2023 World Conference on Lung Cancer (Posters)-EP13.01. Mitotic Counts and Phospho-Histone H3 Index in Grading Pulmonary Neuroendocrine Tumors: Assessment of Interobserver Variability and Utility

EP13.01. Mitotic Counts and Phospho-Histone H3 Index in Grading Pulmonary Neuroendocrine Tumors: Assessment of Interobserver Variability and Utility - PDF(Slides)

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The study presented by Somagattu Sushmitha from AIIMS, New Delhi, focuses on the grading of pulmonary neuroendocrine tumors, specifically typical carcinoids (TC) and atypical carcinoids (AC). Grading is crucial in determining treatment strategies and predicting patient outcomes. The current grading system relies on the assessment of mitotic counts, but there are limitations in accurately identifying mitotic figures, leading to interobserver variability and sampling bias. <br /><br />The study explores the use of phospho-histone H3 (PHH3) as a potential marker for mitotic figures in pulmonary neuroendocrine tumors. PHH3 is specifically expressed during the mitotic phase and has shown promise in improving interobserver agreement and accuracy compared to traditional mitotic counts. <br /><br />The aims and objectives of the study are to evaluate the value of PHH3 immunohistochemistry and digital image analysis in grading the tumors, assess the agreement levels between PHH3 counts and manual mitotic counts, analyze PHH3-labeled nuclei morphology, evaluate interobserver variability, and investigate the correlation between mitotic index-based grade, PHH3-index based grade, tumor stage, and outcomes.<br /><br />The study design involves a combined retrospective and prospective study with a minimum of 30 cases. The inclusion criteria include cases of lung neuroendocrine tumors in resection specimens with adequate tissue preservation and availability of clinical data and patient consent. The pathological examination involves classification based on the 2021 WHO classification using mitotic index and necrosis, pathologist review, and mitotic counts performed by three independent pathologists. PHH3 immunohistochemistry is performed on representative sections, and digital image analysis is conducted to assess PHH3 counts and morphology.<br /><br />The study's key findings demonstrate the potential of PHH3 as a reliable marker for mitotic figures. There is a high interobserver agreement for PHH3 counts compared to manual mitotic counts, and PHH3 counts show a correlation with tumor grade. However, there is a discrepancy between grading based on PHH3 and H&E mitotic counts in 30% of cases, highlighting the need for further study and standardization.<br /><br />In conclusion, PHH3 immunohistochemistry shows promise as a tool for grading pulmonary neuroendocrine tumors, potentially improving accuracy and interobserver agreement. Further research with larger sample sizes and longer follow-up periods is required to determine the full utility and inclusion of PHH3 in grading criteria.

Asset Subtitle

Somagattu Sushmitha

Meta Tag

Speaker Somagattu Sushmitha

Topic SCLC & Neuroendocrine Tumors: Biomarkers & Radiomics

Keywords

pulmonary neuroendocrine tumors

typical carcinoids

atypical carcinoids

grading system

mitotic counts

phospho-histone H3

PHH3 immunohistochemistry

digital image analysis

interobserver variability

tumor grade