(088) Fractional Area of Positive CD117 and PGP9.5 Immunostaining of Vestibular Tissue in Patients with Congenital and Acquired Neuroproliferative Vestibulodynia
Authors: Drian A N , Kim N N , Goldstein S W , Goldstein A S , Yee A , Goldstein I 
Published: May 2023

Abstract

Introduction
Neuroproliferative vestibulodynia (NPV) is a form of provoked vestibulodynia associated with an increased density of positive CD117 immunostaining (consistent with mast cells) and positive PGP9.5 immunostaining (consistent with nerves) in the vestibule. Genetic factors underlie the pathophysiology of NPV. Vestibular fibroblasts from NPV patients versus age matched controls produce higher proinflammatory cytokine levels of interleukins (IL) when provoked with Candida albicans in vitro that may lead to proliferation of C-afferent nociceptors. Two variants of NPV have been described. Congenital NPV (CNPV) is associated with a history of painful vaginal penetration by anything and positive umbilical hypersensitivity. Acquired NPV (ANPV) is associated with new onset entrance dyspareunia that persists, typically after an allergic reaction to a topical agent or after severe/recurrent candidiasis. A new computer-assisted approach using ImageJ can objectively assess both CD117 and PGP9.5 percent area of positive immunostaining (PAPI) in vestibular tissue.

Objective
This study compares for the first time immunohistochemical staining with CD117 and PGP9.5 in vestibular tissue from patients with CNPV and ANPV using ImageJ. This may help us better understand any fundamental pathophysiologic differences between the two variants.

Methods
Vestibular tissue samples from patients with CNPV (n=12) and ANPV (n=13) were formalin-fixed, paraffin-embedded, sectioned (10 μm) and subjected to immunostaining protocols with antibodies to CD117 or PGP9.5. Photomicrographs were obtained using 200x and 400x magnification and fractional area of positive immunostaining was determined using Image J; 3 measurements were performed for each photomicrograph. Pre-operative pain intensity (0 – 10) was assessed in both cohorts with cotton-tipped swab testing throughout the entire vestibule. Duration of symptoms, pain intensity scores, and PAPI between CNPV and ANPV patients were compared by Mann-Whitney test. Aggregate data are reported as median (interquartile range).

Results
At the time of complete vestibulectomy surgery, median ages of the CNPV and ANPV groups were 22 years (21 – 25) and 28 years (25 – 33), respectively. Median duration of symptoms in ANPV patients was 4.0 years (3.0 – 6.5), significantly shorter than CNPV patients (p&lt;0.0001). Median pain intensity scores were 7.7 (6.5 – 8.2) and 5.4 (3.9 – 8.0) in the CNPV and ANPV groups, respectively (p = 0.0503). PAPI was similar for both PGP9.5 (0.314% vs 0.424%) and CD117 (0.680% vs 0.797%) in CNPV and ANPV patients, respectively.

Conclusions
In our patients, the density of immunostaining reflective of nerves and mast cells was similar in patients with congenital and acquired forms of NPV despite the median duration of symptoms being approximately 5 times longer in the congenital group. Self-reported pain intensity was nominally higher in CNPV patients but did not reach statistical significance. ANPV may occur later in life but the suspected underlying regional elevation in cytokines in the vestibule of these patients that leads to the increased density of mast cells and the proliferation of C-afferent nociceptors appears likely to be the same in both variants. Future studies should examine potential differences in pain perception between CNPV and ANPV patients.

Disclosure
No