Malignant transformation of endometriosis and endometriomas

Gonçalo Varela Cunha, SOFIA GONÇALVES ROCHA, Margarida Figueiredo-Dias, Ricardo Roque
In: Academia Oncology · 2026 · vol. 3(3) · doi:10.20935/acadonco8554 · W7214981770
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Abstract

Endometriosis is a chronic inflammatory gynecological disorder characterized by the presence of endometrium-like tissue outside the uterine cavity that remains responsive to hormonal fluctuations. Although a benign condition, it has been consistently associated with an increased risk of ovarian cancer, particularly endometrioid and clear cell carcinomas, giving rise to the concept of endometriosis-associated ovarian cancer (EAOC). Ovarian endometriomas are especially relevant because they combine sustained inflammation, oxidative stress, repeated hemorrhage, and cumulative molecular alterations within a permissive microenvironment. Malignant transformation appears to be a gradual process driven by chronic inflammation, estrogen-dependent signaling, immune dysregulation, oxidative stress, and somatic or epigenetic alterations involving genes such as ARID1A , KRAS , PIK3CA , and PTEN . Atypical endometriosis may represent an intermediate precursor lesion. Clinically, differentiating benign endometriomas from early malignant lesions remains difficult because symptoms and imaging characteristics overlap. Transvaginal ultrasound (TVUS) and magnetic resonance imaging are central to evaluation, whereas serum biomarkers such as cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4) may refine risk assessment. Histopathology remains the diagnostic reference standard. Although women with endometriosis appear to have a higher ovarian cancer risk, the absolute incidence of EAOC remains low and no formal screening strategy is currently recommended. Clinical management therefore relies on individualized risk assessment, with decisions regarding surveillance, medical treatment, surgery, and oncologic treatment tailored to age, menopausal status, reproductive goals, lesion behavior, and tumor stage. A better understanding of the biological mechanisms underlying malignant transformation is needed to improve prevention, risk stratification, early diagnosis, and therapeutic personalization in EAOC.

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