# Diagnostic Utility of Mast Cell Density and Neutrophilic Infiltration for Differentiating Aseptic Loosening From Periprosthetic Joint Infection: A Retrospective Cohort Study

## TL;DR

This study shows that combining mast cell density and neutrophil counts in joint tissue can help distinguish between infection and loosening after joint replacement surgery.

## Contribution

Giemsa-stained mast cell density is introduced as a novel histological marker for diagnosing aseptic loosening.

## Key findings

- Neutrophil counts were significantly higher in periprosthetic joint infection cases compared to aseptic loosening.
- Mast cell density was significantly higher in aseptic loosening cases compared to infection.
- Combining mast cell and neutrophil thresholds achieved 93.2% diagnostic accuracy.

## Abstract

Background

Accurate differentiation between periprosthetic joint infection (PJI) and aseptic loosening (AL) is essential for appropriate surgical planning and optimal postoperative outcomes. Although neutrophil infiltration remains the standard histological marker for diagnosing PJI, it has recognized limitations. Mast cells, which play a role in chronic inflammatory responses, may serve as a complementary biomarker. This study evaluated the combined diagnostic utility of Giemsa-stained mast cell density and neutrophil counts in periprosthetic tissue to distinguish PJI from AL.

Methods

This single-center retrospective cohort study included patients who underwent revision arthroplasty between January 2022 and September 2025. PJI was defined according to the 2018 International Consensus Meeting criteria, whereas AL was diagnosed based on negative microbiological cultures and radiographic evidence of loosening. Periprosthetic tissue samples were stained with H&E for neutrophil assessment and Giemsa stain for mast cell identification. Two blinded observers quantified cells across 10 high-power fields (HPFs; 0.237 mm² per field).

Results

A total of 146 revision cases were analyzed, including 48 PJI and 98 AL cases. Median neutrophil counts were significantly higher in the PJI group than in the AL group (26.5 vs. 1.0 cells/HPF; p < 0.001). Conversely, median mast cell density was significantly higher in AL (11.0 vs. 3.5 cells/HPF; p < 0.001). A neutrophil threshold of ≥5 cells/HPF demonstrated 93.8% sensitivity and 91.8% specificity for diagnosing PJI (area under the curve (AUC) = 0.97). A mast cell cutoff of ≥7 cells/HPF showed 86.7% sensitivity and 85.4% specificity for diagnosing AL (AUC = 0.91). The combined sequential algorithm achieved an overall diagnostic accuracy of 93.2%.

Conclusions

Giemsa-stained mast cell density is a novel, cost-effective histological marker elevated in AL. When combined with neutrophil counts, it improves diagnostic accuracy and may serve as a practical adjunct in the routine pathological evaluation of revision arthroplasty specimens.