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Background: Thoracic switch/sucrose nonfermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4)-deficient (SD) malignancies, including SD undifferentiated tumor (SD-UT) and SD non-small cell lung carcinoma (SD-NSCLC), have been recently described. The cytologic features of these neoplasms in fine-needle aspiration (FNA) and effusion specimens have rarely been reported in the literature. This study aimed to describe and compare the spectrum of cytologic, immunohistochemical, and clinical features of these high-grade malignancies recently encountered at the participating institutions., Methods: This study documented clinical and imaging characteristics of tumors from 27 patients. Sixteen cytomorphologic features and immunohistochemical findings were compared between SD-UT and SD-NSCLC samples., Results: Twenty three FNAs, two bronchial brushings, and two pleural fluids were evaluated, including 17 SD-UT cases (mean patient age, 70 years) and 10 SD-NSCLC cases (mean patient age, 62 years). Both malignancies presented with large thoracic masses and/or hilar/mediastinal lymphadenopathy. All SD-UT cytologic samples had a discohesive or mixed cohesive-discohesive architecture, and most (13 of 17) showed predominant rhabdoid or mixed rhabdoid-epithelioid features. Most SD-NSCLC cytologic samples (nine of 10) were either cohesive or mixed cohesive-discohesive and had a predominantly epithelioid morphology (eight of 10). Keratins and claudin-4 were negative or focally positive in SD-UT samples, whereas they were diffusely positive in SD-NSCLC samples. Both malignancies were negative for TTF-1 and p40/p63 and showed loss of expression of SMARCA4., Conclusions: Although there is considerable clinical and cytopathologic overlap between SD-UT and SD-NSCLC, some key features allow for their distinction. SD-UT is mostly discohesive with rhabdoid or mixed rhabdoid-epithelioid features, whereas SD-NSCLC often has cohesive epithelioid morphology. The combination of clinical presentation, cytomorphology, and immunohistochemistry is essential for a definitive diagnosis., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Atypical squamous cells (ASC) in urine cytology are rarely found, and their clinical significance is not well studied. Previous studies were limited by a small number of cases and a lack of objective grading of ASC and/or their correlation with accompanying urothelial cell abnormality (UCA)., Methods: The institutional database was searched over 10 years for urine cytology reports containing ASC or from patients who had a concurrent diagnoses of high-grade (HG) urothelial carcinoma with squamous differentiation or squamous carcinoma. ASC were defined as keratinized squamous cells and were subcategorized as reactive, koilocytosis, low-grade (LG) atypia, and HG atypia. Correlations with age, sex, specimen type, accompanying UCA, number of ASC, and the risk of HG malignancy (ROHM) were assessed., Results: ASC were present in 0.15% of all urine specimens (123 of 81,018). Slides and clinical follow-up were available on 91 patients (median age, 71 years). LG and HG squamous atypia had ROHMs of 70% and 92%, respectively. ASC not accompanied and accompanied by UCA had ROHMs of 37% and 94%, respectively. Most malignancies (34 of 67; 51%) showed rare ASC in urine. Reactive changes and koilocytosis had 0% ROHM., Conclusions: ASC in urine cytology is a significant finding and is associated with a high ROHM. In the absence of accompanying UCA, LG squamous atypia had a lower ROHM than HG atypia. In the presence of UCA, LG and HG squamous atypia had ROHMs of over 90%. These findings suggest that ASC and their grade of atypia should be noted in the cytology report, and clinicians should be made aware of their clinical significance., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: BRAF V600E mutation is the most common molecular alteration found in papillary thyroid carcinoma (PTC) and has been linked to recurrent disease or possibly more aggressive behavior. Some studies have reported sickle-shaped nuclei (SSN) and plump pink cells (PPC) to be predictive markers of BRAF mutation in FNA cytology. We aimed to evaluate the reproducibility of the aforementioned cytologic features., Methods: A computerized search for diagnosed PTC surgical pathology cases tested for BRAF V600E mutation by Sanger DNA sequencing was performed. Blinded to BRAF results, the corresponding cytology was reviewed for presence of SSN and PPC. Classic nuclear PTC (CNPTC) features, cystic change, and psammoma bodies were also evaluated. The results were correlated with BRAF V600E mutational status and histologic subtypes., Results: Study cohort consisted of 113 cases (74 BRAF V600E mutated, 39 BRAF V600E wild type). SSN and combined CNPTC /SSN had positive predictive value of 74% and 75%, respectively. CNPTC showed 92% sensitivity and 20% specificity. Psammoma bodies had 92% specificity and 5% sensitivity. The presence of combined PPC/SSN showed 80% specificity, 27% sensitivity, and diagnostic accuracy of 45%. CNPTC was seen in 60/61 (98%) SSN and 45/45 (100%) PPC. There was no significant statistical association between SSN, PPC, and CNPTC with specific histologic subtypes and BRAF mutational status., Conclusion: CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings., (© 2024 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Background: Noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP) was introduced in 2016 replacing noninvasive follicular variant of papillary thyroid carcinoma, with recommendations to label them "noncancer." To avoid reducing risk of malignancy (ROM) and overdiagnosing NIFTP as malignant, some authors required restricted cytologic criteria (RC) for a definitive diagnosis of papillary thyroid carcinoma (PTC), including papillae, psammoma bodies. or ≥3 nuclear pseudoinclusions. Since then, NIFTP criteria have been revised, biologic behavior better understood, and incidence reported to be much lower than initially anticipated. This study examines the impact of RC on PTC cytologic diagnoses, ROM, and detection of clinically significant carcinomas (CSC)., Materials and Methods: A total of 207 thyroid FNAs originally diagnosed as PTC and suspicious for PTC (SPTC) with surgical follow-up were evaluated. RC were retrospectively applied to cases as a requirement for diagnosing PTC, and cases that did not meet RC were reclassified as SPTC. ROMs and diagnostic accuracies of pre- and post-RC diagnoses were correlated with followup CSC., Results: RC were met in 118/142 (83%) and 20/65 (31%) of cases originally diagnosed as PTC and SPTC, respectively. Post-RC, 29% (19/65) of CSC originally diagnosed as SPTC were upgraded to PTC, and 17% (24/142) of CSC originally diagnosed as PTC were downgraded to SPTC. No NIFTPs were diagnosed as malignant., Conclusions: RC should not be required for a definitive diagnosis of PTC when other nuclear features of PTC are diffuse and overt. Applying RC, however, helps the pathologist arrive at a more definitive diagnosis of PTC in suspicious cases., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

<b>Background and Objective:</b> <i>Chrysomya albiceps</i> is widely spread worldwide, causing myiasis in both humans and animals and playing a mechanical role in the spreading of helminths, viruses and bacteria. Searching for new and safe alternative control methods is very important to eliminate the transmission of pathogens. This study aims to determine the oviposition-deterrent activity of <i>Juniperus procera</i>, <i>Artemisia absinthium</i>, <i>Rosmarinus officinalis</i> and <i>Hypoestes forskaolii</i> wild plants against adult <i>Chrysomya albiceps</i>. <b>Materials and Methods:</b> The effect of plant extracts from <i>Juniperus procera</i>, <i>Artemisia absinthium</i>, <i>Rosmarinus officinalis</i> and <i>Hypoestes forskaolii</i> plants were tested against adult females of <i>Chrysomya albiceps</i> for oviposition deterrent or repellency. These extracts resulted in oviposition deterrent efficacy for adult females of <i>C. albiceps</i> based on the plant type, plant part (leaves or stems), extract type (methanol, acetone and petroleum ether) and tested dose. <b>Results:</b> The highest anti-oviposition activity against <i>C. albiceps</i> females presented from <i>A. absinthium</i> stems acetone extract at a dose of 1 mg cm<sup>2</sup> by 100 %, while at 0.5 mg cm<sup>2</sup> recorded remarkable repellency by 86.7% as compared with the control treatment. According to the dose-response relationship, <i>A. absinthium</i> methanol and acetone extracts were ED<sub>50</sub> values of 0.85, 0.319 mg cm<sup>2</sup> (leaves) and 1.88, 0.576 mg cm<sup>2</sup> (stems), followed by <i>J. procera</i> methanol extract by 0.983 mg cm<sup>2</sup> (leaves) and 0.98 mg cm<sup>2</sup> (stems), respectively achieved highest oviposition deterrent efficiency as compared with other extracts. <b>Conclusion:</b> The high repellency activities of these extracts can be utilized to stop <i>C. albiceps</i> flies from laying eggs on wounds and transmitting myiasis diseases to humans and animals and could potentially replace pesticides used in the future control programs of flies.

Objectives: Oil Red O (ORO) positivity in bronchoalveolar lavage (BAL) fluid macrophages in the setting of e-cigarette, or vaping, product use-associated acute lung injury (EVALI) has been frequently requested by clinicians based on rare reports and subsequent US Centers for Disease Control and Prevention guidelines. The aim of this study was to determine the specificity of ORO staining in BAL specimens with disease states other than EVALI., Methods: Consecutive BAL specimens (October-December 2019) were stained with ORO. The lipid-laden macrophage index (LLMI) was calculated for each case., Results: We studied BAL samples from 50 patients. Indications for BAL were surveillance bronchoscopy for lung transplantation (27/50), suspected infection (12/50), sarcoidosis/suspected sarcoidosis (3/50), nodules or ground-glass opacities (3/50), hemoptysis (2/50), asthma or eosinophilic pneumonia (2/50), and idiopathic pulmonary fibrosis (1/50). ORO staining was seen in BAL fluid macrophages in 45 of 50 cases (focal in 18, moderate in 23, diffuse in 4); LLMI ranged from 0 to 218. Using a threshold of LLMI of 85 or higher as positive, ORO was positive in 7 of 50 (14%) cases (range, 85-218)., Conclusions: ORO staining in BAL fluid macrophages is not specific for EVALI. Even when an LLMI of 85 or higher is used as a threshold for positivity, ORO positivity occurs in a significant subset of non-vaping-related cases., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Interpretation of Hürthle cell-predominant cytologies (HCP) is very challenging as a majority is diagnosed as indeterminate. Prior studies have reported various cytologic features to help distinguish non-neoplastic (NN) from neoplastic and malignant lesions but had contradicting results. Our aim was to identify risk factors predictive of neoplasm and/or malignancy by correlating cytologic features with clinical and ultrasound findings., Methods: Sixty-nine HCP cases with surgical follow-up were identified, including 35 NN, 20 adenomas, and 14 carcinomas. Ultrasound data were recorded utilizing Thyroid Imaging Reporting and Data System (TI-RADS) and American Thyroid Association (ATA) scoring systems. Sixteen cytologic criteria were evaluated and semi-quantitatively scored. Data were assessed by univariable, multivariable and stepwise logistic regression analysis; and statistical significance achieved at P-value <0.05., Results: On univariable analysis, significant predictors of neoplasm were high cellularity, isolated single cells, absent colloid, non-uniform HC population (anisonucleosis), larger nodule size, and higher ATA score. Large-cell dysplasia and transgressing blood vessels were not found to be significant factors. Multivariable analysis identified a combination of four risk factors (high cellularity, anisonucleosis, absent colloid, and size ≥2.9 cm) that was associated with neoplasm in 10/11 patients. None of 15 patients with zero or 1 out of 4 risk factors had malignancy or neoplasm on follow-up. This model also significantly outperformed ATA and TI-RADS scoring systems., Conclusion: In the absence of four or three risk factors, the model excluded malignancy and neoplasm in all patients. The presence of all four factors predicted neoplasm and malignancy in 91% and 46% of cases, respectively., (© 2022 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

This is a case of a premature infant with stridor, supplemental oxygen requirement, and dysphagia refractory to anti-reflux and anti-inflammatory medications. Endoscopy revealed postcricoid fullness with MRI showing submucosal lobulations. Microscopic resection of an obstructive postcricoid mass resulted in immediate resolution of stridor and oxygen requirement with mild improvement in dysphagia. Pathology demonstrated submucosal fibrosis, edema, and vascularity with no evidence of malignancy, fibromatosis, or cystic/polypoid components. Review of the literature shows that lesions in postcricoid region include amyloidosis, lymphatic malformation, and normal-variant hypertrophy. Surgery should be considered for atypical postcricoid lesions with symptoms refractory to medical management., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The Farasan Archipelago is a group of small coral islands and islets in the southern Red Sea, offshore of the southwestern Kingdom of Saudi Arabia (KSA). These islands are internationally important as breeding sites for turtles and bird species and regionally for its threatened, rare, and endemic flora and other fauna. The beetles (Coleoptera) of the Archipelago have not been previously surveyed. This study presents the first data on the beetle fauna based on a recent survey of the Farasan Archipelago. In total, 179 beetle species (including three synanthropic species) in 145 genera and 31 coleopteran families were determined. The Carabidae are represented by 31 species, followed by the Tenebrionidae (22 species), Chrysomelidae (17 species), Scarabaeidae (13 species), and Coccinellidae (12 species). The genus Lasiocera Dejean, 1831 and the species Amblystomus villiersanus Bruneau de Miré, 1991 (Carabidae) are new for the beetle fauna of the Arabian Peninsula, and eighteen species are new country records for KSA. Sand dune habitats on the islands were inhabited by the greatest number of species in comparison with other habitats. Zoogeographically, the beetle fauna of the Archipelago was dominated by the representatives of the Saharo-Arabian and Afrotropical elements (74 spp., 41.0%). Fourteen species (7.8%) were recognized as cosmopolitan and subcosmopolitan. No species was known to be exclusively endemic to Farasan Archipelago. Eighteen species (10.1%) were endemic to Arabian Peninsula and KSA. Approximately 64.8% (116 spp.) of the archipelago beetle species is found on the KSA mainland and is most closely allied to the south and southwestern KSA regions (sharing 91 spp.). Comparisons of the beetle faunas of the Farasan and Socotra archipelagos indicate that 30 families, 70 genera, and 28 species are shared., (Mahmoud S. Abdel-Dayem, Usama M. Abu El-Ghiet, Tarek M. Elsheikh, Ali A. Elgharbawy, Zarrag I. A. Al-Fifi, Hathal M. Aldhafer.)

Primary effusion lymphoma (PEL) is a rare non-Hodgkin's lymphoma most commonly occurring in the context of human immune deficiency (HIV) infection. Herpes virus 8 (HHV-8) has been associated with PEL and considered to be the etiologic agent. In addition, most cases (60%-90%) also show evidence of Epstein-Barr virus (EBV) infection. We describe here an elderly man who was HIV seronegative and immunocompetent, and presented with worsening weakness and ascites. The diagnosis of PEL was rendered cytologically and supported by the results of flow cytometry. The presence of HHV-8 was demonstrated by immunohistochemistry, whereas EBV-associated genetic material was absent by EBER ISH. No lymphadenopathy or organ involvement with lymphoma was found. Systemic chemotherapy with lenalidomide was started given the poor prognosis and commodities of severe coronary artery disease; however, the patient did not respond and succumbed to his disease in 4 months. We present detailed cytologic and clinical findings of this very rare occurrence, and review literature of all reported PEL cases of HIV-negative, nontransplant, immunocompetent patients., (© 2019 The Authors. Diagnostic Cytopathology published by Wiley Periodicals, Inc.)

Introduction: Polyomavirus cytopathic effect (BK-CPE) is classified as "negative for high-grade urothelial carcinoma" (NHGUC) in the Paris System for Reporting Urinary Cytology. However, polyomaviruses have been historically associated with tumor development and have been recently reported as an independent risk factor for renourinary carcinoma in transplant patients. The aim of the present study was to investigate the relationship between polyomavirus infection in the urinary tract and the subsequent risk of developing high-grade urothelial carcinoma (HGUC) in the general population., Materials and Methods: A retrospective case-control study was conducted to assess BK-CPE in all urinary cytology examinations performed from 2009 to 2011 for cases with an interpretation of NHGUC, NHGUC with BK, atypical urothelial cells (AUCs), or AUCs with BK. The endpoint of the present study was a diagnosis of HGUC on either bladder biopsy or urine cytology for those patients with subsequent follow-up data., Results: A total of 252 cases with a urinary cytology interpretation of NHGUC, 234 with NHGUC + BK, 255 with AUCs, and 64 with AUCs + BK were identified. The surgical and cytological follow-up data showed that the overall risk of the development of HGUC for those with NHGUC, NHGUC + BK, AUCs, and AUCs + BK was 6.0%, 6.8%, 23.5%, and 12.5%, respectively. No statistically significant differences were found between the patients with NHGUC and those with NHGUC + BK. A statistically significant difference was found for patients with AUCs compared with patients with NHGUC + BK and those with AUCs + BK (P < 0.001)., Conclusions: The presence of BK-CPE in urine cytology samples does not increase the overall risk of the development of HGUC. Our results support the recommendation from the Paris System for Reporting Urinary Cytology to place urine samples with BK-CPE in the NHGUC category., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Context: Molecular tests have improved the accuracy of preoperative diagnosis of indeterminate thyroid nodules. The Afirma Gene Sequencing Classifier (GSC) was developed to improve the specificity of the Gene Expression Classifier (GEC). Independent studies are needed to assess the performance of GSC., Objective: The aim was to compare the performance of GEC and GSC in the assessment of indeterminate nodules., Design, Settings, and Participants: Retrospective analysis of Bethesda III and IV nodules tested with GEC or GSC in an academic center between December 2011 and September 2018. Benign call rates (BCRs) and surgical outcomes were compared. Histopathologic data were collected on nodules that were surgically resected to calculate measures of test performance., Results: The BCR was 41% (73/178) for GEC and 67.8% (82/121) for GSC (P < .001). Among specimens with dominant Hürthle cell cytology, the BCR was 22% (6/27) for GEC and 63.2% (12/19) for GSC (P = .005). The overall surgery rate decreased from 47.8% in the GEC group to 34.7% in the GSC group (P = .025). One GEC-benign and 3 GSC-benign nodules proved to be malignant on surgical excision. GSC had a statistically significant higher specificity (94% vs 60%, P < .001) and positive predictive value (PPV) (85.3% vs 40%, P < .001) than GEC. While sensitivity and negative predictive value (NPV) dropped with GSC (97.0% vs 90.6% and 98.6% vs 96.3%, respectively), these differences were not significant., Conclusions: GSC reclassified more indeterminate nodules as benign and improved the specificity and PPV of the test. These enhancements appear to be resulting in fewer diagnostic surgeries., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Metastatic malignancies of unknown primary site (MUP) is the eighth most common form of malignancy, with an estimated 10-15% of oncology patients having a MUP. Fine needle aspiration cytology (FNA) and core needle biopsy (CNB) are often the first procedures utilized in the work-up of these cases and have a pivotal role for the diagnosis of metastases. There is an increasing emphasis on the precise classification of malignancy and determination of primary site of origin, utilizing smaller specimens. Recent available data suggest that there is a management benefit in identifying the primary site and/or specific cell lineage of MUP. In addition, the pathologists are asked to preserve the limited diagnostic material for potential molecular testing, as selected patients may benefit from targeted therapy. However, these tasks can become extremely challenging, especially if there is no previous history of malignancy, prior pathology is not available for review, or there is an unpredictable pattern of metastasis. In this review, we present a contemporary clinicopathologic approach to the work-up of MUP that includes cytomorphology, ancillary studies, and clinicopathologic correlation. The cytohistologic subclassification of malignancies into specific cell lineages and/or morphologic categories is presented. Knowledge of the various patterns of metastasis to common and unusual sites can help narrow down the location of a primary site. The use of ancillary studies with particular emphasis on IHC utilizing an algorithmic approach and the role of molecular analysis as a diagnostic and theranotic test are also discussed. When the cell block and/or CNB lacks sufficient material for ancillary testing, the cell transfer technique may be utilized.

Objectives: Fine-needle aspiration (FNA) of head and neck lymph nodes (LNs) is useful in diagnosing metastatic papillary thyroid carcinoma (PTC) and most commonly shows classic cytologic features of PTC. Metastatic PTC, however, may occasionally present with a pattern unfamiliar to most pathologists: atypical histiocytoid cells (AHCs)., Methods: All PTC thyroidectomy specimens with associated FNA of LNs were retrieved from our files for 2007 to 2013. We aimed to assess cytologic features of metastatic PTC, as well as the presence of AHCs and their morphology., Results: Fifty-six FNAs from LNs with metastatic PTC were reviewed. AHCs were identified in 38 (68%) cases, while only PTC with classic cytologic features was seen in 18 (32%) cases. AHCs did not show diagnostic nuclear features of PTC and presented as large cells with abundant cytoplasm either vacuolated or dense. Nuclei varied from vesicular with prominent nucleoli to dark and smudgy. Thirty-one cases showed mixed AHCs and classic PTC, but seven cases (13% of all metastatic PTCs in LNs) consisted only of AHCs., Conclusions: AHCs are an often unrecognized metastatic morphologic pattern of cystic PTC, as it does not show diagnostic classic nuclear features of PTC. AHCs are the predominant cytologic finding in approximately 13% of metastatic PTCs to neck LNs., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Trichomonas vaginalis is a rare finding in urine cytology specimens, especially those from men; only 2 case reports have been described in the literature. The authors of the current report sought to determine the incidence and clinical significance of this finding in urine cytology in males., Methods: The authors' cytopathology archives were queried for urine cytology specimens that contained Trichomonas over a 30-year period. Clinical information from men with Trichomonas-positive urines was reviewed retrospectively. Slides were reviewed, and the morphologic characteristics of the organisms were recorded., Results: Trichomonas was detected in 73 of 60,000 urine cytology specimens (0.1%). The patients included 45 women and 28 men. Men with Trichomonas in their urine ranged in age from 28 to 87 years (mean age, 67 years; median, 71 years). Trichomonas organisms were round to oval, with eccentric nuclei and cytoplasmic granules. Acute inflammation was observed in 6 of 7 cases. Clinical history was available in 13 of 28 men. Lower urinary tract symptoms were reported in 10 of 13 men, most commonly hematuria; and urethral strictures were identified by cystoscopy in 3 of 13 men. Clinical follow-up was available for 10 of 13 patients; of these, 8 (80%) had received treatment with metronidazole based on urine cytology results., Conclusions: This study is the largest series of Trichomonas infection in men diagnosed by urine cytology in the literature. Most men had no prior diagnosis of trichomoniasis and received specific antibiotic therapy based on their urine cytology results. Urine cytology may represent the initial diagnostic test for Trichomonas in men, and accurate cytologic diagnosis may prevent undesired adverse outcomes for them and their partners. Cancer Cytopathol 2017;125:55-59. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

A novel series of dihydropyrimidines (DHPMs) 4a-j; 2-oxopyran-3-carboxylate 7a,b; 1-amino-1,2-dihydropyridine-3-carboxylate 8; and 1,3,4-oxadiazole derivatives 12 with quinolinyl residues have been synthesized in fairly good yields. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. In vitro antimalarial evaluation of the synthesized quinoline derivatives against Plasmodium falciparum revealed them to possess moderate to high antimalarial activities, with IC50 values ranging from 0.014-5.87 μg/mL. Compounds 4b,g,i and 12 showed excellent antimalarial activity against to Plasmodium falciparum compared with the antimalarial agent chloroquine (CQ).

Background: Gynecologic screening cytology is a complex task that includes microscopic activities and nonmicroscopic activities. The authors sought to determine the amount and percentage of time that cytotechnologists spend on those activities using the ThinPrep imaging system., Methods: In arm 1, a total of 550 consecutive unselected slides were reviewed by 11 cytotechnologists, and the time used for individual subtasks of the screening process was recorded. In arm 2, a total of 20 unselected slides were each screened by 10 different cytotechnologists (200 slides in total) and total screening times and full manual review (FMR) times were recorded., Results: In arm 1, cases with and without FMR required an average of 5.6 minutes and 3.0 minutes, respectively, to screen. Overall, review of fields of view (FOVs) took 95 seconds. FMR took an average of 2.6 minutes. The average screening times for FOV-only cases was significantly longer than the US Food and Drug Administration/Centers for Medicare and Medicaid Services (FDA/CMS) workload limit of 2.4 minutes (P = .005). However, in arm 2, the time needed to screen a case increased by an average of 1 minute compared with arm 1, including 1.1 minute for FOV-only cases and >2 minutes for FMR plus FOV cases. Approximately 100% of cases screened as FOV only exceeded the FDA/CMS workload limit of 2.4 minutes., Conclusions: The FDA/CMS workload limits for FOV-only cases appears to significantly underestimate the time needed to screen those cases, but seems to be appropriate for the majority of FMR plus FOV cases. Approximately 60% and 30% of the time designated to screening slides was spent on nonmicroscopic activities for FOV-only cases and FMR cases, respectively. Cancer Cytopathol 2016;124:501-7. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Previous prospective studies of automated assisted gynecologic screening devices have used a panel of experts for truth determination. We sought to determine the value of this practice. The relative sensitivity of the devices compared with manual screening was calculated using an expert panel for truth determination and compared using likelihood ratios to the relative sensitivity assuming all abnormal cases were truly abnormal. These results show that expert panel review has no significant effect on relative sensitivity at the threshold of ASCUS+ but may have an effect at HSIL+. Trials without expert consensus review may be compared to those with expert consensus review at the threshold of ASCUS+ but may not be reliable at the threshold of HSIL+ without additional confirmatory data., (Copyright © 2013 Wiley Periodicals, Inc.)

Previous prospective studies have shown different results when comparing automated and manual screening of gynecologic cytology. The results of 3 large prospective studies were reviewed and relative sensitivity used as a gold standard. No significant differences could be shown in relative sensitivity between the ThinPrep Imaging System and the FocalPoint GS Imaging System (P > .05). When manual screening was restricted to less than 6 hours per day, 50 or fewer slides per day, and at least 6 minutes per slide (<10 slides/h), the relative sensitivity for automation was significantly lower for atypical squamous cells of undetermined significance and above (ASC+) (0.81; 95% confidence interval [CI], 0.79-0.83) than when manual screening was not restricted (1.07; 95% CI, 1.03-1.10). All 3 sites that screened 10 or more slides per hour manually had a relative sensitivity for automation that was significantly higher for high-grade squamous intraepithelial lesions and above (HSIL+) than for the remaining groups who screened less than 10 slides per hour (1.40 [95% CI, 1.22-1.60] vs 0.97 [95% CI, 0.95-1.00]). These results suggest that location finding of abnormalities (ASC+) may be more strongly associated with time spent screening per day, whereas classification/interpretation skills (HSIL+) may depend on time spent on an individual case. There is no evidence that automated screening devices are more sensitive than manual screening performed at lower well-defined workloads. More restricted workloads (≤41 slides/d, ≤4.5 h/d) for manual screening may perform significantly better than automated screening devices as measured by histologic cervical intraepithelial neoplasia 2 and above.

Based on current literature and the best available research to date, the current FDA workload limits for automated image-assisted screening, including the ThinPrep Imaging System and the FocalPoint GS, of 100 slides/day (imaged only slides counted as 0.5) are extremely high and may be associated with significant reduction in sensitivity. This task force has proposed six recommendations relating to cytotechnologist (CT) workload in automated image-guided Pap test screening, which have already been endorsed by major pathology professional societies. These evidence-based recommendations, however, pertain only to gynecologic specimens with image-assisted screening, as there is no current available data to justify modifying screening practices regarding non-gynecologic specimens. The proposed recommendations are as follow: 1) CT workday should not include more than 7 hours of Pap test screening in a 24-hr period, and an 8-hr shift day must include at least 2 paid mini-breaks of 15 minutes each and a 30-minute lunch break. 2) Future Studies examining CT workload should use actual hours of screening rather than lesser number of hours extrapolated to 8-hour days. 3) Average laboratory CT workload should NOT exceed 70 slides/day (slides counted per 2010 FDA bulletin). 4) Proportion of imaged slides that undergo full manual review should be at least either 15%, or twice (2×) the epithelial cell abnormality (ECA) rate, whichever is greater. 5) ECA-adjusted workload measure is a promising method for calculating and monitoring CT workload, but further studies of this method are necessary before full endorsement. 6) CT productivity and workload limits are just one aspect of a good quality assurance program in a cytology laboratory, so other quality indicators to assess CT performance are essential., (Copyright © 2012 Wiley Periodicals, Inc.)

Context: Two quality metrics for gynecologic cytology are the subject of this review: "prospective rescreening" and "retrospective rescreening.", Objective: To offer consensus best practice approaches based on the College of American Pathologists' laboratory-based survey funded by the Centers for Disease Control and Prevention., Design: The College of American Pathologists submitted a paper-based survey to 1245 laboratories. After review of initial results, follow-up Web-based survey results, and a literature review, consensus best practice statements were presented at a national consensus conference. These statements were discussed and voted upon by conference participants. Results.-A total of 541 laboratories responded to survey questions about prospective and retrospective rescreening. Most laboratories (>85%) prospectively rescreen more than 10% of Pap tests interpreted as negative for intraepithelial lesion or malignancy. Most (72%) report inclusion of less than 20% high-risk cases. Most laboratories use multiple measures to define "high risk." Most laboratories (96.2%) retrospectively rescreen Pap tests from the preceding 5 years only. In most laboratories (71.4%) only Pap test results with high-grade squamous intraepithelial lesion or worse prompt retrospective review., Conclusions: The number of Pap tests from high-risk patients should be maximized in prospective and retrospective rescreening. Unsatisfactory Pap tests should also be included. All readily identifiable high-risk human papillomavirus-positive cases with an interpretation of negative for intraepithelial lesion or malignancy should be prospectively rescreened. Cervical biopsy results with high-grade cervical intraepithelial neoplasia or worse (CIN 2+) should trigger retrospective rescreening. Regular feedback should be provided to cytotechnologists and cytopathologists. Upgraded diagnoses from negative for intraepithelial lesion or malignancy to atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, should be monitored.

Studies examining the effects of increased workload on the performance of individual cytotechnologists are limited. Using FocalPoint GS, the performance of 3 cytotechnologists was evaluated. The study consisted of 3 phases. In phase I, cytotechnologists were asked to screen at their usual pace. In phase II, cytotechnologists were asked to screen as fast as possible without feeling that the quality of their work was diminished. In phase III, cytotechnologists were asked to screen at least 15% more than their daily workload from phase II. Productivity was increased by decreasing the percentage of cases that underwent full manual review (from 38% to 19%) and by decreasing the time spent on each slide (from 5.5 min to 3.7 min). Overall, the total abnormal rate decreased by 31.9% from phase I to phase III of the study. In addition, the false-negative fraction increased significantly, from 1% to 6.9%. Our results indicated a negative association between increased cytotechnologist daily workload with FocalPoint GS and CT screening performance. Workloads were increased by decreasing the time spent reviewing 10 fields of view and the percentage of cases that underwent full manual review.

Previous studies have shown a negative correlation between screening sensitivity using the ThinPrep Imaging System (TIS) and epithelial cell abnormality (ECA) adjusted workload (ECA rate × actual slides screened/day) at the thresholds of atypical squamous cells of undetermined significance (ASCUS) and high-grade squamous intraepithelial lesion (HSIL). We sought to determine if a similar correlation could be shown at the threshold of low grade squamous intraepithelial lesion (LSIL). Using data in seven manuscripts from the literature that contain sufficient information, the change in screening sensitivity using the TIS compared with manual screening was negatively correlated with ECA adjusted workload (y = -3.75x + 54, R(2) = 0.104). Using the sensitivity of manual screening of 79% for manual screening at a threshold of LSIL from the original TIS trial, 100% sensitivity could be achieved at an ECA adjusted workload of approximately seven slides/day, the same workload that achieves 100% sensitivity at a threshold of ASCUS and slightly higher than the threshold for HSIL. We conclude that the ECA adjusted workload is a valuable method to assess workload for the TIS at the threshold of LSIL. Laboratories using the TIS should restrict workload to seven ECA adjusted slides/day (maximum actual slides/day = 700/ECA percentage)., (Copyright © 2010 Wiley Periodicals, Inc.)

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided a set of uniform diagnostic terminology including benign (B), atypia of undetermined significance (AUS), follicular neoplasm (FN), suspicious for malignancy (SM), malignancy (M), and nondiagnostic (ND) for the interpretation of thyroid fine-needle aspiration (FNA). We applied this terminology on our 1,382 thyroid aspirates in a community practice setting, which included 539 cases of B (39%), 376 cases of AUS (27.2%), 116 cases of FN (8.4%), 37 cases of malignant (2.7%), 36 cases of SM (2.6%), and 278 cases of ND (20.1%). Two hundred twenty-one cases (16%) of thyroid FNA had corresponding follow-up thyroidectomies. Each diagnostic category represented a unique association with risk of malignancy and risk of neoplasm. Based on histologic follow-up, the risk of neoplasm (including benign and malignant neoplasm) was B 14%, AUS 44%, FN 67%, SM 77%, and M 100% and the risk of malignancy was B 3%, AUS 6%, FN 22%, SM 56%, and M 100%. The classification and follow-up recommendation of TBSRTC are appropriate for each category. Both B and AUS are low-risk lesions with low probability of malignancy. FN predicts a higher rate for neoplasm but an intermediate rate for malignancy while SM carries a high risk for malignancy., (Copyright © 2011 Wiley-Liss, Inc.)

Previous studies have suggested that the sensitivity of the ThinPrep Imaging System (TIS) for high-grade intraepithelial lesion (HSIL) and worse may be decreased at workloads above 100 slides/day. On the other hand, at a threshold of atypical squamous cells of undetermined significance (ASCUS) and above, sensitivity of the TIS appears to more closely correlated with epithelial cell abnormality (ECA)-adjusted workload (ECA rate × actual slides/day) rather than total workload. We sought to determine if the sensitivity of the TIS for HSIL could also be shown to be correlated with ECA-adjusted workload. The change in sensitivity for HSIL from manual screening to TIS screening consistently correlated negatively with ECA-adjusted workload both in the original Food and Drug Administration trial study and in independent studies available in the literature. Both sources suggest that sensitivity near 100% can be achieved with ECA-adjusted workloads of 5-7 slides/day. For a laboratory with an ECA rate of 10%, this represents a total workload of 50-70 slides/day. We conclude that measuring the ECA-adjusted workload is a valuable method to assess workload for the ThinPrep Imaging System., (Copyright © 2010 Wiley Periodicals, Inc.)

Recent studies have shown that it is possible to correlate workload or epithelial cell abnormality (ECA) adjusted workload with screening sensitivity. The results show that for manual screening of conventional smears or SurePath slides, screening sensitivity begins to fall with workloads as low as 30 slides/day. For review of slides with the ThinPrep Imaging System, screening sensitivity appears to be better correlated with ECA adjusted workload (workload × ECA rate) than workload alone. Screening sensitivity with the ThinPrep imager appears to fall at ECA adjusted workloads of 7 slides/day at a threshold of ASCUS and above and LSIL, and slightly lower for HSIL. This corresponds to 70 slides/day at an ECA rate of 10%. The variance in these models is likely high reflecting a wide range of individual cytotechnologist performance. Strategies to most effectively incorporate this data in the management of workload in the laboratory are reviewed., (Copyright © 2010 Wiley-Liss, Inc.)

Sensitivity for screening gynecologic cytology appears to be correlated with workload, but data in the literature is limited. We gathered all known published data that included independently estimated measures of sensitivity and workload, for manual and automated screening, including individual cytotechnologist (CT) and laboratory data. We then attempted to synthesize the best estimates of sensitivity with workload volume. While this interpretation is limited by the scarcity of collected data and the few assumptions needed to combine the data, our results suggest that manual and automated screening correlate differently with workload. Manual screening was directly related to total workload volume, appeared to reach near 100% sensitivity for some individual CTs at workloads of ~30 slides/day, and decreased to below 80% sensitivity at ~70 slides /day. Most CTs performed at a higher sensitivity than the laboratory averages, but a small subset of CTs had significantly lower sensitivities with similar workload volumes. Sensitivity of automated screening, on the other hand, was more closely correlated with epithelial cell abnormality (ECA)-adjusted workload (ECA × total slides/day). While these results are preliminary and additional studies are warranted to confirm them, our results may be useful in monitoring workload limits in gynecologic cytology., (Copyright © 2010 Wiley-Liss, Inc.)

Major components of good quality assurance (QA) in cytology laboratories are measuring the screening accuracy of cytotechnologists (CTs) and determining appropriate workload limits for them. Currently, the FDA approved workload limits for image assisted Paps, however, are too high. In addition, the CLIA 88 mandated QA measures, by themselves, are insufficient to accurately measure the screening performance of CTs. Although the use of "controls" is fundamental to good practice in the clinical laboratory; this has not been emphasized in gynecologic cytology. In this review, we underscore the importance of using controls, such as monitoring morning and afternoon abnormal rates, in assessing CT performance and assigning reasonable workload limits. Using controls, however, requires significant alteration in the laboratory workflow, and much lower and variable workload limits for CTs, compared to those approved by FDA., (© 2010 Wiley-Liss, Inc.)

Background: With the current and projected shortage of a cytotechnologist (CT) workforce and the desire to reduce laboratory costs, increased productivity with automated assisted primary screening has become an attractive option for many laboratories. To the best of the authors' knowledge, longitudinal studies examining the effect of increasing workload on the performance of individual CTs have not been performed previously., Methods: Using the ThinPrep imaging system (TIS), the performance of 3 CTs with variable levels of experience were evaluated. Their productivity was noted to increase from an average of 87 to 118 slides per day. The analysis included comparisons of error rates, screening rates, and screening times, including a review of 22 fields of view (FOV). Poststudy interviews of the CTs were also performed., Results: Increased workload was found to be proportional to the decreased percentage of cases that underwent full manual review (25.2% to 20.1%; P < .001), and decreased actual screening times (7.3 hours/day to 6.7 hours/day, and 5.0 minutes/slide to 3.7 minutes/slide). This resulted in a lower detection of total abnormal findings (10.4% to 8.3%; P < .001), atypical squamous cells (6.7% to 4.9%; P < .001), and high-grade squamous intraepithelial lesion (0.9 %to 0.7%; P = .37), as well as an increased false-negative fraction rate (3.8% to 7.0%; P = .08)., Conclusions: The results of the current study indicate that an increased average CT workload >100 slides per day with the TIS appears to have been accomplished mostly through a reduction in the amount of time spent reviewing the 22 FOV and the percentage of cases that underwent full manual review, which resulted in a significantly reduced screening performance., ((c) 2010 American Cancer Society.)

The atypical squamous cell to squamous intraepithelial lesion (ASC/SIL) ratio for cytotechnologists (CTs) may correlate with screening sensitivity in some laboratory settings. Whether this ratio can be applied to other laboratory settings is not known. We conducted a survey of nine cytology laboratories and correlated the ASC/SIL ratio of individual CTs with other laboratory characteristics. The ASC/SIL ratio for individual CTs varied from 0.6 to 4.5 (mean: 1.9, median: 1.5). The ASC/SIL ratio within individual laboratories varied up to 567%; 25/78 (32%) CTs had an ASC/SIL ratio of less than 1.5, though only three of nine laboratories had more than one CT with a ratio this low. Laboratories that used 100% location guided screening (ThinPrep Imaging System) were much less likely to have a CT with a ratio <1.5 (1/20, 5%) than laboratories that never used location guided screening (14/34, 42%; P = 0.004). In addition, the normalized variance of these same laboratories that used location guided screening was significantly lower than those that did not (normalized standard deviation 0.32 vs. 0.55, P = 0.004). The ASC/SIL ratios did not correlate with laboratory volume, individual workload, or type of specimen preparation (conventional vs. liquid based). The ASC/SIL ratio for CTs varies widely between and within laboratories, and may correlate with the use of location guided screening. Very low ASC/SIL ratios are unusual, and CTs with low ratios may warrant further evaluation.

Background: Workload is extensively regulated in gynecologic cytology. However, sensitive monitors of excessive workload are not available., Methods: We measured the variation in abnormal (atypical squamous cells [ASC], low-grade squamous intraepithelial lesion [LSIL], and high-grade squamous intraepithelial lesion [HSIL]) rates for 4 cytotechnologists (CTs) among different days of the week and at different times during the day while they were performing primary screening with the ThinPrep Imaging System., Results: Three of 4 CTs detected significantly less abnormal cases on 1 day of the week than another (1 Monday, 2 Friday). Two of those CTs detected significantly fewer total abnormal cases in the afternoon than in the morning; this was strongly correlated with increased speed in the afternoon and decreased detection of ASC cases. HPV + rates for ASC cases dropped as the abnormal rate dropped. The third CT detected significantly fewer ASC cases in the morning; this was counterbalanced by an increase detection of LSIL cases, suggesting a shift in diagnostic threshold between the AM and PM. The difference in abnormal detection rates between morning and afternoon correlated with a false-negative fraction of 0.96., Conclusions: There are significant differences in detection rates of abnormal cases between days of the week and the morning and afternoon. Correlating abnormal rates and workload between the morning and afternoon may represent a sensitive way to detect excessive workload. Because individual CTs may have different responses to workload and no overall pattern emerged, data on their workload and performance need to be tracked individually., ((c) 2010 American Cancer Society.)

The HALO breast Pap test is a new automated nipple aspiration fluid (NAF) system that was recently introduced into the market. In an extensive marketing campaign directed principally toward OB/GYN practices, including endorsements from few local news media, HALO has been promoted as the "new Pap screening test for breast." Physicians are encouraged to perform this test on all women, as part of their annual examination, with claims that HALO will detect breast cancers as early as 10 years before mammography. These arguments are made more appealing to physician's offices by highlighting the potential positive financial impact on their practices, without consuming physician time, as medical assistants or technicians can perform this test. As a result of this directed campaign, cytology laboratories are increasingly confronted with implementing the HALO system and clinicians are increasingly soliciting pathologist's input regarding its validity. Yet, there is no data available regarding this new system, outside rare reports sponsored by the manufacturer. In this discussion, I examine the pros and cons of this new NAF system, including literature review of breast fluid cytology, and how it relates to breast cancer risk assessment., (2009 Wiley-Liss, Inc.)

Distinguishing follicular variant of papillary carcinoma (FVPC) from follicular adenoma and follicular carcinoma can be difficult if nuclear features of papillary carcinoma are not well developed or only focally present. We assessed interobserver and intraobserver agreement among 6 thyroid experts by using 15 cases in which original pathologists suspected FVPC. There was unanimous expert agreement in diagnosing FVPC in only 2 cases (13%) and majority agreement in 6 cases (40%). Unanimous agreement on benign and malignant diagnoses was seen in 4 cases (27%) and majority agreement on malignancy in 8 cases (53%). Intraobserver agreement ranged from 17% to 100%. Histologic features considered most helpful in diagnosing FVPC were nuclear clearing, nuclear grooves, nuclear overlapping and crowding, nuclear membrane irregularity, and nuclear enlargement. This considerable interobserver and intraobserver variability in the diagnosis of FVPC seems to result from lack of agreement on the minimal criteria needed to diagnose FVPC, even among experts.

The National Cancer Institute (NCI) sponsored the NCI Thyroid fine-needle aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters addressing manual and ultrasound guided FNA technique and related issues. Specific topics covered include details regarding aspiration needles, devices, and methods, including the use of core needle biopsy; the pros and cons of anesthesia; the influence of thyroid lesion location, size, and characteristics on technique; the role of ultrasound in the FNA of a palpable thyroid nodule; the advantages and disadvantages of various specialists performing a biopsy; the optimal number of passes and tissue preparation methods; sample adequacy criteria for solid and cystic nodules, and management of adverse reactions from the procedure. (http://thyroidfna.cancer.gov/pages/info/agenda/)

Objective: To evaluate the prevalence and potential pitfalls in making an accurate diagnosis of respiratory herpetic infection., Study Design: Eighteen cases with the diagnosis of herpes simplex virus (HSV) infection were identified from a total of 7,501 (0.24%) respiratory specimens. All cases were evaluated for classic cytomorphologic features of HSV infection and associated cytologic findings. The parameters studied included number of cells with HSV cytopathic effect, intranuclear inclusions, multinucleation, presence of atypical squamous cells, reparative changes, presence and degree of inflammation and associated obscuring factors., Results: Only a minority of cases (28%) had numerous cells with classic viral cytopathic change. Four (22%) of 18 cases showed atypical squamous cells, and 5 (28%) revealed reparative changes. The majority of the cases were associated with inflammation, which was severe in 4 cases (22%). Blood and degenerative changes obscured the cytologic findings in 3 cases (17%). One case showed a necrotic background., Conclusion: Due to the low prevalence of HSV infection in respiratory cytology, a high index of suspicion is necessary for an HSV diagnosis. Pitfalls for a false negative diagnosis include limited number of cells with viral cytopathic change, only mononuclear cells with viral changes and obscuring inflammation or blood. Pitfalls for a false positive diagnosis of malignancy include atypical keratinized squamous cells, atypical repair, cellular degeneration and necrotic background.

Background: Early cytologic detection and treatment of high-grade squamous intraepithelial lesion (HSIL) is critical to cervical cancer prevention. The term atypical squamous cells (ASC), cannot exclude HSIL (ASC-H) was introduced in 2001 in the Bethesda System (TBS 2001) to define changes suggestive, but not diagnostic, of HSIL in the absence of unequivocal squamous intraepithelial lesion (SIL). Previous studies showed that women with ASC-H cytology are at an increased risk of harboring underlying histopathologic HSIL. TBS 2001, however, did not address the significance of finding ASC-H changes in a background of unequivocal low-grade SIL (LSIL). There may be a tendency for cytologists to lump these changes with either LSIL or HSIL, depending on their level of comfort. In their laboratory, the authors have referred to these changes as "LSIL, cannot exclude HSIL" (LSIL-H)., Methods: Between July 2001 and July 2003, all Papanicolaou (Pap) tests that were obtained by using the ThinPrep technique were retrieved from the computer data base at the authors' institution. All categories of squamous cell abnormalities, including LSIL-H, were evaluated for their incidence and follow-up diagnoses of HSIL and more severe lesions (HSIL +). All patients had a minimum of 2 year follow-up by biopsy and cytology (range, 2-4 years)., Results: LSIL-H comprised 0.15% (n = 194) of all Pap tests (n = 129,911) that were evaluated during the study period. Follow-up biopsy was available on 59 patients (30.4%), which showed HSIL + in 40.7% of patients. This rate of associated HSIL + differed significantly from that of LSIL (13%; P < .001) and HSIL (74%; P < .001), but was similar to that of ASC-H (44.6%)., Conclusions: The results from this study showed that patients with cytologic diagnoses of LSIL-H had an intermediate risk of harboring histopathologic HSIL +. This risk was similar to ASC-H but fell between the low risk associated with ACS-US and LSIL and the high risk associated with HSIL cytologic diagnoses. The authors believe that LSIL-H should be considered as a distinct cytologic diagnostic interpretation and should be separated from LSIL and HSIL. Although LSIL-H does not represent a unique biologic entity, it has clinical usefulness because of its high positive predictive value for HSIL + lesions., ((c) 2006 American Cancer Society.)

This study is aimed to investigate the role of reflex high-risk human papilloma virus (HPV) DNA testing as an alternative triage method to colposcopy for women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on Papanicolaou (Pap) tests. Reflex HPV DNA testing using Hybrid Capture II method was carried out on 88 women with ASC-H diagnosed by Thin Prep Pap test. Correlation with follow-up biopsies was available on 42 of these patients. The reflex HPV DNA test showed an overall positive rate of 67% and negative rate of 33% in 88 patients with ASC-H. Using age 30 as the cut off point, the positive rate had increased to 83.3% (35/42) in patients 30 yr or younger, while the positive rate for patients older than 30 yr had decreased to 52.2% (24/46). Follow-up colposcopic biopsy results were available in 35 of 59 HPV-positive women, which revealed 15 (43%) high-grade squamous intraepithelial lesions (HSIL), 12 low-grade squamous intraepithelial lesions (LSIL), and 8 negative for dysplasia. In 7 HPV-negative patients, the follow-up biopsies showed no evidence of HSIL or LSIL. Correlation between clinical risk factors and the HPV results demonstrated no significant differences in HPV positivity between the high-risk and low-risk patients. The high sensitivity (100%) and negative predictive rate (100%) in detecting HSIL in our study provide strong evidence that, instead of automatic referral to colposcopy, reflex HPV DNA testing may be used as an alternative triage method for women diagnosed with ASC-H on Thin Prep Pap test, especially for women older than 30 yr of age.

Background: There exists limited literature comparing ThinPrep (TP) with conventional cytospins (CS) in nongynecologic specimens., Methods: The differences between TP and CS were evaluated for a variety of parameters including cellularity, cytologic morphology, specimen preparation, screening time, laboratory cost effectiveness, cytologist preference, and impact on final diagnosis. Eighty-eight cases including 38 urine, 13 respiratory, and 37 body fluids were prepared simultaneously., Results: TP and CS demonstrated similar cellular yield in the majority of cases. Cytologists preferred TP in 63 (71.6%) and CS in 6 (6.8%) cases; whereas they indicated no preference in 19 (21.6%) cases. Of 14 abnormal cytologies, a more definitive diagnosis of malignancy was rendered by TP in 6 (42.9%) and by CS in 2 (14.3%) cases. TP demonstrated better nuclear chromatin morphology and more uniform distribution of cells. CS showed larger-sized clusters with better preservation of their architecture compared with smaller-sized clusters and significant shrinkage of cell size in TP., Conclusions: TP was preferred over CS in the majority of cases by both cytotechnologists and pathologists. Cellularity, screening time, and specimen preparation were comparable, although the latter was easier to standardize in TP. In abnormal cases, TP was found to be 3 times more helpful than CS in rendering a definitive diagnosis of malignancy. TP, however, was associated with certain artifacts that cytologists must become familiar with when examining such preparations. Although TP was superior to CS in most cases, the application of both methods may be helpful in selected cases in which the TP diagnosis is not conclusive. Finally, TP was found to be more cost effective than CS.

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) diagnosed in core needle biopsy (CNB) are generally regarded as risk indicators for developing invasive ductal or lobular carcinoma in either breast. Currently, there are no well-established guidelines for management of these patients. The most common management options are careful observation and endocrine chemoprophylaxis for high-risk patients. Previous studies had contradicting recommendations regarding follow-up surgical excision (FSE) of CNB yielding ALH or LCIS. These studies, unfortunately, have been limited by their retrospective nature, small number of patients examined, and association with other high-risk lesions. Only CNB diagnosed as pure LCIS or ALH (not associated with other high-risk lesions such as ADH, radial scar, or papilloma) were included in the study. We reviewed 33 CNB (20 ALH and 13 LCIS) with subsequent FSE from 33 patients (age range, 30-83 years; mean, 58 years). Eighteen of these patients were prospectively analyzed, where FSE was performed in an unselected fashion. All CNBs were obtained by mammotome (11-gauge, 30 cases; and 14-gauge, 3 cases). Mammography identified calcifications in 29 cases (88%) and a mass in 4 cases (12%). FSE revealed infiltrating ductal and/or lobular carcinoma in 4 of 13 LCIS (31%). FSE of 20 ALH revealed cancer in 5 cases (25%), including 4 ductal carcinoma in situ (DCIS) and 1 invasive lobular carcinoma. Seven of these nine cancers were associated with calcifications, and two presented as masses. Sampling error and underestimation of cancer (DCIS or invasive carcinoma) was associated with CNB diagnosis of LCIS or ALH in 27% of all cases. Underestimation of cancer was seen in 28% of prospectively examined patients, including 20% of ALH and 38% of LCIS. CNB associated with mass lesions or that showed histologic features of pleomorphic LCIS or extensive classic LCIS had a higher rate of cancer underestimation. Despite removal of all abnormal mammographic calcifications by CNB in 6 patients, one cancer was detected on FSE. To the best of our knowledge, this is the largest study reported to date, and the only one to include prospectively examined patients with no pre-selection bias. Our data strongly suggests that subsequent FSE is warranted in all patients with CNB diagnoses of LCIS or ALH, to exclude the presence of cancer.

The cytologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) can be extremely challenging and may be associated with false negative diagnoses. The purpose of this study was to determine the minimal cytologic criteria needed to identify FVPTC. We examined sixty-nine fine-needle aspiration (FNA) cases, processed with Diff-Quik and Papanicolaou stains, that were either diagnostic or suspicious of FVPTC. All cases had histologic confirmation. These cases included 29 FVPTC, 18 classic papillary thyroid carcinoma (PTC), 17 follicular neoplasm (6 adenomas, 10 carcinomas, 1 neoplasm NOS), 2 lymphocytic thyroiditis and 3 nodular goiter. Seven of the most commonly cited cytomorphologic features, including flat syncytial sheets, nuclear enlargement, fine chromatin, nuclear grooves, nuclear pseudoinclusions, and amount of colloid and cytoplasm, were evaluated. A diffuse distribution of fine chromatin, nuclear grooves, and colloid was seen more often in FVPTC than in follicular neoplasm (p<0.01). The combination of flat/syncytial sheets, nuclear enlargement, and fine chromatin was observed in all our cases of FVPTC, and is therefore considered a sensitive marker in detecting FVPTC. Logistic regression analysis revealed colloid to be the only positive predictor in favor of FVPTC over classic PTC., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To describe 633 cases using the Tao Brush for endometrial biopsy (EBB) in an outpatient setting., Study Design: Histologic follow-up specimens within six months of EBB in an outpatient setting were evaluated over a two-year period. Diagnosis by EBB relied mainly on histologic evaluation of hematoxylin and eosin-stained tissue sections and was complemented by additional cytologic smear examination in our laboratory. Diagnostic categories included the following: nondiagnostic (ND), benign endometrium (BE), hyperplasia without atypia (H), atypia (AT) and atypical hyperplasia (AH)/carcinoma (CA). The correlation between EBB and follow-up histology was analyzed., Results: A total of 633 EBBs were evaluated. Diagnoses were rendered in 569 cases, with a diagnostic rate of 90%. Histologic follow-up was evailable for 156 patients. Twelve AH/CA diagnosed by EBB were confirmed by histologic follow-up as CA. However, there was one false positive case, in which EBB showed AH/CA and dilatation and curettage (D&C) revealed disordered, weakly proliferative endometrium. Nine of 10 EBBs with AT diagnoses were 3 CA, 1 AH and 5 BE on follow-up. Two of eight H had D&C follow-up that also showed H. Histologic follow-up was available in 114 of 538 benign EBBs and showed benign correlation in 112 cases. There were two false negative cases; the EBB diagnoses were atrophic endometrium and weakly proliferative endometrium, while D&C showed focal AH in both cases. Among the ND cases, 18 of 64 had tissue follow-up and disclosed 4 CA, 1 H, 12 BE and 1 ND., Conclusion: EBB is a reliable diagnostic tool for endometrial sampling in an outpatient setting. The sensitivity and specificity in identifying CA among satisfactory specimens is 100% and 96%, respectively, when AT or a more severe diagnosis is made by EBB. Assessment of specimen adequacy is important for pathologists interpreting EBB. In our study, four cases of adenocarcinoma were identified in the follow-up D&C in patients with nondiagnostic EBB.

The gastrointestinal tract is an unusual site for teratomas to occur. Only 4 prior cases of teratomas involving the cecum have appeared in the English literature, the latest published in 1977. To the best of our knowledge, this is the first report to describe fine-needle aspiration cytologic findings in addition to histologic features of a mature cystic teratoma involving the gastrointestinal tract. A 30-year-old man presented with right upper quadrant abdominal pain and a palpable abdominal mass. Radiographic studies identified a mass lesion inferior to the liver and in close association with the ascending colon. Fine-needle aspiration biopsy showed scant keratinous material and anucleated squamous cells. Right colectomy revealed a cystic mass in the wall of the cecum that contained keratinous material and was lined by stratified granular squamous epithelium with sebaceous glands. Clinical and pathologic features with review of the literature are presented, and the differential diagnosis for pericolic cystic masses is discussed in detail.

We examined 200 cases of endometrial brush biopsy (EBB) using the Tao brush and correlated findings with histologic findings from subsequent dilatation and curettage (D&C) or hysterectomy specimens. Diagnosis by EBB relied mainly on histologic evaluation of H&E-stained tissue sections and was complemented by additional cytologic smear examination. EBB correctly detected the following cases: endometrioid adenocarcinoma, 3; complex hyperplasia with atypia, 1; simple hyperplasia without atypia (SH), 2; and benign endometrium, 177. In 3 cases the diagnosis of atrophic endometrium was made by EBB; corresponding D&C specimens were nondiagnostic. Five cases of SH were interpreted by EBB as proliferative endometrium, and 13 endometrial polyps were not identified by EBB. Nine samples were nondiagnostic. Sensitivity and specificity were 100% for detecting atypical hyperplasia and carcinoma. However, it was difficult for EBB to distinguish SH from disordered proliferative endometrium or to diagnose endometrial polyps. We found that diagnosis by EBB is reproducible; a second pathologist blinded to histologic follow-up correctly identified all adenocarcinoma/atypical hyperplasia cases. EBB is an accurate, safe, and easy procedure that is well tolerated by patients and should be considered in the initial evaluation of high-risk outpatients.