Why do some patients with endometriosis have only small lesions yet suffer from unbearable pain, while others with extensive lesions feel almost none? An international team of scientists, in collaboration with the Sbarro Health Research Organization (SHRO), may have found the answer.
Endometriosis currently affects more than 190 million women worldwide. It is among the conditions women fear greatly — both because of the threat to fertility and because of its reputation as a highly distressing disease that significantly reduces quality of life. However, the experiences of patients suffering from it can differ dramatically.
This is because endometriosis is not a uniform disease, even though it is often treated as one. In reality, it behaves like several distinct conditions. Why? Different combinations of six major mechanisms — typically associated with malignant tumors — may be activated, and it is these mechanisms, rather than lesion size, that determine its manifestations.
“If we continue to treat endometriosis as a single disease, we will continue to face delayed diagnoses and trial-and-error treatment,” said Dr. Antonio Giordano, President and Founder of SHRO, describing the study outlined below as a “wake-up call.”
The authors of the study called for the application of precision medicine principles in the diagnosis and treatment of endometriosis, similar to those used in oncology. For example, the average time from the onset of symptoms to the diagnosis of endometriosis and initiation of treatment is currently about seven years.
Historically, endometriosis was classified as a benign gynecological disease. However, according to current knowledge and clinical reports, it is in fact a systemic condition that mimics oncological diseases. Its mechanisms are not yet fully understood, which contributes to the substantial delay in establishing the correct diagnosis and, consequently, to delays in treatment. Moreover, treatment options still have significant limitations, as they rely primarily on empirical hormonal therapies, repeated surgical interventions, and symptomatic management.
Diagnostic delays due to suspected malignancy can also increase anxiety in patients and lead to overtreatment, while simultaneously postponing necessary interventions and allowing disease progression. Altogether, this results in suboptimal or inconsistent outcomes.
According to the authors of the analysis, a fundamental breakthrough will not occur unless the complex biology of endometriosis is more deeply elucidated. They therefore sought new insights through a literature review of studies indexed in the PubMed database, searching for links between endometriosis and malignancies in clinical manifestations and molecular pathways, as well as gaps in translational research and unmet clinical needs. The review included 35 original research articles and comprehensive reviews addressing clinical and molecular parallels, and eight publications focusing on gaps in understanding.
Based on the available data, the authors described six potential functional pathways disrupted in endometriosis. These fundamental processes also contribute to the pathogenesis of oncological diseases. They include disturbances in hormonal signaling, inflammatory processes, oxidative stress, dysregulation of apoptosis, abnormalities in angiogenesis, and signaling pathways leading to invasiveness and epithelial–mesenchymal transition. In endometriotic lesions, multiple pathways associated with malignancies are often activated (such as PI3K/AKT/mTOR, MAPK, NF-κB, Wnt/β-catenin, and JAK/STAT), creating an environment in which endometriosis can behave like a neoplasm, even though it does not meet all the defining characteristics of carcinoma.
Endometriosis often mimics cancer clinically as well. Patients may have elevated tumor markers, solid infiltrates detected by imaging methods (ultrasound, CT, MRI, PET), dissemination of lesions (“metastases”) resembling peritoneal carcinomatosis, or alarming symptoms typical of malignancies (such as rectal bleeding, hematuria, or bowel obstruction). These manifestations may lead to aggressive surgical procedures (for example, radical hysterectomy, bilateral salpingo-oophorectomy, bowel resection, or omentectomy) due to suspected malignancy. Endometriosis also frequently poses a diagnostic challenge for histopathologists, especially in atypical variants of the disease.
The authors emphasize the importance of mapping parallels with carcinomas, which would enable surgical planning with precision comparable to oncology and allow prediction of which lesions can be managed conservatively and which cannot. In this context, endometriosis must be viewed as several distinct diseases, which is essential for the development of rapid diagnostic blood tests and for effective collaboration with patients, who need to understand why treatment approaches may differ and what underlies these differences.
Clinicians should maintain a high index of suspicion for endometriosis in cases of atypical manifestations, extrapelvic lesions, and other findings suggestive of oncological disease, regardless of reproductive age. It is crucial to perceive endometriosis as a systemic rather than purely gynecological condition and to manage it using a multidisciplinary approach, applying existing guidelines appropriately while individualizing care based on clinical presentation and the specific disease profile of each patient.
Editorial Team, Medscope.pro
Sources: 1. Martinelli C., Vidali A., Di Chiara F. et al. Endometriosis: A cancer-mimicking disease and the need for a translational perspective. Ann Res Oncol 2025 Jun; 5 (2): 75–94, doi: 10.48286/aro.2025.107. 2. Endometriosis not only one disease: Research maps six cancer-like “switches” shaping each woman’s symptoms. Newswise, July 16, 2025. Available at: www.newswise.com/articles/endometriosis-not-only-one-disease-research-maps-six-cancer-like-switches-shaping-each-woman-s-symptoms
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