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PA29.{5,10} | Gestational Trophoblastic Disease & Female Genital Morphology — SDL Guide (Part 2)

Cervix & Endometrium — Practical Recognition (Cervicitis and Endometriosis)

The second half of this SDL is your morphology-practical walk-through. The approach for every lesion is: Gross first → Architecture low power → Cell detail high power → Clinical correlate.

Cervicitis

Acute cervicitis: Mucosal surface infiltrated by neutrophils; surface erosion common. Associated with Neisseria gonorrhoeae, Chlamydia trachomatis (intracellular organisms not visible on H&E — require special tests). Clinically: mucopurulent discharge.

Chronic cervicitis: Dense lymphoplasmacytic infiltrate in the stroma; reactive squamous metaplasia in the transformation zone; nabothian cysts (mucus retention) may be grossly visible as pearly white nodules on the ectocervix.

Three-panel histology diagram of chronic cervicitis showing transformation zone squamous metaplasia, dense lymphoplasmacytic stromal inflammation, and a nabothian cyst. — **Panel A:** Low-power 10x H&E overview showing stratified squamous epithelium, endocervical glands, transformation zone, squamous metaplasia, dense lymphoplasmacytic infiltrate in cervical stroma, and nabothian cyst.. **Panel B:** High-power stromal detail showing lymphocytes, plasma cells with eccentric nuclei, and inflamed cervical stroma.. **Panel C:** Focused view of blocked endocervical gland showing mucus retention cyst, flattened gland lining, reactive squamous metaplasia, and retained mucin..

Endometriosis (PA29.10 high-yield practical)

Defined by the triad:
1. Endometrial glands outside the uterine cavity
2. Endometrial stroma surrounding those glands
3. Hemosiderin-laden macrophages (evidence of cyclical hemorrhage)

Gross: chocolate cysts (endometriomas) in the ovary — filled with dark brown, thick, altered blood. Powder-burn lesions on peritoneum.

Histology teaching diagram of ovarian endometrioma showing endometrial glands and stroma in ovarian cortex, fibrous wall, and hemosiderin-laden macrophages with golden-brown pigment. — **Panel A:** Low-power H&E overview showing ovarian cortex, fibrous wall, endometrial gland, endometrial stroma, and hemosiderin pigment.. **Panel B:** Diagnostic triad icons showing endometrial gland, endometrial stroma, and hemosiderin-laden macrophages.. **Panel C:** High-power inset showing hemosiderin-laden macrophages with golden-brown pigment granules in the stroma..

Diagram of a bisected ovarian endometrioma showing a thick cyst wall, dark brown chocolate-coloured contents, and a microscopy inset highlighting endometrial stroma and hemosiderin. — **Panel A:** Gross bisected ovary showing thick-walled endometriotic cyst, chocolate-coloured inspissated blood, ovarian cortex, and cut ovarian surface. **Panel B:** Magnified cyst wall showing fibrotic thick wall, adherent dark brown old blood, and hemosiderin-stained foci. **Panel C:** Simplified H&E microscopy tip showing endometrial stroma, hemosiderin-laden macrophages, and sparse atrophic endometrial glands.

Microscopy tip: The glands may be atrophic or inactive — the stroma and hemosiderin are the more reliable diagnostic features when endometrial glands look bland.

Endometrial Hyperplasia vs Endometrial Carcinoma — Pattern Recognition

Endometrial hyperplasia (WHO classification: simple → complex → atypical) is the morphological spectrum from glandular crowding without atypia to the precancerous lesion with nuclear atypia.

Simple hyperplasia: Increased gland-to-stroma ratio; glands dilated (cystically), lined by bland columnar cells; architecture abnormal but orderly.

Complex hyperplasia: Markedly crowded, back-to-back glands, minimal intervening stroma; no nuclear atypia → low malignant potential.

Atypical hyperplasia: Same crowded architecture PLUS nuclear atypia (large vesicular nuclei, prominent nucleoli, loss of polarity) — the direct precursor to endometrioid carcinoma; ~25–30% risk of progression.

Four-panel H&E comparison showing simple endometrial hyperplasia with cystically dilated glands and ample stroma versus complex atypical hyperplasia with crowded glands, stromal loss, and nuclear atypia. — **Panel A:** Simple hyperplasia at low power: cystically dilated glands, variable gland size, ample intervening stroma, no marked gland crowding.. **Panel B:** Complex atypical hyperplasia at low power: back-to-back crowded glands, complex branching architecture, loss of intervening stroma.. **Panel C:** Simple hyperplasia high-power detail: uniform nuclei, preserved epithelial polarity, absence of significant cytological atypia.. **Panel D:** Complex atypical hyperplasia high-power detail: enlarged hyperchromatic nuclei, nuclear atypia, pseudostratification, loss of polarity, mitotic figure..

Endometrioid endometrial carcinoma (most common type, ~80%):

Gross: Polypoid or fungating mass arising in fundus or posterior wall; pale, soft, friable
Micro: Infiltrative glands with stromal desmoplasia; malignant glands may closely mimic complex atypical hyperplasia, but invasion (irregular infiltration, desmoplastic stroma, back-to-back glands without stroma) confirms carcinoma
Grade is by architectural pattern: Grade 1 = >95% glandular; Grade 3 = >50% solid

Three-panel H&E teaching diagram showing endometrioid endometrial carcinoma at low and higher power with invasive malignant glands, desmoplastic stroma, and comparison to normal endometrium. — **Panel A:** Low-power 4x H&E view showing invasive malignant glands, desmoplastic stroma, irregular infiltrative margin, and magnification box leading to Panel B. **Panel B:** Higher-power 10x H&E detail showing atypical glandular epithelium, crowded malignant glands, mitotic figure, luminal necrotic debris, and surrounding desmoplastic stroma. **Panel C:** Split comparison of normal endometrium with evenly spaced glands and cellular stroma versus carcinoma with crowded irregular glands, cribriform architecture, and reduced intervening stroma.

CLINICAL PEARL

'Atypical hyperplasia' and 'endometrial intraepithelial neoplasia (EIN)' are the same lesion under different classification systems. The 2003 WHO classification uses the 4-tier scheme (simple/complex ± atypia); the EIN schema (more reproducible) uses a single binary: EIN (precancer) vs not-EIN. In practice, when you see 'atypical hyperplasia' in a report, treat it as a high-risk precancer requiring hysterectomy workup, not watchful waiting. Coexistent carcinoma is found in 25–40% of hysterectomy specimens resected for atypical hyperplasia diagnosed on biopsy.

Leiomyoma vs Leiomyosarcoma — Myometrial Tumors

Leiomyoma (fibroid) is the most common benign pelvic tumor in women.

Gross comparison — leiomyoma (white, whorled, circumscribed) vs leiomyosarcoma (soft, fleshy, hemorrhagic-necrotic); side by side; label gross features — click to enlarge

Gross: Well-circumscribed, firm, white, whorled nodules within the myometrium (intramural), projecting into the uterine cavity (submucosal), or beneath the serosa (subserosal). May be multiple. Cut surface: interlacing white bundles with a 'whorled' pattern.

Micro: Uniform spindle cells arranged in intersecting fascicles; no nuclear atypia, few or no mitoses; cells have blunt-ended ('cigar-shaped') nuclei; no necrosis.

Leiomyosarcoma — malignant smooth muscle tumor: de novo, not from leiomyoma.

Gross: Larger, bulky, soft, fleshy, with areas of hemorrhage and necrosis (contrast with the firm, white, dry cut surface of a fibroid).

Micro: The Stanford triad of malignancy — (1) nuclear atypia (pleomorphism, prominent nucleoli), (2) ≥10 mitoses/10 HPF, (3) coagulative tumor cell necrosis. Any two of the three, especially the mitotic count, essentially confirms malignancy.

Side-by-side H&E comparison of leiomyoma with uniform spindle cells and leiomyosarcoma with nuclear atypia, atypical mitoses, and necrosis. — **Panel A:** Leiomyoma showing intersecting fascicles, uniform spindle cells, cigar-shaped nuclei, eosinophilic smooth muscle cytoplasm, and absence of atypia.. **Panel B:** Leiomyosarcoma showing pleomorphic cells, nuclear atypia, atypical mitotic figure, hyperchromatic irregular nuclei, and tumor necrosis.. **Bottom strip:** Key practical comparison: leiomyoma is well circumscribed with bland nuclei and rare mitoses; leiomyosarcoma is infiltrative with pleomorphism, atypical mitoses, and necrosis..

Side-by-side gross comparison of uterine leiomyoma as a circumscribed firm white whorled mass and leiomyosarcoma as a soft fleshy hemorrhagic-necrotic infiltrative mass. — **Panel A:** Leiomyoma: circumscribed intramural mass, firm white-tan cut surface, whorled architecture, compressed surrounding myometrium, no hemorrhagic necrosis.. **Panel B:** Leiomyosarcoma: soft fleshy mass, irregular infiltrative margin, hemorrhagic red-brown areas, yellow-gray coagulative necrosis, non-whorled variegated cut surface.. **Panel C:** Memory rule and diagnostic clue: fibroid equals firm white whorled; leiomyosarcoma equals soft hemorrhagic necrotic; Stanford criteria badge showing atypia, ≥10 mitoses/10 HPF, and coagulative tumor cell necrosis..

Memory rule: Fibroid = firm, white, whorled; Leiomyosarcoma = soft, hemorrhagic, necrotic. If the cut surface looks like 'brain with a bleed' rather than 'white rubber', think sarcoma.

SELF-CHECK

Histological sections of a uterine spindle-cell tumor show: 12 mitoses per 10 HPFs, geographic coagulative necrosis, and moderate nuclear pleomorphism. The most appropriate diagnosis is:

A. Leiomyoma with hyaline degeneration

B. Cellular leiomyoma

C. Leiomyosarcoma

D. Endometrial stromal sarcoma

Reveal Answer

Answer: C. Leiomyosarcoma

The Stanford criteria for leiomyosarcoma require any 2 of: nuclear atypia, ≥10 mitoses/10 HPF, and coagulative tumor cell necrosis. This case has all three: 12 mitoses/10 HPF (exceeds threshold), coagulative necrosis, and moderate pleomorphism — unambiguous leiomyosarcoma. Cellular leiomyoma has increased cellularity but <5 mitoses/10 HPF and no atypia. Endometrial stromal sarcoma arises from the endometrial stroma (not smooth muscle) and has a different immunoprofile (CD10+).