PURPOSEProgrammed 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.METHODSArchival 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.RESULTSTwo 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)CONCLUSIONPD-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.

BACKGROUND:Digital pathology practice is rapidly gaining popularity among practicing anatomic pathologists. Acceptance is higher among the newer generation of pathologists who are willing to adapt to this new diagnostic method due to the advantages offered by whole slide imaging (WSI) compared to traditional light microscopy (TLM). We performed this validation study because we plan to implement the WSI system for diagnostic services.OBJECTIVES:Determine the feasibility of using digital pathology for diagnostic services by assessing the equivalency of WSI and TLM.DESIGN:A laboratory-based cross-sectional study.SETTING:Central laboratory at a tertiary health care center.MATERIALS AND METHODS:Four practicing surgical pathologists participated in this study. Each pathologist blindly reviewed 60 surgical neuropathology cases with a minimum 8-week washout-period between the two diagnostic modalities (WSI vs. TLM). Intraobserver concordance rates between WSI and TLM diagnoses as compared to the original diagnosis were calculated.MAIN OUTCOME MEASURES:Overall intraobserver concordance rates between each diagnostic method (WSI and TLM) and original diagnosis.SAMPLE SIZE:60 in-house surgical neuropathology cases.RESULTS:The overall intraobserver concordance rate between TLM and original diagnosis was 86.3% (range 76.7%-91.7%) versus 80.8% for WSI (range 68.3%-88.3%). These findings are suggestive of the superiority of TLM, but the Fleiss' Kappa statistic indicated that the two methods are equivalent, despite the low level of the K value.CONCLUSION:WSI is not inferior to the light microscopy and is feasible for primary diagnosis in surgical neuropathology. However, to ensure the best results, only formally trained neuropathologists should handle the digital neuropathology service.LIMITATIONS:Only one diagnostic slide per case rather than the whole set of slides, sample size was relatively small, and there was an insufficient number of participating neuropathologists.CONFLICT OF INTEREST:None.

Background: Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. Methods: The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. Results: Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. Conclusion: A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country.

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

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. Cancer (Cancer Cytopathol) 2015;123:306–17 . © 2015 American Cancer Society .

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.

This high-yield reference book focuses on the clinical, technical, and pathological aspects of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Its reviews cover all aspects of EBUS-TBNA, including the clinical perspective, technical aspects of the procedure, and cytomorphology of common and uncommon entities, as well a

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

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.

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.