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PA29.{2-3,9} | Endometrial Hyperplasia, Carcinoma & Uterine Smooth Muscle Tumors — SDL Guide (Part 3)

Uterine Leiomyoma — The Benign Smooth Muscle Tumour

Uterine leiomyoma (commonly called a fibroid, though it contains no fibrous tissue) is the most common tumour in women — found in up to 70% of women over 50, with higher prevalence in women of African descent.

Hormonal dependence:
Leiomyomas are estrogen-dependent and progesterone-dependent (both hormones promote growth). They:
• Grow during the reproductive years and regress post-menopause.
• Enlarge during pregnancy (high estrogen/progesterone).
• Regress with GnRH agonist therapy (chemical menopause).
• Never arise in prepubertal girls.

Pathogenesis: Monoclonal proliferations arising from a single smooth muscle cell. Common cytogenetic abnormalities include deletions/translocations involving chromosomes 7 and 12, and mutations in MED12 (mediator complex — transcriptional regulation).

Gross features:

Gross Cut Surface of Intramural Uterine Leiomyoma

• Well-circumscribed, white-grey, whorled cut surface.
• Firm rubbery consistency.
• A pseudo-capsule of compressed smooth muscle surrounds each nodule (facilitates enucleation).
• Often multiple (average 6–7 per uterus).
• Locations: intramural (most common), submucosal (most symptomatic — distorts cavity), subserosal (can be pedunculated), cervical, broad ligament, intraligamentous.

Secondary changes: Hyaline degeneration (most common), cystic degeneration, calcification ("womb stones" on X-ray), red (carneous) degeneration during pregnancy (acute haemorrhagic infarction → severe pain), sarcomatous change (extremely rare, < 0.1%).

Microscopy:

Leiomyoma at Medium Power: Benign Smooth Muscle Fascicles

• Interlacing fascicles of uniform spindle cells.
• Nuclei: cigar-shaped, blunt-ended, uniform, no atypia.
• Cytoplasm: pale eosinophilic, fibrillar.
• Mitoses: rare (< 5 per 10 high-power fields) — absence of significant mitotic activity is a key benign feature.

Clinical features:
• Abnormal uterine bleeding — menorrhagia (heavy periods) most common; submucosal fibroids cause heaviest bleeding (increased surface area, disrupted haemostatic mechanisms).
• Pressure symptoms — urinary frequency (anterior fibroid on bladder), constipation (posterior fibroid on rectum), venous compression.
• Infertility and recurrent miscarriage — submucosal fibroids distort the uterine cavity.
• Uterine enlargement — irregular, non-tender, firm uterus on examination.

Uterine Leiomyosarcoma — The Malignant Smooth Muscle Tumour

Leiomyosarcoma is the most common uterine sarcoma, accounting for 1–2% of uterine malignancies, but responsible for a disproportionate share of uterine cancer deaths.

Origin: Arises de novo from uterine smooth muscle. It does NOT arise from a pre-existing leiomyoma (a common but incorrect belief).

Gross features:
• Usually a solitary, large (often > 10 cm), fleshy, poorly circumscribed mass.
• Cut surface: variegated, haemorrhagic, necrotic — in stark contrast to the whorled white benign fibroid.
• Infiltrates surrounding myometrium without a true pseudocapsule.

Histological diagnosis — the Stanford criteria (all three required for definitive diagnosis):

Criterion	Threshold
Cytological atypia	Moderate to severe nuclear atypia
Mitotic index	≥ 10 mitoses per 10 HPF
Tumor cell necrosis	Geographic (coagulative) necrosis

Presence of 2 of 3 criteria supports the diagnosis in conjunction with clinical context. Cases not meeting full criteria are classified as smooth muscle tumors of uncertain malignant potential (STUMP).

Leiomyosarcoma: High-Power Histology and Clinical Correlates

Immunohistochemistry: Positive for smooth muscle markers — desmin, smooth muscle actin (SMA), h-caldesmon. Ki-67 proliferation index is markedly elevated (> 20–30%).

Molecular alterations: Unlike carcinoma, leiomyosarcoma does not show PTEN loss or estrogen-pathway molecular events. Common alterations include TP53, RB1, and ATRX mutations.

Clinical behaviour:
• Typically presents in perimenopausal women (mean age 55 years).
• Symptoms: abnormal uterine bleeding, rapidly enlarging pelvic mass, pelvic pain.
• Spread: predominantly haematogenous — lung is the most common metastatic site, then liver. Lymph node metastasis is less frequent than in carcinoma.
• Five-year survival: ~50% for Stage I, dropping to < 15% for Stage III/IV — far worse than endometrioid carcinoma.

Leiomyoma vs Leiomyosarcoma — comparison table:

Feature	Leiomyoma	Leiomyosarcoma
Frequency	Very common	Rare
Multiplicity	Usually multiple	Usually solitary
Post-menopausal behaviour	Regresses	Grows
Gross	Whorled, white, circumscribed	Fleshy, necrotic, infiltrative
Mitoses	< 5/10 HPF	≥ 10/10 HPF
Nuclear atypia	Absent	Severe
Tumor cell necrosis	Absent	Present
Origin	Monoclonal SM cell	De novo from SM
Prognosis	Excellent (benign)	Poor