Adrenal gland cytology reporting: a multi-institutional proposal for a standardized reporting system.

BACKGROUND: With the development of new technologies and the changing patient profiles, cytopathology departments receive increasing numbers of adrenal gland cytology specimens. In this study, the authors analyzed archival adrenal gland cytology cases and attempted to implement a diagnostic reporting system. DESIGN: Retrospective electronic medical record search was performed for adrenal gland cytology specimens in seven tertiary care centers. The cytology diagnoses were grouped in 7 categories: nondiagnostic, nonneoplastic, benign adrenal cortical elements (BACE), primary neoplasm of noncortical origin (NONC), atypia of undetermined significance (AUS), suspicious for malignancy (SM), and malignant (MAL). If available, histopathology results of concurrent and/or follow-up biopsies and/or resections were documented. RESULTS: A total of 473 adrenal gland cytology cases were included. BACE cases comprised 21.8%, whereas MAL cases were 57.5% of all cases. For BACE and MAL categories, there were 100% and 98.9% correlation, respectively, in the cases with histopathology follow-up. Six of 10 NONC cases had histopathology diagnoses and there were 3 pheochromocytomas and 3 schwannomas. Twenty-one AUS cases had histology follow-up and 10 (47.6%) of them were malignant. Six cases of SM had histopathology follow-up, and all of them were malignant on the follow-up. CONCLUSIONS: The authors propose a 7-tier diagnostic scheme for adrenal gland cytology. The risk of malignancy was 98.9% in MAL cases (87/88) in the cohort. The only case with discordance was reported as "adrenal cortical adenoma with marked atypia"' on resection. There was no difference between endoscopic ultrasound-guided and percutaneous methods. Further studies are needed to validate and make this approach universal.

Endoscopic ultrasound (EUS)-guided fine needle biopsy alone vs. EUS-guided fine needle aspiration with rapid onsite evaluation in pancreatic lesions: a multicenter randomized trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard in the diagnosis of solid pancreatic lesions, in particular when combined with rapid onsite evaluation of cytopathology (ROSE). More recently, a fork-tip needle for core biopsy (FNB) has been shown to be associated with excellent diagnostic yield. EUS-FNB alone has however not been compared with EUS-FNA + ROSE in a large clinical trial. Our aim was to compare EUS-FNB alone to EUS-FNA + ROSE in solid pancreatic lesions. METHODS: A multicenter, non-inferiority, randomized controlled trial involving seven centers was performed. Solid pancreatic lesions referred for EUS were considered for inclusion. The primary end point was diagnostic accuracy. Secondary end points included sensitivity/specificity, mean number of needle passes, and cost. RESULTS: 235 patients were randomized: 115 EUS-FNB alone and 120 EUS-FNA + ROSE. Overall, 217 patients had malignant histology. The diagnostic accuracy for malignancy of EUS-FNB alone was non-inferior to EUS-FNA + ROSE at 92.2 % (95 %CI 86.6 %-96.9 %) and 93.3 % (95 %CI 88.8 %-97.9 %), respectively (P = 0.72). Diagnostic sensitivity for malignancy was 92.5 % (95 %CI 85.7 %-96.7 %) for EUS-FNB alone vs. 96.5 % (93.0 %-98.6 %) for EUS-FNA + ROSE (P = 0.46), while specificity was 100 % in both. Adequate histological yield was obtained in 87.5 % of the EUS-FNB samples. The mean (SD) number of needle passes and procedure time favored EUS-FNB alone (2.3 [0.6] passes vs. 3.0 [1.1] passes [P < 0.001]; and 19.3 [8.0] vs. 22.7 [10.8] minutes [P = 0.008]). EUS-FNB alone cost on average 45 US dollars more than EUS-FNA + ROSE. CONCLUSION: EUS-FNB alone is non-inferior to EUS-FNA + ROSE and is associated with fewer needle passes, shorter procedure time, and excellent histological yield at comparable cost.

Immunocytochemistry for diagnostic cytopathology-A practical guide.

Cytological specimens, which are obtained by minimally invasive methods, are an excellent source of diagnostic material. Sometimes they are the only material available for diagnosis as well as for prognostic/predictive markers. When cytomorphology is not straightforward, ancillary tests may be required for a definitive diagnosis to guide clinical management. Immunocytochemistry (ICC) is the most common and practical ancillary tool used to reach a diagnosis when cytomorphology is equivocal, to differentiate entities with overlapping morphological features, and to determine the cell lineage and the site of origin of a metastatic neoplasm. Numerous immunomarkers are available, and some are expressed in multiple neoplasms. To rule out entities within a differential diagnosis, the use of more than one marker, sometimes panels, is necessary. ICC panels for diagnostic purposes should be customised based on the clinical context and cytomorphology, and the markers should be used judiciously to preserve material for additional tests for targeted therapies in the appropriate setting. This review offers a practical guide for the use of ICC for diagnostic cytopathology, covering the most commonly encountered non-hematolymphoid diagnostic scenarios in various body sites.

Evidence-based diagnostic accuracy measurement in urine cytology using likelihood ratios.

INTRODUCTION: Recent cytology classification systems have become more evidence-based and advocate for the use of risk of malignancy (ROM) as a measure of test performance. From the statistical viewpoint, ROM represents the post-test probability of malignancy, which changes with the test result and also with the prevalence of malignancies (or pre-test probability) in each individual practice setting and individual patient presentation. Evidence-based medicine offers likelihood ratios (LRs) as a measure of diagnostic accuracy for multilevel diagnostic tests, superior to sensitivity and specificity as data binarization and information loss are avoided. LRs are used in clinical medicine and could be successfully applied to the practice of cytopathology. Our aim was to establish LRs to compare diagnostic accuracy of The Paris System for Reporting Urinary Cytology (TPS) and of a historic urine cytology reporting system. MATERIALS AND METHODS: We analyzed sequential voided urine cytology cases with histologic outcomes: 188 pre-TPS and 167 post-TPS. LRs were calculated as LR = True positive % (per category)/False positive % (per category) [95% confidence interval] and interpreted LRs = 1 nondiagnostic, LR >1 favor, LR >10 strongly favor, LRs <1 favor exclusion, and LR <0.1 strongly favor exclusion of a target condition, respectively. CATmaker open source software and Fagan nomograms were used for calculation and visualization of the corresponding post-test probability (ROM) of high-grade urothelial carcinoma (HGUC) in various scenarios. RESULTS: Both reporting systems show near-similar performance in terms of LRs, with moderate discriminatory power of negative, suspicious, and positive for HGUC test results. The atypical urothelial cell (AUC) category establishes as indiscriminate LR = 1 in the TPS, whereas in pre-TPS it favored a benign condition. We further demonstrate the utility of LRs to determine individual post-test probability (ROM) in a variety of clinical scenarios in a personalized fashion. CONCLUSIONS: The LRs allow for a quantitative performance measure in case of urine cytology across different scenarios adding numeric information on diagnostic test accuracy and post-test probability of HGUC. The diagnostic accuracy of pre-TPS and post-TPS remained similar for all but the AUC category. With the TPS, the AUC category has become genuinely diagnostically and statistically indeterminate and requires further patient investigations.

A practical guide for ancillary studies in pulmonary cytologic specimens.

Although most pulmonary cytologic specimens obtained by either exfoliation or fine needle aspirates can be reliably and accurately diagnosed based on pure morphologic criteria alone, a small proportion of cases require ancillary studies for either refining a diagnosis, for resolving a differential diagnosis or increasingly, for predictive purposes in primary lung carcinomas. This article aims to provide practical guidance on the use of common ancillary studies in pulmonary cytologic specimens. Cancer Cytopathol 2018;000:000-000. © 2018 American Cancer Society.

Implementing The Paris System for Reporting Urinary Cytology results in a decrease in the rate of the "atypical" category and an increase in its prediction of subsequent high-grade urothelial carcinoma.

BACKGROUND: In the current study, the authors evaluated the impact of implementing The Paris System for Reporting Urinary Cytology (PSRUC) on the prevalence of various cytological categories and their association with a subsequent diagnosis of high-grade urothelial carcinoma (HGUC). METHODS: A comparative study was conducted over the 6-month period before PSRUC implementation (2013), including 1653 patients and 2371 specimens versus a 6-month period after implementation of the PSRUC (2016), including 1478 patients and 2392 specimens. The following cytological categories were correlated with the subsequent biopsy result when available (355 cases): negative for HGUC (NHGUC), atypical urothelial cells (AUC), suspicious for HGUC, and HGUC. RESULTS: Although 18.6% of specimens were diagnosed as AUC in 2013, the percentage was 14.4% in 2016 (P < .0001). Concurrently, the prevalence of the "benign" category increased from 2013 to 2016 (75.4% vs 80%; P < .0001). After implementation of the PSRUC, there was no significant change noted with regard to the association between the categories of NHGUC, suspicious for HGUC, and HGUC and a subsequent HGUC biopsy diagnosis. However, the predictive value of an AUC diagnosis increased from 28.3% to 46.1% (P = .077). Most important, after the implementation of the PSRUC, there was a significant difference noted with regard to the predictive association for HGUC between the NHGUC and AUC groups (13.6% vs 46.1%; P = .003), a difference that was not found to be statistically significant before implementation of the PSRUC (18% vs 28.3%; P = .175). CONCLUSIONS: There was a much higher risk of HGUC conveyed by AUC cytology after implementation of the PSRUC, justifying more aggressive investigations of patients who receive an AUC diagnosis. Cancer Cytopathol 2018;126:207-14. © 2017 American Cancer Society.

Impact of Implementing the Paris System for Reporting Urine Cytology in the Performance of Urine Cytology: A Correlative Study of 124 Cases.

OBJECTIVES: We assessed the performance of urine cytology using the Paris System for Reporting Urine Cytology (PSRUC) in comparison to our current system. METHODS: In total, 124 specimens with histologic correlation were reviewed and assigned to the PSRUC categories: benign, atypical urothelial cells (AUCs), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). Original cytological diagnoses were recorded. RESULTS: Fewer cases were given an AUC diagnosis using the PSRUC in comparison to the original diagnoses (26% vs 39%), while the association of AUCs with subsequent HGUC increased from 33% to 53% with the PSRUC. Using the PSRUC resulted in a higher number of low-grade carcinomas assigned to the benign (40%) rather than the AUC (22%) category. The performance of SHGUC/HGUC diagnoses was similar in both systems (predictive value = 94%). CONCLUSIONS: The PSRUC seems to improve the performance of urine cytology by limiting the AUC category to cases that are more strongly associated with HGUC.

Pap smears with glandular cell abnormalities: Are they detected by rapid prescreening?

BACKGROUND: Rapid prescreening (RPS) is one of the quality assurance (QA) methods used in gynecologic cytology. The efficacy of RPS has been previously studied but mostly with respect to squamous lesions; in fact, there has been no study so far specifically looking at the sensitivity of RPS for detecting glandular cell abnormalities. METHODS: A total of 80,565 Papanicolaou (Pap) smears underwent RPS during a 25-month period. A sample was designated as "review for abnormality" (R) if any abnormal cells (at the threshold of atypical squamous cells of undetermined significance/atypical glandular cells [AGC]) were thought to be present or was designated as negative (N) if none were detected. Each sample then underwent full screening (FS) and was designated as either R or N and also given a cytologic interpretation. RESULTS: The final cytologic interpretation was a glandular cell abnormality (≥AGC) in 107 samples (0.13%); 39 of these (36.4%) were flagged as R on RPS. Twenty-four patients (33.8%) out of 71 who had histologic follow-up were found to harbor a high-grade squamous intraepithelial lesion or carcinoma; 13 of those 24 Pap smears (54.2%) had been flagged as R on RPS. Notably, 11 AGC cases were picked up by RPS only and not by FS and represented false-negative cases; 2 of these showed endometrial adenocarcinoma on histologic follow-up. CONCLUSIONS: Pap smears with glandular cell abnormalities are often flagged as abnormal by RPS, and this results in a sensitivity of 36.4% (at the AGC threshold). Most importantly, some cases of AGC are detected on Pap smears by RPS only, and this demonstrates that RPS is a valuable QA method.

Urine cytology: does the number of atypical urothelial cells matter? A qualitative and quantitative study of 112 cases.

INTRODUCTION: This study presents a detailed and systematic morphological and quantitative analysis of urine cytology specimens in order to determine which qualitative and quantitative features are mostly associated with high-grade urothelial carcinoma (HGUCA). MATERIAL AND METHODS: This study included 112 urine cytology cases with a surgical follow-up within 1 year that were originally reported as "atypical," "suspicious for HGUCA," or "positive for HGUCA." The morphological characteristics as well as the number of abnormal cells were correlated with a diagnosis of HGUCA on follow-up biopsy. RESULTS: Multivariate analysis showed that the presence of hyperchromatic atypical cells with nuclear-cytoplasmic ratio ≥ 0.7 was an independent predictor of HGUCA. Similarly, irregular nuclear membranes, single cells, and pleomorphism correlated with surgical outcome whereas eccentric nuclear location, prominent nucleoli, nuclear-cytoplasmic ratio between 0.5 and 0.7 did not. Cases with ≤10 atypical cells had significantly lower rates of subsequent HGUCA than did those with >10 atypical cells (58% versus 77%). Cases with ≤5 atypical cells (n = 26) showed similar prediction rates (58%) for HGUCA than did those with 6 to 10 atypical cells (n = 12). CONCLUSIONS: The number of atypical urothelial cells is an important criterion that should be taken into account when assigning cases to the "positive" or the "suspicious" categories. A preliminary cutoff of 10 cells appears to be easily applicable and valid from the clinical standpoint.

Endosalpingiosis in axillary lymph nodes simulating metastatic breast carcinoma: a potential diagnostic pitfall.

Intraoperative assessment of sentinel lymph nodes at time of surgical excision of primary breast carcinoma is a crucial step in the determination of cancer extent and the need for further axillary dissection. Benign epithelial inclusions in axillary lymph nodes can mimic metastatic carcinoma and are a well-known pitfall during examination of these nodes in frozen or permanent sections. Most often, these inclusions consists of heterotopic mammary glands and are familiar to the practicing pathologist. Here, however, we present a rare case of endosalpingiosis in the axillary lymph nodes of a breast cancer patient and describe our experience and effort to characterize the lesion. Simulating a metastatic focus of invasive ductal carcinoma, the glandular inclusions lacked myoepithelial cells and failed to stain with myoepithelial markers. However, consistent with a Mullerian origin, the inclusions demonstrated strong staining with PAX-8 and WT-1. Although endosalpingiotic inclusions are not uncommonly encountered in subdiaphragmatic lymph nodes, they are an extremely rare finding above the diaphragm. Pathologists must be aware of these lesions and their ability to imitate metastatic gland-forming carcinoma during frozen section or permanent examination of axillary lymph nodes.

Check Sample Abstracts.

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma occurring in the rectum: a case report and review of the literature.

The primary extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct clinical pathologic entity that develops in diverse anatomic locations such as the stomach, salivary gland, thyroid, lung, and breast; however, colorectal involvement is rare. To the best of our knowledge, only 30 cases of primary rectal MALT lymphoma have been published in the English language literature, mostly from Japan. A single case has been reported from the US before this report. The most common symptoms ranged from asymptomatic to occult or gross gastrointestinal bleeding. Simultaneous involvement of the cecum or colon was seen in 20% of the patients. Ninety percent of the patients were classified as low grade, Stage 1 at the time of diagnosis. Polypoid lesions were 10-fold more common than ulcerative lesions. Seven patients were reported to have H pylori in the stomach. The majority of the patients underwent surgical or endoscopic resection as a cure; however, controversy exists with regards to antibiotic treatment or observation alone because of unknown etiopathogenesis. Infection with microorganisms other than H pylori has been postulated in the development of rectal MALT lymphoma; however, this hypothesis remains unproven. The overall prognosis of rectal MALT lymphoma appears favorable; however, long-term follow-up data is lacking. Therefore, periodic clinical monitoring should be done in these patients.

[Palatal pleomorphic adenoma of an unusual size]. / Alisilmamis büyüklükte damak pleomorfik adenomu.

A sixty-year-old male patient presented with complaints of an intraoral mass, dysphonia, dysphagia, and snoring. Physical examination revealed a mass of 4 x 4 cm extending from the hard palate to the oropharynx. Fine needle aspiration biopsy showed a benign epithelial lesion. The mass was removed through a transoral approach. Histopathologic diagnosis was pleomorphic adenoma. No recurrences or surgery-associated complications were observed during a follow-up period of a year.

Pseudocyst of the umbilical cord with mucoid degeneration of Wharton's jelly.

The perinatal findings of a pregnancy complicated by an umbilical cord abnormality associated with mucoid degeneration of Wharton's jelly are presented. Serial ultrasound examinations were not performed because the patient did not visit our outpatient department regularly. The umbilical cord cyst was not detected on ultrasound until delivery.