Initial endometriosis refers to the earliest morphologic and molecular stage of endometriotic lesion development, preceding the establishment of fully formed, hormonally responsive ectopic endometrial tissue. It represents the transitional phase during which cells acquire endometrial-like characteristics outside the uterine cavity but have not yet developed the architectural complexity, stromal reaction, fibrosis, or chronic inflammation typical of established endometriosis.

Definition and Conceptual Framework

Endometriosis is classically defined as the presence of endometrial-type glands and stroma outside the uterus. However, increasing molecular and developmental evidence suggests that lesion formation is not an abrupt event but a progressive biological process. “Initial endometriosis” denotes the earliest identifiable phase in this continuum, characterized by: 1) Early epithelial implantation or transdifferentiation; 2) Minimal stromal organization and increased micro capillary vessels; 3) Limited inflammatory response and Incomplete hormonal responsiveness as well as absent fibrosis.  This stage may not always meet conventional histologic diagnostic criteria for endometriosis but may represent the biologic precursor to typical lesions. 

Pathogenesis

Initial Endometriosis was proposed by W. Zheng in 2005.  More recent and emerging morphologic and molecular evidence suggests that the majority ovarian endometriotic lesions may originate from fallopian tube epithelium rather than direct implantation of eutopic endometrium. In this model, initial endometriosis reflects a process of epithelial transdifferentiation in which fallopian tube–derived cells acquire endometrial-like characteristics under local hormonal or microenvironmental influences, although the exact mechanisms remain clarified.

Clinical and Biological Significance

Recognition of initial endometriosis is important for several reasons: 1) Understanding Disease Origin – Clarifies whether lesions arise from eutopic endometrium, fallopian tube epithelium, or alternative sources; 2) Precursor Lesion Biology – Provides insight into the early steps preceding ovarian endometriosis and endometriosis-associated ovarian carcinoma;  3) Early Detection and Intervention – Identifying molecular markers of early lesion formation may improve prevention strategies;  4) Clarifying Disease Heterogeneity – Initial lesions may differ biologically depending on their tissue of origin, influencing downstream disease behavior; 5) Can be served as a morphologic biomarker for targeted therapy after the molecular mechanisms revealed.  

Relationship to Disease Progression

Initial endometriosis is thought to precede: 1) Established ovarian endometriosis or endometrioma;  2) Possible deep infiltrating endometriosis;  3) Endometriosis-associated ovarian carcinomas (particularly clear cell and endometrioid types) in a subset of cases and the proposed progression model in selected ovarian cases is: Fallopian Tube Epithelium → Initial Endometriosis → Ovarian Endometriosis → Atypical Endometriosis → Ovarian Endometrioid or Clear Cell Carcinoma.  However, this progression does not occur universally, and most endometriotic lesions remain benign.

Conclusion

Initial endometriosis represents the earliest detectable stage of ectopic endometrial-type tissue development. It is characterized by partial epithelial differentiation, limited stromal organization, and early molecular alterations. Recognition of this stage enhances understanding of disease origin, progression, and potential links to ovarian carcinogenesis. As molecular profiling advances, the concept of initial endometriosis may become increasingly defined by lineage-specific epigenetic and genomic signatures rather than purely morphologic criteria.

References:  

Zheng W, Li N, Wang J, Ulukus EC, Ulukus M, Arici A, Liang SX. Initial endometriosis showing direct morphologic evidence of metaplasia in the pathogenesis of ovarian endometriosis. Int J Gynecol Pathol. 2005 Apr;24(2):164-72. doi: 10.1097/01.rct.0000157091.37057.b4. PMID: 15782073.

Yuan, Z., Wang, L., Wang, Y. et al. Tubal origin of ovarian endometriosis. Mod Pathol 27, 1154–1162 (2014). https://doi.org/10.1038/modpathol.2013.245

Wang Y, Li Q, Zhao R, Wang JY, Wang Y, Lin W, Yuan Z, Zhang J, Fadare O, Wang Y, Zheng W. Fallopian tubal histogenesis of ovarian endometriosis-A study of folate receptor-alpha expression. Front Med (Lausanne). 2023 Mar 2;10:1138690. doi: 10.3389/fmed.2023.1138690. PMID: 36936232; PMCID: PMC10017500.