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Endometrioma Cyst or Chocolate Cyst

ovarian-endometrioma

ENDOMETRIOMA CYST OR CHOCOLATE CYST 

Endometriosis of the Ovaries: What you need to know
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 of neurotransmitter receptors in the ovaries, including those responsive to serotonin and acetylcholine. Indeed, when you consider that a woman’s lifetime of reproductive processes are “the result of a complex feedback system and signaling network between the brain (hypothalamus-pituitary-ovarian axis,) and ovaries”, as well as 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 in the U.S., with an annual fiscal price tag for healthcare costs estimated to be $69.4 billion (2009 figures), 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 Nezhat’s research ,studies and classifications revealed there are actually a few different subtypes of ovarian endometriomas (Type I or primary and Type II or secondary being the two main classifications). Therefore, the disease course and histopathological details can vary considerably. In general, though, under a miscroscope 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.

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: Also referred to as Sampson’s Theory, direct implantation, and/or Nezhat’sinvagination theory when referring to endometriomas, this theory was first postulated as early as the 16th century and suggests that, during menstruation, menstrual blood backs up and spills into the pelvic cavity through the fallopian tubes, causing biologically active endometrial 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 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 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 andmicrovascular 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 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 Theory or Defective Embryogenesis: This theory was alluded to as early as the 19th century and hypothesizes that embryonic cells of the Wolffian or Müllerian ducts for some reason fail to properly migrate to their proper place in the female reproductive tract, i.e., don’t properly migrate to the ovaries (in the case of the Wolfian ducts) or to the uterus, cervix, upper 1/3 of the vagina, or fallopian tubes (in the case of the Mullerian ducts). Instead, these embryonic cells become misplaced in other parts of the body, when the embryo is still developing (during embryogenesis). During puberty or in response to perhaps 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. This means that debates will naturally spill 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) and begin growing from there?

In the case of endometriomas, currently the medical literature appears to show a preference for the /Nezhat’s invagination theory , so we’ll start there. In theNezhat’s invaginationimplantation 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 Primary endometriomas), or onto pre-existing functional ovarian cysts (Type II or Secondary endometriomas). In this implantation theory, the origin of the implanted cells doesn’t really figure into the theory, but there are many who speculate that the cells originate from the fallopian tubes, just as certain ovarian cancers are now known to be derived from the fallopian tubes (i.e. fallopian tube-derived ovarian epithelial cancers (F-OEIs).

Whatever the origin, what the implantation/invaginationtheory suggests happens next is that these abnormal endometrial-like cells begin invaginating (infiltrating) deeply into the ovaries ( Primary  or type 1 Endometrioma )or into the existing functional cyst ( Secondary or type 2 Endometrioma) 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 abd partially of the outside layer of the normal ovarian surface (called the ovarian cortex), while in a Type II endometrioma, the cyst wall is formed from the the existing functional cyst’s. 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 cells found in the uterus. In other words, they are abnormal, mutated cells of unknown origin that act in abnormal, mutated ways.
Nevertheless, endometriotic tissue can behave in a somewhat similar manner as normal endometrial 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 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 cells each month as part of menstruation.  Cell death renders old endometrial cells biologically inactive, so that they stop growing and responding to hormones, allowing for new endometrial 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 and is 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 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 cells. In the case of any type of endometriosis, including endometriomas, dysregulated stem cells may be involved in the formation of new endometrial cells, albeit ones that are misplaced and mutated in structure and function.

Still, the abnormalities don’t stop here, either. Biochemically, an entire range of dysfunction has been noted in endometriosis tissue , including a decreased responsiveness to progesterone, an increased number of estrogen receptors, cell adhesion molecule abnormalities, elevated levels of matrix metalloproteinases (MMPs), significantly increased levels of prostaglandin E2(PGE2), over-expression of aromatase (in particular aromP450), malformations of the extracellular matrix, cystologic (chromosomal) atypia, and other aberrations in gene expression and protein production. Although endometriosis is not cancer, researchers including Dr Farr Nezhat’s research who in addition to being an Endometriosis Expert is a Gynecological Oncologist have also 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. And it is important to emphasize here the role of an Endometriosis Expert Surgeon when treating the ovarian and Fallopian tubes endometriosis. Because if all the surgeon knows is to excise the disease and nothing else , he or she could cause irreparable damage to the reproductive or other organs

In the 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, infertility, obliterated cul-de-sac (Pouch of Douglas), and damage to surrounding organs or structures, such as the bowel, bladder, ureter,fallopian tubes, peritoneum, uterus, rectovaginal septum (cul-de sac), abdominal wall, nerves, ligaments, and 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 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 even 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 to correct.Symptoms are acute and sudden onset of pain in the lower abdomen, usually on one side, along with severe nausea or vomiting.

Large endometriomas in particular may also suddenly rupture, 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 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. Life-threatening cases of ectopic pregnancies are also more common in those with endometriomas and so women should trust their instinct and seek urgent medical care in cases of extreme pain.

Risk Factors
Risk factors of 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 frequent periods or ones that last 7 or more days
  • Have a closed or otherwise blocked hymen (imperforate hymen, congenital aplasia), which blocks the flow of menstrual blood out of your body during menstruation (also called Mayer-Rokitansky-Kster-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 19 out of 1785 patients 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.

Environmental toxins, such as endocrine disrupting chemicals (EDCs) have also been proposed as causing increased susceptibility to endometriosis. In the case of EDCs, though many studies are inconclusive, 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. 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.

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. the traditional diagnostic protocol is to take an “expectant” or “wait and see” approach.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 luteal, and theca luteal cysts
  • Follicular ovarian cysts occur as part of normal monthly ovulation
  • Corpus luteal cysts are more common in pre-menopausal women
  • Corpus luteal 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 septations represent 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, during an ultrasound evaluation, your doctor will also look for signs of anatomical distortion caused by adhesions. In the case of endometriomas, often what occurs is that the ovaries simply cannot be seen at ultrasound, because they are obscured by the endometrioma itself. In other cases, the ovaries are pulled so far down by adhesions that they lie behind the uterus, where they also cannot be seen during ultrasound. Other endometriomas grow so large that they actually displace other organs within the pelvis, including displacement of the bladder, bowel, uterus, ureters, and fallopian tubes. 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:

– Ovarian cancer
– Paraovarian cysts
– Ectopic pregnancy
– Cystadenomas
– Dermoid cysts (teratomas)
– Fibroids
– Polycystic ovaries
– Polyps
– Fistulas , etc.

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

Another diagnostic dilemma: is it cancer or endometriomas?
In cases of suspected ovarian cancer or other cancers of the reproductive tract, surgical evaluation is recommended in order to take a biopsy (with histopathological confirmation) and/or remove the suspicious growth. Although definitive diagnosis can only be obtained by biopsy with histopathological confirmation, 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. Endometriomas may be mistaken as malignant growths – and vice versa, i.e. malignant growths are sometimes dismissed as only being endometriomas. Therefore, doctors must be especially careful when certain red flags are observed. Although ovarian cancer and other cancers are more common as we age, red flags should always be taken seriously for all age groups.

Red flags for ovarian cancer
There are many subtle symptoms of ovarian and other reproductive cancers that we’ve listed here. However, the most important red flags concerning adnexal masses include:

– Any adnexal mass found in postmenopausal women
– Any adnexal mass found in peri-menopausal 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

Red flags for ovarian cancer at ultrasound
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, while a short list of some of the most common are listed below:

– 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?
The overall rate of malignant transformation of endometriosis in general has been reported as approximately 1%.  However, the most common site of this malignant transformation is the ovary. This is why ovarian endometriomas should be watched for any red flags or changes that may suggest cancer.  As the pathologic features of “atypical endometriosis” may constitute a precancerous state, women with atypical endometriosis may be at an increased risk of developing EAOC.  Other risk factors associated with developing 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 peri-menopause. In addition, an association has been noted between unopposed estrogen therapy and the development of endometrioid or clear cell epithelial ovarian tumors. One study found that 62% of those who developed extraovarian cancers arising in endometriosis had received hormone replacement therapy (HRT). “The latest studies suggest that endometriosis-associated ovarian cancer (EAOC) often develops in younger women, with one study reporting the mean age as 47 years old. The good news is that this form of endometriosis-linked cancer generally has better prognostic outcomes, as it’s associated with less aggressive cancers, such as low-grade endometrioid cell types or clear cell epithelial ovarian tumors. “Malignant transformation of extra-ovarian endometriosis is thought to account for approximately 25% of all malignant transformations of endometriosis.”

Summary Cancer Red Flags
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. Cancers can be mistaken for endometriomas, including those in extra-ovarian sites. >>>>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 appear normal. If in doubt, it’s always worth it to have a follow ups to make sure cyst has disappeared or has decreased in size.

At the same time, please also note that there are many benign masses that can have similar clinical and ultrasound characteristics as malignancies, so this list of red flags can in no 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). Ovarian endometriomas are often resistance 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 many debates concerning precisely which surgical methods or instruments should be used. In fact, as one author noted, “”Currently, there is no general consensus regarding the proper management of women with ovarian endometrioma who wish to conceive.” However, there is now a growing body of well-designed medical studies 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 which are recognized best practices and gold standards, as well as evidence based on Drs Nezhat’s published research and more than 3 decades of experience working on the most difficult cases.

Gold Standard: Organ-Preserving  Treatment Options
The gold standard for treatment today is for organ-preserving minimally invasive surgeries, as opposed to the olden days when surgeons simply removed the ovaries rather than attempt to excise the diseased parts.

But before we get to the treatments, a trip back in time might be helpful for some historical perspective. For most of the 20th century, it was a common practice to simply remove a woman’s reproductive organs, rather than try to treat the actual disease. This led to the unfortunate practice of performing hysterectomies and removing the ovaries (oophorectomies) in women with endometriosis.
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. 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. Indeed, Drs Nezhat ate among only a handful of surgeons in the world recognized as having the advanced surgical skills needed to treat endometriomas in a minimally invasive, fertility-sparing way. See below for details.

Establishing an individualized treatment plan
At our center, care is individualized depending on the patient’s concerns regarding her own health. In this section, we’ll provide an overview of everything you need to know about the pharmaceutical treatment options 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.

Pharmaceutical Treatment Options
As mentioned, endometriomas rarely respond to pharmaceutal treatments or hormones. However, there are times when it’s appropriate to start with pharmaceutical options before considering surgery. Among those most widely used include:

– Birth Control Pills
– GnRh agonists analogues and Antagonist
– Pain medication
– Aromatase Inhibitors

Some also use hormonal treatment 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 chance of recurrence and allow body to heal. Studies show that this can be effectively accomplished with continuance use of birth control pills that contain both estrogen and progesterone.
It’s important to point out that, even if pharmaceutical treatment options do help alleviate symptoms, they do not treat underlying disease, only suppresses symptoms. Therefore, surgical removal of endometriomas is recognized as the gold standard in treatment.

Surgical Treatment Options: Overview
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 removed.

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.

Laparoscopic Excision and eradication Surgery: Gold Standard
Laparoscopic eradication surgery for endometriomas (and all forms of endometriosis) is considered the gold standard. The word “excision” simply means cutting out and completely removing diseased tissue. There are many different types of surgical instruments 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 plasma jet. You’ll also hear the terms “ablation” and “fulguration” a lot when researching endometriosis surgery, and we’ll get to those terms below.

However, there are some controversies with respect to which specific instruments or techniques are used. This is because, as mentioned, the ovaries and tubes are very delicate and can easily be damaged if the surgical instruments and/or approaches applied are too aggressive or otherwise not appropriate. Each technique or technology comes with its pros and cons, and so a variety of factors will determine which instrument will be safest and most effective for the individual patient.The surgeon who only has one instrument or knows only one method to treat endometriosis is like a man who only has a hammer for all of the repairs ,that to him everything is a nail . We all know one needs more than a hammer in his tool bus to be able to do a great job.

Of course instruments and methods are not as important as a trained , skilled surgeon. Skilled, experienced surgeons are capable to eradicate the endometriosis many ways without harming the patient,s organs.

For example if a surgeon insists to ” excise “endometriosis off the Fallopian tubes in a young woman trying to get pregnant has a good chance of damaging these sensitive organs . Or a surgeon who insists to ” excise “endometriosis off the ovaries of a woman with low AMH may destroy her chance of getting pregnant.

TWO DIFFERENT TYPES OF ENDOMETRIOMAS : TYPE I AND TYPE II
At surgery, surgeon determine s 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 has 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 which 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 tissue is responsible for the cyst formation.

. These types of endometriomas tend to grow slowly and are small, usually less than 5 cm, with an average range of approximately 1-  2 centimeters large, with a densely adherent fibrous capsule Superficial cysts is limited in size by fibrosis and scarring. Despite their small size, they 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 (outer surface of the ovaries) 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
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 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
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 tissue, while Type IIC’s have 50% or greater is involved with endometrial 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 mm. In Type IIC, the ovarian cortex may be especially strongly attached to the cyst wall, in part due to more adhesions due to more endo, making it difficult to develop a surgical plane between the cyst wall and ovarian capsule to remove the cyst wall.

Controversies in Surgical Treatment .

Removing the cyst wall:
One of the most heated debates regarding endometriomas centers around its cyst wall and how to surgically treat it. 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 95 percent in fact. That is because the cyst wall (endometrial glands and stroma )are not removed and continues to bleed on a monthly basis and fill up the drained cyst again.

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 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, very difficult to do this – few can in fact have the skill to perform this surgery without damaging the ovaries. There is very little margin for error in these advanced minimally invasive surgeries. 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 oovycytes). As well, reconstructive surgery to repair defects in the ovary that the disease caused is also often necessary.


Type I Endometriomas:
Surgical Treatment Best Practices include removal by an experienced surgeon or ablation if any danger of damaging the ovarian tissue.

Type IIA Endometriomas:
Surgical Treatment Best Practices include:

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.

Type IIB

Type IIC
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.

SUMMARY – Delayed Diagnosis Still a Universal Problem
In summary, just like all forms of endometriosis anywhere else in the body, endometriomas can cause severe, chronic pain that significantly impacts all aspects of a woman’s or girl’s life. Making matters worse is that endometriomas are often misdiagnosed for less severe types of ovarian cysts and consequently may not be taken seriously by pediatricians or general practitioners. Pre-teen and teenage girls are especially apt to have their endometriosis and endometriomas misdiagnosed. 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. If you think you’re experiencing the signs and symptoms of endometriomas, do seek out medical attention from an endometriosis specialist if possible, as endometriomas have the potential to cause damage to your ovaries, ovarian function, ovarian reserve, fertility, and surrounding tissues and organs.

For further information please read our complete published papers which you can find here at Nezhat.org .