Are Endometriomas Cancerous? The Risk of Malignancy

Endometriomas are not cancerous. They are benign, blood-filled cysts that form on the ovaries in women with endometriosis. However, they do carry a small but real risk of transforming into ovarian cancer over time, with the overall rate of malignant transformation in premenopausal women sitting around one percent.¹ That risk is low enough that most women with endometriomas will never develop cancer from them, but it is high enough that doctors take it seriously, especially in older patients and those with large or growing cysts.

What an Endometrioma Actually Is

An endometrioma, sometimes called a “chocolate cyst” because of its dark, thick contents, forms when endometrial-like tissue grows on or within the ovary and creates a cyst filled with old blood. Researchers believe they develop either from endometriotic tissue invading functional ovarian cysts or from endometriosis on the ovarian surface that bleeds inward into the cortex.² They can range from tiny to quite large, and many women live with them for years without symptoms beyond the pain and fertility issues common to endometriosis generally.

The vast majority of endometriomas remain benign for life. But the tissue lining these cysts is metabolically active, responds to hormones, and undergoes repeated cycles of bleeding and inflammation. Over many years, that chronic inflammatory environment can, in rare cases, drive genetic changes that push cells toward cancer. When the cyst lining develops increasingly abnormal cellular architecture, pathologists describe it as “atypia,” and moderate-to-severe atypia is considered a potential stepping stone to cancer.³

How Large Is the Cancer Risk, Really?

A large Japanese prospective study followed nearly 6,400 women with ovarian endometriomas for up to 17 years. During that period, 46 developed ovarian cancer. The overall cancer rate was significantly elevated compared to the general population, with a standardized incidence ratio close to nine, meaning these women developed ovarian cancer at roughly nine times the rate you would expect in women without endometriomas.⁴ That sounds alarming in relative terms, but in absolute terms, 46 cases out of nearly 6,400 women over 17 years still represents a low event rate.

A useful way to think about it: endometriomas roughly double or triple the risk of certain ovarian cancers compared to not having them.⁵ But ovarian cancer itself is uncommon, so multiplying a small baseline risk by two or three still leaves you with a small number. The concern is not that most endometriomas will become cancer. It is that the subset that does transform can be aggressive, so identifying which women are at higher risk matters.

Which Types of Ovarian Cancer Are Linked

Endometriomas do not raise the risk of all ovarian cancers equally. The two subtypes most strongly associated with endometriosis are clear cell carcinoma and endometrioid carcinoma.⁶ There is also a possible link to low-grade serous ovarian cancer, though the evidence there is less consistent. Mucinous ovarian cancers do not appear to be connected to endometriosis at all.⁵

A Dutch population-based study found that women with histologically confirmed endometriosis had dramatically elevated rates of these two subtypes specifically: roughly 29 times the rate of endometrioid ovarian cancer and 21 times the rate of clear cell ovarian cancer compared to the general population.⁷ Those multipliers are striking, but again reflect relative rather than absolute risk. A systematic review and meta-analysis confirmed that clear cell carcinoma and endometrioid carcinoma are the dominant subtypes in cancers arising from endometriosis.⁸

This matters clinically because clear cell and endometrioid cancers behave differently from the more common high-grade serous ovarian cancer. They tend to be diagnosed at an earlier stage, which is favorable, but clear cell carcinoma in particular responds poorly to standard platinum-based chemotherapy. Knowing which cancer subtypes are associated with endometriosis helps oncologists tailor treatment if transformation does occur.

Who Is at Higher Risk

Not every woman with an endometrioma faces the same level of concern. Two factors consistently emerge as independent predictors of cancer development: age and cyst size. In the large Japanese cohort, women over 40 and those with endometriomas larger than 9 centimeters had the highest risk.⁴ A separate study of women 45 and older in China found that postmenopausal status carried more than five times the odds of cancer compared to premenopausal status, and tumors 8 centimeters or larger carried about seven times the odds.⁹

That same study found that the risk escalated steeply with age: under two percent among women 45 to 49, close to six percent among those 50 to 54, and ten percent among those 55 to 59.⁹ Having coexisting endometrial disorders also raised the odds roughly fourfold. The practical takeaway is that an endometrioma in a 28-year-old presents a very different risk profile than a large, persistent endometrioma in a 55-year-old. Surveillance and management strategies should reflect this difference.

Another risk factor worth mentioning is recurrence after surgical removal. One study of nearly 500 women who underwent excision of an endometrioma found that all four cases of ovarian cancer that developed in the cohort arose from a recurrent endometrioma. Recurrence itself occurred in about a quarter of patients, and cancer development was significantly associated with it.¹⁰ This suggests that women whose endometriomas come back after surgery deserve close follow-up.

How Doctors Detect Suspicious Changes

Most endometriomas look fairly characteristic on ultrasound: a cyst with homogeneous, low-level internal echoes, sometimes described as having a “ground glass” appearance. The challenge comes when features change. A new solid nodule growing within an endometrioma, especially one that develops its own blood supply, raises a red flag. In one reported case, a solid nodule within an endometrioma that was initially 1 centimeter enlarged over the course of pregnancy and developed vascularity, prompting further investigation with MRI.¹¹

MRI is considered the most specific imaging tool for evaluating whether malignant transformation has occurred. The key signs radiologists look for include solid enhancing nodules within the cyst, nodular internal walls or septations, restricted diffusion on specialized sequences, and a loss of the normal dark signal pattern that endometriomas typically show on certain MRI weightings.¹² Subtraction imaging, which compares scans taken before and after contrast dye injection, is particularly useful because it makes enhancing mural nodules stand out against the bright background of the blood-filled cyst. Enhancing mural nodules are, in fact, the single most sensitive MRI sign of cancer within an endometrioma.¹³

The CA-125 Problem and Better Blood Markers

CA-125 is the blood marker most commonly associated with ovarian cancer screening, but it has a well-known blind spot when endometriosis is in the picture. Endometriosis itself raises CA-125 levels, so an elevated result in a woman with an endometrioma could mean cancer, but it could just as easily mean active endometriosis and nothing more.¹⁴ This overlap makes CA-125 unreliable on its own for distinguishing benign endometriomas from cancerous ones.

HE4, a newer biomarker, performs better in this specific scenario. Studies have found that HE4 levels stay normal in women with endometriosis or other benign ovarian masses but rise significantly in ovarian cancer. When researchers directly compared the two markers in women with endometriomas versus ovarian cancer, HE4 showed meaningful differences between groups while CA-125 did not.¹⁵ Another marker, CA72-4, also showed promise: it was elevated in about two-thirds of cancer patients but stayed low in those with endometriosis alone.¹⁴

Interestingly, CA-125 remains valuable for a different purpose: identifying endometriomas in the first place. A recent study found that CA-125 had excellent diagnostic performance for confirming the presence of an endometrioma, with sensitivity around 86 percent and specificity around 81 percent, outperforming both HE4 and CA19-9 for that particular task.¹⁶ So the two markers serve complementary roles: CA-125 helps confirm that a cyst is an endometrioma, while HE4 helps confirm that it is not cancer.

Why Endometriomas During Pregnancy Can Look Alarming

Pregnancy creates a specific diagnostic trap. Hormonal changes during pregnancy can cause the tissue lining an endometrioma to undergo decidualization, a process where the cells plump up and remodel in response to progesterone. On imaging, a decidualized endometrioma can develop solid-looking nodules, increased blood flow, and rapid growth, all features that look suspicious for malignancy.¹⁷

This mimicry is well-recognized but still catches clinicians off guard. MRI can sometimes help distinguish decidualization from true cancer, but the overlap in appearance is enough that some cases are only resolved by surgical pathology after delivery or during cesarean section.¹⁸ The reassuring part: decidualization is benign and resolves after pregnancy. But the anxiety it generates for both patient and doctor during pregnancy is real, and it is worth knowing about for women who enter pregnancy with a known endometrioma.

Surgery, Fertility, and the Balancing Act

A common question among younger women with endometriomas is whether removing the cyst reduces cancer risk and, if so, at what cost to fertility. Surgery does remove the immediate lesion, but it does not eliminate risk entirely, especially since endometriomas recur in roughly one in four cases. And the surgery itself takes a measurable toll on ovarian reserve. A meta-analysis found that excision of an endometrioma reduced circulating AMH, a marker of how many eggs the ovary has left, by about 40 percent for cysts on one side and close to 57 percent for bilateral cases within the first year after surgery.¹⁹

Some recovery in ovarian reserve markers does occur over the longer term, but levels almost never return to what they were before the operation.²⁰ This creates a genuine tradeoff, especially for women who want children. A small, stable endometrioma in a young woman with good ovarian reserve may be better managed with monitoring than with surgery, while a large or growing endometrioma in an older woman who has completed childbearing may warrant removal precisely because her age puts her in a higher-risk group for transformation.

The ESHRE endometriosis guideline addresses both treatment and the cancer association, providing recommendations that help clinicians navigate these decisions in a structured way.²¹ In practice, management is highly individualized. Factors like age, cyst size, symptom burden, fertility plans, and imaging characteristics all feed into the decision.

Can Hormonal Treatment Lower the Risk?

Oral contraceptives suppress ovulation and reduce menstrual cycling, both of which are thought to drive the inflammatory environment within endometriomas. This mechanism likely explains why hormonal contraceptive use is associated with reduced risk of both endometrial cancer and ovarian cancer more broadly.²² A meta-analysis of oral contraceptive use and endometrial cancer found that longer use produced progressively greater risk reductions, with ten or more years of use associated with roughly a 70 percent lower odds of endometrial cancer.²³

For endometriosis specifically, hormonal suppression is already a first-line treatment for symptom management. The theory that it might also confer some cancer protection is biologically plausible and consistent with the broader evidence, though direct trials proving that oral contraceptives prevent malignant transformation of endometriomas specifically have not been conducted. Still, for women who are managing endometriomas and are not currently trying to conceive, hormonal therapy offers a plausible dual benefit of symptom relief and risk reduction.

What Drives Transformation at the Cellular Level

The chronic inflammation within an endometrioma creates an unusual immune microenvironment. Researchers have found altered levels of inflammatory signaling molecules like interleukins and tumor necrosis factor, along with changes in the number and function of immune cells including natural killer cells, dendritic cells, and monocytes when comparing endometriosis-associated ovarian cancers to both normal tissue and benign endometriosis.²⁴ Changes in complement and inflammasome pathways add further evidence that the immune system plays a role in whether transformation occurs.

This is an area where the research is genuinely thin compared to what we know about, say, high-grade serous ovarian cancer genetics. The rarity of malignant transformation makes it difficult to assemble large enough study populations to fully map the molecular pathway from benign endometrioma to cancer. What researchers can say is that iron-mediated oxidative stress from the repeated bleeding within the cyst, combined with chronic immune activation and hormonal stimulation, creates conditions favorable for DNA damage and eventual malignant change. But predicting which individual endometriomas will take that path remains beyond current tools.

Malignancy in Endometriosis Outside the Ovary

Most attention focuses on ovarian endometriomas, but endometriosis can grow in many locations throughout the pelvis and occasionally farther afield. Malignant transformation of extraovarian endometriosis is even rarer than ovarian transformation, and when it does occur, the cancer subtypes look different. The most common histological type is endometrioid adenocarcinoma, accounting for roughly 69 percent of cases, followed by sarcomas at about 25 percent and clear cell carcinoma at around 5 percent.²⁵ The relatively high proportion of sarcomas is unusual and distinct from the ovarian pattern, where sarcomas are uncommon.

These cases tend to arise in sites like the rectovaginal septum, abdominal wall (particularly in cesarean section scars), and the bowel. Because they are so rare, there is no standard surveillance protocol. Most are discovered incidentally or when a known endometriosis implant begins growing unexpectedly, develops a solid mass, or causes new symptoms that imaging cannot easily explain. Awareness of the possibility matters more than any specific screening test.

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