Activated mast cells and nerve fiber proximity in the eutopic endometrium and myometrium of women with endometriosis: a double-immunostaining study

To quantify morphologically degranulating tryptase-positive mast cells (aMCt) and examine their spatial relationship with nerve fibers in the eutopic endometrium, endometrial–myometrial interface, and myometrium of women with endometriosis. Cross-sectional histological study of archival specimens using double immunostaining. Academic tertiary pathology service. Hysterectomy specimens from women with surgically and histologically confirmed endometriosis (n = 14). None. Densities of aMCt (cells/mm²) and nerve fibers (fibers/mm²), compartment-specific distribution, and the number of aMCt located within the prespecified proximity threshold of nerve trunks. aMCt were rare in the functional endometrial layer (< 1 cell/mm²) and sparse and unevenly distributed in the basal layer (11.6 ± 4.7 cells/mm²). The most prominent descriptive finding was a higher aMCt density in the myometrium (88.6 ± 44.0 cells/mm²) than in the sampled endometrial layers. Mean myometrial aMCt densities were descriptively similar in proliferative- and secretory-phase specimens (89.7 ± 16.9 and 87.1 ± 19.1 cells/mm², respectively). Nerve fibers were identified in the basal layer (11.6 ± 4.7 fibers/mm²) but were infrequent in the functional layer (< 0.1 fibers/mm²). In selected specimens, 6–12 aMCt were observed around individual nerve trunks, predominantly in secretory-phase tissue at the endometrial–myometrial interface and within the myometrium. However, most aMCt were distributed independently of neural structures. aMCt were infrequently observed in the available coexisting adenomyosis and fibroid tissue. In this small descriptive series, morphologically degranulating tryptase-positive mast cells were more frequently observed in the myometrium than in the sampled endometrial layers. A consistent spatial association between aMCt and nerve fibers was not demonstrated. Occasional proximity, observed mainly in secretory-phase specimens, is hypothesis-generating and should not be interpreted as evidence of temporal regulation, pain generation, or a causal neuroimmune interaction. Larger controlled studies incorporating standardized spatial analyses and clinical pain phenotyping are required.