Definition/General

Introduction:
-Endometrial Endometriosis is the presence of ectopic endometrial glands and stroma outside the uterine cavity
-It represents benign but locally aggressive tissue
-The ectopic endometrium responds to hormonal cycles
-It can cause chronic pelvic pain, infertility, and adhesions.
Origin:
-Multiple theories exist: Retrograde menstruation (Sampson's theory)
-Coelomic metaplasia
-Vascular/lymphatic dissemination
-Direct transplantation
-Müllerian remnants
-Stem cell theory
-Likely multifactorial etiology.
Classification:
-Ovarian endometriosis (endometriomas)
-Deep infiltrating endometriosis (DIE)
-Superficial peritoneal endometriosis
-Rectovaginal endometriosis
-Extragenital endometriosis
-rASRM staging: Stage I (minimal) to IV (severe).
Epidemiology:
-Affects 10-15% of reproductive-age women
-Peak incidence in 3rd-4th decades
-Present in 40-50% of infertile women
-Familial clustering observed
-Higher prevalence in nulliparous women
-Delayed childbearing increases risk.

Clinical Features

Presentation:
-Chronic pelvic pain (most common)
-Dysmenorrhea (progressive)
-Infertility (30-50% of cases)
-Dyspareunia
-Ovarian masses (endometriomas)
-Bowel symptoms (if bowel involved)
-Urinary symptoms (if bladder involved).
Symptoms:
-Cyclic pelvic pain
-Severe dysmenorrhea
-Chronic pelvic pain
-Deep dyspareunia
-Infertility
-Heavy menstrual bleeding
-Bowel symptoms (dyschezia, rectal bleeding)
-Bladder symptoms (dysuria, hematuria).
Risk Factors:
-Nulliparity
-Early menarche
-Short menstrual cycles
-Heavy menstrual flow
-Delayed childbearing
-Family history
-Müllerian anomalies
-Low BMI
-Alcohol consumption.
Screening:
-Transvaginal ultrasound
-MRI (for deep endometriosis)
-CA-125 (elevated in severe cases)
-Laparoscopy (gold standard)
-Physical examination
-Clinical history crucial
-No effective screening test for asymptomatic women.

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Gross Description

Appearance:
-Chocolate cysts (ovarian endometriomas)
-Blue-black nodules on peritoneum
-Red, brown, or black lesions
-Powder-burn lesions
-White scars and adhesions
-Thickened, fibrotic tissue
-Hemorrhagic areas.
Characteristics:
-Cystic lesions with thick, brown fluid
-Nodular lesions on peritoneal surfaces
-Fibrous adhesions
-Retracted, puckered areas
-Vascular congestion
-Hemorrhage and hemosiderin deposition
-Variable sizes.
Size Location:
-Common sites: Ovaries (60-70%)
-Uterosacral ligaments
-Pouch of Douglas
-Rectovaginal septum
-Bowel (rectosigmoid)
-Bladder
-Lung (rare)
-Size ranges from microscopic to >10cm.
Multifocality:
-Multifocal disease common (80-90%)
-Bilateral ovarian involvement (50%)
-Associated adhesions
-Deep infiltrating components
-Extragenital sites possible
-Progressive disease over time.

Microscopic Description

Histological Features:
-Ectopic endometrial glands
-Endometrial stroma
-Hemorrhage and hemosiderin deposition
-Chronic inflammation
-Fibrosis and adhesions
-Smooth muscle metaplasia
-Cystic dilatation of glands.
Cellular Characteristics:
-Benign endometrial epithelium
-Endometrial stromal cells
-Hemosiderin-laden macrophages
-Chronic inflammatory cells
-Fibroblasts and myofibroblasts
-Smooth muscle cells
-No significant atypia.
Architectural Patterns:
-Glands and stroma together diagnostic
-Cystic spaces lined by endometrial epithelium
-Stromal breakdown and hemorrhage
-Pseudoxanthomatous reaction
-Fibrotic response
-Loss of normal architecture.
Grading Criteria:
-Active endometriosis: Fresh hemorrhage, active glands
-Inactive endometriosis: Fibrosis, hemosiderin, minimal glands
-Atypical endometriosis: Nuclear atypia (rare)
-Assessment of hormonal activity
-Extent and depth evaluation.

Immunohistochemistry

Positive Markers:
-CD10 positive (endometrial stroma)
-ER positive
-PR positive (variable with cycle)
-Cytokeratin positive (glands)
-CD68 positive (macrophages)
-Smooth muscle actin (if smooth muscle metaplasia)
-Calretinin (in some stromal cells).
Negative Markers:
-p53 wild-type
-Ki-67 low
-CEA negative
-Inhibin negative
-Chromogranin negative
-TTF-1 negative.
Diagnostic Utility:
-CD10 confirms endometrial stromal origin
-ER/PR show hormonal responsiveness
-Cytokeratin highlights glandular component
-CD68 identifies macrophages
-p53 excludes malignancy
-Combination of markers diagnostic.
Molecular Subtypes:
-Ovarian endometriosis
-Peritoneal endometriosis
-Deep infiltrating endometriosis
-Rectovaginal endometriosis
-Extragenital endometriosis
-Atypical endometriosis (rare).

Molecular/Genetic

Genetic Mutations:
-ARID1A mutations (ovarian endometriosis)
-PIK3CA mutations
-PTEN alterations
-KRAS mutations
-TP53 mutations (atypical endometriosis)
-Chromosomal aberrations
-Somatic mosaicism.
Molecular Markers:
-Aromatase overexpression
-Prostaglandin E2
-Matrix metalloproteinases
-VEGF expression
-Inflammatory cytokines
-Oxidative stress markers
-Progesterone resistance markers.
Prognostic Significance:
-Benign condition but locally aggressive
-Risk of malignant transformation (0.7-1%)
-Endometrioid and clear cell carcinomas associated
-Atypical endometriosis higher risk
-Infertility significant impact
-Recurrence after conservative surgery.
Therapeutic Targets:
-Hormonal therapy: GnRH agonists
-Progestins
-Aromatase inhibitors
-LNG-IUD
-Anti-inflammatory agents
-Surgical excision
-Assisted reproductive techniques
-Novel targeted therapies.

Differential Diagnosis

Similar Entities:
-Adenomyosis
-Hemorrhagic corpus luteum
-Ovarian carcinoma
-Adenosarcoma
-Endometrial stromal sarcoma
-Deciduosis
-Ectopic pregnancy.
Distinguishing Features:
-Endometriosis: Glands and stroma together
-Endometriosis: Outside uterus
-Adenomyosis: Within myometrium
-Hemorrhagic corpus luteum: No endometrial tissue
-Carcinoma: Nuclear atypia and invasion
-Deciduosis: Pregnancy-related.
Diagnostic Challenges:
-Minimal endometriosis versus adhesions
-Atypical endometriosis versus carcinoma
-Fibrotic endometriosis versus scar tissue
-Sampling adequacy
-Crush artifact
-Associated malignancy risk.
Rare Variants:
-Polypoid endometriosis
-Atypical endometriosis
-Endometriosis with smooth muscle metaplasia
-Endometriosis with clear cell change
-Pseudoxanthomatous endometriosis
-Endometriosis-associated carcinoma.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Patient Information

Name: [Patient Name]\nAge: [X] years\nMRN: [Medical Record Number]\nDate of Procedure: [Date]

Clinical History

Clinical indication: [Pelvic pain/Dysmenorrhea/Infertility/Pelvic mass/Other]\nSymptoms: [Chronic pelvic pain/Severe dysmenorrhea/Deep dyspareunia/Cyclical symptoms]\nImaging: [Ultrasound/MRI findings]\nProcedure: [Laparoscopic excision/Ovarian cystectomy/Other]

Specimen Received

Specimen type: [Ovarian cyst wall/Peritoneal biopsy/Nodular tissue/Other]\nAnatomic location: [Right/Left ovary/Pouch of Douglas/Uterosacral ligament/Other]\nSpecimen size: [X] cm\nFixative: 10% neutral buffered formalin

Gross Examination

[Ovarian cyst: The specimen consists of a cyst wall measuring [X] cm with a smooth external surface. The cyst contains thick, brown, chocolate-colored fluid. The cyst wall is [thin/thick] and shows [smooth/nodular] inner surface.]\n[Peritoneal/Nodular tissue: The specimen consists of [X] cm of [tan/brown/hemorrhagic] tissue fragments with a [smooth/irregular/nodular] surface.]\nThe tissue is entirely submitted for histological examination in [X] cassettes.

Microscopic Examination

Sections show ectopic endometrial glands and stroma, confirming the diagnosis of endometriosis. The endometrial glands are lined by [benign epithelium/epithelium showing secretory changes/atrophic epithelium] without nuclear atypia. The surrounding stroma consists of spindle-shaped cells typical of endometrial stroma. [Fresh hemorrhage/Old hemorrhage] and hemosiderin-laden macrophages are [prominent/present/minimal]. The endometriosis appears [active with fresh hemorrhage and glandular activity/inactive with fibrosis and hemosiderin]. [Chronic inflammation/Fibrosis/Adhesions] are [present/absent]. [Nuclear atypia] is [absent/present - describe if present].

Immunohistochemistry (if performed)

CD10: [Positive in endometrial stroma]\nEstrogen Receptor: [Positive/Negative]\nProgesterone Receptor: [Positive/Negative]\nOther markers: [As clinically indicated]

Final Diagnosis

ENDOMETRIOSIS\n\nAnatomic location: [Right/Left ovary/Peritoneum/Uterosacral ligament/Other]\nActivity: [Active/Inactive]\nAtypia: [Absent/Present]\nSize: [X] cm (when measurable)

Comments

• Endometriosis is diagnosed by the presence of both endometrial glands and stroma outside the uterine cavity.\n• This is a benign condition with a small risk of malignant transformation (0.7-1%).\n• Associated malignancies include endometrioid and clear cell carcinomas.\n• [Atypical endometriosis, if present, carries a higher risk of malignant transformation.]\n• Clinical correlation recommended for staging and comprehensive treatment planning.\n• Regular follow-up advised, especially in cases with atypical features.

Reported By

Dr. [Pathologist Name], MD\nConsultant Pathologist\nDate: [Report Date]