Endometrial Pathology

Endometrial Cycle & AUB - Phases & Bleed Clues

• Endometrial Cycle (Menstrual Cycle): Governed by ovarian hormones.
  • Proliferative Phase (Follicular): Estrogen-driven (E₂).
    • Endometrial glands & stroma proliferate; glands are straight, tubular.
  • Secretory Phase (Luteal): Progesterone-driven (P₄) post-ovulation.
    • Glands become tortuous ("saw-tooth"), coiled; subnuclear glycogen vacuoles appear, then luminal secretions. Spiral arteries lengthen & coil. Stromal edema, predecidual changes.
• Abnormal Uterine Bleeding (AUB):
  • 📌 PALM-COEIN classifies causes:
    • Structural (PALM): Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia.
    • Non-structural (COEIN): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified.
  • Key endometrial AUB links: Polyps, hyperplasia/malignancy, ovulatory dysfunction (e.g., anovulation → unopposed estrogen).

⭐ In anovulatory cycles, persistent estrogen stimulation without progesterone opposition leads to continuous endometrial proliferation, resulting in fragile, unstable endometrium prone to irregular and often heavy bleeding (dysfunctional uterine bleeding).

Endometrial Hyperplasia - Overgrowth Alarms

• Definition: Abnormal proliferation of endometrial glands relative to the stroma, leading to an increased gland-to-stroma ratio.
• Risk Factors: Chronic unopposed estrogen exposure.
  • Obesity (peripheral conversion of androgens).
  • Polycystic Ovarian Syndrome (PCOS), anovulatory cycles.
  • Exogenous estrogen therapy (without progestin).
  • Tamoxifen (estrogenic effect on endometrium).
• WHO 2014 Classification & Progression Risk:

  Category	Key Feature	Progression to Carcinoma
  Hyperplasia without Atypia	Glandular crowding, no atypia	Low risk (~1-3%)
  Atypical Hyperplasia / EIN	Cytological atypia present	High risk (~25-45%)

• Molecular: PTEN tumor suppressor gene inactivation is a common early event in EIN.
• Clinical: Often presents as abnormal uterine bleeding (AUB).

⭐ Atypical hyperplasia/EIN is considered a direct precursor to endometrioid endometrial adenocarcinoma.

• Progression Pathway:

Endometrial Carcinoma - Cancerous Chaos

• Most common gynecologic malignancy in developed countries.
• Two main types:

• FIGO Grading (Endometrioid): Based on % solid growth.
  • Grade 1: ≤5% solid growth
  • Grade 2: 6-50% solid growth
  • Grade 3: >50% solid growth
• Lynch Syndrome (HNPCC):
  • ↑ Risk of endometrioid type (MSI pathway).

⭐ TP53 mutations are characteristic of Type II (e.g., serous) endometrial carcinomas, associated with aggressive behavior and poor prognosis.

Benign & Inflammatory Issues - Polyps, Infections & Scars

• Endometrial Polyps
  • Benign localized endometrial overgrowths; may cause Abnormal Uterine Bleeding (AUB).
  • Histology: Thick-walled blood vessels, fibrous stroma.
  • Associated with Tamoxifen.
• Endometritis (Inflammation of endometrium)
  • Acute Endometritis
    • Key: Neutrophilic infiltration of endometrial glands/stroma.
    • Causes: Postpartum, post-miscarriage, Intrauterine Device (IUD).
  • Chronic Endometritis
    • Key: Plasma cells in endometrial stroma (diagnostic hallmark).
    • Causes: Pelvic Inflammatory Disease (PID), Tuberculosis (TB), IUD, retained products of conception. 📌
    • Tuberculous Endometritis (subtype): Caseating granulomas, acid-fast bacilli; common cause of infertility in India.

⭐ Plasma cells in endometrial stroma are the hallmark of chronic endometritis.

• Asherman Syndrome
  • Intrauterine adhesions/synechiae (fibrous bands).
  • Causes: Aggressive curettage (D&C), severe endometritis.
  • Clinical: Amenorrhea/hypomenorrhea, infertility, recurrent pregnancy loss.

High‑Yield Points - ⚡ Biggest Takeaways

• Endometrial hyperplasia without atypia rarely progresses to cancer; atypia (EIN) is precancerous.
• Type I Endometrioid carcinoma: estrogen-driven, from hyperplasia, PTEN/KRAS mutations.
• Type II Serous carcinoma: aggressive, p53 mutation, in older women, atrophic endometrium.
• Asherman syndrome: intrauterine adhesions causing amenorrhea/infertility, post-curettage.
• Endometrial polyps: benign; can cause abnormal uterine bleeding (AUB).
• Adenomyosis: endometrial tissue in myometrium; causes dysmenorrhea, menorrhagia.
• Chronic endometritis: plasma cells in stroma; linked to PID, IUDs, TB.