# Transitional Lesions, One More Step Towards Understanding the Pathogenesis of Adenomyosis

## TL;DR

This study explores immune cell changes in adenomyosis, suggesting mast cells may play a key role in disease progression and pain.

## Contribution

The study introduces a novel multiplex technique to analyze immune cell phenotypes in adenomyosis across menstrual cycle phases.

## Key findings

- Transitional and adenomyotic lesions showed reduced T, NK, B, macrophage, and dendritic cell infiltrates compared to healthy endometrium.
- Mast cells were significantly elevated in transitional lesions, suggesting a role in tissue remodeling and inflammation.
- Findings support the TIAR hypothesis and highlight mast cells as potential therapeutic targets.

## Abstract

Background/Objectives: Adenomyosis is a benign gynecological disorder associated with abnormal uterine bleeding, dysmenorrhea, and subfertility. Its pathogenesis has not yet been elucidated. The most widely accepted theory points to repeated mechanical or hormonal stress at the endometrial–myometrial interface, leading to activation of the tissue injury and repair (TIAR) mechanism. Studies suggest that the immune system may play a role in disease pathogenesis, but inconsistencies persist due to differences in studied samples and evaluated menstrual cycle phases. The goal of our study was to apply a novel technique (multiplex) to investigate different immune cell phenotypes in uteri from adenomyosis patients according to the cycle phase. Methods: This study analyzed immune cell populations in adenomyotic uteri using immunohistochemistry and multiplex immunofluorescence on 30 adenomyotic and 15 healthy hysterectomy samples. Results: Compared to eutopic endometrium, transitional and adenomyotic lesions displayed reduced immune infiltrates, particularly T cells, NK cells, B cells, macrophages, and dendritic cells. Conversely, mast cells were significantly elevated in transitional lesions. Conclusions: The present study suggests mast cell implication in adenomyosis development and pain, through their implication in tissue remodeling, angiogenesis, and neurogenic inflammation. Transitional lesions highlighted the progressive nature of adenomyosis, supporting the TIAR hypothesis. These findings emphasize the importance of mast cells in disease progression and underscore the need for further studies to explore immune-targeted therapies.