Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens.

CONTEXT: -The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material. OBJECTIVE: -To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non-small cell lung carcinoma using cytologic preparations. DESIGN: -Nine cytopathologists from different institutions submitted cases of non-small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times. RESULTS: -Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases × 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%). CONCLUSION: -Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience.

Respiratory Cytology--Current Trends Including Endobronchial Ultrasound-Guided Biopsy and Electromagnetic Navigational Bronchoscopy: Analysis of Data From a 2013 Supplemental Survey of Participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT: Nongynecologic cytology (NGC) practices are expanding in relationship to historical gynecologic cytology screening programs. Bronchopulmonary cytology is experiencing an evolution regarding new procedural types. The College of American Pathologists (CAP) tracks practice patterns in NGC by developing questionnaires, surveying participants, and analyzing respondent data. OBJECTIVE: To analyze responses to a 2013 CAP supplemental survey from the Interlaboratoy Comparison Program on bronchopulmonary NGC. DESIGN: The "NGC 2013 Supplemental Questionnaire: Demographics in Performance and Reporting of Respiratory Cytology" was mailed to 2074 laboratories. RESULTS: The survey response rate was 42% (880 of 2074) with 90% of respondents (788 of 880) indicating that their laboratories evaluated cytology bronchopulmonary specimens. More than 95% of respondents indicated interpreting bronchial washings (765 of 787) and bronchial brushings (757 of 787). A minority of laboratories (43%, 340 of 787) dealt with endobronchial ultrasound-guided samples, and an even smaller fraction of laboratories (14%, 110 of 787) saw cases from electromagnetic navigational bronchoscopy. Intraprocedural adequacy assessments by pathologists (and less often by cytotechnologists or pathologists-in-training) were routinely performed in percutaneous transthoracic aspiration cases (74%, 413 of 560) with less involvement for other case types. Most laboratories reported that newly diagnosed primary pulmonary adenocarcinomas were triaged for molecular testing of epidermal growth factor receptor and anaplastic lymphoma kinase. CONCLUSIONS: The parameters examined in this 2013 survey provide a snapshot of current pulmonary cytopathology practice and may be used as benchmarks in the future.

Pancreatobiliary duct brushing cytopathology: an analysis of the CAP Non-Gynecologic Cytology (NGC) program for pancreatic pathology 2000-2011.

INTRODUCTION: The College of American Pathologists (CAP, Northfield, Illinois) monitors performance in cytologic analysis to evaluate the standard of practice and consider strategies for method improvement. MATERIALS AND METHODS: 5700 responses to 97 pancreatobiliary tract brushing slide challenges were collected by the CAP Non-Gynecologic Cytopathology (NGC) Program, between 2000 and 2011. Analysis examined participant agreement with the general diagnostic categories of benign or malignant. Suspicious responses were classified as concordant with slides having a positive general diagnosis. Conventional smears with Pap stain and Romanowsky stain were evaluated in addition to CytoSpin, ThinPrep, and SurePath preparations. A nonlinear mixed model was fit with 3 factors-general diagnosis, participant type, and preparation type. RESULTS: Overall concordance rate was 91.7%. Preparation type and general diagnosis were significantly associated with the concordance rate. The interaction term between these two factors was also statistically significant, with ThinPrep performing marginally better for positive cases and CytoSpin performing better for negative cases. Conventional smears did not perform as well as CytoSpin, ThinPrep, or SurePath. CONCLUSIONS: Participants performed well with greater than 90% agreement with the target diagnostic category. There was no significant difference between cytotechnologists and pathologists. Small significant differences were found between preparations types. The statistical differences between concentration techniques may be due to dissimilarities in the quantity of cells and quality of cytomorphology, thus affecting the interpretations by participating laboratories.

Performance Characteristics of Adenoid Cystic Carcinoma of the Salivary Glands in Fine-Needle Aspirates: Results From the College of American Pathologists Nongynecologic Cytology Program.

CONTEXT: Although the cytomorphology of adenoid cystic carcinoma (ACC) has been well described, the accuracy of this diagnosis in fine-needle aspirates (FNAs) of the salivary glands has not been extensively evaluated. OBJECTIVE: To assess participants' responses in the College of American Pathologists (CAP) Nongynecologic Cytology (NGC) Program to determine the accuracy and false-negative rate of ACC cases in salivary gland FNAs. DESIGN: A retrospective review of the CAP NGC Program's cumulative data from 2000-2010 was performed for the general and the specific reference diagnosis categories for ACC in salivary gland FNAs according to preparation and participant types. RESULTS: Of 5156 responses, the overall concordance rates for both the general category of malignancy and the specific category of ACC were 63.6% (3279 of 5156) and 38.6% (1966 of 5088), respectively, with a false-negative rate of 36.4% (1877 of 5156). The most frequent false-negative responses were pleomorphic (1080) and monomorphic (526) adenoma (1614 of 5088, 31.5%), while lymphoma was the most frequent malignant misinterpretation. There was a significant statistical difference in concordance to the reference interpretation between the reader types: 39.9% (1006 of 2521) concordance rate for pathologists compared to 33.8% (503 of 1488) for cytotechnologists. However, there was no significant statistical difference for concordance to the general category or reference interpretation, based on preparation type (Papanicolaou versus modified Giemsa stained). CONCLUSIONS: In this interlaboratory comparison educational program, accurate identification of ACC has shown to be problematic, with ACC representing an important cause of false-negative responses. The most common diagnostic pitfall is distinguishing this entity from pleomorphic and monomorphic adenoma in the benign category and from lymphoma and adenocarcinoma in the malignant one.

Performance Characteristics of Urinary Tract Cytology: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: Urine cytology is used in the evaluation of hematuria or to follow patients with known urothelial neoplasia. OBJECTIVE: To investigate the performance characteristics of urinary cytology challenges in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. DESIGN: Participant responses from 2000 to 2010 were evaluated for the reference diagnoses of high-grade urothelial carcinoma (HGUC), squamous cell carcinoma, adenocarcinoma, and benign diagnoses (including polyomavirus infection and ileal loop urine). Responses were compared for differences in sample preparation (conventional, liquid based, and cytospin) and participant type (laboratory, pathologist, cytotechnologist). RESULTS: There were 96 093 responses (46 637 pathologists [48.5%], 29 976 cytotechnologists [31.2%], and 19 480 laboratories [20.3%]); 69 814 of 74 821 responses (93.3%) for the general category positive for malignancy and 18 698 of 21 272 responses (87.9%) for positive for malignancy were concordant. Of the malignant reference diagnoses, 83.3% (59 985 of 71 581), 43.9% (732 of 1667), and 49.1% (370 of 756) were correctly identified as HGUC, adenocarcinoma, and squamous cell carcinoma, respectively. However, 802 of 1669 adenocarcinoma challenges (48.1%) and 275 of 755 squamous cell carcinoma challenges (36.4%) were misdiagnosed as HGUC. For the benign cases, the most common diagnostic pitfall was overinterpretation of ileal loop urines (330 of 5291; 6.2%) and Polyomavirus challenges (220 of 3535; 6.2%) as HGUC. For the general diagnosis of positive for malignancy, cytotechnologists performed slightly better that pathologists (94.5% [23 553 of 24 924] versus 92.3% [36 210 of 39 230]), whereas the reverse occurred for the negative category (85.6% [6423 of 7503] versus 88.8% [10 427 of 11 742]). CONCLUSIONS: Although the participants performed well in accurately classifying cases as benign and malignant, there were difficulties with the correct identification of adenocarcinoma and squamous cell carcinoma cases and with overinterpretation of ileal loop and Polyomavirus challenges as HGUC.

Do liquid-based preparations of pulmonary bronchial brushing specimens perform differently from classically prepared cases for the diagnosis of malignancies? Observations from the College of American Pathologists interlaboratory comparison program in nongynecologic cytology.

CONTEXT: Pulmonary bronchial brushing specimens can be processed by liquid-based or conventional methods. The ability to accurately diagnose a pulmonary malignancy with a liquid-based preparation (LBP) versus a conventional preparation may differ. OBJECTIVE: To compare the performance of LBPs of malignant pulmonary bronchial brushing specimens with the performance of conventional preparations. DESIGN: Participant responses from 553 malignant pulmonary bronchial brushing samples were evaluated for concordance with the general diagnosis. The performance of LBPs was compared with that of classic preparations. A nonlinear mixed model was used to analyze the performance by reference diagnosis, preparation type, program years, participant type, and the interaction terms between these 4 factors. RESULTS: Concordance with the general category of malignant disease was observed in 95.2% of conventional Papanicolaou-stained, 90.9% of modified Giemsa-stained, and 96.9% of LBP (P < .001) samples. The results were significantly different between individual reference diagnoses (P < .001). The performance of LBPs was consistently higher for most diagnoses and was significantly better for squamous cell carcinoma (P = .005), small cell carcinoma (P < .001), and metastatic carcinoma not otherwise specified (P < .001). All participant types performed significantly better with LBPs of small cell carcinoma. Pathologists and cytotechnologists performed significantly better with LBPs of squamous cell carcinoma. A significantly higher concordance was observed between the general diagnosis and program years 2007-2011 versus 2001-2006 (P = .006). CONCLUSIONS: Liquid-based preparations performed better than conventional methods, with significantly higher performance in squamous cell, small cell, and metastatic carcinomas. Improved performance over time may reflect more frequent use of LBP methods and increased familiarity with interpreting the morphologic findings.

Human papillomavirus testing and reporting rates in 2012: results of a College of American Pathologists national survey.

CONTEXT: College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratory parameters. OBJECTIVE: To evaluate changes in laboratory human papillomavirus (HPV) testing patterns in laboratories incorporating HPV testing with Papanicolaou tests in 2012. DESIGN: Data were analyzed from the CAP HPV Supplemental Questionnaire distributed to 1771 laboratories participating in either CAP HPV or CAP Papanicolaou proficiency testing in 2013. RESULTS: A total of 1022 laboratories (58%) responded. There were more high-risk (HR) HPV tests performed per institution as compared to previous surveys. There were more HPV tests performed within an institution as compared to previous surveys. Hybrid Capture 2 (HC2) remains the most common method (42.4%, 239 of 564); Cervista and cobas methods are used in 37.2% (210 of 564) and 14.9% (84 of 564) of laboratories, respectively. Human papillomavirus testing is offered as a reflex test after a Papanicolaou test result of atypical squamous cells of undetermined significance (ASC-US) in 89.6% of laboratories (476 of 531); as a cotest for women aged 30 years and older in 60.3% (404 of 531); as reflex testing after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) in 42.7% (320 of 531); and as reflex testing after atypical glandular cells (AGC) in 27.3% (145 of 531). The HPV-positive rates for ASC-US and ASC-H were similar in 2012 and 2006. Cervista (49.2%, 88 of 179) and Roche cobas (27.4%, 49 of 179) are the most common methods used for genotyping. Most laboratories use the CAP Human Papillomavirus for Cytology Program for proficiency testing. CONCLUSIONS: There was an increase in annual volume of HR-HPV testing with a shift toward in-house HR-HPV testing. Genotyping volumes also increased. HC2 and Cervista are most commonly used, with an increasing volume of Roche cobas testing. The most common indication for HPV testing among all laboratories was ASC-US reflex testing, but an increase in HPV cotesting was observed. The data provide an update into persisting and newer trends in HPV testing practices.

Nongynecologic cytology practice patterns: a survey of participants in the College of American Pathologists interlaboratory comparison program in nongynecologic cytopathology.

CONTEXT: Nongynecologic cytology (NGC) practices are expected to expand relative to gynecologic cytology. The College of American Pathologists attempts to track practice patterns in NGC using a self-reported questionnaire. OBJECTIVE: To analyze self-reported laboratory staffing and practices from a 2010 survey relating to NGC specimens, stains, preparation, procedures, and ancillary testing. DESIGN: The "NGC 2010 Demographics and Supplemental Questionnaire: Current Nongynecologic Practices in Cytopathology Laboratories" was mailed to 2059 laboratories. RESULTS: Survey response rate was 51% (1048 of 2059), predominantly from voluntary, nonprofit hospitals, where NGC samples were reviewed in nontraining settings by pathologists without American Board of Pathology Added Qualification in Cytopathology. Cytotechnologists reviewed NGC cases in 67.4% (675 of 1002) of laboratories. The annual mean and median volumes of NGC cases were 1927 and 858, respectively. Laboratories used more than one method to process NGCs; cell-blocks were most frequently used (930 of 1029; 90.4%) and were created with centrifugation to pellet (538 of 961; 56%). Direct smears were second in preparation frequency; discrete staining was preferred to batch staining. Nongynecologic cytology was used for molecular studies in 34.9% (350 of 1002) of laboratories, most commonly for fluorescent in situ hybridization of urine specimens. Flow cytometric immunophenotyping was performed by 55.9% (554 of 991) and immunohistochemistry by 91.9% (911 of 991) of the responding laboratories. Most laboratories (911 of 993; 91.7%) report specimen completion in 2 or fewer days. Cytohistologic correlation was performed by 71.6% (722 of 1008) of the laboratories both concurrently and retrospectively. CONCLUSION: The various parameters examined in the 2010 survey provide a benchmark for future efforts in quality assurance and process improvement in NGC.

Recruitment of CD34(+) fibroblasts in tumor-associated reactive stroma: the reactive microvasculature hypothesis.

Reactive stroma co-evolves with cancer, exhibiting tumor-promoting properties. It is also evident at sites of wound repair and fibrosis, playing a key role in tissue homeostasis. The specific cell types of origin and the spatial/temporal patterns of reactive stroma initiation are poorly understood. In this study, we evaluated human tumor tissue arrays by using multiple labeled, quantitative, spectral deconvolution microscopy. We report here a novel CD34/vimentin dual-positive reactive fibroblast that is observed in the cancer microenvironment of human breast, colon, lung, pancreas, thyroid, prostate, and astrocytoma. Recruitment of these cells occurred in xenograft tumors and Matrigel plugs in vivo and was also observed in stromal nodules associated with human benign prostatic hyperplasia. Because spatial and temporal data suggested the microvasculature as a common site of origin for these cells, we analyzed microvasculature fragments in organ culture. Interestingly, fibroblasts with identical phenotypic properties and markers expanded radially from microvasculature explants. We propose the concept of reactive microvasculature for the evolution of reactive stroma at sites of epithelial disruption common in both benign and malignant disorders. Data suggest that the reactive stroma response is conserved among tissues, in normal repair, and in different human cancers. A more clear understanding of the nature and origin of reactive stroma is needed to identify novel therapeutic targets in cancer and fibrosis.

Primary pulmonary non-small cell carcinomas: the College of American Pathologists Interlaboratory Comparison Program confirms a significant trend toward subcategorization based upon fine-needle aspiration cytomorphology alone.

Context.-Subtyping of non-small cell lung carcinomas (NSCLCs) is necessary for optimal patient management with specific diagnoses triggering specific molecular tests and affecting therapy. Objective.-To assess the accuracy of the participants of the College of American Pathologists Interlaboratory Comparison Program in diagnosing and subtyping NSCLC fine-needle aspiration (FNA) slides, based on morphology alone, considering preparation and participant type and trends over time. Design.-The performance of program participants was reviewed for the 5-year period spanning 2007-2011. Lung FNA challenges with reference diagnoses of adenocarcinoma and squamous cell carcinoma (SCC) were evaluated for diagnostic concordance by using a nonlinear mixed model analysis. Results.-There were 10 493 pathologist and 6378 cytotechnologist responses with concordance rates of 97.4% and 97.9% for malignancy, respectively. Overall concordance rates for subcategorization were 54.6% for adenocarcinoma and 74.9% for SCC. For the exact reference diagnoses, pathologists performed better for adenocarcinoma and cytotechnologists performed better for SCC. Accurate subcategorization of adenocarcinomas significantly increased over time with 31.5% of adenocarcinomas classified as NSCLC in 2007 and 25.5% of adenocarcinomas classified as NSCLC in 2011 (P < .001). In comparing preparation types, modified Giemsa-stained smears showed the lowest overall concordance (46.8%). Modified Giemsa-stained smears with SCCs were the least likely to be accurately subcategorized (36.4%). Conclusions.-Participants are proficient at interpreting NSCLCs as malignant by FNA but are less successful at subcategorization with cytomorphology alone. During the study period, a statistically significant trend was confirmed toward greater accuracy of subcategorization of adenocarcinomas, suggesting that participants are cognizant of the impact that more specific cytomorphologic interpretations have in directing molecular triage and therapy.

Room for improvement: initial experience with anal cytology: observations from the College of American Pathologists interlaboratory comparison program in nongynecologic cytology.

CONTEXT: Anal cytology is being used more frequently for anal cancer screening, yet many cytologists are unfamiliar with it. OBJECTIVE: To describe the performance of anal cytology in the College of American Pathologists' Interlaboratory Comparison Program in Non-Gynecologic Cytology (CAP NGC) educational slide program during a 6-year time span, from 2006 to 2011, using participant responses (pathologist, cytotechnologist, and laboratory). DESIGN: Concordance rates for the target diagnosis and general category for each slide challenge were analyzed. Four main factors were included in the analysis: (1) general category or specific responses, (2) program year from 2006 to 2011, (3) participant type (pathologist, cytotechnologist, or overall laboratory), and (4) preparation type (liquid-based or conventional). RESULTS: Participants most frequently correctly classified negative for intraepithelial lesion or malignancy, low-grade squamous intraepithelial lesion, and herpes simplex virus infection, with concordance rates of 78.8%, 85%, and 80.2%, respectively. Performance on challenges with target diagnoses of high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, and ameba was poor, with concordance rates of 57.1%, 56.2%, and 41.5%, respectively. Significant improvement during the 6 years was seen in the concordance rates of participants' responses for low-grade squamous intraepithelial lesion challenges but not for HSIL. There was no significant difference in performance by slide preparation type. CONCLUSIONS: The poor performance on anal cytology in the CAP NGC program, especially with regard to correct identification of HSIL and squamous cell carcinoma, indicates that there is a need for continued education about anal cytology.

Cytology of spontaneous nipple discharge--is it worth it? Performance of nipple discharge preparations in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: The usefulness of spontaneous nipple discharge analysis is controversial. Nipple discharge preparations are rare in clinical practice and malignant cases are exceptional. The College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology has included nipple discharge preparations since its inception. OBJECTIVES: To evaluate participant responses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology to assess the accuracy of cytologic interpretation of nipple discharge preparation. DESIGN: General diagnostic category (benign, suspicious, malignant), participant type (pathologist, cytotechnologist), stain (Papanicolaou, modified Giemsa), and program year (2005-2009) were analyzed using χ(2) and a nonlinear mixed model for slide factor correlation structure. RESULTS: Of 2506 responses, 1280 (51%) were malignant, 171 (7%) were papillary, and 1055 (42%) were benign. There were 222 discordant general category responses with a false-positive/suspicious rate of 12.8% and a false-negative rate of 3.4%. The most common false-negative diagnosis was mastitis/abscess (125 of 1272 responses; 9.8%). The most common false-positive response was papillary lesion (26 of 457 responses; 5.7%). There were no differences between stains or years. Cytotechnologists performed better than pathologists; pathologists had a higher false-negative rate than cytotechnologists (15.3% versus 7.9%, P < .001). CONCLUSIONS: There is poor accuracy in evaluating nipple discharge preparation in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. If the findings in the program parallel clinical practice, nipple discharge preparations may adversely impact patient care. A benign nipple discharge cytologic diagnosis does not exclude malignancy, and the false-positive/suspicious rate requires confirmation of a malignant nipple discharge prior to definitive patient management.

Thyroid lobectomy for indeterminate FNA: not without consequences.

BACKGROUND: Thyroid nodules are exceedingly common, and the cytologic interpretation of fine needle aspiration (FNA) findings has been the reference standard for diagnosing nodules as benign, atypia or a follicular lesion of undetermined significance, suspicious for follicular or Hürthle cell neoplasm, suspicious for malignancy, or malignant. Many patients undergo thyroid lobectomy for indeterminate FNA findings (atypia or a follicular lesion of undetermined significance or suspicious for follicular or Hürthle cell neoplasm), although the risk of malignancy is low. The general data have quoted a 20% risk of hypothyroidism after lobectomy. The purpose of the present study was to determine the risk of hypothyroidism after lobectomy in our diverse population. METHODS: The pathology records from a large county hospital were reviewed to identify patients with indeterminate FNA findings. The incidence of hypothyroidism was determined by the need for thyroid hormone replacement therapy. Categorical variables were compared using the chi-square and continuous variables using the Mann-Whitney U test. RESULTS: A total of 655 FNAs were performed during the study period, and 60 resulted in indeterminate cases. Of these 60 patients, 17 subsequently underwent diagnostic lobectomy. The mean age was 52.8 ± 16.5 years, 88% were women, and 67% were Hispanic and 22% were African American. Only 6% had a final diagnosis of cancer, and eight patients (47%) became hypothyroid postoperatively. CONCLUSIONS: The incidence of hypothyroidism after diagnostic thyroid lobectomy in our patient population was much higher than previously reported. It is necessary to preoperatively counsel patients about this increased risk, in addition to the usual risks of nerve palsy and bleeding, with thyroid lobectomy. As testing of thyroid nodules evolves, the expense of preoperative testing should be weighed against the increased incidence for lifelong thyroid hormone replacement.

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.

Anal cytology as a predictor of anal intraepithelial neoplasia in HIV-positive men and women.

Human immunodeficiency virus (HIV)-infected individuals have increased risk of anal intraepithelial neoplasia (AIN) and squamous cell carcinoma (SCC). Cytologic screening is invaluable in the detection of cervical neoplasia, therefore many clinicians have adopted anal cytology as part of anal cancer screening in patients at high-risk for anal neoplasia. The purpose of this study is to determine whether anal cytology is a valuable screening test for identifying AIN in HIV+ patients. The cohort included 228 HIV+ patients who underwent anal cancer screening with collection of 318 anal cytology specimens between January 2006 and December 2009. Of this group, 74 (32.5%) patients had associated anal biopsies within a 6-month period, with a total of 89 comparison cases. The anal cytology samples were classified using the 2001 Bethesda System terminology. The sensitivity of anal cytology in detecting ASC-US, AIN 1-3 or SCC was 93%. Cytology was 88% sensitive for detecting low-grade AIN (AIN 1), but only 20% sensitive for detecting high-grade AIN (AIN 2-3) or SCC. Atypical squamous cells of undetermined significance cases were distributed evenly between low- and high-grade AIN, with two cases having normal histology. Only six cases had negative cytology, all of which were associated with AIN on biopsy, for a false negative rate of 7%. Anal cytology is a good predictor of AIN, as confirmed by the high degree of sensitivity. However, there is poor correlation between the cytological and histological grade of AIN. Cytology underestimates the grade of dysplasia compared to the corresponding biopsy.

Jejunal intussusception due to malignant phyllodes tumor of the breast.

Phyllodes tumors are rare fibroepithelial neoplasms of the breast; classified as benign, borderline, or malignant based on the mitotic activity, cellular atypia, and stromal overgrowth. Wide surgical excision is the treatment of choice. The most common locations for metastasis are lung, bone, and liver; small intestinal metastasis is extremely rare. Here we present the first patient with jejunal metastases and intussusception due to malignant phyllodes tumor of the breast. Adjuvant treatment of malignant phyllodes tumor needs to be investigated.

In situ hybridization signal patterns in recurrent laryngeal squamous papillomas indicate that HPV integration occurs at an early stage.

Laryngeal papillomas are benign tumors that frequently recur and can compromise airways. We investigated HPV genotype, physical status, and protein expression in juveniles versus adults. Thirty-five laryngeal papilloma specimens were obtained from ten juveniles (1-16 years) and eleven adults (24-67 years). In cases of recurrent papillomatosis (7 juveniles, 7 adults), the first and last papillomas were assayed. HPV type was determined by GP5+/6+ PCR and dot blot hybridization. In situ hybridization (ISH) was performed on 34 specimens; the data were recorded in terms of diffuse (episomal HPV) and punctate (integrated HPV) signal patterns. Immunohistochemistry for the HPV L1 capsid protein, a marker of HPV productive status, was performed on 32 samples. All samples tested HPV positive: HPV 11 in 2/10 (20.0%) juveniles and 5/11 (45.5%) adults; HPV 6 in 7/10 (70%) juveniles and 5/11 (45.5%) adults; and HPV 6/11 double infection was noted in one juvenile and one adult. ISH signals (punctate ± diffuse) were detected among 7/10 (70.0%) juveniles and 7/11 (63.6%) adults. L1 staining was detected in 1/9 (11.1%) juveniles and 6/10 (60.0%) adults (P = 0.06). These data support the idea that integration of low-risk HPV types into the cell genome is an early and common event in the etiology of juvenile and adult recurrent laryngeal papillomas. Productive HPV infections may be more common in adults; accordingly, constant laryngeal re-infection by HPV shed from a productive lesion may contribute to adult recurrent lesions, whereas the mechanism of papilloma recurrence in juveniles may be more attributable to HPV integration.

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.

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.