinoma in effusion cytology

cMYC expression in thyroid follicular cell-derived carcinomas: a role in thyroid tumorigenesis

Abstract Background cMYC regulates approximately 15% of human genes and is involved in up to 20% of all human cancers. Reports discussing cMYC protein expression in thyroid carcinomas are limited, with controversies pertaining to cMYC expression patterns noted in the literature. The aims of the current study were to clarify patterns and intensities of cMYC expression in follicular cell-derived thyroid carcinomas across a spectrum of cancer morphologies and disease aggressivities, to correlate cMYC with BRAFV600E expression, and to evaluate the potential role of cMYC in progression of well-differentiated thyroid carcinomas into less well-differentiated carcinomas. Methods Immunohistochemical studies using specific monoclonal antibodies for cMYC and BRAFV600E were performed on tissue microarrays built from follicular cell-derived thyroid carcinomas (25 papillary, 24 follicular, 24 oncocytic variant of follicular, and 21 undifferentiated). In addition, cMYC IHC testing was also performed on whole tissue tumor sections from a subset of patients. Nodular hyperplasia cases were used as non-neoplastic controls. Appropriate positive and negative controls were included. Results cMYC was expressed almost exclusively in a nuclear fashion in both thyroid carcinomas and nodular hyperplasias. cMYC expression was weakly positive in both nodular hyperplasias and well-differentiated carcinomas. The majority of undifferentiated carcinomas (UDCs) showed strong nuclear cMYC positivity. PTC cases that were positive for cMYC (6/25) harbored the BRAF V600E mutation. A correlation was confirmed between cMYC intensity and tumor size in UDCs. UDC cases that developed out of well-differentiated thyroid carcinomas showed frank overexpression of cMYC in the undifferentiated tumor components. Conclusions Our study suggests that nuclear overexpression of cMYC correlates with tumorigenesis / dedifferentiation in follicular cell derived thyroid carcinomas, a concept that has not been shown before on whole tissue sections