The role of monitoring interpretive rates, concordance between cytotechnologist and pathologist interpretations before sign-out, and turnaround time in gynecologic cytology quality assurance: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 1.

CONTEXT: The College of American Pathologists (CAP) conducted a national survey of gynecologic cytology quality assurance (QA) practices. Experts in gynecologic cytology were asked to join 5 working groups that studied the survey data on different aspects of QA. Evaluating the survey data and follow-up questions online, together with a review of pertinent literature, the working groups developed a series of preliminary statements on good laboratory practices in cytology QA. These were presented at a consensus conference and electronic voting occurred. OBJECTIVE: To evaluate a set of QA monitors in gynecologic cytology. Working group 1 evaluated (1) monitoring interpretive rate categories for Papanicolaou tests (Pap tests), (2) concordance of cytotechnologist and pathologist interpretations before sign-out, and (3) turnaround time for Pap tests. DATA SOURCES: The statements are based on a survey of gynecologic cytology QA practice patterns and of opinions from working group members and consensus conference attendees. CONCLUSIONS: The outcomes of this process demonstrate the current state of practice patterns in gynecologic cytology QA. Monitoring interpretive rates for all Bethesda System categories is potentially useful, and it is most useful to monitor interpretive rates for cytotechnologists individually and in comparison to the entire laboratory. Laboratories need to determine what level of discrepancy between cytotechnologist and pathologist interpretations of Pap tests is important to track. Laboratories should consider formalizing procedures and policies to adjudicate such discrepant interpretations. Turnaround time should be monitored in gynecologic cytology, but individual laboratories should determine how to measure and use turnaround time internally.

Evaluating the significance of location of lymph node metastasis and extranodal disease in women with stage IIIC endometrial cancer.

OBJECTIVE: To determine the prognostic significance of location of lymph node metastasis and extranodal disease for women with stage IIIC endometrial cancer. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Statistical analysis used Chi-square test, Kaplan-Meier method, and Cox proportional hazards model. RESULTS: A total of 2559 women were identified; 1453 stage IIIC1, and with 906 stage IIIC2 tumors. Compared to stage IIIC1; more stage IIIC2 patients demonstrated high-risk factors such as grade III disease (p<0.001), unfavorable histologic types (p=0.01), concurrent disease at other extrauterine sites (p<0.001), and greater than two positive lymph nodes (p<0.001). While the 5-year disease specific survival was comparable (p>0.05) among node positive patients found to have positive peritoneal cytology (44.0%), adnexal/serosal metastasis (42.9%), and vaginal/parametrial involvement (41.8%); it differed individually in all three categories from those with nodal metastasis alone (67.0%, p<0.001). Among women with extranodal disease, the location of nodal metastasis had no effect on survival (HR=0.92; 95% CI, 0.74-1.14). For women with node only stage IIIC tumors, those patients with positive para-aortic nodes were more likely to die from their tumors (HR=1.40; 95% CI, 1.12-1.75). CONCLUSION(S): Location of lymph node metastasis is prognostic in patients with nodal disease alone, and not in those with extranodal disease. Extranodal disease is associated with a poor prognosis and should be regarded in conjunction with location of lymph node metastasis for risk-stratification in stage IIIC endometrial cancer.

Comparison of ThinPrep preparations to other preparation types in gastrointestinal cytology: observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT: Differences in participant responses for ThinPrep (TP) and non-ThinPrep (NTP) preparations for gastrointestinal cytology challenges, which circulated in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC), may help to identify performance variations between preparation types. OBJECTIVE: To compare the performance of TP-prepared slides of gastrointestinal exfoliative cytology specimens to that of NTP preparations in the CAP NGC program. DESIGN: Participant responses between 2000 and 2007 were evaluated for esophageal wash/brush, gastric wash/brush, and biliary tract brush specimens with a reference diagnosis of adenocarcinoma, squamous cell carcinoma, carcinoid, or spindle cell neoplasm. ThinPrep challenges were compared with NTP preparations (conventional smears, cytospins) for discordant responses. RESULTS: In all, 6023 pathologist responses and 3825 cytotechnologist responses were reviewed. Non-ThinPrep preparations comprised 93% (n = 11 588) of the challenges, while 7% (n = 912) were TP material. A match for a "positive/suspicious" diagnosis was seen in 88.5% of NTP and 95.9% of TP preparations (P < .001). These results were statistically significant when the specific reference diagnosis was adenocarcinoma (P < .001). Overall performance of cytotechnologists was not different from that of pathologists (89.2% versus 89.0%; P = .75). Cytotechnologists had better performance for detecting squamous cell carcinoma (96.3% versus 92.6%; P < .001), while pathologists had better performance for detecting spindle cell neoplasm (79.7% versus 42.9%; P < .001). CONCLUSIONS: ThinPrep preparations performed significantly better than NTP preparations in gastrointestinal cytology specimens circulated in an interlaboratory comparison program. Performance varied by reference interpretation, with the best performance for the interpretation of adenocarcinoma. Cytotechnologists and pathologists performed at the same level overall, but with differences for the diagnosis of spindle cell neoplasm and squamous carcinoma.

Do liquid-based preparations of urinary cytology perform differently than classically prepared cases? Observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT: The cytomorphology of liquid-based preparations in urine cytology is different than classic slide preparations. OBJECTIVES: To compare the performance of liquid-based preparation specimens to classically prepared urine specimens with a malignant diagnosis in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. DESIGN: Participant responses between 2000 and 2007 for urine specimens with a reference diagnosis of high-grade urothelial carcinoma/carcinoma in situ/dysplasia (HGUCA), squamous cell carcinoma, or adenocarcinoma were evaluated. ThinPrep and SurePath challenges were compared with classic preparations (smears, cytospins) for discordant responses. RESULTS: There were 18 288 pathologist, 11 957 cytotechnologist, and 8086 "laboratory" responses available. Classic preparations comprised 90% (n = 34 551) of urine challenges; 9% (n = 3295) were ThinPrep and 1% (n = 485) were SurePath. Concordance to the general category of "positive-malignant" was seen in 92% of classic preparations, 96.5% of ThinPrep, and 94.6% of SurePath challenges (P < .001). These results were statistically different for the exact reference interpretation of HGUCA (P < .001) but not for adenocarcinoma (P = .22). Cytotechnologists demonstrate statistically better performance for the general category of "positive-malignant" compared with pathologists for all urinary slide types and for the exact reference interpretation of HGUCA (94% versus 91.1%; P < .001) but not adenocarcinoma (96.3% versus 95.8%; P = .77) or squamous cell carcinoma (93.6% versus 87.7%; P = .07). CONCLUSIONS: Liquid-based preparations performed significantly better in urinary cytology challenges when evaluating malignant categories in the College of American Pathologists interlaboratory comparison program. The liquid-based preparation challenges also performed better for the exact reference interpretation of HGUCA, but no difference was observed for adenocarcinoma challenges. Cytotechnologists perform better than pathologists for all slide types, as well as those demonstrating HGUCA. These results suggest that liquid-based preparations facilitate a more accurate diagnosis than conventional preparations.

The value of monitoring human papillomavirus DNA results for Papanicolaou tests diagnosed as atypical squamous cells of undetermined significance: a College of American Pathologists Q-Probes study of 68 institutions.

CONTEXT: Papanicolaou (Pap) tests are often diagnosed as atypical squamous cells of undetermined significance (ASC-US). Human papillomavirus (HPV) DNA testing has been proposed as a quality metric for this diagnosis. OBJECTIVE: To measure the frequency of HPV positivity in Pap tests diagnosed as ASC-US and to examine laboratory variables that are associated with institutional deviation from the mean percent of HPV positivity. DESIGN: As part of a College of American Pathologist Q-Probes program, 68 participating laboratories retrospectively identified approximately 50 consecutive ASC-US Pap tests that had HPV testing results. RESULTS: The mean percentage of HPV positivity for ASC-US was 43.74% among institutions surveyed, but it had a broad distribution, with an SD of 17.77%. Associations were found for lower difference of the institutional mean from the surveyed interinstitutional mean percentage of positive HPV with (1) higher numbers of Pap tests in the past year that had HPV testing, (2) in-house HPV testing, and (3) teaching hospitals. All 3 factors correlated with a larger volume of Pap tests per institution. An association was found between patient age and the probability of a positive HPV result, indicating a dependence upon prevalence of HPV. CONCLUSIONS: Larger volumes of Pap tests may offer an opportunity to gain greater comfort in interpreting Pap tests. While there is significant variability in interinstitutional HPV-positive rates in ASC-US Pap tests, monitoring the HPV-positive rate in ASC-US Pap tests is a valuable broad measure of quality. Performance beyond 2 SDs of the mean should prompt reassessment of diagnostic criteria used in the evaluation of Pap tests and/or investigation of the prevalence of HPV positivity in the population from which the Pap tests are obtained.

Interobserver variability in the fine needle aspiration biopsy diagnosis of follicular lesions of the thyroid gland.

OBJECTIVE: To study the degree of interobserver variability in the interpretation of fine needle aspiration (FNA) biopsies of the thyroid, specifically in the categorization of follicular lesions (FLs), and to examine the accuracy of FNA diagnosis of FLs with surgical follow-up. STUDY DESIGN: Fifty cases were chosen with surgical follow-up and a cytologic diagnosis of either FL (21) or follicular neoplasms (29). Representative slides were selected for each case and circulated to 4 pathologists for review. Interobserver variability was assessed using pairwise K statistics. Accuracy of the cytologic diagnoses in predicting a nonneoplastic or neoplastic outcome was determined by measuring sensitivity and specificity. Likelihood ratios and receiver operator characteristic curves were calculated for each reviewer. RESULTS: Interobserver agreement between the 4 pathologists was fair to substantial (K scores, 0.199-0.617). The accuracy of the 4 pathologists' cytologic diagnoses in predicting the surgical outcome was 77-90% for follicular neoplasms and 53-74% for nonneoplastic diagnoses. CONCLUSION: FLs present diagnostic difficulties as to cytologic categorization. A wide range of interobserver agreement was found in this study of 4 pathologists from the same institution. Some pathologists make greater use of intermediate categories, such as FL, favor nonneoplastic, or FL, favor neoplastic, whereas others show more definitive categorization into benign and neoplastic groups.

Fine needle aspiration biopsy of vertebral lesions.

OBJECTIVE: To evaluate the accuracy of fine needle aspiration biopsy (FNAB) in the diagnosis of vertebral lesions. STUDY DESIGN: Eighty-nine FNAB cases of vertebral lesions from January 1996 to December 2001 were retrieved from the Allegheny General Hospital laboratory information system. The cases were reviewed and correlated with clinical findings, including previous clinical history, primary site of malignancy and final pathologic diagnosis. RESULTS: ENAB diagnoses were malignant in 43 cases, benign in 35, suspicious in 1, unsatisfactory in 7 and false negative in 3. Previous clinical history included malignancy (37 patients), osteomyelitis and systemic disease (11), and nonspecific or no history (41). In 34 cases (38.2%) both aspirates and core biopsies were available, and the diagnoses correlated in 29/34 cases (85%). Surgical or core biopsies in the unsatisfactory/suspicious group showed malignancy in 4 cases (50%). The sensitivity of FNAB of vertebral lesions was 96%, specificity 100%, positive predictive value 100% and negative predictive value 92%, with no false positive cases. CONCLUSION: FNAB of vertebral lesions is an effective, sensitive and specific procedure in the diagnostic workup of a patient with or without a prior history of malignancy. Surgical pathology examination, including core biopsies of unsatisfactory or suspicious lesions, can further improve the diagnostic yield.

Role of cytology in the diagnosis of Barrett's esophagus and associated neoplasia.

We studied 327 consecutive paired esophageal biopsies and brushing specimens obtained during the same endoscopic session to evaluate the role of cytology for the diagnosis of Barrett's esophagus (BE) and/or surveillance for associated dysplasia. A diagnosis of BE was based on the cytologic presence of goblet cells. Cases were reviewed and categorized into: 1) benign esophageal lesions (125 cases), with 48 cases of Candida (32 cases diagnosed by both techniques and 16 diagnosed only by cytology), 3 cases of herpes simplex with only 1 case diagnosed by cytology, and 74 cases of inflammation and/or repair; 2) benign BE (141 cases), with 74 cases (52%) diagnosed by both techniques, 11 cases by cytology only (8%), and 56 cases (40%) by histology only; 3) low-grade dysplasia (LGD, 30 cases), with 5 cases (17%) diagnosed with both specimens, one case (3%) by cytology only, and 24 cases (80%) by histology only; 4) high-grade dysplasia (HGD, 10 cases), with 8 cases (80%) diagnosed with both specimens, 1 case (10%) by cytology, and 1 case (10%) by histology; and 5) carcinomas (23 cases), with 20 cases (87%) diagnosed with both specimens, 2 cases (9%) by cytology only, and 1 case (4%) by histology only. Our results support the high degree of diagnostic accuracy of cytology for the diagnosis of Barrett's-associated HGD and/or carcinoma, and moderate sensitivity for BE.

Cytohistologic discrepancies: a means to improve pathology practice and patient outcomes.

The use of cytohistologic discrepancies to investigate and reduce error seldom is studied. All gynecologic discrepancies (n = 283; 0.87% and 7.37% of all cytologic and histologic cases, respectively) and nongynecologic discrepancies (n = 146; 2.26% and 0.44% of all cytologic and histologic cases, respectively) for 26 months were classified as sampling or interpretive. Specimen type and pathologist discrepancy percentages, effect of discrepancies on patient outcome, and interobserver agreement of discrepancies were evaluated. Discrepancies were interpretive in 67% and 34% of gynecologic and nongynecologic cases, respectively. Statistically significant associations were seen between individual pathologist and discrepancy percentages. Breast (1.2%) and bronchial (0.8%) cytologic diagnoses had the highest discrepancy percentages. The kappa scores ranged from 0.02 to 0.45 for pairwise agreement of discrepant cases. Of nongynecologic interpretive discrepancies available for review, 63% (27/43) and 14% (6/43) were of no or minor clinical significance, respectively. Cytohistologic correlation is a useful tool to monitor performance and to identify specimen types prone to error.

Atypical squamous metaplasia of seromas in breast needle aspirates from irradiated lumpectomy sites: a potential pitfall for false-positive diagnoses of carcinoma.

The presence of squamous metaplasic cells is an uncommon finding in fine-needle aspiration (FNA) biopsies of the breast. We report that FNA smears containing atypical squamous metaplastic cells derived from the lining of seroma-type cavities following lumpectomy and irradiation in patients with breast cancer can be a potential pitfall for a false-positive diagnosis of recurrent malignancy. Four fine-needle breast aspirates from two adult patients with previous histories of invasive breast carcinoma were retrieved. One specimen was from a 56-yr-old female, while the remaining three FNAs aspirates were from a 75-yr-old female. Both patients presented with indurated cystic lesions arising at irradiated lumpectomy sites. The cytospins from the 56-yr-old patient showed markedly atypical cells having enlarged, degenerating, hyperchromatic nuclei and surrounding dense cytoplasm with sharp borders that were suspicious for carcinoma. A mastectomy revealed irradiation changes and atypical squamous metaplastic cells lining a cystic cavity consistent with a seroma, but there was no evidence of residual cancer. After three aspirations yielded "atypical" diagnoses, the second patient underwent core needle biopsies that also revealed changes consistent with a seroma cavity lined by atypical squamous metaplastic cells. We believe this is the first report of squamous metaplasia occurring in a seroma cavity following lumpectomy and irradiation of the breast. The squamous metaplastic cells in aspirates of these cystic lesions may display significant cellular atypia that can potentially result in a false-positive diagnosis of malignancy.