Endometriosis

Definition

Endometriosis is defined by the presence of endometrial glands and stroma in locations outside the uterus. It occurs in approximately 5-10% of women of reproductive age, and in nearly half of women with infertility. It is frequently multifocal.

Robbins & Kumar Basic Pathology, p. 689
Bailey and Love's Short Practice of Surgery 28th Ed., p. 1602

Types

There are three main types:

Type	Description
Superficial peritoneal endometriosis	Lesions on pelvic peritoneal surfaces
Ovarian endometriosis (endometrioma)	Cysts filled with old blood ("chocolate cysts")
Deep infiltrating endometriosis (DIE)	Tissue >5 mm beneath the peritoneum; involves uterosacral ligaments, vagina, bowel, bladder, ureters

Risk of malignant transformation is mainly confined to deep infiltrating endometriosis (ovarian endometrioid and clear-cell carcinomas). There is also an association with non-Hodgkin's lymphoma.

Pathogenesis

The exact mechanism remains uncertain. Four leading theories are proposed:

Regurgitation (Sampson) theory - retrograde flow of menstrual endometrium through the fallopian tubes implants at ectopic pelvic sites. This is the most widely accepted mechanism.
Benign metastasis theory - endometrial tissue spreads to distant sites (bone, lung, brain) via blood vessels and lymphatics.
Metaplastic theory - coelomic epithelium (pelvic mesothelium), which shares embryological origin with the müllerian ducts, undergoes metaplastic differentiation into endometrium. This explains thoracic and other distant sites.
Extrauterine stem/progenitor cell theory - bone marrow-derived stem cells differentiate into ectopic endometrial tissue.

Once implanted, endometriotic tissue is not simply "misplaced endometrium" - it exhibits distinct biology: elevated aromatase (local estrogen synthesis), increased PGE2, VEGF, and matrix metalloproteinases (MMPs), some secreted by recruited activated macrophages. This creates a self-sustaining pro-inflammatory, pro-angiogenic, estrogen-dependent microenvironment.

Pathogenesis of endometriosis - showing retrograde menstruation, endometriotic implants, aromatase/PGE2/angiogenic factor production by endometrial stromal cells and activated macrophages (COX-2 upregulated), promoting survival of ectopic tissue

Fig. 17.9 - Robbins & Kumar: Pathogenesis of endometriosis

Common Sites

Ovaries (most common)
Pouch of Douglas
Uterosacral ligaments
Fallopian tubes
Pelvic peritoneum
Rectosigmoid colon (12-37% of cases have GI involvement)
Less commonly: periumbilical tissues, laparotomy scars, diaphragm, pleura, lungs (causing catamenial haemoptysis or recurrent pneumothoraces)

Morphology

Lesions appear grossly as red-brown nodules ranging from microscopic to 1-2 cm. Classic descriptions include:

"Powder burn" or "gunshot" lesions - black, dark brown, or bluish puckered nodules with surrounding fibrosis
Red/flame-like lesions - atypical vesicular or haemorrhagic implants
White plaques - scarring lesions
Endometriomas ("chocolate cysts") - ovarian cysts 3-5 cm filled with thick dark brown fluid (degenerated blood); found in 17-44% of women with endometriosis; densely adherent to the peritoneal ovarian fossa

Widespread lesions cause fibrous adhesions that obliterate the pouch of Douglas and distort pelvic anatomy.

Histologically: diagnosis requires both endometrial glands AND stroma at the ectopic site.

Ovarian endometrioma ("chocolate cyst") - cut section of ovary showing large cystic masses filled with degenerated dark brown blood

Fig. 17.10 - Robbins & Kumar: Ovarian endometriosis (chocolate cyst)

Clinical Features

Symptoms

Dysmenorrhoea (pain related to menstruation) - most common pain symptom
Chronic pelvic pain (cyclical and non-cyclical)
Deep dyspareunia (pain during intercourse)
Dyschezia (pain on opening the bowels)
Dysuria
Infertility - presenting complaint in 30-40% of patients
Haematuria, rectal bleeding (haematochezia)
Fatigue
Recurrent haemoptysis / pneumothorax (thoracic endometriosis)

A significant proportion of women remain asymptomatic. No single symptom or set of symptoms reliably predicts endometriosis, as many overlap with IBS or interstitial cystitis.

Disease Extent

Ranges from a few peritoneal lesions on normal-looking pelvic organs all the way to deep endometriosis with large endometriomas, extensive fibrosis of uterosacral ligaments, and adhesion-related distortion of pelvic anatomy.

Diagnosis

Gold standard: laparoscopy with histological confirmation

Non-invasive tools (transvaginal/transrectal ultrasound) can reliably detect only severe forms - endometriomas and deep pelvic endometriosis
MRI detects haemosiderin deposits and can demonstrate low-signal fibrotic plaques, obliteration of the pouch of Douglas, and involvement of the rectosigmoid

Sagittal T2-weighted pelvic MRI showing low-signal nodularity obliterating the pouch of Douglas (arrow) with tethering and angulation of the rectal wall from a deep rectovaginal endometriotic nodule (arrowhead)

Fig. 22.61 - Grainger & Allison's Diagnostic Radiology: Deep endometriosis on MRI

There is currently no internationally accepted classification system. The Endometriosis Fertility Index (EFI) has good predictive value for fecundity after surgical treatment. Note that disease severity on classification systems correlates poorly with symptom severity.

Management

Medical

Category	Agents
NSAIDs / COX-2 inhibitors	First-line for pain
Aromatase inhibitors	Target local estrogen production
Combined oral contraceptives	Suppress ovarian cycle
Progestogens	Suppress endometrial activity
GnRH agonists/antagonists	Induce pseudo-menopause
Levonorgestrel-releasing IUS	Effective for pain and bleeding

Surgical

Laparoscopic excision or ablation of lesions - preferred approach
Drainage/cystectomy for endometriomas
For DIE: may require bowel resection, ureteric dissection, or partial cystectomy
Hysterectomy (with/without bilateral salpingo-oophorectomy) - definitive treatment for women who have completed childbearing
Surgery for infertility aims to restore normal anatomy

Fertility-Specific

The EFI guides prognosis after surgery
Assisted reproductive technology (IVF) is an option when surgery does not restore fertility

Complications & Associations

Infertility (30-40% of cases)
Increased risk of ovarian cancer (endometrioid and clear-cell subtypes)
Non-Hodgkin's lymphoma association
Bowel obstruction, ureteric obstruction from DIE
Recurrent pneumothoraces (catamenial pneumothorax) from thoracic disease
Fibrous adhesions leading to chronic pelvic pain and anatomical distortion

Recent Evidence (PubMed, 2024-2026)

A 2024 systematic review (PMID 39067455) highlights the central role of fibrosis in endometriosis pathogenesis and as a potential therapeutic target, beyond the traditional estrogen-focused model.
A 2025 systematic review and meta-analysis (PMID 39946383) found that physical activity and exercise are safe and beneficial for women with endometriosis, improving pain and quality of life.
A 2025 systematic review (PMID 39373298) confirms persistent diagnostic delay of 5-12 years across regions, driven by symptom normalisation, misdiagnosis, and limited access to laparoscopy.

Sources: Robbins & Kumar Basic Pathology, p. 689 | Bailey and Love's Short Practice of Surgery 28th Ed., p. 1602-1603 | Grainger & Allison's Diagnostic Radiology, p. 591

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