Biomedical subjects

David C Wilbur

Publications and source records attributed to David C Wilbur.

At least 19 recordsLinked to original sources

PubMed2006

Human papillomavirus testing using hybrid capture II with SurePath collection: initial evaluation and longitudinal data provide clinical validation for this method.

BACKGROUND: Testing for human papillomavirus (HPV) is an integral part of equivocal cervical cytology triage. Clinical validation of non-FDA (Food and Drug Administration)-approved methods is therefore important because of the high volume of such tests and the implications for missed high-grade lesions if test performance is not optimal. METHODS: A preinitiation study and 17 months of follow-up data using Hybrid Capture II (HC II) HPV detection with SurePath (SP) sample collection were analyzed. Results of HPV tests on abnormal cytology samples were collected and compared with follow-up results. HPV-positive rates were determined in cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL), and follow-up rates of cervical intraepithelial neoplasia (CIN) were determined in HPV-positive and -negative cases of atypical squamous cells of unknown significance (ASC-US). Rates were compared with published data using FDA-validated methods. RESULTS: The preinitiation study showed the test method to be 100% sensitive for the detection of LSIL (20 cases) and HSIL (8). The ASC-US follow-up study (2319 cases with 625 having biopsy results) showed that the rate of CIN III+ in HPV +/- cases was 7.8%/1.4%, and of CIN II+ was 17.5%/4.3%, respectively. The positive predictive values/negative predictive values (PPV/NPVs) (CIN II+) for the test were 17.5%/95.7%, respectively. CONCLUSIONS: Published FDA-validated HPV testing follow-up data show that the expected rates of CIN III+ and CIN II+ in the HPV-negative ASC-US population are 1.4% and 5%, respectively, with PPV/NPVs (CIN II+) of 20%/99%, respectively. By comparison, the present data using HC II with SP show strong similarity, indicating clinical validity for the use of this method.

Carcinoma, Squamous Cell↗

PubMed2006

The role of immunolocalization of CD57 and GLUT-1 in cell blocks in fine-needle aspiration diagnosis of papillary thyroid carcinoma.

BACKGROUND: CD57 (Leu7), a marker for natural killer lymphocytes, and glucose transporter-1 (GLUT-1), a facilitative cell surface glucose transport protein, are expressed in a wide spectrum of epithelial malignancies. The usefulness of CD57 and GLUT-1 immunostaining was evaluated as an adjunct to assist in the diagnosis of papillary carcinoma in fine-needle aspirations (FNAs) of the thyroid. METHODS: Immunohistochemical staining for CD57 and GLUT-1 was performed on paraffin-embedded cell blocks of 50 thyroid FNA cases with the following cytologic diagnoses: 1) papillary carcinoma (15 cases); 2) atypical cytology, cannot exclude papillary carcinoma (14 cases); and 3) benign thyroid (21 cases). RESULTS: Fourteen of 15 cases with an unequivocal diagnosis of papillary carcinoma were positive for CD57 and 1 case was negative for CD57. Tissue follow-up confirmed papillary carcinoma in all 15 cases. Of the 14 cases with a diagnosis of atypical cytology, cannot exclude papillary carcinoma, 6 cases were positive for CD57 and subsequent excision confirmed papillary carcinoma in all 6 cases. The remaining 8 cases negative for CD57 included surgically confirmed goiter (5 cases), adenoma (2 cases), and papillary carcinoma (1 case). The follicular cells in all 21 cases with a cytologic diagnosis of benign thyroid were negative for CD57. Histologic follow-up of these cases confirmed the benign cytologic diagnoses. GLUT-1 was negative in all cases. The sensitivity and specificity of CD57 was 91% and 100%, respectively. CONCLUSIONS: CD57 immunostaining is a useful adjunct for the diagnosis of papillary thyroid carcinoma in cell block material. Although negative staining for CD57 does not completely exclude papillary carcinoma, positive staining aids in the accurate diagnosis of malignancy in cytomorphologically equivocal cases. GLUT-1 did not prove to be a useful marker in distinguishing papillary carcinomas.

Biomarkers, Tumor↗

PubMed2006

The utility of GLUT-1 immunolocalization in cell blocks: An adjunct to the fine needle aspiration diagnosis of cystic squamous lesions of the head and neck.

BACKGROUND: Cytologic distinction of metastatic cystic squamous cell carcinoma (SCC) from benign squamous cell lesions, especially the ones with superimposed inflammatory atypia, can be very challenging. The authors evaluated the usefulness of glucose transporter-1 (GLUT-1) immunostaining as an adjunct to fine-needle aspirations of squamous lesions of the head and neck. METHODS: Immunohistochemical staining for GLUT-1 was performed on paraffin-embedded cell blocks of 28 cases with the following cytologic diagnoses: 1) metastatic SCC (11 cases); 2) atypical squamous cells, SCC [corrected] cannot be excluded (6 cases); and 3) cytologic findings consistent with branchial cleft cyst (BCC) (11 cases). RESULTS: All 11 cases with an unequivocal cytologic diagnosis of metastatic SCC were positive for GLUT-1. Tissue follow-up confirmed metastatic SCC in all 11 cases. The squamous cells in all 11 cases with cytologic findings consistent with BCC were negative for GLUT-1; tissue follow-up confirmed diagnoses of BCC in 8 cases. In the remaining 3 cases, excision was not performed, and, clinically, no recurrences were identified at 28, 20, and 16 months of follow-up. Of the 6 cases with cytologic diagnosis of atypical squamous cells, 3 were negative and 3 were positive for GLUT-1. Subsequent excisional biopsies in these cases revealed 4 cases of metastatic SCC (3 positive and 1 negative for GLUT-1), 1 case of BCC (negative for GLUT-1), and 1 case of thyroglossal duct cyst (negative for GLUT-1). CONCLUSION: GLUT-1 immunostaining is a useful adjunct in differentiating benign and malignant squamous lesions in cell-block material. Although negative staining for GLUT-1 does not exclude malignancy, positive immunoreactivity for GLUT-1 may aid in accurate diagnosis of malignancy in cytomorphologically equivocal squamous lesions of the head and neck.

Biopsy, Fine-Needle↗

PubMed2006

The potential for failure in gynecologic regulatory proficiency testing with current slide validation criteria: results from the College of American Pathologists Interlaboratory Comparison in Gynecologic Cytology Program.

CONTEXT: Current regulatory proficiency testing scoring results in an automatic failure for identifying high-grade squamous intraepithelial lesion (HSIL) as negative. OBJECTIVE: The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology data from January 2004 to April 2005 were analyzed to estimate the percentage of failure based on negative responses for HSIL and validation criteria. DESIGN: More than 15,000 participants received field-validated and educational slide sets for conventional, ThinPrep, and SurePath modules. Educational sets fulfilled the validation criteria of the Center for Medicare and Medicaid Services, which required the consensus diagnosis of biopsy-proven HSIL (not field-validated) after review by 3 pathologists. The College of American Pathologists field validation required at least 20 responses to the HSIL+ series, with 70% matched to HSIL+ (standard error < or = 0.05). Minimum regulatory proficiency testing failure estimates were based on incorrect negative responses for the reference category of HSIL. RESULTS: For both cytotechnologists and pathologists, there was a statistically significant higher failure rate for slides that were not field-validated versus those that were field-validated. In conventional modules, 5.3% of the slides that were not field-validated were called negative, versus 1.2% of the field-validated slides. In all liquid-based preparations, 4.0% of the non-field-validated versus 2.2% field-validated slides were called negative. Pathologists would have failed more often than cytotechnologists for the slides that were not field-validated, whereas there was no statistical difference in failure performance with field-validated slides. CONCLUSIONS: Failures were significantly greater with the slides that were not field-validated for both conventional and liquid-based preparations (ThinPrep only) and have implications for both regulatory proficiency testing and expert legal review. Poor performance of pathologists relative to that of cytotechnologists may reflect a lack of prescreening of slides or scope of practice issues.

Clinical Competence↗

PubMed2006

Distinguishing carcinoid tumor of the mediastinum from thymoma: correlating cytologic features and performance in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: The cytologic features of carcinoid tumor in mediastinal fine-needle aspiration are well described. Nevertheless, this tumor may be difficult to distinguish from thymoma in this site. OBJECTIVE: We sought to correlate the cytologic features of carcinoid tumor of the mediastinum in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology with the frequency of misclassification as thymoma. DESIGN: We reviewed 446 interpretations from 18 different cases of carcinoid tumor in mediastinum and correlated the cytologic features with performance. RESULTS: Cases were more frequently classified as thymoma (158 responses, 35%) than as carcinoid tumor (126 responses, 28%). The best-performing case was classified as carcinoid tumor only 56% of the time. Three cytologic patterns were identified. Four cases consisted of isolated round cells with salt-and-pepper chromatin. Four cases consisted of isolated spindle and round cells with salt-and-pepper chromatin. The remaining 10 cases consisted of cohesive fragments of crowded cells with finely granular chromatin showing numerous pyknotic cells mimicking lymphocytes. Prominent vasculature patterns were not a feature of any of the cases. There was no correlation between any pattern and the rate of classification as carcinoid tumor or thymoma (P > .05). CONCLUSIONS: Carcinoid tumor of the mediastinum is frequently misclassified as thymoma in this program. Although some cytologic patterns resemble thymoma, the lack of correlation of these patterns with performance suggests that at least part of the reason for misclassification may be failure to consider the correct diagnosis or a lack of familiarity with discriminating cytologic criteria.

Biopsy, Fine-Needle↗

PubMed2006

Fine-needle aspiration biopsy of lymphoproliferative disorders--interpretations based on morphologic criteria alone: results from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: Diagnosis of lymphoproliferative disorders is one of the most challenging tasks faced by the cytologist. The initial cytomorphologic evaluation of lymphoproliferative lesions directs the choice of ancillary studies that ultimately lead to a diagnosis based on the World Health Organization classification system using a composite of clinical, morphologic, immunophenotypic, and molecular features. OBJECTIVE: To evaluate the ability of participating laboratories in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology to appropriately categorize lymphoproliferative lesions based solely on cytomorphologic criteria. DESIGN: Laboratory responses for lymph node aspirates were examined. All responses were based on review of glass slides without ancillary immunologic or molecular data available. The benchmarking data provided for each specific diagnosis were analyzed, with a focus on the performance for evaluation of lymphoproliferative lesions. RESULTS: Based on morphology alone, responses for lymph node aspirates in the Non-Gynecologic Cytopathology program were correct to the exact reference diagnosis for 87.1% of Hodgkin lymphoma. Non-Hodgkin lymphoma was identified in 69.5% of the large cell non-Hodgkin lymphoma cases, of which 66.8% were correctly classified as large cell type. Non-Hodgkin lymphoma was identified in 68.1% of non-Hodgkin lymphoma, other than large cell cases, and of these, 94.7% were identified as other than large cell type. CONCLUSIONS: The spectrum of specific responses was consistent for lymphoproliferative lesions, with a reasonable differential diagnosis based on cytomorphology alone, which, in practice, facilitates the appropriate choice of immunophenotypic markers and other ancillary studies.

Biopsy, Fine-Needle↗

PubMed2006

Fine-needle aspirates of hepatocellular carcinoma that are misclassified as adenocarcinoma: correlating cytologic features and performance in the College of American Pathologists Nongynecologic Cytology Program.

CONTEXT: The cytologic features of hepatocellular carcinoma in fine-needle aspirates are well described. While some cases are easily distinguished from adenocarcinoma, poorly differentiated tumors can be difficult to differentiate. We reviewed the cytologic findings for 9 aspirates from cases of hepatocellular carcinoma that were frequently misclassified as adenocarcinoma and compared them with another 10 cases of hepatocellular carcinoma that were rarely misclassified. OBJECTIVE: To compare the cytologic features of cases of hepatocellular carcinoma in fine-needle aspirates that were both rarely and frequently misclassified as adenocarcinoma. DESIGN: We reviewed a total of 762 interpretations from 19 different cases of hepatocellular carcinoma in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program. RESULTS: Overall, cases that were frequently misclassified as adenocarcinoma were misclassified 39% of the time (range, 18%-70%), while cases that were rarely misclassified were classified as adenocarcinoma 2% of the time (range, 0%-8%). The difference was statistically significant (P < .001). On review, 4 cytologic patterns were found. The most common pattern for cases that were rarely misclassified was prominent trabeculae of cells and endothelial cells wrapping the trabeculae (6/10 cases vs 2/9 cases that were frequently misclassified). The most common pattern among cases that were frequently misclassified was clusters of cells with granular cytoplasm and associated stripped nuclei (5/9 cases vs 2/10 cases that were rarely misclassified). However, the distribution of neither pattern was significantly different (P = .16 for both). One case with large atypical granular cells, as seen in the fibrolamellar variant, was rarely misclassified. The remaining 3 cases (2 frequently misclassified, 1 rarely misclassified) had a nonspecific a pattern of cells with granular cytoplasm without obvious trabeculae or stripped nuclei. CONCLUSION: Correctly classifying hepatocellular carcinoma by cytology alone remains a significant challenge. While some patterns are more common in cases that performed well and other patterns are more common in cases that performed poorly, there was no significant difference in the distribution of these patterns. These results suggest that people should support their interpretations of aspirations with either immunologic evidence, biopsy evidence, or review by an experienced cytopathologist. Continued educational efforts in this area may be of value.

Adenocarcinoma↗

PubMed2005

A novel automated screening and interpretation process for cervical cytology using the internet transmission of low-resolution images: a feasibility study.

BACKGROUND: Transmission over the Internet of low-resolution images acquired by automated screening of cervical cytology specimens has the potential to provide remote interpretation and, hence, centralization of a cytology workforce. METHODS: Liquid-based cervical cytology slides were scanned using the FocalPoint(R) System. Ten black-and-white images that had the greatest probability of containing abnormality were acquired from each of 32 reference slides (16 negative samples, 3 samples of atypical squamous cells of uncertain significance, 5 samples of low-grade squamous intraepithelial lesions [LSIL], 5 samples of high-grade squamous intraepithelial lesions [HSIL], 1 adenocarcinoma in situ sample, and 2 carcinoma samples) and were transmitted as e-mail attachments in JPEG format to remote reading stations. The slides were interpreted independently by two pathologists and were assigned to either of two groups: 1) suspicious for >or=HSIL or 2) <or=LSIL. The interpretations were compared with the reference diagnoses. The specimens were then randomized, and the image sets were redistributed to the pathologists for another round of interpretation and scoring. RESULTS: The initial and subsequent trials yielded similar results. Pooling the interpretations of the two pathologists, the concordance rate between reference and assigned diagnostic groups for each of the two trials was 84%, the false-positive rate was 8.3%, and the false-negative rate was 37.5%. Review of the discrepant slides revealed subtle cellular changes that may be utilized to reduce errors and, with training, to optimize sensitivity and specificity. CONCLUSIONS: This procedure showed promise for allowing remote interpretation of device-selected images. The procedure may represent an effective way to centralize cervical cytology services and to allow the provision of services to previously unscreened populations that lack an effective cytology infrastructure.

Adenocarcinoma↗

PubMed2005

Cytomorphology of gastric and duodenal epithelium and reactivity to B72.3: a baseline for comparison to pancreatic lesions aspirated by EUS-FNAB.

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has become a widely used method of pre-operatively evaluating pancreatic masses. This technique introduces gastrointestinal contamination into the specimen, which poses a diagnostic pitfall. The cytomorphologic features of these contaminants have not been fully characterized. The current study was designed to systematically document the cytomorphology of gastric and duodenal epithelium on fixed and air-dried smears, as well as ThinPrep (TP) preparations, and to assess the reactivity of the epithelial cells to the tumor marker B72.3 so as to establish a baseline for future comparative studies with EUS-FNAB of the pancreas. Air-dried and fixed smears and TP specimens were obtained using a cytobrush from gastric (GM) and duodenal (DM) mucosa from 14 Whipple specimens. Cytologic features of cell architecture, cellular features and smear background were analysed. Immunocytochemical staining with B72.3 was performed in 10/14 cases. Mucin was present in all preparations except one case from the duodenum. It was consistently present as isolated thick to thin clumps but never as diffuse 'colloid-type' mucin; it was most prominent on air-dried smears, and most abundant from the GM. Epithelial cells were admixed with mucin, but degenerated cells and inflammation were not present within the mucin. Mucin on TP appeared as fragmented wisps of pale blue staining material. Background inflammation and debris were not significant findings. The epithelial cells were arranged in large and small monolayered sheets. Smaller groups were more common from GM on smears and more abundant on TP than smears. Luminal edges (DM>GM) were a prominent feature, with a brush border noted in DM. The nuclei of GM and DM were round, evenly spaced and without atypia, and dense, non-vacuolated cytoplasm was the rule, with the exception of goblet cells and occasional gastric foveolar cells noted in one case. In both GM and DM, B72.3 stained goblet cells with a strong, coarsely granular pattern and stained epithelial cells focally in a finely granular, punctate, perinuclear distribution; mucin also stained strongly in all cases. These baseline characteristics provide a template for assessing mucin and epithelial GM and DM contamination on pancreatic EUS-FNAB specimens.

Antibodies, Neoplasm↗

PubMed2005

Measuring the significance of field validation in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology: how good are the experts?

CONTEXT: Expert opinion is often used as a gold standard for gynecologic cytology in the evaluation of new technologies, in the legal setting, and in the validation of cases for use in educational programs and proficiency testing. However, the reliability of expert opinion alone in selecting slides of a specific cytodiagnosis that can be reproducibly and reliably identified by subsequent reviewers has not been determined. OBJECTIVE: To assess the ability of expert opinion to select slides that are validated in subsequent reviews. DESIGN: In the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, each case in every cytodiagnostic category is accepted for circulation only after review by 3 expert cytopathologists. The percentage of these cases that could not be reliably and reproducibly identified by program participants for each cytodiagnostic category ("failed field validation") was determined during the duration of the program from 1989 to 2004. RESULTS: More than 10,000 conventional smears and ThinPrep cases were selected by the expert panel for circulation. Of these selected slides, 19% of conventional smears and 15% of ThinPrep specimens failed field validation. Compared with the overall slide performance, significantly higher percentages (P < .001) of conventional smears with reference diagnoses of unsatisfactory (51.7%), repair (58%), or low-grade intraepithelial lesion (31.8%) and of ThinPrep specimens with reference diagnoses of unsatisfactory (54.5%) and repair (76.9%) failed field validation. In contrast, significantly lower percentages of conventional smears with reference diagnoses of squamous cell carcinoma (4.5%), high-grade squamous intraepithelial lesion (9%), Trichomonas vaginalis infection (11.7%), or herpes (9.9%) and of ThinPrep specimens with reference diagnoses of adenocarcinoma (5.1%), herpes (2.1%), and fungal organism consistent with Candida (8.4%) failed field validation (P < .001 for all). CONCLUSIONS: Between 15% and 19% of gynecologic cytologic cases that have been selected by expert cytopathologists as good examples of cytodiagnostic abnormalities fail field validation. The proportion of cases failing field validation varies with cytodiagnostic category, but it occurs in all cytodiagnostic entities.

Clinical Competence↗

PubMed2005

Distinguishing carcinoid tumor from small cell carcinoma of the lung: correlating cytologic features and performance in the College of American Pathologists Non-Gynecologic Cytology Program.

CONTEXT: The cytologic features of carcinoid tumor of the lung are well described. Nevertheless, some carcinoids may be difficult to distinguish from small cell carcinomas. OBJECTIVE: To correlate the cytologic features of individual cases of carcinoid tumor of the lung in fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program with the frequency of misclassification as small cell carcinoma. DESIGN: We reviewed 1100 interpretations from 26 different cases of carcinoid tumor in lung fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program and correlated the cytologic features with the performance in the program. RESULTS: Cases were divided into those that were frequently misclassified as small cell carcinoma (at least 20% of the responses, 19 cases) and those that were infrequently misclassified as small cell carcinoma (<10% of all responses, 7 cases). All cases had areas with classic features of carcinoid tumor. Cases were reviewed independently by 3 cytopathologists specifically looking for cytologic features that might be responsible for misclassification as small cell carcinoma. All 7 cases that were infrequently misclassified consisted of numerous monotonous well-preserved tumor cells that were either entirely round or were a mixture of round and spindle-shaped cells. Six of 7 cases showed a prominent streaming vascular pattern with tumor cells attached to the endothelial cell core. In contrast, cases that were frequently misclassified had 1 of 6 patterns that were not seen in cases that were rarely misclassified. These 6 patterns were: (1) poorly preserved and pale-staining cells with fine chromatin and a suggestion of molding (5 cases); (2) numerous large, well-preserved, spindle-shaped cells (2 cases); (3) numerous cells varying markedly in both size and shape (both round and spindle-shaped cells), with a common finding of degenerated, smudgy, small round and spindle-shaped cells (9 cases); (4) hypocellular specimens (8 cases); (5) obscuration of cells by blood (2 cases); and (6) tumor cells present predominantly in groups, with few isolated cells (8 cases). In none of these cases were mitoses or true necrosis identified. CONCLUSIONS: Frequent misclassification of carcinoid tumor as small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with specific cytologic features, some of which are common in small cell carcinoma (fine chromatin, molding, smudgy chromatin) and others that are not (spindle-shaped cells). In addition, hypocellular specimens or specimens with cellular obscuration performed poorly, along with specimens exhibiting absence of the commonly described carcinoid feature of streaming vascularity. Awareness of these patterns may aid in avoiding misdiagnosis.

Biopsy, Fine-Needle↗

PubMed2005

Distinguishing small cell carcinoma from non-small cell carcinoma of the lung: correlating cytologic features and performance in the College of American Pathologists Non-Gynecologic Cytology Program.

CONTEXT: The cytologic features of small cell carcinoma of the lung are well described. Nevertheless, some small cell carcinomas may be difficult to reproducibly distinguish from non-small cell carcinomas, and this distinction carries significant clinical importance. OBJECTIVE: To correlate the cytologic features of individual cases of small cell carcinoma of the lung in fine-needle aspiration specimens from the College of American Pathologists Non-Gynecologic Peer Comparison Cytology Program with the frequency of misclassification as non- small cell carcinoma. DESIGN: We reviewed 1185 interpretations of 23 different cases of small cell carcinoma in lung fine-needle aspiration specimens and correlated the cytologic features noted in these cases with performance in the program. RESULTS: Cases were divided into those that were frequently misclassified as non-small cell carcinoma (at least 10% of the responses, 11 cases) and those that were infrequently misclassified as non-small cell carcinoma (<5% of all responses, 12 cases). All cases had areas on the slides with classic features of small cell carcinoma. However, 10 of 11 cases that were frequently misclassified as non-small cell carcinoma had cells with either increased cytoplasm (4 cases), cytoplasmic globules (so-called paranuclear blue bodies) (3 cases), or apparent intracytoplasmic lumina (3 cases). These features were not identified in cases that were infrequently misclassified (P = .005). In addition, cases more frequently misclassified as non-small cell carcinoma tended to show better overall cellular and group preservation. CONCLUSIONS: Frequent misclassification of small cell carcinoma as non-small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with the presence of cytoplasmic features that may suggest non-small cell carcinoma or with the presence of paranuclear blue bodies. Misclassification in this program may reflect a variety of factors, including the variation in the cytologic features of individual cases, but also the lack of wide recognition that some features of non-small cell carcinoma may also be noted in well-preserved cases of small cell carcinoma.

Biopsy, Fine-Needle↗

PubMed2005

Measuring the significance of participant evaluation of acceptability of cases in the College of American Pathologists Interlaboratory Comparison Program in cervicovaginal cytology.

CONTEXT: The quality of gynecologic cytology slides within educational and proficiency testing programs may deteriorate during use. Participant evaluation of the acceptability of these slides subsequent to possible deterioration is not known. OBJECTIVE: To assess participants' evaluation of the acceptability of slides circulating within an educational gynecologic cytology glass slide program. DESIGN: The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology is a peer comparison and educational program that evaluates the ability of the participants to correctly classify gynecologic cytology preparations. The program uses both expert review and field validation to select slides for the graded portion of the program. Participants were asked to assess the acceptability of slides within the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, and their responses were assessed with respect to type of slide preparation, validation status, and reference diagnosis. In addition, we compared the cytodiagnostic discordancy rates of slides that were deemed acceptable by participants with those that were deemed unacceptable. SETTING: Participant assessments were derived from pathologists and cytotechnologists from cytology laboratories of all types. RESULTS: A total of 17,210 slide interpretations were reviewed, and 2.91% of the cases were labeled unacceptable by participants. For all slides, the percentage of cases called unacceptable varied from 1.65% for cases with a reference interpretation of herpes to 45% for cases with a reference interpretation of unsatisfactory. The percentage of slides deemed unacceptable was higher for validated slides than for educational slides (3.27% vs 2.55%, P = .006). The discordancy rate (to reference diagnosis series) for cases deemed unacceptable was significantly higher than the discordancy rate for cases deemed acceptable for both validated (10.39% vs 1.76%) and educational slides (21.72% vs 3.53%, P < .001). CONCLUSION: Greater than 97% of all slides in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology were judged acceptable by participants. Despite expert review and field validation, a small percentage of slides (almost 3%) in this program were deemed unacceptable by participants. These results support the use of participant evaluation of cases to continually improve the quality of cases in this program.

Clinical Competence↗

PubMed2005

Fine-needle aspirates of adenocarcinoma/metastatic carcinoma that resemble hepatocellular carcinoma: correlating cytologic features and performance in the College of American Pathologists Nongynecologic Cytology Program.

CONTEXT: The cytologic features of adenocarcinoma/ metastatic carcinoma in liver fine-needle aspirates are well described. We review the cytologic findings from 16 aspirates of adenocarcinoma/metastatic carcinoma that were frequently misclassified as hepatocellular carcinomas and compare them with 17 cases that were rarely misclassified. OBJECTIVE: To compare the cytologic features of adenocarcinoma/metastatic carcinoma in fine-needle aspiration specimens of the liver that were frequently misclassified as hepatocellular carcinoma with those of aspirates that were rarely misclassified. DESIGN: We reviewed a total of 1712 interpretations from 33 different cases of adenocarcinoma/metastatic carcinoma tumor in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program. RESULTS: Overall, cases that were frequently misclassified as hepatocellular carcinoma were misclassified on average 26% of the time (range, 13%-54%), while infrequently misclassified cases were interpreted as hepatocellular carcinoma on average 0.7% of the time (range, 0%-3%). The difference was statistically significant (P < .001). On review, cases that were frequently misclassified most often had moderate amounts of granular cytoplasm (16/16 cases) and round nuclei with even chromatin (13/16 cases). Trabeculae (3/16 cases), bare nuclei (2/16 cases), and endothelial wrapping (1/16 cases) were also occasionally present. In contrast, cases that were rarely misclassified were more likely to have areas with cells showing scant cytoplasm that were crowded and overlapped or molded (13/17 cases) and contained dark hyperchromatic chromatin (13/17 cases) compared to cases that were frequently misclassified (P < .001 and P = .002, respectively). Trabeculae (2/17) and bare nuclei (2/17 cases) were also rarely present. CONCLUSION: Cases of adenocarcinoma/metastatic carcinoma with moderate amounts of granular cytoplasm and round nuclei with even chromatin are frequently misclassified as hepatocellular carcinoma. Recognition of this problem, attention to cytologic criteria, and frequent use of immunohistochemical studies and core biopsy may help avoid this pitfall.

Adenocarcinoma↗

PubMed2005

Fine-needle aspiration of pulmonary hamartoma: a common source of false-positive diagnoses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT: We use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to evaluate the accuracy of fine-needle aspiration (FNA) biopsy for diagnosing pulmonary hamartoma (PH). OBJECTIVE: To use the performance characteristics of the PH cases in the Nongynecologic Cytology Program to determine the accuracy of FNA for identifying these lesions and to determine potential sources of interpretative errors. DESIGN: A retrospective review of the College of American Pathologists Nongynecologic Cytology cumulative data from 1997 to 2003 was performed to identify the overall accuracy of FNA for diagnosing PH and to determine the most common interpretative pitfalls. The slides from each of the cases of PH in the Nongynecologic Cytology Program were then reviewed in an effort to identify the cytologic characteristics that contributed to the poor performance of these cases. RESULTS: A total of 766 participant responses for 19 PH FNA specimens were reviewed. The specificity of FNA for making the correct general reference interpretation of benign was 78%. The false-positive rate was 22%, with the most common false-positive diagnoses being carcinoid tumor, adenocarcinoma, and small cell carcinoma. The overall accuracy for making the correct specific reference diagnosis of PH was 26%. Microscopic review of the individual cases revealed possible explanations for some of the interpretative errors and the most frequent false-positive interpretations. CONCLUSIONS: Cytologists should be aware of the potential false-positive interpretations that can occur in FNAs of PH and the potential reasons for these inaccuracies in order to minimize clinically significant diagnostic errors.

Biopsy, Fine-Needle↗

PubMed2005

Pitfalls in salivary gland fine-needle aspiration cytology: lessons from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT: We use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to identify common diagnostic errors in salivary gland fine-needle aspiration (FNA). OBJECTIVE: To identify salivary gland FNA cases with poor performance characteristics in the Nongynecologic Cytology Program surveys, so that the most common diagnostic pitfalls can be avoided. DESIGN: A retrospective review of the College of American Pathologists Nongynecologic Cytology Program's cumulative data from 1999 to 2003 revealed the most common false-positive and false-negative interpretations on FNA for common salivary gland lesions. Slides that performed poorly were then reviewed to identify the cytologic characteristics that may have contributed to their poor performance. RESULTS: A total of 6249 participant responses with general interpretations of benign (n = 4642) or malignant (n= 1607) were reviewed. The sensitivity and specificity of the participant responses for correctly interpreting the cases as benign or malignant were 73% and 91%, respectively. Benign cases with the highest false-positive rates were monomorphic adenoma (53% false-positive), intraparotid lymph node (36%), oncocytoma (18%), and granulomatous sialadenitis (10%). Malignant cases with the highest false-negative rates were lymphoma (57%), acinic cell carcinoma (49%), low-grade mucoepidermoid carcinoma (43%), and adenoid cystic carcinoma (33%). Selected review of the most discordant individual cases revealed possible explanations for some of the interpretative errors. CONCLUSIONS: These data confirm the difficulty associated with interpretation of salivary gland FNA specimens. Cytologists should be aware of the potential false-positive and false-negative interpretations that can occur in FNAs from this organ site in order to minimize the possibility of diagnostic errors.

Biopsy, Fine-Needle↗

PubMed2004

FocalPoint slide classification algorithms show robust performance in classification of high-grade lesions on SurePath liquid-based cervical cytology slides.

The FocalPoint Primary Screening System (FPPS) operates by assigning scores to each slide relative to the probability that an abnormality is present. This information ranks each slide within five "quintiles" (1 = highest risk, 5 = lowest risk) of the "review" population, allowing examining cytologists to understand the risk inherent in each slide. Such information helps to make the primary and quality control rescreening processes most efficient. This study examines the efficiency of AutoPap scoring and, thus, stratification of high-grade cases within a clinical trial setting. A total of 1,275 SurePath (TriPath, Burlington, NC) slides were screened on the FPPS. There were 124 high-grade cases in the set (32 HSIL, 5 AIS, and 87 cancers) as determined by cytologic truth adjudication. The efficiency of FPPS ranking was determined by analysis of the numbers of high-grade cases ranked into quintiles 1 (top 20%) and 1+2 (top 40%). FPPS places cases scored as "unsatisfactory" (HSIL, 3; Cancer, 18) into quintile 5 to ensure a manual review. These cases were excluded from the analysis. Overall, 58% of high-grade slides were classified as Q1 and 83% were classified as Q1+Q2. For HSIL, 66% were classified as Q1 and 90% as Q1+Q2. For Cancer, 59% were classified as Q1 and 84% as Q1+Q2. No high-grade slides were ranked in the lower "no review" population (slides that would receive no manual examination). The results confirm the robust performance of the FPPS classification algorithm. Far more high-grade slides are classified into the top two quintiles than would be expected by random chance alone (20% and 40%, respectively). These results validate the safety and effectiveness of this device on SurePath liquid-based slides.

Algorithms↗

PubMed2004

Bethesda 2001 implementation and reporting rates: 2003 practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

CONTEXT: The 2001 Bethesda System for the reporting of cervical cytology specimens and the use of new liquid-based and human papillomavirus testing technologies have led to changes in cervical cytology reporting practices. OBJECTIVES: To analyze current laboratory reporting practices using Bethesda 2001 terminology and to compare results with previous survey data from 1996. DESIGN: Questionnaire survey mailed to 1751 laboratories in mid-2003. PARTICIPANTS: Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. RESULTS: Of the 759 responding laboratories, most (85.5%) had implemented Bethesda 2001 terminology, and the majority had adopted major changes, such as elimination of the benign cellular changes category and the satisfactory but limited category. The median reporting rate for low-grade squamous intraepithelial lesion was 2.1%, compared to a 1996 median rate of 1.6%, but the increase was confined to liquid-based preparations. Reporting rates for high-grade squamous intraepithelial lesion (median, 0.5%) and atypical squamous cells (ASC) had changed little. Most ASC cases were subclassified as "undetermined significance" (median, 3.9%) with ASC, cannot exclude high-grade SIL accounting for a minority (median, 0.2%). The median ratio of ASC to squamous intraepithelial lesions and carcinomas (SIL+) was 1.4 and was lower than the 1996 median ratio of 2.0. Median reporting rates for squamous abnormalities for 2002 were noted to be significantly higher for liquid-based preparations than for conventional smears, while median ASC/SIL+ ratios were lower. Most laboratories offer human papillomavirus testing, but almost half (47%) of laboratories do not know the percentage of positive testing results in patients with ASC. CONCLUSIONS: Most laboratories have implemented Bethesda 2001 terminology. New criteria and liquid-based methods have led to an increase in low-grade squamous intraepithelial lesion reporting rates and a decrease in ASC/ SIL+ ratios when compared with 1996 data. Liquid-based preparations have higher median squamous intraepithelial lesion rates and lower ASC/SIL+ ratios than conventional smears.

Cervix Uteri↗