Superficial Peritoneal Endometriosis Beyond Surgical Diagnosis: A Narrative Review of Emerging Functional and Molecular Perspectives

Background and Objectives: Superficial peritoneal endometriosis (SPE) remains one of the most difficult endometriosis phenotypes to diagnose non-invasively, because lesions are frequently small, multifocal, and poorly detectable using conventional imaging. Diagnostic laparoscopy therefore remains the reference standard for direct visualization of superficial peritoneal lesions. However, the inconsistent relationship between visible lesion burden and pain severity, together with the multifactorial nature of chronic pelvic pain, highlights the limitations of a purely lesion-based diagnostic model. This narrative review reassesses SPE from a cautious functional and molecular perspective, focusing on clinically established evidence, emerging but incompletely validated tools, and hypothesis-generating concepts. The novelty of this review lies in its specific focus on SPE as an unresolved diagnostic phenotype and in the proposed integration of surgical diagnosis, expert imaging, pain phenotyping, empirical treatment response, and molecular research within a non-replacement framework. Materials and Methods: A narrative literature review was performed using PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library for English-language articles published between January 2010 and April 2026. The search focused on SPE, diagnostic laparoscopy, dynamic transvaginal ultrasound, sliding sign, chronic pelvic pain, hormonal treatment response, neuroinflammation, liquid biopsy, circulating biomarkers, epigenetics, and microbiome research. Results: Dynamic transvaginal ultrasound, sliding sign assessment, pelvic organ mobility evaluation, and tenderness-guided examination may provide indirect functional information in selected patients with suspected SPE, but they remain operator-dependent and insufficiently standardized for this phenotype. Response to hormonal therapy may support clinical reasoning, but it has low specificity and may also reflect improvement of adenomyosis, primary dysmenorrhea, ovulation-related pain, abnormal uterine bleeding, or other estrogen-sensitive conditions. Liquid biopsy and molecular biomarkers, including circulating microRNAs, extracellular vesicles, cell-free DNA, inflammatory mediators, epigenetic signatures, adipokine-related markers, and microbiome-related signals, remain investigational and require phenotype-specific validation. Conclusions: Functional and molecular stratification of suspected SPE represents a promising research direction rather than a current clinical standard. Laparoscopy remains essential when definitive diagnosis or surgical treatment is required, particularly in patients with infertility, refractory symptoms, suspicious imaging, or suspected complex disease. Future validated models may help integrate clinical phenotype, expert imaging, treatment response, pain mechanisms, and molecular profiles to support more individualized and selective diagnostic pathways.