Benchmarking cytology support for ROSE during endoscopic and bronchoscopic procedures.

INTRODUCTION: There has been an increase in endoscopic and bronchoscopic biopsies as minimally invasive methods to obtain specimens from gastrointestinal (GI) or pancreatobiliary lesions and thoracic or mediastinal lesions, respectively. As hospitals undertake more of these procedures, it is important to consider the staffing implications that this has on cytopathology laboratories with respect to support for rapid on-site evaluation (ROSE). MATERIALS AND METHODS: Volume and time data from endoscopic ultrasound and bronchoscopic procedures (including endobronchial ultrasound-guided transbronchial needle aspirations and small biopsies with touch preparation) in the GI suite, bronchoscopy suite, or operating room were reviewed for 2 months at 2 different medical centers with ROSE services provided by cytologists or fellows physically present at the procedure and cytopathologists located remotely using telecytology. Statistical analysis was performed to investigate significant trends based on the location of the biopsies and other factors. RESULTS: A total of 16 proceduralists performed 159 procedures and submitted 276 different specimens during 16 total weeks at 2 institutions. The total ROSE time for the on-site personnel to cover these procedures was 109.3 hours (bronchoscopy, 62.3 hours [57%]; GI, 29.8 hours [27%]; OR, 17.2 hours [16%]), which represents an average of 0.69 hour (41.4 minutes) per procedure or 0.40 hour (24.0 minutes) per part, with the shortest procedure times per sample recorded during bronchoscopy. When stratified by practice volume for individual proceduralists, the average time per specimen sample submitted was shorter for proceduralists with high volume practices and was most pronounced during bronchoscopy procedures. CONCLUSIONS: Endoscopic and bronchoscopic procedures account for an increasing amount of the ROSE time for the cytology team. On average, each ROSE procedure takes 0.69 hour (41.4 minutes) or approximately 0.40 hour (24.0 minutes) per specimen, with shorter time requirements for specimens obtained in bronchoscopy procedures and for operators with high volume practices for endobronchial ultrasound-guided transbronchial needle aspirations. This provides important benchmarking data to calculate staffing needs for cytology to provide ROSE support for different proceduralists.

Reassessing the optimal volume for malignancy detection in serous fluid cytology.

BACKGROUND: The international system for reporting serous fluid cytopathology (TIS) recommends submitting at least 50-75 mL of serous fluid to decrease false-negative results. However, prior studies did not agree on specific volume requirements or consensus adequacy criteria. Our study aims to assess whether fluid volume affects the adequacy rate and to assess the minimum volume necessary for optimal adequacy in pleural and peritoneal fluids. METHODS: A total of 8530 serous fluid cytology cases were identified in the laboratory information system. Differences in mean fluid volume received in the laboratory were compared using an ANOVA Games-Howell test based on TIS category. The percentage of malignant diagnoses across the volume ranges of 0 to 5 mL, 5 to 10 mL, 10 to 25 mL, 25 to 50 mL, 50 to 75 mL, 75 to 100 mL, 100 to 150 mL, 150 to 250 mL, 250 to 500 mL, 500 to 2000 mL was compared in pleural and peritoneal fluids using a chi-square test, and a SiZer analysis was performed. RESULTS: Mean fluid volume in inadequate, atypical, and negative cases was significantly lower compared to positive cases. A SiZer analysis showed a positive relationship between the malignancy fraction of pleural and peritoneal fluids and fluid volume. The percentage of malignant diagnoses in pleural and peritoneal fluid samples increased significantly up to a volume range of 75-100 mL. CONCLUSIONS: There is a significant relationship between fluid volume, adequacy and detection of malignancy in serous effusion cytopathology. The malignancy fraction increases with larger fluid volumes but at least 75-100 mL of fluid should be submitted for optimal diagnosis of malignancy in pleural and peritoneal fluids.

Comparison of quantitative internal and external measures of performance for trainees in cytopathology fellowships.

INTRODUCTION: Cytopathology fellowships need measures to assess performance of fellows. We sought to compare several internal quantitative assessment metrics in our fellowship with external metrics, such as performance on the American Society of Cytopathology (ASC) Progressive Evaluation of Competency (PEC) examination and United States Medical Licensing Examination (USMLE). METHODS: Quantitative parameters generated from our laboratory information system (LIS) on cytopathology fellows were evaluated over 6 years, including case volume and diagnostic discrepancies, in addition to ASC PEC and USMLE scores. For discrepancy reports, interpretations made by the fellow were compared with that of the cytopathologist, and classified as none (concordant), minor (<2-levels) or major (≥2-levels). RESULTS: We evaluated internal and external metrics on 13 fellows over 6 years. The program average diagnostic concordance rate was 89.9%, with an average major discrepancy rate of 1.5%, and an average monthly case volume of 260 cases. More fellows with above-average ASC PEC performance showed above-average concordant diagnoses and lower case volume, while below-average PEC scores were seen more often with higher major discrepancy rates. More fellows with above-average USMLE scores had higher case volumes, while low USMLE scores showed a trend towards higher major discrepancy rates. CONCLUSION: Our fellowship program has used a variety of internal and external measures of performance for cytopathology fellows. Although the findings show no statistically significant finding correlating performance, these quantitative parameters generated from our LIS were helpful to identify areas of improvement, facilitate comparison to peers, and provide case volume documentation.

Lessons learned from clinical trial queries on small biopsy collections: importance of rapid on-site evaluation.

INTRODUCTION: Small biopsies and cytology specimens have become increasingly important for clinical trials and biomarker testing. Thus, institutions must ensure that adequate lesional material meeting the specifications for a multitude of different protocols is available. This can be achieved using rapid on-site evaluation (ROSE). The aim of the present study was to determine the recent clinical trial biopsy characteristics and study the feedback on these collections at our institution. MATERIALS AND METHODS: Clinical trial biopsies performed at our institution and trial feedback (including "queries") were analyzed from the 2017 to 2019. The query data were reviewed in detail, in addition to any protocol modifications related to biopsy requirements and study protocol changes. RESULTS: A total of 698 biopsy collections were performed for clinical trial purposes for 95 trials, with most requiring biopsies at >1 time point (63.2%), for phase I or II trials (92.6%), and for specific tumor types (67.4%). Only 18 of the trials (18.9%) requiring fresh tissue biopsies provided feedback. The feedback included data from 90 cases (12.9%), of which 27 (30.0%) had queries regarding insufficient (n = 10; 37.0%) or borderline (n = 17; 63.0%) tumor tissue. Only 1 (3.7%) of these had had ROSE by cytology. ROSE was performed in accordance with institutional guidelines (45.3%), as required by the study (1.1%), or because of trial modification (5.3%). CONCLUSIONS: The present investigation has shown the high volume of clinical trial biopsies managed at our academic cancer center. Feedback from the trials was low at 18.9% and frequently involved suboptimal cases without ROSE used at acquisition. This has led to more widespread adoption of ROSE to mitigate insufficient biopsy specimens and repeat procedures. The high volume of clinical trial biopsies and variability in trial needs necessitates a collaborative multidisciplinary network, including cytology services, to facilitate these important biopsies for patients with cancer.

Cytologic Evaluation of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy.

OBJECTIVES: Novel immunotherapeutic options for refractory metastatic cancer patients include adoptive cell therapies such as tumor infiltrating lymphocytes (TILs). This study characterizes the clinicopathologic findings in a cohort of TIL specimens. METHODS: Patients with metastatic malignancy who were eligible had TILs from their metastases grown and expanded and then sent to pathology. RESULTS: A total of 11 TIL specimens (10 melanoma, 1 adenocarcinoma) from patients enrolled in an experimental clinical trial were reviewed. All specimens showed more than 200 lymphoid cells, stained positive for lymphoid markers confirming an activated cytotoxic T-cell immunophenotype, and morphologically showed an intermediate-sized population with immature chromatin and frequent mitoses. Six cases (55%) showed large cells with nucleomegaly and prominent nucleoli. CONCLUSIONS: This report is the first describing cytopathologic findings of autologous TIL therapy including adequacy guidelines and expected cytomorphologic and immunophenotypic findings. To meet this novel clinical demand, a predefined cytology protocol to rapidly process and interpret these specimens needs to be established.

Cell block preparation in urine cytology: examination of utility and workflow in an academic practice.

INTRODUCTION: Urine cytology is a common non-invasive test to screen for urothelial carcinoma. Urine cell blocks may sometimes be prepared as a diagnostic aid (eg, to characterize architecture or perform immunohistochemistry). The aim of this study was to determine whether routinely preparing cell blocks on urine specimens improves diagnostic sensitivity. MATERIALS AND METHODS: Three time periods were compared: time period 1 (prior to November 2009; 1437 consecutive selected cases), when cell blocks were rarely prepared; period 2 (November 2009 to May 2010; 1230 selected cases), when cell blocks were prepared on all cases; and period 3 (after May 2010; 1499 consecutive selected cases), when cell blocks were made only when indicated (for samples with substantial cellular pellets or when requested by a pathologist). RESULTS: Patient demographics and the type of specimens received were relatively similar during the 3 time periods. Increased preparation of cell blocks was not accompanied by a notable improvement in specimen adequacy rate, given that <1%, 2%, and 1% of samples were unsatisfactory for the 3 periods. Only the proportion of atypical cases differed during the time periods, being highest in period 1 (23%), but lower in periods 2 and 3. Turnaround time was fastest for period 1 (mean: 47 hours, median: 33 hours), and slower for period 2 and period 3. CONCLUSION: These data show that routinely preparing cell blocks for urine samples did not improve our laboratory's specimen adequacy rate. Nonetheless, cell block preparation on urine samples did help lower the proportion of atypical diagnoses, when routinely or selectively prepared. Because preparation of cell blocks on all urine cases can be costly and only provides minimal added clinical benefit, our recommendation is to rather judiciously utilize cell blocks when screening urine cytology samples.

Clinical trial cytology: Use of on-site evaluation of small biopsy and FNA samples for clinical trials and biomarker research studies.

BACKGROUND: After increased requests for biopsies for clinical trials and biomarker research, the University of Pittsburgh Medical Center created a clinical trial research service that partnered pathology, radiology, and medicine to facilitate rapid on-site evaluation (ROSE) of fine-needle aspiration (FNA) and/or core needle biopsy (CNB) samples to confirm the presence of tumor in these studies. METHODS: Clinical trial coordinators organized biopsies for patients needing tumor samples for trials, and informed the cytopathology and radiology team. ROSE was performed to confirm the presence of sufficient tumor in FNA specimens and/or touch preparations of CNB. RESULTS: A total of 79 cases from a total of 14 clinical trials were evaluated with ROSE, 77 of which (97%) were for research only. There were 53 cases (67%) from breast/ovarian cancer studies that were initiated between 2008 and 2009, whereas 26 cases (33%) included a variety of other tumors for studies that were started between 2011 and 2014. The majority required CNB samples (60 cases; 76%), 20% of which used an FNA for needle placement before obtaining CNB material and 56% of which had touch preparations of the CNB evaluated without a preceding FNA. The concordance rate for ROSE with final adequacy of the sample was 96% to 100%. CONCLUSIONS: The study institution has experienced an increase in the number of clinical trial studies requesting ROSE to confirm the presence of tumor in a variety of malignancies. Cytology laboratories can help with patient care by offering ROSE to determine the adequacy of clinical trial material to minimize the submission of unsatisfactory or nonrepresentative material. Developing a clinical research service enhances communication and the processing of novel research specimens for cancer patients. Cancer Cytopathol 2018. © 2018 American Cancer Society.