Endometriosis is not a type of cancer, but a chronic condition where tissue similar to the uterine lining grows outside the uterus. This misplaced tissue, known as lesions, responds to hormonal cycles by shedding and bleeding inside the pelvic cavity, causing significant chronic pain, inflammation, and scar tissue formation. Although benign, the disease is sometimes confused with malignancy due to its aggressive, invasive nature and ability to spread to organs like the ovaries, bowel, and bladder. This invasive behavior necessitates a detailed understanding of its distinction from cancer and its extremely rare potential for malignant transformation.
The Fundamental Difference Between Endometriosis and Cancer
The core distinction between endometriosis and cancer lies in the cellular makeup and biological behavior of the tissue. Endometriosis is a benign condition, meaning the cells in the misplaced tissue are generally normal and lack the uncontrolled, destructive cellular mutation seen in malignancy. The cells of an endometriotic lesion still resemble the glandular and stromal cells of the inner uterine lining.
Cancer, by contrast, is characterized by cells that have undergone genetic mutations leading to abnormal, unregulated growth and division. The defining feature of cancer is widespread metastasis, where malignant cells break away and travel through the body to form secondary tumors far from the primary site. While endometriosis demonstrates local invasion into adjacent tissues, its cells do not have the inherent capability for distant metastasis or the autonomous, destructive proliferation that is the hallmark of a true malignancy.
The Rare Event of Malignant Transformation
While endometriosis is benign, a very rare process known as malignant transformation can occur, leading to endometriosis-associated ovarian cancer (EAOC). This transformation is an infrequent event, increasing the overall lifetime risk of ovarian cancer from about 1.4% in the general population to approximately 1.9% for women with endometriosis.
The mechanism linking endometriosis to cancer is rooted in chronic inflammation and oxidative stress within the endometriotic lesions, particularly ovarian endometriomas. The constant exposure to blood and iron within the cysts creates a highly reactive microenvironment that generates reactive oxygen species, which damage cellular DNA. This DNA damage, combined with chronic inflammation, drives the accumulation of specific genetic mutations over time.
Mutations in tumor suppressor genes, such as PTEN and ARID1A, are frequently observed in endometriotic tissue adjacent to malignant tumors, suggesting they are early events in the transformation process. This concept suggests that multiple genetic hits are required for a benign endometriotic cell to fully transition into a cancerous cell. The loss of ARID1A expression, often alongside mutations in genes like PIK3CA, is seen as a key step that drives the ultimate cellular conversion to malignancy.
Specific Cancers Linked to Endometriosis
The association between endometriosis and cancer is not generalized to all types of malignancy but is highly specific to certain histological subtypes of ovarian cancer, primarily epithelial ovarian cancers. The most commonly linked cancers are the clear cell carcinoma and the endometrioid carcinoma subtypes. The risk increase for these specific subtypes is significantly higher than for other types of ovarian cancer, such as high-grade serous carcinoma.
For women with endometriosis, the risk of developing clear cell ovarian cancer is estimated to be tripled to fourfold, and the risk for endometrioid ovarian cancer is approximately doubled or tripled. These two subtypes account for a small percentage of all ovarian cancers but are disproportionately found in women with a history of endometriosis. The specific presence of ovarian endometriomas, which are fluid-filled cysts, may carry an even higher risk for the development of these type I ovarian cancers. Extremely rare cases of malignant transformation have also been reported in deep infiltrating lesions of the bowel or bladder.
Clinical Surveillance and Risk Management
For individuals diagnosed with endometriosis, understanding the risk for malignant transformation translates into a focus on appropriate clinical surveillance and risk mitigation strategies. Patients with large or complex ovarian endometriomas, especially those with atypical features seen on imaging, may be recommended for more frequent monitoring. This typically involves regular pelvic imaging, such as transvaginal ultrasound, to track the size and appearance of the cysts for any concerning changes.
Hormonal treatments, specifically long-term use of combined oral contraceptives (OCPs), are associated with a reduced overall risk of ovarian cancer, including the subtypes linked to endometriosis. OCPs mitigate risk by suppressing ovulation and reducing the monthly hormonal stimulation and bleeding within the endometriotic lesions.
In some cases, particularly for postmenopausal women or those with large endometriomas, surgical removal of the lesions or ovaries may be discussed as a risk-reducing measure, though the evidence for routine risk-reducing surgery is often considered inconclusive. Any sudden change in pelvic pain, unexplained weight loss, or abnormal post-menopausal bleeding should prompt immediate medical evaluation, as these may be signs requiring further investigation beyond routine endometriosis management.