Comparison of Tissue Yield Using Frictional Fabric Brush Versus Sharp Curettage For Endocervical Curettage.

OBJECTIVE: The aim of the study was to evaluate and compare the diagnostic yield of conventional endocervical curettage (ECC) with fabric-based ECC in a consistent physician group. MATERIALS AND METHODS: This is a retrospective case-control study of patients who underwent ECC both before and after introduction of a fabric-based ECC device. Histologic examination of curettings was categorized as satisfactory, limited, or inadequate. The Kruskall-Wallis test was used to compare proportions of gross descriptions and final diagnoses between groups. RESULTS: Between January 2010 and July 2011, 9234 ECCs were performed using conventional ECC technique. From September 2011 to October 2013, 774 ECCs were performed with the fabric-based ECC. Using the conventional ECC technique, 7809 (84.6%) of specimens were satisfactory, 1037 (11.2%) were limited, and 388 (4.2%) were inadequate and repeat biopsy was recommended. With fabric ECC, 705 (91.1%) of specimens were satisfactory, 64 (8.3%) were limited, and 5 (0.6%) were inadequate, and repeat biopsy was recommended. There were significantly fewer inadequate specimens with the fabric-based ECC (4.2% vs 0.6%, p < .001). CONCLUSIONS: Fabric-based ECC may significantly decrease inadequate and limited ECC specimens.

The College of American Pathologists' first 3 years' experience with high-risk human papillomavirus proficiency testing for cytology and other laboratories.

CONTEXT: The College of American Pathologists (CAP) Human Papillomavirus (High-Risk) Survey for Cytopathology and Other Laboratories (CHPV) meets the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) requirements for 5 proficiency testing challenges analyzed 3 times per year. This study reports laboratory performance for CHPV from 2008 through 2010. OBJECTIVE: To identify trends in proficiency testing performance for subscribers to the CAP CHPV. DESIGN: CHPV responses were evaluated by using a nonlinear mixed model (significance level of .05) with a 2-factor interaction term and repeated measures component, comparing year, media, method, and intended response. Media types included Digene transport, SurePath, ThinPrep media, or a mixture of media types. Proficiency testing challenges validated at 80% consensus. RESULTS: All challenges validated; 476 laboratories submitted 14 911 responses with 14 620 correct responses (98%). There were no differences between positive or negative challenges, or rate of correct responses; significant differences existed between media types by year and methods. Digene and ThinPrep media performed better than SurePath (P < .001; P = .03). There was a statistically significant difference between methods (P < .001); "other commercial kits," "other (noncommercial)" tests, and Third Wave performed more poorly than others. CONCLUSIONS: Laboratories performed well when testing for human papillomavirus in CHPV during a period of 3 years. All challenges performed to the 80% threshold. Significant differences were found between methods and media. The CAP CHPV survey provides useful information for laboratories choosing human papillomavirus testing methods.

Performance differences between conventional smears and liquid-based preparations of thyroid fine-needle aspiration samples: analysis of 47,076 responses in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology.

CONTEXT: Controversy exists about whether thyroid fine-needle aspirates (FNAs) should be processed with conventional smears or liquid-based preparations (LBPs). OBJECTIVE: To compare the performance of conventional smears to LBPs for thyroid FNA slides circulated in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. DESIGN: Participant responses for thyroid FNA slides were compared with the reference diagnosis at the level of 3 general diagnostic categories: negative, suspicious (which included only follicular and Hürthle cell neoplasm), and malignant. For specific reference diagnoses of benign/goiter and papillary thyroid carcinoma, the participants' specific diagnoses were analyzed and poorly performing slides were rereviewed. RESULTS: The 47, 076 thyroid FNA slide responses, between 2001 and 2009, included 44, 478 responses (94%) for conventional smears and 2598 responses (6%) for LBPs. For the general reference category negative, participant responses were discrepant in 14.9% of conventional smears compared with 5.9% for LBPs (P < .001). The specific reference diagnosis of benign/goiter was misdiagnosed as a follicular neoplasm in 7.8% of conventional smears, compared with 1.3% of LBP. For the general reference category of malignant, participant responses were discrepant in 7.3% of conventional smears compared with 14.7% of LBPs (P < .001). The specific reference diagnosis of papillary thyroid carcinoma was misdiagnosed as benign/goiter in 7.2% of LBPs, compared with 4.8% of conventional smears (p <.001). CONCLUSIONS: LBPs performed worse than conventional smears for cases with a reference diagnosis of papillary thyroid carcinoma. However, LBPs performed better than conventional smears for cases with a benign reference diagnosis. Specific features in thyroid FNAs that may improve the diagnostic accuracy of LBPs and conventional smears are described.

A retrospective review of UroVysion fish interpretations over 8.6 years: a major shift in the patient test population.

UroVysion FISH detects chromosomal aberrations associated with urothelial carcinoma. In our laboratory, UroVysion FISH was initially evaluated manually with a change to image-aided interpretation using the BioView Duet imaging system. This retrospective study examined diagnostic findings over an 8.6 year period, with 1,869 manual interpretations over 4.8 years and 3,936 image-aided interpretations over 3.8 years. Although the initial goal was to evaluate possible impacts of the imaging system on diagnostic interpretations, the most important finding was that the demographics of the test population changed significantly. Female specimens increased incrementally from an average of 29% compared to 43% of the samples during periods of manual interpretation versus image-aided interpretation, respectively. The shift may reflect a gradual increase in the percentage of low-risk hematuria patients being evaluated for initial diagnosis of bladder cancer, rather than bladder cancer recurrence. Interpretation rates, evaluated separately for males and females, changed significantly over the test period. Male interpretation results were negative (75.1 vs. 67%), positive (18.6 vs. 14.6%), unsatisfactory (5.0 vs. 16.9%), and equivocal (1.4 vs. 1.5%) during periods of manual versus image-aided interpretation, respectively (Fisher Exact Test P-value = <0.0001). For females, results were negative (86.1 vs. 79.3%), positive (9.2 vs. 11.1%), unsatisfactory (2.8 vs. 8.9%), and equivocal (1.8 vs. 0.7%) over the same periods (Fisher Exact Test P-value = <0.0001). Logistic regression analysis identified the change in test population as the variable with the greatest impact on observed interpretation rate changes.

Performance characteristics of mucinous (colloid) carcinoma of the breast in fine-needle aspirates: observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: Mucinous breast carcinoma has characteristic cytologic features, but few studies exist that analyze the reproducibility of this diagnosis. OBJECTIVE: To analyze participants' diagnosis of mucinous carcinoma in breast fine-needle aspiration (FNA) slides distributed in an educational interlaboratory peer comparison program. DESIGN: Participant responses for FNA slides with a reference diagnosis of mucinous carcinoma, distributed between 2001-2008 in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology, were evaluated for concordance with the general category and reference diagnosis of mucinous carcinoma. RESULTS: Of 8061 responses, 6353 (78.8%) were categorized as malignant; 775 (9.6%) as suspicious; and 933 (11.6%) as negative. The most frequent incorrect responses for the benign category included fibroadenoma (51.7%), nonspecified benign lesion (12%), fibrocystic changes (7.8%), and fat necrosis/granulomatosis/foreign body reaction (6.9%). Conventional Papanicolaou-stained preparations were reviewed for 58.7% (4732) of responses; of these, 39.4% (3177) were from modified Giemsa-stained smears and 1.9% (152) from ThinPrep slides. Papanicolaou-stained conventional smears had the lowest concordance (86.5%) when compared to modified Giemsa-stained smears (91.2%) and ThinPrep challenges (92.1%) (P < .001). Participants specifically diagnosed mucinous carcinoma 37.3% of the time, and modified Giemsa-stained challenges performed best (43.1%, P < .001). There was no significant difference between cytotechnologists' and pathologists' responses (87.9% versus 88.2%; P  =  .69). CONCLUSIONS: Mucinous carcinoma in FNA was not accurately identified in a glass slide interlaboratory comparison program. We observed better performance with modified Giemsa-stained and ThinPrep slides than with Papanicolaou-stained preparations. The most common response for the benign category of mucinous carcinoma was fibroadenoma. Increased awareness of the cytologic features of mucinous carcinoma may improve accuracy in breast FNA.

Allele-specific PCR with competitive probe blocking for sensitive and specific detection of BRAF V600E in thyroid fine-needle aspiration specimens.

OBJECTIVE: To detect BRAF V600E mutation in thyroid fine-needle aspiration (FNA) slides and needle rinses (NR). STUDY DESIGN: Tumor-enriched DNA was extracted from FNA smears, formalin-fixed paraffin-embedded (FFPE) sections, or NR specimens from 37 patients with confirmed papillary thyroid carcinoma or benign findings. An allele-specific primer selectively amplified the 1799 T>A BRAF mutation while simultaneously blocking amplification of wild-type (WT) BRAF with an unlabeled probe during PCR. Mutation detection was accomplished by melting analysis of the probe. RESULTS: Allele-specific/blocking probe PCR confirmed the BRAF mutation status for 20 of 24 paired FNA/FFPE samples previously tested by fluorescent probe real-time PCR. For the other 4 cases, the sensitive PCR method detected the BRAF mutation in all paired FNA/FFPE samples. Previously, the mutation had been detected in only the FFPE samples. The BRAF mutation was also detected in some NR specimens. CONCLUSION: Treatment of patients with thyroid nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a sensitive test that can detect low levels of BRAF V600E mutation in a WT background. We report increased detection of BRAF V600E in FNA specimens using allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%.

Gynecologic cytology proficiency testing failures: what have we learned?: observations from the college of american pathologists gynecologic cytology proficiency testing program.

CONTEXT: In 2006, the first gynecologic cytology proficiency tests were offered by the College of American Pathologists. Four years of data are now available using field-validated slides, including conventional and liquid-based Papanicolaou tests. OBJECTIVE: To characterize the pattern of error types that resulted in initial proficiency-test failure for cytotechnologists, primary screening pathologists, and secondary pathologists (those whose slides are prescreened by cytotechnologists). DESIGN: The results of 37 029 initial College of American Pathologists Papanicolaou proficiency tests were reviewed from 4 slide-set modules: conventional, ThinPrep, SurePath, or a module containing all 3 slide types. RESULTS: During this 4-year period, cytotechnologists were least likely to fail the initial test (3.4%; 614 of 18 264), followed by secondary pathologists (ie, those reviewing slides already screened by a cytotechnologist) with a failure rate of 4.2% (728 of 17 346), and primary pathologists (ie, those screening their own slides) having the highest level of failure (13.7%; 194 of 1419). Failure rates have fallen for all 3 groups over time. Pathologists are graded more stringently on proficiency tests, and more primary pathologists would have passed if they had been graded as cytotechnologists. There were no significant differences among performances using different types of slide sets. False-positive errors were common for both primary (63.9%; 124 of 194 errors) and secondary (55.6%; 405 of 728 errors) pathologists, whereas automatic failures were most common for cytotechnologists (75.7%; 465 of 614 errors). CONCLUSIONS: The failure rate is decreasing for all participants. The failures for primary pathologist screeners are due to false-positive responses. Primary screening cytotechnologists and secondary pathologists have automatic failures more often than do primary screening pathologists.

Osteoclastic and pleomorphic giant cell tumors of the pancreas: A review of clinical, endoscopic, and pathologic features.

Giant cell tumors of the pancreas come in three varieties-osteoclastic, pleomorphic, and mixed histology. These tumors have distinctive endoscopic, clinical, and cytological features. Giant cell tumors have a controversial histogenesis, with some authors favoring an epithelial origin and others favoring a mesenchymal origin. The true origin of these lesions remains unclear at this time. These are also very rare tumors but proper identification and differentiation from more common pancreatic adenocarcinoma is important. The risk factors of these tumors and the prognosis may be different from those associated with standard pancreatic adenocarcinoma. Recognition of these differences can significantly affect patient care. These lesions have a unique appearance when imaged with endoscopic ultrasound (EUS), and these lesions can be diagnosed via EUS guided Fine Needle Aspiration (FNA). This manuscript will review the endoscopic, clinical, and pathologic features of these tumors.

Comparison of ThinPrep UroCyte and cytospin slide preparations for gastrointestinal specimens: evaluation and retrospective performance review.

Gastrointestinal (GI) tract cytology has high specificity but poor sensitivity for detecting GI tract cancer. Newer methods of slide preparation may improve cytology performance and additionally permit molecular slide-based assays that could improve diagnostic accuracy. A split-sample validation study compared slides prepared using ThinPrep UroCyte filters or a cytocentrifuge method with respect to cellularity, stain quality, and interpretation. In this 15-slide split-sample study, UroCyte slide preparations were judged to be superior to cytocentrifuge preparations, and the method was implemented for GI cytology in December 2006. To assess diagnostic performance for GI cytology, we retrospectively reviewed outcomes for one year before and after implementation of UroCyte filter slide preparation. Sensitivity, specificity, positive predictive value, and negative predictive value for both slide preparations were largely equivalent to one another and compared favorably with values in the literature, but varied greatly depending on how atypical and suspicious-atypical cases were defined for calculations. For biopsied biliary samples, the highest sensitivities were observed when all atypical and suspicious-atypical cases were considered positive for malignancy, but were lower when suspicious-atypical cases were considered positive and atypical cases were considered negative for malignancy. This highlights the difficulty with comparing studies that define atypical classes differently, and points to the need for a well-defined approach to performance evaluation that relates directly to how diagnostic information is used clinically. We conclude that the UroCyte filter slide preparation is valid for evaluation of GI cytology specimens and may simplify adjunct molecular testing such as FISH. This is the first reported use of UroCyte filters for preparation of GI specimens.

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.

Integrating a FISH imaging system into the cytology laboratory.

We have implemented an interactive imaging system for the interpretation of UroVysion fluorescence in situ hybridization (FISH) to improve throughput, productivity, quality control and diagnostic accuracy. We describe the Duet imaging system, our experiences with implementation, and outline the financial investment, space requirements, information technology needs, validation, and training of cytotechnologists needed to integrate such a system into a cytology laboratory. Before purchasing the imaging system, we evaluated and validated the instrument at our facility. Implementation required slide preparation changes, IT modifications, development of training programs, and revision of job descriptions for cytotechnologists. A darkened room was built to house the automated scanning station and microscope, as well as two imaging stations. IT changes included generation of storage for archival images on the LAN, addition of external hard drives for back-up, and changes to cable connections for communication between remote locations. Training programs for cytotechnologists, and pathologists/fellows/residents were developed, and cytotechnologists were integrated into multiple steps of the process. The imaging system has resulted in increased productivity for pathologists, concomitant with an expanded role of cytotechnologists in multiple critical steps, including FISH, scan setup, reclassification, and initial interpretation.

"FISHing" to detect urinary and other cancers: validation of an imaging system to aid in interpretation.

BACKGROUND: The UroVysion Bladder Cancer Kit detects amplifications of chromosomes 3, 7, and 17, and the deletion of 9p21, by fluorescence in situ hybridization (FISH). Because manual interpretation of UroVysion FISH is time consuming and can be challenged by variable probe signal strengths and background labeling, the authors investigated an automated image analysis system to improve throughput, productivity, quality control, and accuracy. METHODS: The authors evaluated the interactive BioView Duet imaging system as an aid to UroVysion FISH interpretation in a 2-armed, blinded comparison with manual screens of the same 135 consecutive cases. Manual and Duet-assisted interpretations were compared with respect to concordance, reproducibility, and timing. RESULTS: Eighty-one cases were interpreted as positive or negative with 94% concordance and a kappa value of 0.84 between manual and Duet-aided interpretations. Three cases that ultimately were judged positive were detected with the aid of Duet but were missed with a manual screen. A final interpretation could not be given for approximately 25% of Duet-scanned cases. Duet-aided interpretation was highly reproducible for patient and control slides. Pathologist evaluation time per case was 4 minutes compared with 30 minutes for manual interpretation. Cytotechnologist involvement added 18 minutes for a total of 22 minutes, a savings of 8 minutes per case. CONCLUSIONS: Duet-aided interpretations were at least equivalent to manual interpretations. The system permitted interactive review of abnormal cells and had the ability to evaluate the same cells for brightfield cytology followed by FISH. The image processing and analysis tools of the Duet system enhanced the morphology skills of cytology professionals in providing accurate interpretations.

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.

Guidelines for the reporting of nongynecologic cytopathology specimens.

CONTEXT: Gynecologic cytology terminology and report formatting have been nationally standardized since the implementation of The Bethesda System of 1988, but standard reporting for nongynecologic cytology has never been formally addressed on the same scale. OBJECTIVES: To promote patient safety through uniform reporting in nongynecologic cytology (including fine-needle aspiration cytology) and to improve communication between laboratories and health care providers. DATA SOURCES: Sources include the College of American Pathologists Cytopathology Resource Committee; the College of American Pathologists Council on Scientific Affairs Ad Hoc Committee on Pathology Report Standardization; the College of American Pathologists Laboratory Accreditation Program inspection checklists; the Joint Commission for Accreditation of Healthcare Organizations; and the Clinical Laboratory Improvement Amendments of 1988. CONCLUSIONS: We describe the major elements of quality nongynecologic cytology reporting and discuss areas of controversy in cytology reporting. Standardized nongynecologic specimen reporting will expand the concept of common report elements already widely implemented in gynecologic cytology reporting. The intent is to improve communication with the health care team while remaining in compliance with federal mandates and accreditation guidelines.

Automatic failure in gynecologic cytology proficiency testing. Results from the College of American Pathologists proficiency testing program.

CONTEXT: Automatic failure in gynecologic cytology proficiency testing occurs when a high-grade lesion or carcinoma (HSIL+, Category D) is misinterpreted as negative for intraepithelial lesion or malignancy (Category B). OBJECTIVES: To document the automatic failure rate in 2006 and 2007 from the College of American Pathologists proficiency testing program (PAP PT) and compare them to projected values from 2004. DESIGN: Identify automatic failures from PAP PT in 2006 and 2007 and compare the rates of failure regarding participant and preparation type to validated slides in the College of American Pathologists Interlaboratory Comparison Program in 2004. RESULTS: There were 65 264 participant responses for HSIL+ slides included in this analysis from 2006 and 2007. Overall, 1% (666 of 65 264) of the HSIL+ responses were classified as negative, resulting in automatic failure for the participant. There were significantly fewer automatic failures in 2007 as compared with either 2006 or projected from 2004 data (P < .001). Conventional preparations had a lower automatic failure rate than liquid-based preparations but only for 2006. Both pathologists and cytotechnologists interpreting liquid-based preparations faired better than projected from 2004 data. CONCLUSIONS: The automatic failure rate in PAP PT is lower than expected based on 2004 data from the College of American Pathologists Interlaboratory Comparison Program. Automatic failures are a relatively small component (1% or less) of proficiency testing failures. The rate of automatic failure decreased from 2006 to 2007 and may be due to loss of poor performers in the testing pool, the test-taking environment, or removal of less robust slides from the program.

B-RAF V600E mutational analysis of fine needle aspirates correlates with diagnosis of thyroid nodules.

OBJECTIVE: A mutation of B-type RAF kinase (B-RAF) represents the most common genetic alteration in papillary thyroid cancer (PTC), possibly signifying a more aggressive biology. Fine needle aspiration (FNA) represents the most useful initial diagnostic tool of thyroid nodules. Molecular analysis of the mutation status of B-RAF in thyroid nodule FNAs may provide guidance for treatment planning. STUDY DESIGN: Cross-sectional study. SUBJECTS AND METHODS: A retrospective chart review was undertaken for clinically relevant data of papillary thyroid cancer (PTC), follicular variant of PTC (FV-PTC), and nonmalignant goiters. After blinded pathologic review, histologic and cytologic samples were analyzed by LightCycler PCR (LCPCR) with allele-specific fluorescent probe melting curve analysis (FMCA) for the V600E mutation of B-RAF. RESULTS: Of the 45 patient samples analyzed, B-RAF mutation was found to be significantly higher in papillary carcinomas when compared to follicular variant of papillary thyroid carcinomas (55.6% vs 14.3%, P = 0.05). Pathologic B-RAF mutational status significantly correlated with cytologic B-RAF mutational status (P < 0.0001), cytologic interpretation (P = 0.012), and histologic diagnosis (P = 0.011). CONCLUSIONS: Determination of B-RAF V600E mutation of thyroid nodule FNAs by LCPCR may be a useful tool to guide treatment planning. These data support investigating the utility of this molecular marker in a prospective manner.

Parathyroid fine-needle aspiration cytology in the evaluation of parathyroid adenoma: cytologic findings from 53 patients.

This study was designed to assess the utility of fine-needle aspiration cytology (FNAC) in the preoperative localization of parathyroid adenoma (PA). Fifty-seven samples from fifty-three cases of PA (four patients had bilateral disease) were obtained by ultrasound (US)-guided fine-needle aspiration. Parathyroid hormone (PTH) estimation was performed on the supernatant of the aspirated fluid on all cases. Subsequently, all of them underwent cytologic evaluation. The cytology slides were evaluated using the following criteria: Cellularity, architectural patterns, bare nuclei in the background, nuclear morphology, and background features (colloid-like material or macrophages). Parathyroid cells were seen in 23 samples (40.4%). The cellularity of the smears was insufficient for interpretation in 16 samples (28.1%); and thyroid follicles and colloid were seen in 18 samples (31.5%). Majority of the samples with parathyroid cells showed moderate cellularity with monomorphous round to slightly oval cells predominantly arranged in loose two-dimensional clusters with occasional papillary fragments. Majority of them exhibited a stippled nuclear chromatin. No significant pleomorphism, mitotic activity, or prominent nucleoli were observed. Most samples showed bare nuclei in the background. In conclusion, US-guided FNAC has its limitations because of low sensitivity in primary localization of the parathyroid adenoma in cases of primary hyperparathyroidism and is not a useful mode of investigation in cases of PA.

Changes in participant performance in the "test-taking" environment: observations from the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program.

CONTEXT: Because the consequences of making an interpretive error on a proficiency test are more severe than those made on an educational challenge, the same slide may exhibit different performance characteristics in the 2 different settings. OBJECTIVE: The results of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program (PAP PT) provide the opportunity to compare the performance characteristics of the field-validated slides in the PAP PT environment with those of the same graded slides in the College of American Pathologists Educational Program (formerly known as the PAP Program). DESIGN: All participant responses for negative (category B) and positive (categories C and D) validated slides in the 2006 PAP PT were used to determine the error rates of participants. These data were compared with the historical error rates observed on the same validated slides in the graded PAP Program. RESULTS: The performance characteristics of the slides in the PAP PT environment were statistically different from those in the Educational PAP Program. In proficiency testing both cytotechnologists (P < .001) and pathologists (P = .002) were more likely to interpret validated category B slides as category C or D and less likely to interpret category C slides as category B (P < .001). These differences were more pronounced among cytotechnologists than among pathologists. CONCLUSIONS: In the test-taking environment, both cytotechnologists and pathologists appear to use a defensive strategy that results in "upgrading" of category B slides. This trend is more pronounced among cytotechnologists.

Check Sample Abstracts.

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP.

A phase II study of erlotinib as initial treatment for patients with stage IIIB-IV non-small cell lung cancer.

INTRODUCTION: Erlotinib improves survival in patients with advanced non-small cell lung cancer who have been previously treated with systemic chemotherapy. The current trial was designed to evaluate erlotinib as a primary therapy before chemotherapy in patients with minimally restricted eligibility criteria. METHODS: Eligibility criteria included stage IIIB/IV or recurrent non-small cell lung cancer, no prior chemotherapy for systemic disease, performance status = 0 to 1, no history of brain metastases, and weight loss less than 10%. Patients received erlotinib 150 mg/d until objective or symptomatic progression when they were offered conventional chemotherapy. The primary end point was progression-free survival. RESULTS: Forty patients were accrued. The median age was 65 years, 35 had performance status = 1, 8 were never-smoker, and 23 were former smokers. Histologies were adenocarcinoma in 22 and squamous cell in six. The major toxicity was rash (grade 1, 12; grade 2, 16; grade 3, 3). Partial responses were observed in six (15%), stable in 11 (28%), and progressive disease in 23 (58%). The median time on erlotinib was 8 weeks. The median survival was 50 weeks with 1, 2, and 3 years survivals of 44%, 18%, and 16%. Retrospective epidermal growth factor receptor mutational analysis was performed in 18 subjects and four mutations (22%) were identified. Only 25 patients have received subsequent chemotherapy (too early, 4; refused, 9; and unable because of performance status, 2), and, of these, 9 (36%) achieved unconfirmed responses. CONCLUSIONS: Despite a modest response rate, lack of enrichment for never-smokers and absence of conventional chemotherapy in many patients, the median and long-term survivals were comparable with those expected after conventional sequencing of chemotherapy. Erlotinib as initial therapy was well tolerated and warrants randomized evaluation as first-line treatment for advanced lung cancer.