Ann T. Moriarty

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age‐appropriate screening strategies, including the use of cytology and high‐risk human papillomavirus (HPV) testing, follow‐up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.

American cancer society, american society for colposcopy and cervical pathology, and american society for clinical pathology screening guidelines for the prevention and early detection of cervical cancer

Abstract An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections.

Etiology of pure tricuspid regurgitation based on anular circumference and leaflet area: Analysis of 45 necropsy patients with clinical and morphologic evidence of pure tricuspid regurgitation

Despite recent renewed interest in the detection of tricuspid valve regurgitation by echocardiographic and Doppler techniques, little morphologic information is available on dysfunctioning tricuspid valves. This report describes 45 necropsy patients with clinical and morphologic evidence of pure (no element of stenosis) tricuspid regurgitation and provides morphometric observations (anular circumference, leaflet area) of the tricuspid valve useful in determining the etiology of pure tricuspid regurgitation. Of 45 patients, 24 (53%) had pure tricuspid regurgitation resulting from an anatomically abnormal valve (prolapse in 7, papillary muscle dysfunction in 6, rheumatic disease in 5, Ebsteins anomaly in 3, infective endocarditis in 2, carcinoid tumor in 1), and 21 (47%) had an anatomically normal valve with systolic pulmonary artery hypertension (cor pulmonale in 12, mitral stenosis in 9). Anular circumference was dilated (greater than 12 cm) in patients with various causes of pulmonary hypertension, floppy valve and Ebsteins tricuspid anomaly. Leaflet area was increased in floppy valve and Ebsteins anomaly. Of the 45 patients, 24 had pulmonary systolic artery pressure measurements available for correlation with tricuspid valve morphology. Pulmonary artery pressures accurately predicted morphologically normal from abnormal valves in 16 patients (89%). Morphologic overlap occurred in six patients with pulmonary pressures of 41 to 54 mm Hg. Of these six, the additional knowledge of normal or dilated anular circumference correctly separated valves with normal and abnormal leaflets.

Practices of participants in the college of american pathologists interlaboratory comparison program in cervicovaginal cytology, 2006.

CONTEXT Liquid-based preparations (LBPs) and human papillomavirus testing have led to changes in cervical cytology practices. The College of American Pathologists attempts to track practice patterns using a supplemental questionnaire, which allows laboratories to report diagnostic practices. OBJECTIVE To analyze the 2006 reporting practices and to compare the results with the 2003 survey data. DESIGN Questionnaire was mailed to 1621 laboratories. Participants included laboratories enrolled in the 2006 College of American Pathologists Gynecologic Proficiency Testing Program or the educational Interlaboratory Comparison Program in Gynecologic Cytology. RESULTS Of the 679 responding laboratories (response rate, 42%), most (97.8%; n = 664) had implemented the Bethesda 2001 terminology. The median rate for all preparations with low-grade squamous intraepithelial lesions was 2.5% (2.9% for LBPs) compared with a 2003 median rate of 2.1%; the increase was confined to LBPs. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little. High-grade squamous intraepithelial lesions and unsatisfactory rates varied at statistically significant levels between types of LBPs. Most atypical squamous cell cases were subclassified as undetermined significance (median, 4.3%). The median ratio of atypical squamous cells to squamous intraepithelial lesions and carcinomas for all specimen types combined was 1.5, similar to the 2003 median ratio of 1.4. The median rates for findings of squamous cell abnormalities for 2006 were significantly higher for LBPs than for conventional smears. CONCLUSIONS Most responding laboratories have implemented the Bethesda 2001 terminology. There is an increase in LBP low-grade squamous intraepithelial lesion rates when compared with 2003 data. Liquid-based preparations have higher median squamous intraepithelial lesion and atypical squamous cell rates.

Hodgkin's disease variant of Richter's syndrome : Report of a case with diagnosis by fine needle biopsy

BACKGROUND Chronic lymphocytic leukemia (CLL) with transformation into large cell lymphoma (Richters syndrome) is a well-documented phenomenon. Only rarely does CLL terminate in Hodgkins disease (HD) as Richters syndrome. Reports of Hodgkins variant of Richters syndrome proven by histologic and immunohistologic evaluation have been published, but no cytologic reports of this entity exist. Distinguishing between large cell lymphoma and HD as variants of Richters syndrome is essential because of recent reports of improved prognosis in HD. CASE We report a case of a 65-year-old male previously diagnosed with CLL who subsequently developed fever, fatigue, an intraabdominal mass and enlarged periaortic lymph nodes. Fine needle biopsy (FNB) and immunophenotyping by flow cytometry of the mass revealed cytologic and immunophenotypical cells of CLL admixed with binucleate and multinucleate cells with prominant eosinophilic nucleoli consistent with Reed-Sternberg cells. CONCLUSION This is the first reported case of HD variant of Richters syndrome diagnosed by FNB. As FNB becomes more common in the follow-up of lymphoreticular diseases, cytologists should be aware of this unusual HD variant of Richters syndrome.

Endometrial Cells in Cervical Cytology: Review of Cytological Features and Clinical Assessment

Abstract: The 2001 Bethesda System for Reporting Cervical Cytology recommends reporting benign exfoliated endometrial cells in women age 40 and older, and a review of the literature supports this recommendation. Stromal cells and histiocytes do not need to be reported. The effect of hormonal therapy on endometrial shedding is reviewed. Clinical information should be provided to the laboratory so that appropriate educational notes can be appended to the cytology report. Benign endometrial cells in premenopausal women in the first half of the cycle are not associated with significant pathology and such women do not need additional evaluation. Significant pathology is also unlikely in the second half of the cycle and evaluation may not be required unless clinically indicated. Initial evaluation of other women with benign endometrial cells may include either endometrial sampling or transvaginal ultrasound. Atypical endometrial cells are associated with a higher rate of significant pathology and should lead to additional evaluation. Additional prospective studies on the management of patients with endometrial cells on Pap tests are needed.

Human Papillomavirus Testing and Reporting Rates: Practices of Participants in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology in 2006

CONTEXT Oncogenic, high-risk human papillomavirus (HR-HPV) testing is used to evaluate women who are older than 20 years with atypical squamous cells of undetermined significance (ASC-US) and in conjunction with a screening Papanicolaou test in women older than 30 years. OBJECTIVES To evaluate the 2006 laboratory practice data from laboratories incorporating human papillomavirus (HPV) testing with the Papanicolaou test. DESIGN To use the College of American Pathologists (CAP) Supplemental Questionnaire Survey for 2006 to determine laboratory practices of participants in the CAP Interlaboratory Comparison Program in Cervicovaginal Cytology. RESULTS A total of 679 laboratories responded to the questionnaire. Most (73%) refer HPV testing to reference laboratories. Nine percent perform HPV testing in cytology. Forty-five percent offer low-risk HPV (LR-HPV) testing. The most common reflex is ASC-US, although HR-HPV is also offered with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or any other Papanicolaou test result. Digene Hybrid Capture II is the most common method. Human papilloma virus median test volumes are 55 monthly. Frequency distributions of HPV test volumes are significantly different from those found in 2003. Laboratories performing in-house testing reported significantly higher monthly HPV volumes (P < .001). Median rates for HR-HPV positivity are 36.6% for ASC-US, 50.0% for atypical squamous cells, cannot exclude HSIL (ASC-H), and 4% for women 30 years of age and older in conjunction with a screening Papanicolaou test. CONCLUSIONS Reference HPV testing remains the most common pattern. The most common reflex indication is for ASC-US, but HPV testing is modified locally to include a variety of scenarios. LR-HPV testing is commonly offered despite its lack of clinical significance. These data form a baseline for ongoing monitoring of HPV testing practice trends.

Prior high-risk human papillomavirus testing and papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: Results of a retrospective multicenter study

CONTEXT Persistent high-risk human papillomavirus (hrHPV) infection is essential for the development of cervical cancer and its precursor lesions. High-risk HPV testing has a higher sensitivity than cytology does for detecting cervical epithelial lesions. However, a large study from a single institution showed 31% of patients with invasive cervical cancer had negative baseline hrHPV testing within 5 years preceding the diagnosis. OBJECTIVE To investigate the limitation of hrHPV testing in detecting invasive cervical cancer. DESIGN Cases from 2012 with a histologic diagnosis of invasive cervical carcinoma were retrieved from multiple institutions. From those records, prior hrHPV testing and Papanicolaou test results in the 5 years before the cancer diagnosis were recorded. RESULTS Seventy patients with cervical carcinoma were included in the study. Negative HPV test result rates were 9% (5 of 53), 23% (6 of 26), and 25% (2 of 8) during the periods of less than 1 year, 1 to 3 years, and 3 to 5 years before the histologic diagnoses, respectively. Negative Papanicolaou testing results in the same time intervals were 3.4% (2 of 59), 33% (10 of 30), and 40% (6 of 15). Although the HPV(-) rate seemed to be different among different HPV test methods, no statistical significance was detected because of small sample size. Negative hrHPV rates in patients with adenocarcinoma were similar to those in patients with squamous cell carcinoma. CONCLUSIONS These data expose limitations for the potential use of primary HPV testing. In addition, current screening guidelines recommending cotesting at 5-year intervals should be evaluated further with additional historic data collection because there are women with negative results for both Papanicolaou tests and hrHPV testing within the period of 3 to 5 years before an invasive carcinoma diagnosis.

The Tahoe Study: bias in the interpretation of Papanicolaou test results when human papillomavirus status is known

CONTEXT Knowledge of human papillomavirus (HPV) status is expected to bias the morphologic evaluation of Papanicolaou (Pap) test results. OBJECTIVE To characterize Pap test result interpretive bias when the HPV status is known at the microscopic evaluation. DESIGN Forty HPV-positive liquid-based Pap test results initially interpreted as negative for squamous intraepithelial lesion or malignancy were selected from a quality assurance program, separated into 2 groups of 20 slides each, and circulated in 2 groups to 22 members of the College of American Pathologists Cytopathology Committee. Each member reviewed each case and indicated whether the result was negative for squamous intraepithelial lesion or malignancy or was an epithelial cell abnormality (ECA). The participants assessed the severity of ECAs using the Bethesda System. The participants were not informed of the HPV status in the initial review round. Each group of 20 slides was then distributed to the opposite group (to avoid slide recall), and the participants were informed that all slides were from patients who were high-risk HPV positive. Differences in the responses between groups were analyzed by χ(2) test and Cochran-Mantel-Haenszel test at the .05 significance level. RESULTS Without knowledge of the HPV status, slides were more often categorized as negative for squamous intraepithelial lesion or malignancy and less likely identified as an ECA (P < .001). There was an increase across all categories of ECAs in the biased responses compared with the unbiased responses (P = .002). CONCLUSIONS Knowledge of positive HPV status biases morphologic Pap test result interpretation. If the HPV status is positive, observers are more likely to report a Pap test result as abnormal across all categories of ECAs.