背景:神经增生性前庭痛(NPV),引起的生殖器疼痛,以严重的异常性疼痛和痛觉过敏为特征,通过免疫组织化学染色(>8CD117阳性免疫染色细胞/100倍显微镜视野)而不是通过苏木精和伊红染色在切除的前庭组织中得到证实。
目的:在这项研究中,我们试图评估在前庭切除术期间获得的组织样本的免疫染色,并将结果与患者预后相关联。
方法:在2019年6月至2022年12月期间接受前庭切除术的符合NPV标准的患者(n=65)组成了研究队列。我们通过免疫组织化学染色对前庭组织的病理学进行评估,包括通过CD117(肥大细胞标记)定量肥大细胞和通过蛋白质基因产物(PGP)9.5(神经元标记)定量神经纤维。我们通过手动计数和计算机辅助组织学分析分析了725张免疫染色组织切片的显微照片(100倍和200倍),并将这些数据与临床评估相关联。
结果:结果包括CD117和PGP9.5免疫染色在1:00-11:00时和12:00时前庭区域的密度,和患者报告的评估性功能的结果,疼痛,苦恼,和症状改善。
结果:所有65例NPV患者(中位年龄26岁),45人终身,20人获得净现值,PROs和外阴镜检查记录了严重的疼痛,并且有>8个CD117免疫阳性细胞/100倍显微镜视野。细胞计数值中值在1:00-11:00和12:00前庭区域相似(28.5和29.5/100×场,分别)。同样,标记)和神经纤维通过蛋白质基因产物(PGP)9.5(神经元标记)。我们通过手动计数和计算机辅助组织学分析分析了725张免疫染色组织切片的显微照片(100倍和200倍),并将这些数据与临床评估相关联。
结果:结果包括CD117和PGP9.5免疫染色在1:00-11:00时和12:00时前庭区域的密度,和患者报告的评估性功能的结果,疼痛,苦恼,和症状改善。
结果:所有65例NPV患者(中位年龄26岁),45人终身,20人获得净现值,PROs和外阴镜检查记录了严重的疼痛,并且有>8个CD117免疫阳性细胞/100倍显微镜视野。细胞计数值中值在1:00-11:00和12:00前庭区域相似(28.5和29.5/100×场,分别)。同样,两个区域CD117免疫染色的中位面积相似(0.69%和0.73%).在这些相同区域中,PGP9.5免疫染色的中值面积为0.47%和0.31%。在终身与获得性NPV患者中,用棉头拭子测试确定的疼痛评分名义上较高,在1:00-11:00时间区域达到统计学意义(P<.001)。在终身与获得性NPV患者中,McGill疼痛问卷情感子量表维度的中位数得分也显着较高(P=.011)。在苏木精和伊红结果与肥大细胞或神经元标志物的密度之间没有观察到相关性。值得注意的是,63%的患者队列报告患有与肥大细胞活性异常相关的其他病症。
结论:NPV的病理主要位于前庭上皮基底膜和上皮下基质,没有可见的外阴镜检查结果,使临床诊断具有挑战性。
■这项研究的优势包括大量的组织,据我们所知,这是12:00前庭的首次评估。主要限制是来自疾病状态内的单个时间点的标本和缺乏对照组织。
结论:用CD117和PGP9.5对切除的前庭组织进行免疫组织化学染色导致NPV的组织学确认,表明NPV是涉及所有前庭区域的田间疾病,对疼痛被忽视和经历过负面心理社会影响的患者进行验证,并赞赏这种染色可以增进知识。
BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8
CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining.
OBJECTIVE: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes.
METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by
CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments.
RESULTS: Outcomes included density of
CD117 and PGP9.5 immunostaining in the 1:00-11:00 o\'clock and 12:00 o\'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement.
RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o\'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments.
RESULTS: Outcomes included density of
CD117 and PGP9.5 immunostaining in the 1:00-11:00 o\'clock and 12:00 o\'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement.
RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o\'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of
CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o\'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity.
CONCLUSIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging.
UNASSIGNED: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues.
CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.