Endometriosis

Endometriosis is a common and clinically important problem in women of childbearing age. It is classically defined as the presence of functional endometrial glands and stroma outside the uterine cavity and musculature ¹. This is distinct from adenomyosis, in which endometrial tissue is confined to the uterine musculature. Size may is highly variable, ranging from microscopic endometriotic implants to large cysts (endometriomas).

Epidemiology

Typically endometriosis presents in young women, with a mean age of diagnosis of 25-29 years-old⁴, although it is not uncommon among adolescents. Up to 5% of cases are diagnosed in postmenopausal women. Potential risk factors include family history and short menstrual cycles. Racial predisposition remains controversial ^5,7.

It is difficult to ascertain the overall prevalence of endometriosis, but in women who underwent laparoscopy for various reasons, the prevalence is was follows: ⁵

• asymptomatic women (laparoscopy for tubal ligation): 1-7%
• primary infertility: 17-50%
• pelvic pain: 5-21%

Clinical presentation

Symptoms

• infertility: 30-50% of women with endometriosis are infertile ¹⁵
• pelvic pain: including dyspareunia, dysmenorrhea, chronic pelvic pain
  • NB: pain is not always cyclic ¹²
• unusual symptoms
  • gastrointestinal involvement: catamenial diarrhoea, rectal bleeding and constipation
  • vesical involvement: urgency, frequency, haematuria
  • thoracic involvement: pleuritic chest pain, pneumothorax, pleural effusions or cyclic haemoptysis
• asymptomatic: especially if the disease is isolated to the peritoneum

Examination findings

• non-specific, and stage of disease does not necessarily correlate with the severity of the symptoms ¹⁶
• tenderness along the adnexa and uterosacral ligaments, cul-de-sac +/- thickening or nodularity
• rectovaginal or adnexal masses

Pathology

The pathogenesis of endometriosis remains unclear and is subject to much debate; potential mechanisms include:

• metastatic theory: transplantation of endometrial cells (via retrograde menstruation, lymphatic or vascular dissemination, iatrogenic implantation) with probable immune/hormonal/inflammatory mediators ⁸; supporting this theory is that up to 90% of women have bloody peritoneal fluid during the perimenstrual period ⁹
• metaplastic theory: retroperitoneal deep endometriosis may originate from metaplasia of Müllerian remnants located in the rectovaginal septum ¹⁰
• induction theory: whereby shed endometrium releases substances that induce undifferentiated mesenchyme to form endometriotic tissue ²

See the illustration of theories of endometriosis.

Macroscopic

Macroscopic appearances vary depending on the duration of disease and depth of penetration:

• superficial
  • superficial endometriosis: Sampson syndrome
  • nodules or plaques of varying size from a few millimetres to 2 cm in diameter
  • the amount of pigment appears to increase with the age of the lesion; initially they appear as white plaques, non-pigmented clear vesicles or red petechiae or flame-like areas; as they age the colour changes to bluish/brownish lesions - these are referred to as “powder burns”, representing haemolysed blood encased in fibrotic tissue ¹¹
  • additionally, appearance not only varies with age but also with the phase of the menstrual cycle
• deep: penetrating into the retroperitoneal space or the wall of the pelvic organs to a depth of at least 5 mm, and comprises nodules, cysts and secondary scarring ³
• endometriotic cysts (a.k.a. endometriomas or "chocolate cysts")
  • most commonly occur in the ovaries and are the result of repeated cyclic haemorrhage within a deep implant
  • often there is complete replacement of ovarian tissue
  • cyst walls may become thick and fibrotic with dense adhesions, with lining that varies in contour (smooth to shaggy) and colour (pale-to-brown)
• adhesions and fibrosis can distort normal pelvic anatomy and lead to the obliteration of the pouch of Douglas

Location

The most common locations for endometriotic deposits are the ovaries; then in the pelvic peritoneum. Less common locations include C-section scars (scar endometriosis), deep subperitoneal tissues, gastrointestinal tract, bladder, chest and subcutaneous tissues. The pouch of Douglas, uterosacral ligament and torus uterinus are the most common pelvic sites of involvement ¹³.

Deep pelvic endometriosis is divided into:

• anterior cul-de-sac
  • endometriosis of the bladder detrusor with associated adhesion and anteflexed uterus
  • vesicovaginal septal involvement typically more caudal
• posterior cul-de-sac
  • retroperitoneal lesions and dependent intraperitoneal locations that may result in infiltrating lesions
  • adhesions between the anterior rectal wall and posterior vaginal fornix
  • rectovaginal septal involvement
• pelvic side wall
  • including ureteral lesions said to arise from extension of pelvic foci and ovarian endometriosis
• gastrointestinal tract
  • implantation occurs in 12-37% of patients
  • rarely proximal to the terminal ileum ¹
  • rectosigmoid > appendix > caecum > distal ileum
• urinary tract
  • involvement is typically asymptomatic except with severe pelvic disease ²⁰
  • bladder > distal ureter

Extra-abdominal locations include:

• chest
  • uncommon
  • almost exclusively right sided
  • usually in the setting of long-standing (>5 years) pelvic endometriosis
• cutaneous disease
  • scars (scar endometriosis)
  • abdominal wall and recesses (e.g. inguinal hernias)
  • cervix: associated with cone biopsy
  • labia/vulva (via the round ligament)
  • canal of Nuck
  • inguinal region (inguinal endometeriosis)

Radiographic features

Although laparoscopy continues to be the gold standard for the diagnosis of endometriosis, MRI is increasingly being used, especially to evaluate deep disease, with high sensitivity (90%) and specificity (91%) ²⁰. Ultrasound is predominantly used to evaluate the ovaries and to assess the pelvis in the workup for pelvic pain or infertility.

Ultrasound

Ultrasound is poor at detecting peritoneal implants (~11%) ²¹, and although it is unable to detect adhesions, it is able to dynamically assess mobility and fixation.

Ultrasound is better at detecting endometriomas:

• homogenous, focal lesions with low-level echoes, reminiscent of the testicle
• they are typically unilocular, but may be multilocular, containing thin or thick septations
• may be multiple
• may contain mural nodules (a finding also found in ovarian neoplasms)
  • if these mural nodules are hyperechoic, these have a high predictive value for endometrioma over non-endometrial lesions ²²
• colour Doppler: no internal vascularity
• as opposed to many other ovarian cysts, endometriomas do not resolve

Despite repeated haemorrhage, findings of acute haemorrhage are uncommon in endometriomas (<10%), such as layering blood products or retractile thrombus ²².

MRI

Technique: pelvic MRI protocol - endometriosis.

MRI has a greater specificity for the diagnosis of endometriomas than the other non-invasive imaging techniques ¹ and thus has a role to play in the evaluation of adnexal masses, as well as assessing for response to medical therapy (see below) potentially eliminating the need for follow-up laparoscopy. Typically the lesions that can be detected with MRI are those that contain blood products ²³.

• haemorrhagic “powder burn”
  • lesions appear bright on T1 fat saturated sequences
• small solid deep lesions
  • may be hyperintense on T1 and hypointense on T2
• adhesions and fibrosis
  • isointense to pelvic muscle on both T1 and T2 weighted images
  • spiculated low signal intensity stranding that obscures organ interfaces ¹
  • distortion of normal anatomy
    • posterior displacement of the uterus and ovaries
    • angulation of bowel loops
    • elevation of the posterior vaginal fornix
  • loculated fluid collections
  • hydrosalpinx
• endometriomas
  • <5 mm: early stage disease; >15 mm: advanced disease
  • shading sign ²⁵: may be less likely to respond to medical treatment ²⁸
  • low T1 and T2 due to tissue and haemosiderin-laden macrophages ¹
  • diagnostic criteria:
    • multiple cysts with T1 hyperintensity OR
    • one or more cysts with high T1 and shading on T2

• uterosacral involvement ¹³
  • normal uterosacral ligaments are smooth and of regular contour
  • irregular margins
  • asymmetry
  • nodularity and thickening medially (>9 mm) ¹³
  • altered T2 signal: isointense (50%), hypointense (40%) or hyperintense (10%) compared to myometrium
  • if bilateral uterosacral involvement with additional involvement, torus uterinus involvement results in an arciform abnormality
• vaginal involvement
  • loss of hypointense signal of the posterior vaginal wall on T2
  • thickening, nodules and/or masses also potentially seen
• pouch of Douglas
  • partial to complete obliteration
  • suspended or lateralised fluid collections
• rectovaginal septum
  • nodules or masses that have passed through the lower border of the posterior lip of the cervix
• gastrointestinal tract
  • MRI has a low sensitivity (33%) for detecting rectal lesions ¹³ due to artefacts related to rectal content;  sensitivity may be increased with the use of  water enema, endovaginal coils and phased array coils ²⁰
    • rectal wall thickening
    • anterior displacement of the rectum
    • abnormal angulation
  • loss of fat plane between uterus and bowel
  • inflammatory response due to repeated haemorrhage can lead to adhesions, strictures and bowel obstructions
• urinary tract
  • bladder
    • localised or diffuse bladder wall thickening
    • signal intensity abnormality
    • nodules or masses usually located at the level of the vesicouterine pouch
    • involvement of bladder mucosa is rare
• chest
  • catamenial pneumothorax
  • haemothorax
  • lung nodules
• cutaneous tissues
  • nodules
• malignant transformation
  • solid enhancing components

Limitations of MRI

Despite all the advantages of MRI over all other imaging modalities, it nonetheless has a number of limitations, including:

• non-pigmented lesions will not be hyperintense on T1, and thus harder to see
• small foci may have variable signal intensity:
  • may appear similar to normal endometrium: low T1, high T2
  • hypointense on all sequences
  • hyperintense on all sequences ¹
• plaque-like implants are difficult to delineate ²⁶
• adhesions cannot be directly identified, usually relying on distortion of normal anatomy to imply their existence ²⁶

Treatment and prognosis

Treatment of endometriosis can be “expectant”, medical or surgical.

Medical treatment

Targets hormonal regulation, and includes medication with:

• danazol (a synthetic androgen): suppresses oestrogen production
• gonadotropin releasing hormone (GRH) analogues: control the menstrual cycle
• oral contraceptive pill: suppresses cyclical haemorrhage

Surgery

• laparoscopic (conservative surgery)
  • adhesiolysis
  • partial cystectomy for resection of anterior cul-de-sac involvement provided ureteric re-implantation does not need to be performed
  • uterosacral ligament excision
  • used in combination with vaginal approach for vaginal disease
• laparotomy
  • hysterectomy and oophorectomy
  • bowel involvement

Complications

Malignant transformation of an endometrioma has been documented, but is rare, occurring in <1% of cases. It is usually in the form of endometrioid carcinoma, or less commonly clear cell carcinoma. Yearly ultrasound examinations of endometriomas have been advocated by some.

Differential diagnosis

Differential considerations on MRI for endometriomas include:

• dermoid cysts
  • endometriomas have homogeneous high signal intensity on T1 which does not suppress on T1FS, unlike a dermoid which shows signal drop out on fat suppression images and chemical shift artefact
• haemorrhagic ovarian cysts: endometriomas rarely present with acute symptoms and do not resolve over time
• mucinous lesions: e.g. ovarian mucinous tumours
  • increased signal on T1 but less intense than fat or blood