(026) CORRELATIONS BETWEEN IMMUNOHISTOCHEMICAL AND PAIN-RELATED ASSESSMENTS IN NEUROPROLIFERATIVE VESTIBULODYNIA: AN UPDATE IN 102 PATIENTS
Authors: Chung HS , Kim NN , Goldstein SW , Goldstein I 
Published: December 2024

Abstract

Introduction
Neuroproliferative vestibulodynia (NPV) is confirmed by immunohistochemical (IHC) staining of excised vestibular specimens. Compared to controls, specimens from NPV patients contain &gt;8 mast cells per high-power field (HPF) and increased density of nerve endings. A 2024 publication of 65 patients with IHC confirmed diagnosis of NPV assessed correlations between patient-reported pain-related measures and computer-assisted histometry of excised vestibulectomy specimen IHC stained with CD117 (marker for mast cells) and PGP9.5 (marker for nerves). There were no statistically significant correlations between mean fractional area of immunopositive staining and multiple pain-related assessment scores; we hypothesized that there was a threshold of mast cell and nerve accumulation, above which there was no increase in pain scores.

Objective
To determine whether reviewing additional charts of NPV patients would result in statistically significant correlations between immunopositive staining and pain-related assessments.

Methods
Charts of patients who underwent complete vestibulectomy between January 2023 and February 2024 were reviewed and their data added to the original set from the 2024 publication. Tissue sections from the 1:00-11:00 and/or 12:00 regions of the vestibule were examined. High-resolution images were captured using a microscope at 100x and 200x magnification. At least 2 photomicrographs/magnification were taken for each tissue section, including epithelial basement membrane and adjacent subepithelium, representative of the majority of immunostained tissue (Fig. 1). Fractional area of positive immunostaining of all photomicrographs was determined using computer-assisted histometry by ImageJ. Mean fractional area was determined from 3 measurements of each photomicrograph. Correlations were made between density of IHC staining and the following assessments: Female Sexual Function Index (FSFI) pain domain, Short Form McGill Pain Questionnaire (SF-MPQ), cotton-tipped swab testing (1:00–11:00 and 12:00 vestibule), and patient global impression of improvement (PGI-I). Data were analyzed using Spearman correlations and the Mann–Whitney test.

Results
37 charts of NPV patients were added to the original 65, resulting in 102 patients reviewed who underwent vestibulectomy between November 2019 and February 2024, for a total of 1091 photomicrographs analyzed. In the previous study, there were no statistically significant correlations between CD117- or PGP9.5-immunopositive mean fractional area and the FSFI pain domain, SF-MPQ scores, cotton-tipped swab test pain score, or PGI-I. Adding IHC data from the additional 37 patients confirmed no statistically significant correlations between CD117 or PGP9.5 immunopositive mean fractional area and the multiple pain assessments (Fig. 2).

Conclusions
The lack of correlations between immunopositive staining and multiple clinical assessment scores in patients with severe vestibular pain suggests a non-linear threshold for mast cell accumulation and nerve proliferation that results in pain symptoms for NPV patients. Adding data from an additional 37 patients for a total of 102 patients did not change this observation. We hypothesize that once a theoretical threshold for accumulation of mast cells and nerves is reached, additional accumulation does not result in worsened clinical symptoms. This can account for the variability in pain scores among NPV patients and explain why a complete vestibulectomy may be the appropriate treatment no matter the results of the multiple pain assessments once pain is experienced from clinically suspected NPV.

Disclosure
No.