# Reproducibility Examination of Histopathological Growth Patterns of Liver Metastases in a Retrospective, Consecutive, Single-Center, Cohort Study with Literature Review

## TL;DR

This study shows that liver metastasis growth patterns can be reliably assessed by pathologists and trainees with at least two years of experience.

## Contribution

The study includes the largest number of board-certified pathologists and trainees in a reproducibility analysis of histopathological growth patterns.

## Key findings

- Excellent interobserver agreement was observed among specialist trainees and board-certified pathologists.
- Overall agreement among all seven evaluators was good with an ICC of 0.822.
- This is the first study to include a comprehensive literature review on HGP reproducibility.

## Abstract

Objectives: Histopathological growth patterns (HGPs) of liver metastases have been shown to possess prognostic significance. To date, only 2 studies have evaluated the reproducibility of HGP assessment. The aim of our study was to assess the interobserver reproducibility of HGP classification in liver metastases. Methods: A retrospective, consecutive, single-center cohort study was conducted, including patients who underwent surgical resection for liver metastases at the University of Szeged between 2011 and 2023. A comprehensive database was established, incorporating basic histopathological data for each case. Histological slides were independently reviewed by 2 pathologists, 3 pathology specialist trainees, and 2 medical students with varying levels of experience in gastrointestinal pathology. Interobserver agreement was evaluated using intraclass correlation coefficients (ICC) and Fleiss’ kappa. Results: The study included resection specimens from 205 patients, comprising 336 metastatic lesions, predominantly of gastrointestinal origin (n = 188). Excellent interobserver agreement was observed among specialist trainees (ICC = 0.911) and board-certified pathologists (ICC = 0.984). Overall agreement among all 7 evaluators was good (ICC = 0.822). Conclusions: Our findings demonstrate that HGPs can be reliably assessed by individuals with at least 2 years of experience in general pathology. To our knowledge, this is the first study to include the largest number of board-certified pathologists and pathology specialist trainees in a HGP reproducibility analysis. Additionally, no comprehensive literature review on this topic has been previously conducted.