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Ovarian Endometriosis – Ovarian Endometriotic Cysts

Ovarian Endometriosis
Also called Endometriomas, Ovarian Endometriotic Cysts

Endometriomas still mistaken for functional ovarian cysts: The ovaries are one of the most complex and important organs of the female anatomy, not just for their life-giving properties, but also because of their dual role as endocrine organs (glands) that produce some of a woman’s most vital hormones, such as androgen, estrogen, and progesterone. However, the amazing feats of your ovaries don’t stop there; they also produce essential paracrine-autocrine hormones like oxytocin, relaxin, inhibin, activin, and follistan.

There is even growing evidence that the ovaries communicate with important neurotransmitters like acetylcholine and dopamine in ways previously unrecognized. As well, researchers now believe that the ovaries also produce their own non-neuronal sources of key neurotransmitters. Indeed, when you consider that a woman’s lifetime of reproductive processes are regulated by a “complex feedback system and signaling network between the brain (hypothalamus-pituitary-ovarian axis,) and ovaries”,  and between the ovaries, fallopian tubes, uterus, thyroid, and adrenal glands, then you begin to appreciate just how important the ovaries are to a woman’s overall physiology.

With the ovaries playing such vast and crucial roles in a woman’s health, as you can imagine, when endometriosis affects the ovaries it can potentially cause pathological outcomes that may negatively impact a woman’s health in a variety of ways. In less severe or asymptomatic cases, mild pain and menstrual irregularity may be the only discernible symptoms.

However, the most serious potential outcomes of untreated or poorly treated ovarian endometriosis can be devastating and include irreversible organ dysfunction, debilitating chronic pelvic pain, irreversible depletion of ovarian reserve, sub-fertility, infertility, and other potential complications that call for urgent medical intervention.  Recent studies also suggest that endometriosis of the ovaries is associated with a higher risk of ovarian cancer as well.

As one of the leading causes of hysterectomy and hospitalization, with an economic burden estimated to be $119 billion globally in medical costs and lost productivity, endometriosis also represents one of the most serious public health issues of our era.

Yet, despite such potential for severe medical consequences, many women and girls still do not receive the timely and expert medical care needed in order to properly diagnose and treat ovarian disease caused by endometriosis. In fact, diagnostic delays of up to 7-10 years are still occurring today. This is why we’ve provided this detailed section and latest research on the subject of ovarian endometriosis, so that you can be your own advocate and seek out the best medical care possible.

Endometriotic Ovarian Cysts (Endometriomas): Overview
As you may already know, endometriotic growths can have a wide range of characteristics, consistencies, and colors. Macroscopically, they can appear as tiny superficial lesions to large cysts to deeply invasive nodules. There are also mixed and atypical forms, so not all growths fall neatly into just one category.

Due to such a wide variety of manifestations, there is still intense debate about just how to classify these various forms of endometriosis (and even whether they represent the same disease!). However, the endometriosis scientific community now generally agrees that there are three clinically distinct forms of endometriotic growths that are encountered most often:

1) Peritoneal endometriosis (also referred to as superficial lesions)
2) Deeply infiltrating endometriosis (DIE) (also referred to as deep adenomyotic nodules)
3) Cystic Ovarian (Endometriomas)

As the third category suggests, the most common type of endometriosis to affect the ovaries is a benign, estrogen-dependent ovarian cyst referred to as an endometrioma (endometriomas in the plural). Endometriomas – also referred to as endometriod cysts or chocolate cysts – occur in an estimated 17% – 50+% of those with endometriosis in other parts of the body and appear to be more common in those with more advanced disease. There are other types of endometriotic growths that can occur on the ovaries, such as superficial lesions, and even non-cystic deep nodules. However, the vast majority of endometriotic growths of the ovaries – up to 90% – tend to develop into cystic endometriomas.

One of the most distinguishing features of typical endometriomas is that they are usually filled with a thick fluid of degenerated blood products (colloquially referred to as “old blood”) that looks dark brownish-red to the naked eye. It was this characteristic coloring that led the early 20th century endometriosis pioneer, John A. Sampson, to give endometriomas the nickname, ‘chocolate cysts.’

As it turns out, Drs. Nezhats’ research revealed that there are actually a few different subtypes of ovarian endometriomas (Type I & Type II).Therefore, the disease course and histopathological details can vary considerably. In general, though, under a microscope an endometrioma’s characteristic thick brownish cystic fluid usually contains hemolyzed blood products, hemosiderin macrophages, traces of endometrial-like glandular epithelium cells and stroma, fibrotic tissue, and other cellular debris.

Unlike functional ovarian cysts that arise as part of a woman’s normal monthly ovulatory cycle, endometriomas usually do not resolve on their own and therefore may require some form of medical or surgical intervention at some point. In fact, not only do endometriomas usually fail to resolve on their own, they may continue to grow quite large –grapefruit size or larger – as they fill with blood each month in response to menstrual cycles.

Though endometriomas usually occur in women and girls of reproductive age, there are reported cases of endometriomas developing in women during menopause and in pre-menarche girls. And, like all forms of endometriosis, there is no cure for endometriomas and they may continuously recur and exist as a chronic condition, even after they are surgically removed.

ovarian-endometrioma

What causes endometriomas?
As with all types of endometriosis, the etiology of endometriomas remains unknown and is surrounded by controversy. Like so many other complex diseases, the cause is likely multifactorial, involving multiple genes and factors. Potential factors include hereditary predisposition, epigenetic mutations, dysfunctional endocrine or immune systems, stem cells disorders, and environmental factors such as xenoestrogens (estrogen mimics) and other endocrine disrupting chemicals (EDCs).
As for specific theories of pathogenesis, most can be divided into two main categories:

1) Uterine Origin
2) Non-uterine Origin

You’ll see these two distinct theoretical concepts emerge quite clearly in the following five most commonly cited theories of pathogenesis:

1) Retrograde Menstruation Theory: Menstruation Theory was first postulated as early as the 17th century and suggests that, during menstruation, menstrual blood backs up and spills into the pelvic cavity through the fallopian tubes, causing biologically active endometrial-like cells to become transplanted (implanted) throughout the pelvic cavity, where they continue to grow and respond to monthly hormonal triggers.

2) Lymphatic or Hematogenous Dissemination Theory: Also referred to as benign metastasis, the Lymphatic or Hematogenous Dissemination theory shares similarities with the retrograde menstruation theory, in that it proposes biologically active endometrial-like cells from menstrual blood or uterine origin migrate to other parts of the body and begin growing onto other organs and structures. However, instead of retrograde menstruation as the mechanism of spread, the lymphatic/ hematogenous theory posits that endometrial-like cells are instead disseminated from the uterus and throughout the body via the lymphatic system and/or through blood vessels. Studies have shown this process to be possible. For example, endometriosis within lymph nodes has been documented in 6-7% of women at lymphadenectomy and microvascular studies have demonstrated that fluids from the uterus can travel directly to the ovaries through the lymph system. This theory could help explain the presence of endometriotic lesions occurring in sites distant from the uterus, such as in the lungs, chest cavity, and brain.

3) Coelomic Metaplasia Theory: Coelomic refers to the epithelium layer that lines the surface of the inside of the body and abdominal organs. Metaplasia is the abnormal change (transformation or differentiation) of one cell type into another type. Putting the two terms together, the Coelomic Metaplasia theory proposes that endometriosis develops when epithelial cells of the mesothelial membrane, which comprises the outermost layer of the peritoneal cavity and abdominal organs, undergo metaplastic transformation and change into endometrial-like cells. Metaplastic transformation is a known precursor associated with many other diseases and is thought to result when normal tissue is subjected to repeat injury, which in turn causes genetic mutations to occur at the cellular level. Common factors that can cause injury to the tissues of our body include immunological dysfunction (auto-immune), epigenetic mutations, infections which lead to chronic inflammation, environmental toxins, or lifestyle factors, such as cigarette smoking.

4) Müllerian or Embryonic Rest Theory/Defective Embryogenesis: This theory was alluded to as early as the 19th century and hypothesizes that embryonic cells of the Wolffian (mesonephric) or Müllerian (paramesonephric) ducts for some reason fail to properly migrate to their proper place in the female reproductive tract. Defective Wolffian duct migration affects the ovaries, while Müllerian duct defects affect the uterus, cervix, upper 1/3 of the vagina, and/or fallopian tubes. As a result of these errors during embryogenesis, the Wolffian and/or Müllerian embryonic cells remain misplaced in parts of the body where they don’t belong. It is hypothesized that, during puberty or perhaps due to other triggers (such as estrogen mimetics in the environment), these misplaced cells begin growing in response to estrogen and develop into endometriotic lesions.

5) Stem Cell Theory: The stem cell theory is one of the latest hypotheses to emerge and suggests that dysregulated endometrial stem/progenitor cells migrate to various parts of the body and differentiate into endometriotic tissue. Stem cells are present in menstrual blood, so it is possible that retrograde menstruation can spread these cells into the pelvic cavity or through lymphatic dissemination. However, stem cells can also derive from bone marrow or other sources besides menstrual blood or a uterine origin  This means that the stem cell theory has explanatory power in cases where menstrual blood or a uterine influence cannot be factors, such as in instances where endometriosis has developed in men, fetuses, premenarcheal girls, or in post-hysterectomy or post-menopausal women. Stem cell dysfunction as a disease-causing agent is not a new concept in medicine and has been proposed as the cause of other diseases, including cancers.

How do endometriomas form?
As we’ve noted, the “why” of endometriosis remains unknown and is a subject of intense debate. As such, these debates have naturally spilled over into the “how” category, meaning that there is also controversy about how ovarian endometriomas form as well. For example, do normal ovarian cells mutate and transform into endometriosis (Metaplasia Theory/Defective Embryogenesis), or do endometrial-like cells somehow migrate and implant onto the surface (Implantation Theories (ie, Retrograde Menstruation/Lymphatic/Stem Cell/ Nezhat’s Invagination Theory) and begin growing from there?

In the case of endometriomas, currently the medical literature appears to show a preference for Nezhat’s Invagination Theory, so we’ll start there. In Nezhat’s Invagination-Implantation Theory, ovarian endometriotic cysts are thought to develop when endometrial-like cells similar to those found in the mucosal layer of the uterus (the endometrium) implant and invaginate onto the surface of one or both ovaries (Type I or Secondary Endometriomas), or onto pre-existing functional ovarian cysts (Type II or Secondary Endometriomas). In this scenario, the origin of the implanted cells doesn’t really figure into the equation, but some theorize that the cells may originate from the fallopian tubes, just as certain ovarian cancers do, which are now aptly named, fallopian tube-derived ovarian epithelial cancers (F-OEIs).

Whatever the origin, what the implantation/invagination theory suggests happens next is that these abnormal endometrial-like cells begin invaginating (infiltrating) deeply into the ovaries (Type I Primary) or into the existing functional cyst ( Type 2 Secondary) until a pocket or pseudo-cyst is eventually formed. In the case of a Type I endometrioma, the pseudo-cyst wall is comprised of endometrial glands and stroma and partially of the outside layer of the normal ovarian surface (called the ovarian cortex). In the case of a Type II endometrioma, the endometrioma’s cyst wall is formed from the existing functional cyst’s wall. However, the endometrioma also usually grows an entirely new and secondary cyst wall made up of endometrial-like glands and stroma: in other words, endometriosis.

Endometriosis vs normal endometrium: similarities and differences
It’s important to emphasize that the endometrial-like glands and stroma found in endometriosis are molecularly, structurally, functionally, morphologically, and genetically quite different from normal endometrial-like cells found in the uterus. In other words, they are abnormal, mutated cells of unknown origin that act in abnormal, mutated ways.

Nevertheless, some endometriotic tissue can behave in a somewhat similar manner as normal endometrial-like tissue, meaning that it can thicken, proliferate (mitosis), migrate, form new blood vessels (angiogenesis), “bleed”, shed, and regenerate in response to the cyclical hormonal triggers that cause menstruation.  However, unlike normal endometrial-like cells, these misplaced and mutated endometrial-like cells, along with any blood or byproducts they create, are not able to exit the body, but instead accumulate and continue to grow inside the ovarian endometrioma.

Of course, even if the products of ovarian endometriomas could somehow exit the body, this wouldn’t solve the problem. This is because endometriotic tissue is dysregulated in many other ways that contribute to the disease process.  For example, endometriotic cells appear to exhibit a marked resistance to the cyclical cell death (apoptosis) which occurs in normal endometrial-like cells each month as part of menstruation.  Cell death renders old endometrial-like cells biologically inactive, allowing for new endometrial-like cells to grow in their place. A reduction in apoptosis could be one of the mechanisms which endometriosis uses to effectively avert its own intended demise and remain in a biologically – and pathologically – active state of abnormal proliferation.

Making matters worse is that endometriosis exhibits significant immunological dysfunction, including the over-expression of pro-inflammatory cytokines like interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF), all of which contribute to a chronic up-regulation of painful, tissue-damaging inflammatory processes. Paradoxically, studies also show that endometriotic growths can exhibit too much immune system tolerance (i.e., immune suppression), such as reduced activity of cytotoxic T lymphocyte cells and natural killer cells (NK) cells, and reduced levels of cytokine-secreted helper T cells and B-lymphocyte-produced autoantibodies.

A growing body of evidence also suggests that abnormalities of the eutopic endometrium of women with endometriosis may be contributing to the development of endometriosis, including endometriomas. Some significant differences from healthy controls include the over-expression of aromatase, increased resistance to immune system attacks, increased proliferative capacity, increased proteolytic capacity, elevated levels of urokinase-type plasminogen activator (uPA), and increased estrogen expression. Chemokine 8 (CXCL8 or Il-8), is another type of cytokine that’s expressed at significantly higher levels in the eutopic endometrium of women with endometriosis. It’s believed to help endometriosis survive by activating the phosphatase and tensin homolog and phosphorylation of Akt (better known as the PTEN-AKT pathway), which in turn enhances endometriosis’s resistance to apoptosis while increasing its ability to proliferate.

Some hypothesize that stem cell dysfunction may also be a contributing factor in the disease process. In normal eutopic endometrium, endometrial stems cells are believed to play a role in the reparative and regenerative stages of the menstrual cycle, during which time they may help rebuild the endometrial lining by forming new endometrial-like cells. In the case of any type of endometriosis, including endometriomas, dysregulated stem cells may be involved in the formation of new endometrial-like cells, albeit ones that are misplaced and mutated in structure and function.

Still, the abnormalities don’t stop here. Biochemically, an entire range of dysfunction has been noted in endometriosis tissue, including:

Although endometriosis is not cancer, endometriosis experts and gynecologic oncologists like Dr. Farr Nezhat have found that some of these same types of genetic, immunological, and biochemical abnormalities play a role in the development of many cancers as well.

Potential damage that endometriomas can cause
When you realize that this disease process can occur throughout the body, month after month, and year after year in the case of delayed diagnoses, you can begin to understand just how potentially destructive endometriomas can be if left untreated. In t case of ovarian endometriomas in particular, they can continue to grow larger each month as they become filled with old blood and other cellular debris. As a result, chronic and severe inflammation, infections, formation of scar tissue (adhesions), fibrotic tissue, and abscesses can ensue.

The attendant damage that these pathological processes can cause is potentially devastating, and can include:

  • irreversible ovarian damage or dysfunction
  • subfertility or infertility
  • depletion of ovarian reserve
  • obliterated cul-de-sac (rectovaginal septum/Pouch of Douglas)
  • damage to surrounding organs or structures like:
    – bowel
    – bladder
    – ureter
    – peritoneum
    – fallopian tubes
    – abdominal wall
    – pelvic & back muscles
    – nerves
    – ligaments
    – veins, etc

If endometriomas rupture – and they often do – the cystic fluid can spill into the pelvic cavity and onto the other organs and structures in the abdomen. As a result, other organs and structures can also become potentially diseased with new endometriotic growths and entangled in thick webs of adhesions (scar tissue) and inflammation. In severe cases, the extent of disease can be so great, that the entire pelvic cavity can essentially become encased in scar tissue; what’s known as the so-called “frozen pelvis.”  This scar tissue is not innocuous and actually can distort the anatomy so extensively that it too can potentially cause severe organ dysfunction or failure to the ovaries, fallopian tubes, and surrounding organs.

In terms of symptoms, the potential result for a woman or girl suffering from endometriomas is a seemingly endless cycle of pain, pain, and more pain, along with the added emotional distress of possibly facing fertility dysfunction and other serious chronic health issues.

Symptoms of Endometriomas
Despite such potential for destruction, endometriomas may actually be asymptomatic or even inactive in some cases. However, when they are symptomatic, endometriomas can cause the same excruciating pain as endometriosis can in other parts of the body, including severe pain with menstruation (dysmenorrheal) and/or ovulation, chronic pelvic pain any time of the month, heavy menstrual bleeding (menorrhagia ), menstrual bleeding that lasts longer than 7 days, painful sexual intercourse (dyspareunia), sub-fertility, infertility, bladder symptoms (urgency, pain, hematuria (blood in urine)), bowel dysfunction (severe constipation lasting weeks, painful bowel function (dyschezia), blood in stool, diarrhea) severe abdominal bloating, irregular menstruation, abnormal vaginal bleeding, and chronic pain which radiates throughout the lower pelvic region, including the lower back, hips, and legs.

Symptoms that require urgent medical attention
As mentioned earlier, endometriomas can cause serious health risks that require immediate medical attention. For example, sometimes endometriomas become so enlarged that they cause the ovary to twist out of its natural position (called torsion), which can cut off the ovary’s blood supply and lead to tissue death (necrosis), organ failure, and serious infections, including sepsis: In other words, very serious medical consequences that often require immediate surgical intervention. Symptoms are acute, with sudden onset of pain developing in the lower abdomen, usually on one side, along with severe nausea or vomiting.

Large endometriomas in particular may suddenly rupture as well, which can cause acute pelvic pain that also calls for immediate medical attention, in the same way that a burst appendix is considered a medical emergency. In fact, a hemorrhaging or ovarian cyst rupture is among the most common gynecologic conditions associated with emergency room visits each year. The symptoms of a ruptured ovarian endometrioma (or other ruptured ovarian cysts) are severe onset of acute pain, usually on one side of the lower abdomen, with symptoms mimicking and often mistaken for a burst appendix if the pain occurs on the right side of the abdomen. Women with endometriosis of any type are also at risk for developing life-threatening cases of ectopic pregnancies which require urgent surgical intervention.

As you can see, endometriomas can cause serious medical consequences if left untreated. Therefore, even if you are not sure about symptoms, it’s best to err on the side of caution and seek urgent medical care if you are experiencing extreme pain.

Risk Factors
Risk factors that increase your risk of developing endometriomas are essentially the same as those for endometriosis, and include:

  • Having a mother or sister with endometriosis incurs an approximately 6-fold increase of risk
  • Started your period at a young age
  • Never had children
  • Have very heavy periods, or frequent periods, or ones that last 7 or more days
  • Have a closed or otherwise blocked hymen which blocks the flow of menstrual blood out of your body. Conditions include (imperforate hymen, congenital aplasia, and Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome).
  • Have other uterine abnormalities such as a double uterus, septate uterus, or bicornuate uterus
  • Have fibroids

Those with endometriosis in other parts of the body are also more likely to develop endometriomas as well. For example, one study reported that only 1.06% of patients (19 out of 1785) had ovarian endometriomas without any other pelvic endometriosis. Endometriomas also appear to be more common in those with more advanced disease (Stage III-IV).

Medicines that contain supraphysiologic doses of hormones that affect the endocrine system may also influence the growth of endometriomas. For example, women undergoing IVF treatments or other hormonal treatments to stimulate ovarian production of follicles are at higher risk of developing or enlarging existing endometriomas.

As mentioned earlier, environmental toxins, such as endocrine disrupting chemicals, have also been proposed as causing increased susceptibility to endometriosis. Although many studies on environmental factors are inconclusive, in the case of EDCs like diethylstilbestrol, some researchers have reported finding a “twofold increased risk of endometriosis in women exposed to diethylstilbestrol in utero.” 

DIAGNOSING ENDOMETRIOMAS: OVERVIEW
Although clinical signs and symptoms and imaging technologies may suggest endometriomas, the only way to definitively diagnosis endometriotic growths of any kind is to inspect the inside of the body through an invasive surgical procedure referred to as laparoscopy, during which time biopsy specimens are taken for histopathological confirmation of the presence of endometrial-like glandular epithelium cells and stroma.

However, before a surgeon undertakes this invasive procedure, he or she will go through a detailed diagnostic analysis that includes a review of symptoms, family history, past medical history, physical exam, non-invasive imaging scans, and other tests. During these initial diagnostic steps, Dr. Camran Nezhat and Azadeh Nezhat in California ,Dr Farr Nezhat in NY and Dr Ceana Nezhat in Atlanta schedule as much time as you need so that you have ample opportunity to discuss what your health goals, fertility concerns, and treatment options may be.

Transvaginal & Transabdominal Ultrasound
In high risk patients or in cases of suspected ovarian cancer or other cancers, immediate surgical evaluation may be warranted .That is, in some patients with suspicious masses of any kind found on ultrasound to be growing on or near ovaries. In general, though, a routine in-office transvaginal ultrasound is the preferred first line imaging modality due to its low cost, safety, and relative accuracy, with a sensitivity of 73% and specificity of 94%. It’s important to point out that ultrasound actually cannot detect most forms of endometriosis, particularly flat lesions or smaller growths. Nevertheless, ultrasound can at least show that a mass is growing on or near the ovaries (referred to as adnexal masses) and is especially helpful in distinguishing between solid masses and fluid-filled cysts.

Diagnostic Dilemma: Endometriomas vs. Functional Ovarian Cysts
As noted earlier, endometriosis in general is still under-diagnosed, with average diagnostic delays of approximately 7-10 years, or more in some cases. However, endometriomas can sometimes pose an even greater diagnostic challenge, as they can be mistaken for functional ovarian cysts which grow each month as part of a woman’s normal monthly ovulatory cycle.

Pre-teen and teenage girls are especially apt to have their endometriosis and/orendometriomas misdiagnosed. Therefore, this is one of the first conditions on the list of differential diagnoses that your doctor should try to rule out during an ultrasound evaluation of your lower abdomen.

The traditional diagnostic protocol for suspected functional ovarian cysts is to take an “expectant” or “wait and see” approach.This is because, unlike most endometriomas, the vast majority of functional ovarian cysts are harmless, temporary structures that almost always shrink on their own within 4-8 weeks, usually without symptoms and usually without the need for any medical intervention, except perhaps over-the-counter pain medication for those experiencing mild pain. However, in some cases they may persist, cause pain, bleeding (hemorrhagic ovarian cyst), rupture, or cause other symptoms similar to endometriomas.

To help distinguish between functional ovarian cysts and endometriomas, your doctor will consider a number of clinical signs and symptoms. For example, endometriomas may be suspected if the patient has already been diagnosed with endometriosis in other parts of her body.  Bilateral masses (growths on both of the ovaries) are also more common with endometriomas than with functional ovarian cysts (some studies suggest up to half are bilateral). And, as mentioned, endometriomas also rarely resolve on their own and may even continue growing larger. As such, if a follow-up ultrasound evaluation 8 weeks later reveals that the mass is still present and/or has grown larger, this usually rules out functional ovarian cysts.

Other Characteristics of Functional Ovarian Cysts Include:

  • Most common type of ovarian cysts in women of reproductive age
  • Three types: follicular, corpus luteum, and theca lutein cysts
  • Follicular ovarian cysts occur as part of normal monthly ovulation
  • Corpus luteum cysts are more common in pre-menopausal women
  • Corpus luteum cysts are the type that turn into hemorrhagic ovarian cysts most often
  • Caused by fluctuations of hormones throughout a woman’s menstrual cycle
  • Usually regress spontaneously within 4-8 weeks
  • Rarely bigger than 10 cm, but can range from a few centimeters to over one foot
  • Can bleed, cause pain, and exhibit other symptoms similar to endometriomas
  • Can rupture or bleed, necessitating surgical intervention

Functional Ovarian Cysts at Ultrasound
On ultrasound evaluation, endometriomas and functional ovarian cysts can also have distinct characteristics. In the case of functional ovarian cysts, they often appear:

  • small, less than 10 centimeters (cm) in diameter
  • mobile
  • smooth surface, with regular borders
  • unilocular (single chambered)
  • unilateral (one side of the ovaries)
  • thin cyst wall (<5 mm)
  • simple cystic structure

Endometriomas at Ultrasound
In contrast, endometriomas are considered complex cysts because they often have more than one characteristic (cystic parts, solid parts, etc). During an ultrasound inspection, this means that the mass will have a mixed appearance, with some areas showing heightened echogenicity (a lot of echo, which looks light gray or white-ish), or other parts will be anechoic (no echo, which looks black), or hypoechoic (low level echoes, dark gray). Endometriomas may also form cysts within cysts, which can be discerned as a honeycomb-like structure during ultrasound.

Other sonographic characteristics commonly associated with endometriomas include:

  • Round, homogenous fluid-filled mass
  • Mainly low-level echoes but mixed with some anechoic and/or echogenic loci
  • Grainy, dark gray appearance
  • Thickened cyst wall (>5 mm)
  • Irregular cyst wall (nodular, lobulated, not uniform, etc)
  • Fibrotic tissue
  • Thick septationsrepresent multiple cyst walls
  • Solid areas
  • Multilocular (multi-chambered, cysts within cysts)
  • Complexity – mixed with solid and cystic fluid
  • May show a hypervascular wall on color Doppler ultrasound
  • More often develop as multiple cysts and more often bilateral (on both ovaries)

Adhesions at ultrasound: Anatomical distortions caused by adhesions
Since endometriomas are associated with substantial potential for adhesion-formation (scar tissue), during an ultrasound evaluationyour doctor will also look for signs of anatomical distortion caused by adhesions. In the case of endometriomas, the ovaries may be pulled so far down by adhesions that they lie behind the uterus, where they cannot be seen during ultrasound.

Other common ultrasound findings indicative of adhesions include:

  • Ovaries and/or the mass appear pulled down and stuck to the bowel
  • Ovaries and/or the mass and fallopian tube appear stuck together
  • Ovaries and/or the mass, appear pulled down and stuck to the top of the uterus
  • Ovaries and/or the mass appear pulled down and stuck to the top of the bladder
  • Anatomical distortions of the ureters
  • Anatomical distortions of the bowel (unusual bowel loops, etc)
  • Anatomical distortions of pelvic ligaments or the abdominal wall
  • Elevated posterior vaginal fornix

Other types of adnexal masses
There are many other types of adnexal masses that your doctor would try to rule out as part of a differential diagnosis. Some of these include:

 

Your doctor would evaluate all clinical signs and symptoms, along with imaging tests, to help narrow the diagnosis.

Ovarian cancer or endometriomas?
In cases of suspected ovarian cancer or other cancers of the reproductive tract, immediatesurgical evaluation is recommended in order to take a biopsy (with histopathological confirmation) and remove the suspicious growth.

However, before undergoing surgery, there are several red flags that doctors know to look for when it comes to clinical signs and symptoms, risk factors, and ultrasound results that indicate a mass may be malignant. Taking extra care to review all data is especially important in all adnexal masses, but especially for endometriomas, which are often mistaken for malignant growths. However, worse than that type of false positive is a false negative – that is, when a true malignant growth is dismissed as only being a benign endometrioma, which has been reported in the medical literature.  It’s also important to remember that, although ovarian cancer and other cancers are more common as we age, red flags should always be taken seriously for all age groups.

Ovarian cancer Ultrasound Red flags
There are many subtle symptoms of ovarian and other reproductive cancers that we’ve listed here. However, the most important red flags observed during an ultrasound inspection of an adnexal mass include:

  • Any adnexal mass found in postmenopausal women
  • Any adnexal mass found in perimenopausal women
  • Any fast-growing complex septated mass with cystic and solid parts at any age
  • Any large mass, greater than 10 cm in diameter at any age
  • Any fast-growing mass at any age

Under ultrasound inspection, cancerous growths may also present with distinct characteristics, including:

  • Large, greater than 10 cm in diameter
  • Fixed (not mobile)
  • Irregular borders
  • Surface papillations (ie, non-smooth surface)
  • Mixed with both solid & cystic parts
  • Thick septa (greater than 2 mm)
  • Ascites
  • Matted bowel
  • More often bilateral
  • Cul-de-sac nodules
  • Degenerating or necrotic appearing
  • Nodular septa
  • Color Doppler vascular flow in the cystic structure

Other red flags
A more extensive list of other clinical symptoms that have been associated with ovarian and other reproductive cancers can be found here. However, a short list of common symptoms associated with reproductive cancers includes:

  • Enlarged lymph nodes
  • Vaginal bleeding or spotting in post-menopausal
  • Sudden unexplained weight loss or loss of appetite
  • Excessive abdominal bloating

Can Endometriomas Turn into Cancer?
Dr. Farr Nezhat’s groundbreaking research into the connections between endometriosis and certain cancers confirmed that women with endometriosis do have a significantly increased risk of developing certain types of ovarian cancers. However, the overall rate of malignant transformation is still very low, and has been reported as approximately 1%.

With the ovaries being one of the most common sites of malignant transformation, this is another reason that ovarian endometriomas should be taken seriously and carefully monitored for any red flags or changes that may suggest cancer.

Other risk factors associated with developing endometriosis-associated ovarian cancer (EAOC) include having had a long history of ovarian endometriomas, i.e. those who developed them at an early age. As well, malignant transformation may be affected by hormonal changes that are associated with the onset of menopause or perimenopause.

In addition, an association has been noted between unopposed estrogen therapy and the development of serous, endometrioid, and clear cell epithelial ovarian tumors. For example, one study found that 62% of those who developed endometriosis-associated ovarian cancer had received hormone replacement therapy (HRT).

It’s also very important to point out that endometriosis-associated ovarian cancer is more likely to develop in younger women, with one study reporting the mean age as 47 years old. In contrast, 63 is the average age that other forms of ovarian cancer is first diagnosed. This is a significant clinical difference that should be taken into account when evaluating women with endometriosis for any red flags associated with cancer.

A type of unusual endometriotic growth called “atypical endometriosis” may also constitute a precancerous state and is associated with an increased risk of developing endometriosis-associated ovarian cancer. Therefore, be sure to ask your doctor whether any of your endometriosis biopsies came back as atypical.

The good news is that endometriosis-linked cancer generally has better prognostic outcomes, as it’s associated with less aggressive cancers, such as low-grade serous, endometrioid carcinomas, and clear cell epithelial ovarian tumors.

Summary Cancer Red Flags
False Negatives:When considering these red flags, it’s important to note that there have been numerous cases documented in the medical literature when cancerous growths did not exhibit any of the typical red flag signs associated with malignancy, looked utterly benign on ultrasound, and were only found to be malignant during surgery. As mentioned, a cancerous growth can also easily be misdiagnosed as a benign endometrioma because they can appear very similar on ultrasound inspection and can cause similar symptoms.  Therefore, we do urge patients to trust their instincts if they sense that there is something wrong with their health, even if preliminary imaging tests come back asnormal. If in doubt, it’s always worth it to get a second opinion. As for suspected benign cysts, do make sure to schedule a follow-up appointment 4-8 weeks after the first diagnosis to make sure that the growths have in fact disappeared or decreased in size.

False Positives:At the same time, and as mentioned,there are many benign masses that can have similar clinical and ultrasound characteristics as malignancies, so this list of red flags does not in any way stand as definitively proof that a mass is cancerous. In fact, the majority of adnexal masses that doctors end up investigating do turn out to be benign. Endometriomas, in particular, are notorious for bearing a striking resemblance to endometriod carcinomas and are commonly misdiagnosed as such. Nevertheless, we felt it was important to share this information, since ovarian cancer and other cancers of the female reproductive tract are sometimes misdiagnosed until they’ve reached a late stage.

Treatment Options: Overview
Treatment option for ovarian endometriomas can include hormonal suppressive therapies to minimally invasive surgery to remove the entire cyst (cystectomy). At our center, care is individualized to align with the patient’s overall health and fertility goals. In this section, we’ll provide an overview of everything you need to know about the medical treatments now available, as well as surgical treatment options that Drs. Nezhat pioneered, which have been widely accepted as the gold standard of care in the treatment of endometriomas.

Medical Treatment Options
Ovarian endometriomas are often resistant to hormonal suppressive therapies and so surgery is usually considered the treatment of choice with the highest chance of reducing symptoms and reducing chance of recurrence. However, there are times when it’s appropriate to start with medical therapies before considering surgery.

The most common medical treatment options include:

  • Birth Control Pills
  • GnRh analogs (agonists and antagonists)
  • Pain Medication
  • Aromatase Inhibitors

Some also use hormonal suppressants before surgery, to reduce the inflamed tissue and make surgery easier. Others prefer to see what’s going on without suppressive therapies. Hormonal therapies can also be used after surgery, to reduce the chance of recurrence and allow the body to heal. Studies show that a significantly reduced chance for recurrence can be effectively accomplished with the use of continuous birth control pills that contain low doses of both estrogen and progesterone.

It’s important to point out that, even if pharmaceutical treatment options do help alleviate symptoms, they do not treat the underlying disease; they only suppress symptoms. Therefore, surgical removal of endometriomas is recognized as the gold standard in treatment.

Surgical Treatment Options: Overview
Gold Standard: Organ-Preserving Treatment Options

Today, organ-sparing minimally invasive surgery is the undisputed gold standard for treating ovarian endometriomas. However, it was not too long ago that the surgical convention was to remove the ovaries entirely (bilateral oophorectomy) rather than attempt the more difficult surgery of removing just the diseased areas. Hysterectomies were also considered the standard treatment for women with endometriosis. And prior to the introduction and acceptance of minimally invasive surgery (aka, video laparoscopy), this meant that all of these surgeries were performed via very painful, large incision laparotomies that were associated with very high and very serious complication rates.

Thankfully, the late 20th century emergence of minimally invasive surgery utterly revolutionized medicine and led to organ-sparing surgery becoming the gold standard and preference of most women.

Indications for surgical intervention may include unresolved chronic pelvic pain, infertility, and dyspareunia that has not responded to medical therapy. However, if there is an ovarian cyst of any kind that is hemorrhaging and not resolving on its own, it may need to be surgically removed immediately, rather than waiting to try other medical options. In women with infertility, endometriomas may also be excised prior to the use of assisted-reproductive technologies, such as IVF. Large endometriomas are also candidates for surgery over medical therapies or expectant management (wait & see approach), as they have a higher risk of rupture and torsion. Surgery may also be advisable because ovarian cancer is more common in women with endometriosis, with ovarian tumors thought to arise from approximately 1% of ovarian endometriosis. Therefore, surgically removing all remnants of endometriomas and other endometriotic growths may decrease the risk of future malignancy.

However, organ-sparing surgery is usually significantly more difficult to perform, as advanced reconstructive surgical techniques are usually required. This is especially true for endometriosis surgeries involving the ovaries, where exceptional skill is needed to remove all disease without damaging these delicate organs. This is why it’s so important to seek out a recognized endometriosis expert surgeon like Drs. Nezhat, who are among only a handful of surgeons in the world recognized as having the advanced surgical skills needed to treat ovarian diseases like endometriomas in a minimally invasive, fertility-sparing way.

Which Surgical Method is Best?
Even though organ-sparing minimally invasive surgery is considered the treatment of choice for endometriomas, there are many debates concerning precisely which type of surgical methods or instruments should be used. The controversy is even more pronounced when issues of fertility factor into the debate. In fact, one author noted several years ago that “there is no general consensus regarding the proper management of women with ovarian endometrioma who wish to conceive.”

Fast forward several years and we do now see a growing body of well-designedstudies that do provide at least some evidence as to which practices appear to provide the greatest relief from symptoms, with the least likely chance for recurrence and least likely chance for damaging the ovaries. Of course, an important caveat to keep in mind is that medical care must always be individualized to the specific needs of the patient. Therefore, the following summaries are meant to serve as guidelines that have been established by Drs. Nezhat’s published research and more than three decades of experience working on the most difficult cases and which are recognized in the field as best practices and gold standards.

Laparoscopic Excision and Eradication Surgery: Gold Standard
Laparoscopic excision and/or eradication surgery is considered the surgical gold standard for treating endometriosis. The word “excision” simply means to cut out and completely remove diseased tissue. There are many different types of surgical instruments and methods that can excise and cut out diseased tissue, including old-fashioned surgical scissors, scalpels, and electrocautery, to more advanced technologies such as harmonic scalpel, lasers and the plasma jet.

Aggressive Excision?
Each technique or technology comes with its pros and cons, and so a variety of factors will determine which instrument or method will be safest and most effective for the individual patient. One thing is certain, though: the surgeon who knows only one method to treat endometriosis is like the man who only has a hammer and therefore treats everything as if it were a nail. And so it follows, the surgeon needs more than a hammer in his or her toolbox in order to provide the safest and most effective surgical treatment options.

This brings us to the issue of excision, which, as mentioned, is the standard surgical treatment option for most forms of endometriosis. However, in certain delicate organs like the ovaries or Fallopian tubes, aggressive excisional techniques may not be appropriate. For example, if a surgeon uses the excisional techniques intended for deeply infiltrating endometriosis on the Fallopian tubes of a patient trying to conceive, this would very likely cause irreparable damage to organ function and fertility. The same is true for attempting to use aggressive excisional techniques on the ovaries of a patient with low AMH, in which case the surgeon may destroy her chance of getting pregnant.

This is why Drs. Nezhat use safer and more precise methods to completely eradicate endometriosis on delicate organs. Laser eradication of endometriosis is particularly effective, as it allows the surgeon to excise the diseased areas with precision measuring in the microns, without penetrating too deeply into healthy tissue like less precise methods do. In cases where biopsies have already been done, experienced endometriosis surgeons like Drs. Nezhat can also use the surgical techniques of laser ablation, fulguration, and/or vaporization to completely remove endometriotic growths. Unfortunately, these methods have gotten a bad reputation because non-endometriosis specialists and/or less experienced surgeons often misapply these techniques and miss deeper lesions as a result.

Of course instruments and methods are not as important as a trained, skilled surgeon. Skilled, experienced surgeons know how to eradicate all endometriosis using different surgical techniques and without harming the patient’s organs or surrounding healthy tissue.

Two Different Types of Endometriomas: Type I and Type II
Before determining which surgical technique to apply, at surgerythe surgeon must first determine what type of endometriomas are present. As it turns out and as mentioned, there is more than one type, a breakthrough discovery which occurred in the early 1990s, when Nezhat et al were the first to report that there were actually two histopathologically distinct types of endometriomas: Type I and Type II. Classified based on size, cyst contents, ease of removal of the capsule, adhesions of the cyst to other structures and location of superficial endometrial implants relative to the cyst wall.
This crucial new insight had immense clinical significance because these two different types of endometriomas require quite different surgical management.  Unfortunately, the majority of surgeons still do not know how to tell the difference between these two types of endometriomas, which can result in sub-optimal surgical outcomes for patients. Therefore, we recommend seeking out an experience endometriosis specialist if you suspect you may have endometriomas. Below we’ve listed the ways specialists are able to distinguish between these two different types of endometriomas.

Type I or Primary Endometriomas
As mentioned, Type I and Type II endometriomas are two distinct classifications of endometriomas which arise from two distinct mechanisms of pathogenesis. Type I endometriomas are considered primary endometriotic cysts, as they are histopathologically more consistent with other types of endometriotic growths that occur in other parts of the abdominal cavity, in that they always have endometrial-like glands and stroma present. In Type I Endometriomas, the ectopic endometriotic cells begin growing on the ovarian cortex, which is the outer surface layer of the ovary. In some cases, the lesions remain superficial, with very little invasion into the underlying tissue. However, in other cases, the endometriotic cells invaginate deeply into the ovarian tissue, creating a pseudocyst that has a cyst wall resting on the ovarian cortex, which is a normal and vital part of the ovary itself. Unlike other types of ovarian cysts, Type I endometriomas are filled with a thick, dark brown fluid, which is comprised mostly of old blood.   Invagination of a plaque of endometriosis into the cortex and stroma of the ovary and subsequent hemorrhage from endometrial-like tissue is responsible for the cyst formation.

Type I endometriomas tend to grow slowly and are small, usually less than 5 centimeters, with an average range of approximately 1-2 centimeters in diameter. A densely adherent fibrous capsule also usually encapsulates Type I endometriomas. In fact, it is the presence of this fibrosis and scar tissue that keeps these endometriomas from growing larger. Despite their small size, Type I endometriomas are usually the most difficult to surgically remove because they tend to develop more fibrosis and adhesions and because their cyst wall is severely incorporated into the ovarian tissue that could be inadvertently damaged during surgery for removal of the cyst.Therefore, these endometriomas should only be treated by an expert surgeon.

Type II or Secondary Endometriomas
Type II endometriomas are hemorrhagic follicular or luteal cysts involved with, or invaded by, cortical endometriosis implants. In Type II endometriomas, the endometriotic cells invaginate into a pre-existing follicular or luteal cyst, which is a type of ovarian cyst that arises as a normal part of the monthly ovulatory cycle. In this Type II scenario, the cyst cell wall is not made of the crucial ovarian cortex, as is the case in a Type I endometrioma, but instead has a wall formed from the pre-existing cyst. Even so, great care is needed in order to surgically remove these cysts as well, as they can and do adhere to the stroma of the ovaries.

These secondary endometriomas are further divided into three subclasses – IIA, IIB, IIC – distinguished by the relationship of cortical endometriosis with the cyst wall.

Type IIA Endometriomas
Type IIA endometriomas are usually larger than their Type I counterparts (2 cm – 6 cm or more), hemorrhagic follicular or luteal cysts in which the endometrial implants are superficial and have not penetrated into the cyst wall or only barely, with less than 10% of endometrial-like tissue within the cyst wall. This makes the Type IIA variety distinctive histopathologically, as they show either no or very little evidence of endometrial glands or stroma in the lining of their cyst walls under microscopic analysis.  As a result, the cyst walls are more easily separated from the ovarian cortex than is the case with other types of endometriomas.

Type IIB and IIC Endometriomas
Type IIB and IIC endometriomas are also hemorrhagic follicular or luteal cysts, but with endometrial implants that have deeply invaded the cyst wall, and with progressively more endometrial invasion in type IIC compared to type IIB. In Type IIB, between 10%-50% of the cyst wall is involved with endometrial-like tissue, while Type IIC’s have 50% or greater involved with endometrial-like tissue. These endometriomas may be preliminarily diagnosed visually during surgery by their yellowish appearance and difficulty of removal, with the basis of distinguishing between Type IIB and IIC being the progressive difficulty in removing the cyst wall from the ovarian cortex.

Type IIB and IIC endometriomas also grow larger than any other types and are associated with more adhesions. They may be firmly attached to the pelvic side wall and/or back of the uterus, and may easily rupture when surgically freeing them from their adherence to surrounding organs or anatomical structures. Type IIB and IIC endometriomas may also have cyst walls as thick as 5 millimeters (mm). In Type IIC, the ovarian cortex may be especially strongly attached to the cyst wall, due to the presence of more endometriosis, which in turn leads to the development of more adhesions. This factor in particular makes it difficult to develop a surgical plane between the cyst wall and ovarian capsule to remove the cyst wall.

All Type II endometriomas should be completely aspirated and then removed with the least amount of trauma to the ovary as possible. However, to rule out malignancy and to confirm the diagnosis, a frozen biopsy sample can be taken intra-operatively, before proceeding with any surgical intervention. After surgical removal, a hormonal suppressive medical therapy can be given for 6-8 weeks post-operatively, to help promote the healing of the ovary and reduce the chance for recurrence.

Other Controversies: Removing the Cyst Wall:
One of the most heated debates regarding endometriomas centers around its cyst wall and how to surgically treat it. As mentioned, in certain types of endometriomas (Type I and Type IIC), the cyst wall – also referred to as the cyst capsule – can be so strongly attached to the ovarian surface that surgically removing it can potentially cause damage to the adjacent healthy ovarian tissue and decrease ovarian reserve. Therefore it has been an accepted practice for surgeons to simply drain the cyst contents, or drain and ablate the inside surface of the cyst wall. Ablating the inner lining of the cyst wall was supposed to destroy any endometriosis cells present, while draining the cyst deflated it, thereby reducing its size.

The problem with these techniques is that they are associated with a very high chance of recurrence, as high as 90% in fact. This is because the cyst wall is where the endometriosis is actually present. Therefore, if the cyst wall is not removed, this means the endometriosis is not removed. As such, the cyst would just fill up with blood again and cause inflammation and scar tissue on a monthly basis.

Laparoscopic Ovarian Cystectomy
It was Dr. Nezhat who was among the first to notice that completely removing the cyst wall using excision significantly reduced the recurrence rate to as low as 5.8%, from more than a 90% rate of recurrence associated with the traditional method involving just drainage & ablation. The complete surgical removal of an ovarian cyst of any kind is referred to as an ovarian cystectomy.
However, these are some of the most difficult surgeries to perform, with very little margin for error. If done incorrectly, an inexperienced surgeon could potentially cause damage to ovaries, leading to new pain symptoms, organ dysfunction, and potentially compromised fertility (irreversible damage to the ovarian reserve and oocytes). As well, reconstructive surgery to repair defects in the ovary that the disease caused is also often necessary. Yet, even to this day, Drs. Nezhat are among only a handful who have the skill and experience needed to perform such advanced reconstructive surgeries in a minimally invasive way and without damaging the ovaries. 

Summary: Delayed Diagnosis Still a Universal Problem
When it comes to ovarian endometriomas, the bottom line is that it’s crucial to seek out an experienced endometriosis specialist. There’s just too much at stake to take risks with your health and fertility. Delayed diagnoses also continue to be a significant problem that exposes women and girls to years of unnecessary suffering and preventable damage to internal organs and fertility. Therefore, as we’ve mentioned in other sections, it’s important to trust your own instincts when it comes to your own health. You’ve lived in your body your whole life, so your instincts are valid and should be honored by doctors.

For further information, please read our complete published papers which you can find here.

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