(268) The Limited Role of Routine Pathology Examination in Neuroproliferative Vestibulodynia
Authors: Goldstein I , Kim NN , Goldstein SW , Drian A , Yee A 
Published: February 2024

Abstract

Introduction
Neuroproliferative vestibulodynia (NPV) is suspected in women with entrance dyspareunia, vestibular allodynia, and hyperalgesia, after ruling out other causes. If conservative biopsychosocial treatments in patients with suspected NPV are unsuccessful, vestibulectomy may be an appropriate option. Excised vestibular surgical specimens are sent for routine pathology assessment, including hematoxylin and eosin (H&E) staining.

Objective
To review reports of gross and microscopic pathology examinations of excised vestibular specimens from a cohort of patients with NPV and compare immunohistochemical (IHC) staining density between subgroups classified by severity of subepithelial inflammatory infiltrate.

Methods
Excised specimens from NPV patients, the 1:00-11:00 region (n = 63) and 12:00 region (n = 54) of the vestibule, were placed in 10% formalin prior to pathology examination. Routine pathology assessment included gross examination and cytological characterization of H&E-stained vestibular tissue for malignancy, viral nuclear changes (in addition to P16 staining), and quality of the vestibular epithelium and subepithelial inflammatory infiltrate. Severity of this infiltrate was classified by the pathologist as mild, mild-moderate, moderate, or severe. Additional vestibular tissue sections were processed for IHC staining for CD117 and PGP9.5, protein markers consistent with mast cells and nerves, respectively. Mast cell counts and immunopositive mean fractional area for CD117 and PGP9.5, separated into subgroups based on severity of subepithelial inflammatory infiltrate, were compared using Kruskal-Wallis test.

Results
Gross examinations of the 1:00-11:00 and 12:00 regions of vestibular tissue showed mean dimensions (length, width, thickness) to be 5.8 x 2.1 x 0.6 cm and 1.0 x 0.7 x 0.3 cm, respectively. Microscopic examinations revealed no malignant cells in any specimen and viral nuclear findings were consistent with HPV in 3 specimens. Vestibular tissue was characterized as non-reactive squamous epithelium in 90.5% and 92.6% of specimens for the 1:00-11:00 and 12:00 regions, respectively. Mature lymphocytes were found in the subepithelial stromal infiltrate of 67% of specimens in both the 1:00-11:00 and 12:00 regions. Severity of subepithelial stromal infiltrate was reported as: mild in 67% and 65%; mild-moderate in 5% and 4%; moderate in 14% and 15%; and severe in 14% and 17% of cases for the 1:00-11:00 and 12:00 regions, respectively. Amongst the subgroups categorized by severity of inflammatory infiltrate, there were no significant differences for CD117-immunopositive cell counts or mean fractional area of CD117 and PGP9.5 in the 1:00-11:00 and 12:00 regions.

Conclusions
No significant differences were found between subgroups of severity of subepithelial inflammatory infiltrate and IHC data. While routine pathology examination including H&E staining is standard for vestibulectomy specimens, such standardized assessment did not provide any insight into the severe allodynia and hyperalgesia associated with NPV, and further, was not useful for confirmation of the diagnosis of NPV. To better understand NPV, excised vestibular tissue should also be stained for CD117 and PGP9.5.

Disclosure
No.