Mast cell characterization, density, and distribution in placenta accreta spectrum: A histological, histochemical and immunohistochemical analysis.

The placenta accreta spectrum (PAS) is a group of disorders characterized by abnormal trophoblastic invasion, often associated with decidual defects, stromal remodeling, and immune dysregulation, resulting in serious obstetric complications. Mast cells (MCs), known for their roles in tissue remodeling, angiogenesis, and inflammation, have not been fully explored in the context of PAS. This study aimed to investigate the morphological, phenotypic, and quantitative alterations of MCs in PAS compared to normal placentas using a multimodal histopathological approach. Placental tissues from PAS cases and gestational age-matched controls were examined using hematoxylin and eosin (H&E), toluidine blue (TB), Alcian blue/safranin (A/S), and immunohistochemistry (IHC) with anti-tryptase antibodies. MC density, distribution, morphology, and activation status were assessed in the decidual, villous, and myometrial compartments and statistical comparisons were made using t-tests and two-way ANOVA. The results showed a significant increase in MC density in PAS placentas across all staining methods (p < 0.05). Histochemical stains revealed a greater number of morphologically activated MCs, particularly connective tissue-type mast cells (CTMCs), in PAS tissues. IHC confirmed elevated counts of tryptase-positive MCs exhibiting features of degranulation, especially in areas adjacent to trophoblastic invasion and stromal disruption. Statistical analysis indicated a significant effect of both diagnosis and staining technique on MC counts (p < 0.001). These findings suggest that MCs are increased and activated in PAS, with potential roles in extracellular matrix (ECM) degradation, inflammation, and abnormal implantation. The predominance of CTMCs and their spatial association with invasive extravillous trophoblasts point to a contributory role in PAS pathophysiology. Further research using expanded immunomarker panels, functional assays, and more diverse study populations is needed to determine whether MCs are causal agents or secondary responders in PAS and to assess their potential as diagnostic or therapeutic targets.