Endometrial Pathology

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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. Proliferative vs Secretory Endometrium Histology
  • 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:
    CategoryKey FeatureProgression to Carcinoma
    Hyperplasia without AtypiaGlandular crowding, no atypiaLow risk (~1-3%)
    Atypical Hyperplasia / EINCytological atypia presentHigh 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 Hyperplasia Histology

Endometrial Carcinoma - Cancerous Chaos

  • Most common gynecologic malignancy in developed countries.
  • Two main types:
FeatureType I (Endometrioid)Type II (e.g., Serous)
Prevalence~80%~15-20%
EstrogenDependent (unopposed E2)Independent
PrecursorHyperplasia/EINAtrophy; Serous intraepithelial ca. (SEIC)
Age (Typical)PerimenopausalPostmenopausal (older)
PrognosisGoodPoor
MutationsPTEN, KRAS, ARID1A, PIK3CA, MSITP53
  • 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). Chronic endometritis histopathology with plasma cells
      • 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.

Practice Questions: Endometrial Pathology

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What is the most common histological variety of uterine carcinoma?

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Flashcards: Endometrial Pathology

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Endometrial carcinoma from the _____ pathway has a serous, papillary histology

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Endometrial carcinoma from the _____ pathway has a serous, papillary histology

sporadic

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