Endometriosis is a chronic, non-cancerous condition that affects an estimated 10% of people of reproductive age globally. It is characterized by severe pelvic pain, painful periods, and can contribute to infertility, making it a significant quality-of-life concern. While the disease is overwhelmingly benign, a scientific link exists between long-standing endometriosis and a very specific, though rare, risk of malignant change. This transformation, which predominantly involves the ovaries, raises questions about the long-term prognosis of the disease.
Understanding Endometriosis
Endometriosis is defined by the presence of tissue similar to the endometrium, the lining of the uterus, growing outside the uterine cavity. These growths are commonly found on the ovaries, fallopian tubes, and the surfaces of other pelvic organs. The misplaced tissue responds to hormonal signals, particularly estrogen, by building up and breaking down, much like the normal uterine lining. Since this blood has no exit from the body, it causes inflammation, scarring, and the formation of cysts, often leading to chronic pain. The condition is considered estrogen-dependent and involves a significant inflammatory response.
The Malignant Transformation Link
While endometriosis is a benign disorder for the vast majority of patients, scientific evidence confirms a rare but definite risk of malignant transformation. This process is collectively known as Endometriosis-Associated Ovarian Cancer (EAOC). The cumulative lifetime risk of this transformation for a person with endometriosis is very small, estimated to be less than 1%.
The theories behind this cellular change focus on the unique microenvironment of endometriotic lesions. Chronic inflammation and the iron-rich oxidative stress from recurrent bleeding within the lesions are thought to cause DNA damage in the ectopic cells. This damage, combined with a state of hyperestrogenism, can drive the transition from benign endometriotic cells to atypical, and eventually, malignant cells.
The malignant change is often observed as a transition zone where benign endometriotic tissue progresses into atypical endometriosis before developing into a carcinoma. Genetic alterations have been identified in this pathway, notably mutations in the ARID1A gene, a tumor suppressor involved in chromatin remodeling. These ARID1A mutations are frequently found in both atypical endometriosis and the associated ovarian cancers, suggesting they are a step in the carcinogenic process.
Specific Associated Cancer Types
The malignant transformation of endometriosis is highly specific to two distinct pathological subtypes of ovarian cancer. These two types, Endometrioid Ovarian Carcinoma and Clear Cell Ovarian Carcinoma, account for the majority of EAOCs. The presence of pre-existing endometriosis is found in 21% to 54% of cases of these specific cancer types.
Endometrioid Ovarian Carcinoma is named for its cellular resemblance to endometrial cancer, and it is the most frequently reported malignancy arising from endometriosis. Clear Cell Ovarian Carcinoma is the other main subtype, and it is particularly associated with endometriotic cysts. These two cancer types are categorized as Type I ovarian tumors, which tend to grow more slowly and are often confined to the ovary at the time of diagnosis.
The precursor lesion for these malignancies is typically an endometrioma, an endometriotic cyst located on the ovary. The chronic irritation and inflammatory state within these ovarian cysts create the ideal conditions for the cellular changes that lead to these carcinomas. The risk for developing Clear Cell Carcinoma has been reported to be up to 11 times higher in women with endometriosis.
Identifying Elevated Risk Factors
Although the overall risk for any person with endometriosis is low, certain clinical factors may elevate the risk within this small subgroup and warrant closer monitoring. A long-standing history of the disease is a factor, especially if the lesions persist into postmenopausal age. The highest incidence of EAOC is typically seen in patients in their 50s and 60s.
The size and location of the endometriotic lesions are significant clinical indicators of risk. The presence of large endometriomas, defined as ovarian cysts greater than 9 centimeters, warrants careful surveillance. Furthermore, women with the more severe forms of the disease, such as deep infiltrating endometriosis and ovarian endometriomas, face a significantly higher risk compared to those with superficial disease.
Routine cancer screening for all individuals with endometriosis is not currently recommended due to the rarity of the malignant transformation. Clinical monitoring, such as regular imaging and symptom assessment, is focused on those with elevated risk factors, such as large or growing ovarian masses, or those who are past reproductive age.