Tumor Area Positivity (TAP) score of programmed death-ligand 1 (PD-L1): a novel visual estimation method for combined tumor cell and immune cell scoring.

BACKGROUND: Determination of programmed death-ligand 1 (PD-L1) protein expression level in tumor cells and tumor-associated immune cells is critical for identifying patients eligible for immunotherapy. PD-L1 manual scoring algorithms can generally be divided into two categories: cell counting and visual estimation. Cell counting can be time-consuming and is not in sync with pathology practice, which classically uses a Gestalt approach based on pattern recognition and visual estimation. In this study, we introduce the Tumor Area Positivity (TAP) score, which is a novel, straightforward method for scoring tumor cells and immune cells together using visual estimation. METHODS: To demonstrate the reproducibility of TAP scoring among pathologists, between- and within-reader precision studies were performed both within (internal) and outside of (external) our organization. We also compared the TAP score to the Combined Positive Score (CPS), which is based on cell counting, for concordance and time efficacy. RESULTS: The average positive agreement, average negative agreement, and overall percent agreement between and within readers were all above 85% for both internal and combined external reader precision studies. TAP score had high concordance rate at 5% cutoff compared with CPS at cutoff 1: positive percent agreement, negative percent agreement, and overall percent agreement were all above 85%. CONCLUSIONS: Our study showed the TAP scoring method to be straightforward, significantly less time-consuming, and highly reproducible with a high concordance rate between TAP score and CPS.

Pathology Education Powered by Virtual and Digital Transformation: Now and the Future.

CONTEXT.­: Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change. OBJECTIVE.­: To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development. DATA SOURCES.­: Sources were a literature review and the personal experience of authors and educators. CONCLUSIONS.­: High-quality digital pathology tools and resources have permeated all the major niches within anatomic pathology and are increasingly well applied to clinical pathology for learners at all levels. Coupled with other virtual tools, the training landscape in pathology is highly enriched and much more accessible than in the past. Digital pathology is well suited to the demands of peer-to-peer education, such as in the introduction of new testing, grading, or other standardized practices. We found that digital pathology was well adapted to apply our current understanding of optimal teaching strategies and was effective at the undergraduate, graduate, postgraduate, and peer-to-peer levels. We curated and tabulated many existing resources within some segments of pathology. We identified several best practices for each training or educational stage based on current materials and proposed high-priority areas for potential future development.

Programmed Cell Death Ligand 1 Pathologist Training in the Time of COVID-19: Our Experience using a Digital Solution.

The COVID-19 pandemic presented numerous challenges to the continuity of programmed cell death ligand 1 (PD-L1) assay training events conducted by our organization. Under typical conditions, these training events are face-to-face affairs, where participants are trained to assay algorithms on glass slides during multi-headed scope sessions. Social distancing measures undertaken to slow pandemic spread necessitated the adaptation of our training methods to facilitate assay training and subsequent continuation of clinical trials. The present report details the creation and use of the Roche pathology training portal (PTP) that allowed for remote training to diagnostic assay algorithms. The PTP is a web-based system comprised of a learning management system (LMS) coupled to an image management system (IMS). Whole slide images (WSIs) were produced using a DP200 instrument (Roche, Pleasanton, CA) and these scan files were then uploaded to an IMS. Courses were created on the LMS using annotated WSIs that were shared with enrolled pathologists worldwide during assay training events. These courses culminated in assay certification examinations, where pathologists evaluated test-case WSIs and evaluated these cases within the LMS. Trainee submissions were analyzed for pass/fail status by comparing user data entries with consensus scores on these test-case WSIs. To date, 47 pathologist trainings have occurred and of these, 44 have successfully passed the associated assay certification exam on the first attempt (93% 1st-try pass rate). The PTP allowed roche to continue training sites during the COVID-19 pandemic, and these early results demonstrate the capability of this digital solution regarding PD-L1 diagnostic assay training events.

Quantitative Image Analysis for Tissue Biomarker Use: A White Paper From the Digital Pathology Association.

Tissue biomarkers have been of increasing utility for scientific research, diagnosing disease, and treatment response prediction. There has been a steady shift away from qualitative assessment toward providing more quantitative scores for these biomarkers. The application of quantitative image analysis has thus become an indispensable tool for in-depth tissue biomarker interrogation in these contexts. This white paper reviews current technologies being employed for quantitative image analysis, their application and pitfalls, regulatory framework demands, and guidelines established for promoting their safe adoption in clinical practice.

Delta-like Protein 3 Prevalence in Small Cell Lung Cancer and DLL3 (SP347) Assay Characteristics.

CONTEXT.­: Delta-like protein 3 (DLL3) is a protein that is implicated in the Notch pathway. OBJECTIVE.­: To present data on DLL3 prevalence in small cell lung cancer and staining characteristics of the VENTANA DLL3 (SP347) Assay. In addition, the assay's immunoreactivity with other neoplastic and nonneoplastic tissues is outlined. DESIGN.­: Individual formalin-fixed, paraffin-embedded specimens of small cell lung cancer and tissue microarrays comprising neoplastic and nonneoplastic tissues were procured. Sections were cut and stained with DLL3 (SP347) assay. The slides were examined to determine prevalence, staining characteristics, and immunoreactivity. RESULTS.­: Cytoplasmic and/or membranous staining was observed in 1040 of 1362 specimens of small cell lung cancer (76.4%). Homogenous and/or heterogeneous and partial and/or circumferential granular staining with varied intensities was noted. Immunoreactivity was also observed in other neoplastic and nonneoplastic tissues. CONCLUSIONS.­: Our study findings provided the profile of DLL3 staining characteristics that can be used for determining the level of DLL3 expression in small cell lung cancer.

Frequency and characterization of celiac ganglia diagnosed on fine-needle aspiration.

INTRODUCTION: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is frequently used to sample intra-abdominal lesions and lymph nodes. Celiac ganglia normally located near the celiac artery may be sampled during these procedures. The aim of this study was to determine the frequency of detection and cytologic findings of celiac ganglia diagnosed on FNA. MATERIALS AND METHODS: A 14-year retrospective review of radiologic and endoscopic FNA cases involving the celiac region was performed. Cases in which ganglia were reported were further analyzed and slides reviewed. RESULTS: A total of 354 patients underwent FNA of a suspected celiac lymph node (334 patients) or celiac mass (20 cases). In 9 of these patients (2.5%), ganglion cells were identified. These were identified in cases only after 2008 via EUS-guided FNA. Aspirates were hypocellular and bloody. Large ganglion cells were either sparsely dispersed or present in clusters. Ganglion cells had a low N: C ratio, granular cytoplasm with neuromelanin, and eccentric small round nucleus with a prominent nucleolus. One specimen had concomitant pancreatic adenocarcinoma. None of these cases had a false positive on-site adequacy assessment or final misdiagnosis. CONCLUSIONS: These data show that celiac ganglia may be infrequently encountered, especially with intra-abdominal EUS-guided FNA targeting nodes or masses near the celiac region. Therefore, cytologists should be aware of the possibility of finding ganglionic cells in EUS-guided FNA samples.