Expression of Immune Response Markers in Arab Patients With Lung Cancer.

PURPOSE: Programmed death-ligand 1 (PD-L1) is a marker for checkpoint inhibitor use in the management of solid tumors, especially in non-small-cell lung cancer (NSCLC). Our study was aimed at determining the patterns of PD-L1 expression and cluster of differentiation 8 (CD8) immunostains in patients with NSCLC in the Arab population. METHODS: Archival tumor tissue from patients with a confirmed diagnosis of NSCLC were obtained and stained for PD-L1 with antibody 22C3, using immunohistochemistry staining and giving the tumor proportion score (TPS) as a percentage from 0%-100% of stained tumor cells. Tumors were categorized into negative expressers (TPS < 1%), low positive (TPS, 1%-49%), and high positive (TPS, 50%-100%). Correlation of expression with clinical and pathologic features, including CD8-positive (CD8+) lymphocyte density, was also analyzed. RESULTS: Two hundred patients with NSCLC were included in the study from 6 centers in Saudi Arabia and Algeria. Median age was 65 years (28-93 years), and the majority were men (75%) with stage 4 NSCLC (64%). The TPS was high in 37 patients (18%), low in 60 patients (30%), and negative in 103 patients (52%). In a univariate analysis, the following were significant predictors of any PD-L1 expression (> 1%): male sex, being Saudi national patients, high expression of CD8+, and presence of tumor-infiltrating lymphocytes. In the multivariate analysis, only high expression of CD8+ cells (≥ 2+) was significant, with an odds ratio of 4.4 (95% CI, 1.5 to 12.9; P = .003). CONCLUSION: PD-L1 expression in our population is similar to the published literature and correlated with the density of CD8+ cells. Validation of the predictive value of this marker in our population and identifying easier and reliable methods to test for it are warranted.

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.

Cytopathology of pulmonary adenocarcinoma with a single histological pattern using the proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification.

BACKGROUND: Guidelines for histological subtyping in patients with surgically resected lung adenocarcinoma (ADC) were recently proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. The objective of the current study was to investigate the cytomorphology of these subtypes of ADC in cases with matched histology specimens demonstrating a single pure subtype. METHODS: The authors reviewed their database for patients with histological diagnoses of primary lung ADC with a single histological pattern observed on surgical resection and investigated the cytological findings in 18 matched cytology specimens to eliminate sampling issues in cases of mixed ADC. RESULTS: Resections were classified as acinar (7 specimens), solid (6 specimens), lepidic (2 specimens), mucinous (2 specimens), and papillary (1 specimen). Cytology specimens demonstrating a solid pattern had a predominance of 3-dimensional clusters (5 of 6 vs 0 of 12 specimens) (P = .0007, Fisher exact test), necrotic background (3 of 6 vs 0 of 12 specimens) (P = .02), pleomorphic nuclei (6 of 6 vs 1 of 12 specimens) (P = .0004), irregular nuclear contours (6 of 6 vs 3 of 12 specimens) (P = .009), and nuclear enlargement (5 of 6 vs 2 of 12 specimens) (P = .01) compared with the nonsolid patterns. Nuclear pseudoinclusions were present only in nonsolid patterns (5 of 12 specimens), although this finding was not statistically significant (P = .05) CONCLUSIONS: Cytological features of lung ADC subtypes proposed by the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification overlap. However, architectural and nuclear features may be helpful, particularly in distinguishing the prognostically adverse solid pattern from other patterns.

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.

Pancreatic fine-needle aspiration cytopathology: an analysis of the CAP NGC program for pancreatic FNA 2003-2011.

INTRODUCTION: The College of American Pathologists monitors quality in cytologic analysis in its nongynecologic cytology sample program. We report the performance of participating laboratories in pancreatic fine-needle aspiration sample analysis. MATERIALS AND METHODS: We evaluated 23,079 responses to 392 pancreatic fine-needle aspiration slide challenges that were collected between January 6, 2003 and December 31, 2011. The analysis examined concordance to the reference diagnosis as well as performance of conventional Papanicolaou smears, Romanowsky smears, CytoSpin and ThinPrep preparations. A nonlinear mixed model was fit with 3 factors: reference diagnosis, reader type, and preparation type. RESULTS: Overall concordance rate was 93.2%, 94.8% for ductal adenocarcinoma, and 96.2% for interpretation of malignancy in cases of neuroendocrine tumors. There was no difference in performance between pathologists and cytotechnologists. In negative/benign preparations, there was a 76.3% concordance to the reference diagnosis. There was 89.2% sensitivity for diagnosis of malignancy when adenocarcinoma was present and 72.8% specificity for a benign non-neoplastic diagnosis with a tendency to overcall and demonstrate insecurity by providing a number of incorrect diagnoses for benign entities. Sensitivity of an exact diagnosis of neuroendocrine lesion when a neuroendocrine tumor is present was 79%. Concordance for diagnosis of mucinous cystic neoplasm without cytologic atypia was problematic at 46.4% with participants yielding an erroneous interpretation of adenocarcinoma one-third of the time. CONCLUSIONS: Participants performed well in recognizing adenocarcinoma, but they overcalled negative samples. Findings can provide focus for education and suggest that efforts be directed at benign pancreatic samples, neuroendocrine cytomorphology, and mucinous neoplasms.

Correlation of cytomorphology and molecular findings in EGFR+, KRAS+, and ALK+ lung carcinomas.

OBJECTIVES: There is increasing emphasis on the subclassification of non-small cell lung carcinomas (NSCLCs) and molecular features to guide treatment. Histologic studies have suggested some morphologic features predominating in tumors. Our aim was to determine if mutated cases had distinct cytomorphology. METHODS: A retrospective study was designed to retrieve all cytopathology cases of NSCLC that had mutation studies for EGFR or KRAS or fluorescence in situ hybridization studies for ALK between 2007 and 2012. All slides from available mutation-positive cases were reviewed, and cytomorphologic features were correlated to mutation status. RESULTS: Of the cases with molecular testing, 62 (39%) of 160 were positive for mutation, including 39 (31%) positive for KRAS, 20 (14%) for EGFR, and 4 (3%) for ALK (one case positive for both EGFR and ALK). More of ALK+ and KRAS+ cases had a diagnosis of NSCLC-favor adenocarcinoma or NSCLC not otherwise specified than did EGFR+ cases (25; 51% vs 5%). Eosinophilic granular cytoplasm was seen in more ALK and KRAS cases than in EGFR cases (100; 32% vs 6%). CONCLUSIONS: Cytologic features of ALK+ and KRAS+ tumors included more nuclear pleomorphism, necrosis, and a less vacuolated cytoplasm than did EGFR+ tumors, which may explain the less definitive subclassification in ALK+ and KRAS+ tumors.

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.

Cytopathology of extracranial ectopic and metastatic meningiomas.

INTRODUCTION: Extracranial meningiomas may infrequently be encountered as ectopic or metastatic tumors. Their rarity and unique cytomorphology often pose significant diagnostic dilemmas. The aim of this study was to report our experience with a series of ectopic and metastatic meningiomas, characterizing their cytomorphology with histological correlation. MATERIALS AND METHODS: A retrospective analysis involving 13 patients with cytological preparations from extracranial meningiomas was performed. Cytology cases were correlated with available surgical resection specimens. Data regarding clinical findings, tumor information, cytomorphology, follow-up histological features and immunohistochemistry were recorded and analyzed. RESULTS: There were 5 cases with metastases and 8 ectopic meningiomas. Metastases occurred in the scalp/skull, lung, paraspinal soft tissue and liver. Primary ectopic meningiomas were located in the paranasal sinuses and ear, orbit and neck. Cytomorphological features characteristic of meningiomas were identified in the majority of samples including tightly cohesive clusters of spindled cells, whorls, intranuclear inclusions, nuclear grooves and psammomatous calcification. Unusual cytomorphological features identified in only a few cases included epithelioid cell predominance, abundant inflammatory cells, small-cell change, papillary structures and pseudoacinar growth. Metastatic tumors exhibited more nuclear atypia and occasionally mitoses or necrosis. Meningiomas were shown to be immunoreactive for epithelial membrane antigen, pancytokeratin and vimentin. CONCLUSION: Although rare, extracranial meningiomas can be encountered in cytologic specimens and should be included in the differential diagnosis when characteristic morphological features of meningiomas are seen. Cytopathologists should be aware that these lesions could be mistaken for other tumors, especially when confounded by atypia and unusual cytomorphological features.

Evaluation of endobronchial ultrasound-guided fine-needle aspirations (EBUS-FNA): correlation with adequacy and histologic follow-up.

BACKGROUND: Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) is a minimally invasive modality for diagnosing mediastinal lesions. When determining adequacy, EBUS-FNAs are evaluated for diagnostic material or sufficient lymphoid tissue. In this study, the authors evaluated their experience with EBUS-FNAs and correlated the findings with adequacy and histologic follow-up. METHODS: EBUS-FNAs were retrospectively reviewed over a 3-year period and correlated with the clinicopathologic findings, adequacy, and histologic follow-up. RESULTS: In total, 593 EBUS-FNAs were obtained from 356 patients, including 420 (71%) satisfactory (SAT) cases, 107 (18%) less than optimal (LTO) cases, and 66 (11%) unsatisfactory (UNSAT) cases. The overall diagnostic yield was 71%, and the mediastinal (N2) lymph nodes had better yield (72%) than the peripheral intrapulmonary and hilar (N1) lymph nodes (64%). Histologic follow-up was available in 203 cases (34%), and malignancy was identified in 7 UNSAT cases (23%), 6 LTO-negative cases (11%), and 4 SAT cases (3%) with a negative cytologic diagnosis. In the suboptimal cases with follow-up, 79% were benign and 21% were malignant on follow-up, including 25 (14%) with fibrosis or hyalinization. The sensitivity, specificity, and positive and negative predictive values in the study were 80%, 100%, 100%, and 95%, respectively. CONCLUSIONS: The current data demonstrated that EBUS-FNA has good sensitivity, high specificity, and a higher diagnostic yield for N2 lymph nodes compared with N1 lymph nodes. The data also illustrate the finding that suboptimal cases have a greater risk of false-negative diagnoses and a 21% chance of malignancy, including processes with fibrosis or hyalinization.

Cytomorphology of unusual primary tumors in the Pap test.

Rare entities in the Pap test, which include neoplastic and non-neoplastic conditions, pose challenges due to the infrequent occurrence of many of these entities in the daily practice of cytology. Furthermore, these conditions give rise to important diagnostic pitfalls to be aware of in the Pap test. For example, cases with adenoma malignum (AM) have been called benign. Recognition of these conditions can help correctly interpret Pap tests as abnormal and thereby ensure that patients get appropriately diagnosed. In this paper, we illustrate and discuss selected uncommon primary neoplastic lesions of the cervix and the vagina that may be seen in Pap test, with a focus on cytomorphology, differential diagnosis and the role of possible ancillary studies. These cases include high-grade squamous intraepithelial lesion cells with small cell morphology; small cell carcinoma; large neuroendocrine carcinoma; glassy cell carcinoma; AM; malignant mixed Müllerian tumor; clear cell carcinoma and primary malignant melanoma. Recognition of these rare variants/neoplasms is important so that involved Pap tests are not diagnosed as benign and that patients with these conditions get additional follow-up.

Implementation of the Bethesda System for Reporting Thyroid Cytopathology: observations from the 2011 thyroid supplemental questionnaire of the College of American Pathologists.

CONTEXT: Although information about the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been widely disseminated since its inception in 2007, the extent of its implementation and impact on daily practice has not been formally evaluated. OBJECTIVES: To assess the extent of uptake of TBSRTC across pathology laboratories and to evaluate its impact on daily practice by collating participant responses to the 2011 supplemental thyroid questionnaire of the College of American Pathologists. DESIGN: A questionnaire was designed to gather information about various aspects of TBSRTC and mailed in June 2011 to 2063 laboratories participating in the College of American Pathologists cytopathology interlaboratory comparison program. The participating laboratories' answers were collated and summarized. RESULTS: Seven hundred and seventy-seven laboratories (37.6%) returned the survey. Although 60.9% (n = 451) and 17.1% (n = 127) of laboratories reported using TBSRTC or planning to use it in the near future, respectively, 22% (n = 163) had no plans to implement TBSRTC. Of the latter, 32% (n = 70) stated that they were unaware of this classification system. The majority (78.3%, n = 343) of the laboratories used TBSRTC as published in the Thyroid Bethesda System atlas, whereas 21.7% (n = 95) used it with minor modifications. Most reported that the use of TBSRTC had caused either no change (n = 67, 15.2%) or only minor changes (n = 353, 80.2%) in the terminology and diagnostic criteria previously used in their laboratories. CONCLUSIONS: According to the collected data, TBSRTC is generally well implemented in pathology laboratories. However, because approximately a third of those not using this terminology are not aware of it, additional educational efforts regarding TBSRTC are warranted.

Cytomorphology of Boerhaave's syndrome: A critical value in cytology.

Spontaneous esophageal perforation into the pleural cavity (Boerhaave's syndrome) is a rare life-threatening condition, which requires early diagnosis and urgent management. The diagnosis of such critical condition in many cases is delayed because of atypical clinical presentation, resulting in increased morbidity and mortality. Cytological examination of pleural fluid can provide early, fast and accurate diagnosis of such critical condition and help in better and early management of this disease. We describe a case of an 81-year-old female with esophageal perforation who presented with a left sided pleural effusion. The correct diagnosis was established in this case by observing gastrointestinal-like fluid characteristics of the thoracic drainage upon cytological and chemical analyses and the rupture was confirmed by esophagography. The cytological examination of pleural fluid revealed benign reactive squamous cells, fungal organisms, bacterial colonies, and vegetable material consistent with a ruptured esophagus. Cytological examination of pleural fluid is a rapid and accurate technique that can help in establishing the diagnosis of this challenging entity and guide initiation proper management of this unusual entity.

Indeterminate pediatric thyroid fine needle aspirations: a study of 68 cases.

OBJECTIVE: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a reporting scheme for thyroid fine needle aspiration (FNA) and includes three indeterminate categories with different management strategies. This study analyzes indeterminate thyroid FNAs in children, and correlates these findings with the histological features. METHODS: A total of 179 thyroid FNA specimens were retrieved from children. Cases were categorized by TBSRTC. Only cases diagnosed as atypia (AUS)/follicular lesion of undetermined significance (FLUS), suspicious for follicular or oncocytic neoplasm (SFON), or suspicious for malignancy (SM) were selected and correlated with the nodule size and histological follow-up. RESULTS: Sixty-eight cases were identified, including 43 (63%) AUS/FLUS diagnoses, 19 (28%) SFON, and 6 (9%) SM. On follow-up, 48% were malignant, including 28% AUS/FLUS cases, 58% SFON, and 100% SM. The average size of the malignant lesions diagnosed preoperatively as AUS/FLUS was 1.5 cm (range 0.7-4.5), compared to 3.3 cm (range 1.2-6.6) in SFON and 2.8 cm (range 0.7-3.8) in SM. Malignancies included 92% papillary thyroid carcinoma (PTC), 77% of which were the follicular variant of PTC (FVPTC) and 8% follicular carcinomas. The AUS/FLUS cases were largely due to compromised specimens (49%) and the highest malignancy rate occurred in those with cytological atypia (50%). CONCLUSIONS: This study shows an incremental risk of malignancy within the indeterminate categories using TBSRTC in children. Malignant nodules with a preoperative AUS/FLUS diagnosis tended to be smaller than those with a SFON or SM diagnosis, and the vast majority of malignancies were PTC, with a high proportion being FVPTC.

The cytological features of mammary analogue secretory carcinoma: a series of 6 molecularly confirmed cases.

BACKGROUND: Mammary analogue secretory carcinoma (MASC) of the salivary glands is a newly described tumor entity associated with the t(12;15)(p13;q25) ETV6-NTRK3 translocation. Early studies have shown this tumor to be a distinct entity with histologic, biologic, and clinical differences from acinic cell carcinoma and adenocarcinoma, not otherwise specified. Because this tumor was described only recently, it remains relatively unknown outside of head and neck specialty pathology centers. METHODS: In the current study, 6 cases of fine-needle aspiration cytology from histologically and/or molecularly confirmed cases of MASC are presented. RESULTS: Using cytomorphology, MASC primarily raises the differential diagnosis of an oncocytic salivary gland tumor but there are some features that can suggest the specific diagnosis of MASC. The 6 cases presented in the current study all demonstrated at least focal cytoplasmic vacuolization and papillary formations on smears. MASC can be differentiated from acinic cell carcinoma by a lack of periodic acid-Schiff diastase-positive zymogen granules and S-100 protein positivity. CONCLUSIONS: The results of the current study the ability of ETV6 break-apart fluorescence in situ hybridization to detect gene rearrangement on cell block material. This is the first report of a case of MASC prospectively diagnosed on a cytology specimen.

Diagnostic digital cytopathology: Are we ready yet?

BACKGROUND: The cytology literature relating to diagnostic accuracy using whole slide imaging is scarce. We studied the diagnostic concordance between glass and digital slides among diagnosticians with different profiles to assess the readiness of adopting digital cytology in routine practice. MATERIALS AND METHODS: This cohort consisted of 22 de-identified previously screened and diagnosed cases, including non-gynecological and gynecological slides using standard preparations. Glass slides were digitalized using Aperio ScanScope XT (×20 and ×40). Cytopathologists with (3) and without (3) digital experience, cytotechnologists (4) and senior pathology residents (2) diagnosed the digital slides independently first and recorded the results. Glass slides were read and recorded separately 1-3 days later. Accuracy of diagnosis, time to diagnosis and diagnostician's profile were analyzed. RESULTS: Among 22 case pairs and four study groups, correct diagnosis (93% vs. 86%) was established using glass versus digital slides. Both methods more (>95%) accurately diagnosed positive cases than negatives. Cytopathologists with no digital experience were the most accurate in digital diagnosis, even the senior members. Cytotechnologists had the fastest diagnosis time (3 min/digital vs. 1.7 min/glass), but not the best accuracy. Digital time was 1.5 min longer than glass-slide time/per case for cytopathologists and cytotechnologists. Senior pathology residents were slower and less accurate with both methods. Cytopathologists with digital experience ranked 2(nd) fastest in time, yet last in accuracy for digital slides. CONCLUSIONS: There was good overall diagnostic agreement between the digital whole-slide images and glass slides. Although glass slide diagnosis was more accurate and faster, the results of technologists and pathologists with no digital cytology experience suggest that solid diagnostic ability is a strong indicator for readiness of digital adoption.

Screening and dotting virtual slides: A new challenge for cytotechnologists.

Digital images are increasingly being used in cytopathology. Whole-slide imaging (WSI) is a digital imaging modality that uses computerized technology to scan and convert entire cytology glass slides into digital images that can be viewed on a digital display using the image viewer software. Digital image acquisition of cytology glass slides has improved significantly over the years due to the use of liquid-based preparations and advances in WSI scanning technology such as automatic multipoint pre-scan focus technology or z-stack scanning technology. Screening cytotechnologists are responsible for every cell that is present on an imaged slide. One of the challenges users have to overcome is to establish a technique to review systematically the entire imaged slide and to dot selected abnormal or significant findings. The scope of this article is to review the current user interface technology available for virtual slide navigation when screening digital slides in cytology. WSI scanner vendors provide tools, built into the image viewer software that allow for a more systematic navigation of the virtual slides, such as auto-panning, keyboard-controlled slide navigation and track map. Annotation tools can improve communication between the screener and the final reviewer or can be used for education. The tracking functionality allows recording of the WSI navigation process and provides a mechanism for confirmation of slide coverage by the screening cytotechnologist as well as a useful tool for quality assurance. As the WSI technology matures, additional features and tools to support navigation of a cytology virtual slide are anticipated.

Cytomorphology of unusual infectious entities in the Pap test.

Rare entities in the Pap test, including neoplastic and non-neoplastic conditions, pose challenges due to their infrequent occurrence in the daily practice of cytology. Furthermore, these conditions give rise to important diagnostic pitfalls. Infections such as tuberculosis cervicitis may be erroneously diagnosed as carcinoma, whereas others, such as schistosomiasis, are associated with squamous cell carcinoma. These cases include granuloma inguinale (donovanosis), tuberculosis, coccidioidomycosis, schistosomiasis, taeniasis, and molluscum contagiosum diagnosed in Pap tests. Granuloma inguinale shows histiocytes that contain intracytoplasmic bacteria (Donovan bodies). Tuberculosis is characterized by necrotizing granulomatous inflammation with Langhans-multinucleated giant cells. Coccidioidomycosis may show large intact or ruptured fungal spherules associated with endospores. Schistosoma haematobium is diagnosed by finding characteristic ova with a terminal spine. Molluscum contagiosum is characterized by the appearance of squamous cells with molluscum bodies. This article reviews the cytomorphology of selected rare infections and focuses on their cytomorphology, differential diagnosis, and role of ancillary diagnostic studies.