# Precancerous Gallbladder Lesions in Cholelithiasis: A Histopathological Study

## TL;DR

This study examines precancerous changes in the gallbladder of patients with gallstones, finding that chronic gallstones are linked to early cancer-like changes that could help detect gallbladder cancer earlier.

## Contribution

The study provides new evidence on the histopathological progression of precancerous gallbladder lesions in cholelithiasis, supporting the metaplasia-dysplasia-carcinoma sequence.

## Key findings

- Epithelial hyperplasia was the most common histopathological change observed in gallbladders with cholelithiasis.
- Low-grade dysplasia and intestinal metaplasia were also frequently detected, suggesting a progression toward cancer.
- Serum alkaline phosphatase levels increased significantly with disease severity, indicating tissue injury.

## Abstract

Background: Gallbladder cancer (GBC) is highly prevalent in Northern and Eastern India and often diagnosed late, leading to poor outcomes. Identifying precursor lesions is essential, as the metaplasia-dysplasia-carcinoma sequence plays a central role in gallbladder carcinogenesis. This study examines precancerous mucosal changes in cholelithiasis and evaluates their histopathological patterns and clinical relevance for early detection.

Materials and methods: This cross-sectional study included 100 patients with ultrasonography-confirmed cholelithiasis who underwent cholecystectomy at Sir Sunderlal Hospital, Banaras Hindu University. Patients with hepatic or metabolic comorbidities were excluded. Clinical characteristics and hematological and biochemical parameters were recorded. Resected gallbladder specimens were examined for microanatomical and histological alterations. Statistical analysis was performed using IBM Corp. Released 2026. IBM SPSS Statistics for Windows, Version 26. Armonk, NY: IBM Corp., with p<0.05 considered significant.

Results: A total of 100 patients with cholelithiasis were stratified into four clinical severity grades. Of these, 36 were male, and 64 were female. The mean age showed no significant variation across the groups (p = 0.480), indicating a uniform age distribution among the study population. Serum alkaline phosphatase levels showed a marked, statistically significant rise with increasing severity (p < 0.0001). Significant inter-group differences were also observed in hemoglobin, platelet count, bilirubin fractions, total protein, urea, and selected anthropometric parameters (p < 0.05). Histopathological evaluation revealed epithelial hyperplasia as the most common lesion (58%), followed by low-grade dysplasia (22%) and intestinal metaplasia (10%), while normal mucosa was seen in only 10% of cases (p < 0.001). These findings demonstrate a clear progression of microanatomical alterations consistent with the metaplasia-dysplasia-carcinoma sequence.

Conclusion: Chronic cholelithiasis was associated with significant mucosal changes, mainly epithelial hyperplasia, intestinal metaplasia, and low-grade dysplasia, supporting the metaplasia-dysplasia-carcinoma sequence. Alkaline phosphatase levels rose progressively with disease severity, indicating ongoing tissue injury. These findings highlight the importance of routine histopathological examination for early detection of precursor lesions.