Author: PathologyMCQ Editorial Team
Category: Gynaecological Pathology – Uterine Mesenchymal Tumours
Last Updated: October 2026 (WHO Female Genital Tumours, 6th edition)
Read Time: 15 minutes
Difficulty: Moderate–difficult (MD/DNB, FRCPath, NEET-SS)
At a glance
- What: the commonest pure uterine sarcoma, accounting for roughly 1–2% of uterine malignancies and a large share of uterine sarcomas.
- Diagnosis rests on H&E: moderate to severe atypia, tumour cell necrosis and mitoses per mm², with different thresholds for spindle, epithelioid and myxoid subtypes.
- WHO 6th edition: all female genital mesenchymal tumours now sit in one Mesenchymal tumours chapter; new or renamed neighbours include SMARC-deficient sarcoma, NTRK-rearranged spindle cell sarcoma and undifferentiated uterine sarcoma not classified further.
- In this post: a 4-tab virtual slide viewer (leiomyosarcoma H&E, SMA, h-caldesmon, Ki-67), annotated slides, updated tables and 10 interactive MCQs including 4 slide-based questions.
What is uterine leiomyosarcoma?
Uterine leiomyosarcoma (uLMS) is a malignant tumour of myometrial smooth muscle. It typically presents in perimenopausal or postmenopausal women as a large, solitary, soft, fleshy mass with haemorrhage and necrosis, sometimes discovered unexpectedly after myomectomy or morcellation of a presumed fibroid. It behaves aggressively, with early haematogenous spread to the lungs.
What changed in the WHO 6th edition (Female Genital Tumours)
| Topic | WHO 5th edition (2020) | WHO 6th edition |
|---|---|---|
| Where mesenchymal tumours sit | Separate sections by site (uterine corpus, lower genital tract, ovary, peritoneum) | One Mesenchymal tumours chapter for the whole female genital tract |
| Smooth muscle tumours | Uterine leiomyoma, IV leiomyomatosis, STUMP, metastasizing leiomyoma, uterine leiomyosarcoma; LPD listed under peritoneum | Leiomyoma, STUMP, leiomyosarcoma, intravenous leiomyomatosis, metastasizing leiomyoma and leiomyomatosis peritonealis disseminata grouped together |
| Undifferentiated sarcoma | Undifferentiated uterine sarcoma | Undifferentiated uterine sarcoma not classified further, emphasising exclusion of defined entities |
| Molecularly defined neighbours | SMARCA4-deficient uterine sarcoma; NTRK-rearranged spindle cell neoplasm (emerging) | SMARC-deficient sarcoma and NTRK-rearranged spindle cell sarcoma listed in the chapter |
| Leiomyosarcoma subtypes | Spindle, epithelioid, myxoid | Spindle, epithelioid, myxoid (unchanged) |
Diagnostic criteria by subtype
| Subtype | Criteria for leiomyosarcoma | Mitotic threshold |
|---|---|---|
| Spindle (conventional) | At least 2 of 3: moderate to severe atypia, tumour cell necrosis, high mitotic count | ≥4 mitoses/mm² (≥10 per 10 HPF of 0.55 mm) |
| Epithelioid (>50% epithelioid) | At least 1: moderate to severe atypia, tumour cell necrosis, mitoses above threshold | ≥1.6 mitoses/mm² (≥4 per 10 HPF) |
| Myxoid | Infiltrative border plus at least 1: moderate to severe atypia, tumour cell necrosis, mitoses above threshold | >0.4 mitoses/mm² (>1 per 10 HPF) |
Atypia, tumour cell necrosis and mitotic counting
Moderate to severe cytological atypia
- Atypia that is visible at low power (×4–10): enlarged, hyperchromatic, pleomorphic nuclei with coarse chromatin and nucleoli.
- Usually diffuse; focal bizarre nuclei in an otherwise bland tumour suggest leiomyoma with bizarre nuclei instead.
- Atypical mitoses support malignancy.
Tumour cell (coagulative) necrosis vs infarct-type necrosis
| Feature | Tumour cell necrosis (worrisome) | Infarct-type necrosis (benign) |
|---|---|---|
| Transition | Abrupt edge between viable and necrotic tumour | Gradual, through a zone of granulation tissue or hyalinisation |
| Necrotic cells | Ghost cells with atypical nuclear outlines | Mummified, hyalinised cells |
| Around vessels | Viable tumour cuffs around vessels in necrotic areas | No perivascular sparing |
| Inflammation and haemorrhage | Little | Haemorrhage, haemosiderin and inflammation common |
Counting mitoses
- Count in the most mitotically active areas and express the result per mm²; 10 HPF of 0.55 mm diameter equals 2.4 mm².
- Avoid counting pyknotic or apoptotic nuclei and mast cells; PHH3 immunostaining can help in difficult cases.
- Sample generously: at least one block per centimetre of tumour diameter is a common practical rule for suspicious smooth muscle tumours.
Spindle, epithelioid and myxoid leiomyosarcoma
| Feature | Spindle | Epithelioid | Myxoid |
|---|---|---|---|
| Architecture | Long intersecting fascicles | Sheets, nests or cords of round to polygonal cells | Hypocellular, abundant myxoid matrix |
| Cytology | Cigar-shaped nuclei, eosinophilic cytoplasm | Eosinophilic or clear cytoplasm, can mimic carcinoma | Stellate or spindle cells, often deceptively bland |
| Key pitfall | Cellular leiomyoma, ESS | PEComa, UTROSCT, carcinoma, PSTT | Myxoid leiomyoma, IMT, myxoid ESS |
| Must-do stains | Desmin, h-caldesmon, CD10 | Add HMB-45, melan-A, cathepsin K, keratin, inhibin | Add ALK; consider PLAG1 or ESS fusion testing |
See the smooth muscle pattern on real slides: the virtual slide viewer below has leiomyosarcoma H&E with SMA, h-caldesmon and Ki-67.
Virtual slides · real cases
Leiomyosarcoma morphology and smooth muscle stains
These slides are from an oral cavity leiomyosarcoma, which shows the same smooth muscle morphology and immunoprofile used to diagnose uterine tumours.
What to look for
Drag to pan · pinch or double-tap to zoom · use the + / − buttons
Annotated slides
Use the region selector to jump to the labelled features: fascicles, atypical nuclei and mitoses in the leiomyosarcoma, and the arterioles and permeative border of the endometrial stromal sarcoma.
Leiomyosarcoma, H&E (annotated)
Leiomyosarcoma H&E
Uterine endometrial stromal sarcoma (annotated mimic)
[openseadragon_viewer dzi=”2025/08/c7/c7″ regions=”2025/08/c7/reg.json”]
Leiomyoma variants, STUMP and leiomyosarcoma
| Entity | Atypia | Mitoses | Tumour cell necrosis |
|---|---|---|---|
| Usual and cellular leiomyoma | None to mild | Low | Absent (infarct-type allowed) |
| Mitotically active leiomyoma | None to mild | Raised, up to about 6/mm² (≈14 per 10 HPF) | Absent |
| Leiomyoma with bizarre nuclei | Focal or multifocal bizarre nuclei | Low (usually <2/mm²) | Absent |
| FH-deficient leiomyoma | Eosinophilic nucleoli with perinucleolar halos; may have bizarre nuclei | Low | Absent |
| STUMP | Exceeds leiomyoma but does not meet leiomyosarcoma, for example: necrosis of uncertain type; atypia with borderline mitoses; tumour cell necrosis alone without atypia or raised mitoses; very high mitoses without atypia or necrosis | ||
| Spindle leiomyosarcoma | Any 2 of 3: moderate to severe atypia, tumour cell necrosis, ≥4 mitoses/mm² | ||
STUMP is a diagnosis of last resort after thorough sampling. Most behave benignly, but recurrences occur (more often with epithelioid and myxoid morphology), so follow-up is advised.
Immunohistochemistry and molecular pathology
- Smooth muscle markers: desmin, h-caldesmon and SMA are usually positive (may be reduced in epithelioid and myxoid tumours). CD10 can be positive and is a pitfall.
- Supportive of malignancy: aberrant p53 (overexpression or null), diffuse p16 and a high Ki-67 index. None replaces the H&E criteria.
- ER and PR: variable, often reduced compared with leiomyoma.
- Molecular: complex karyotypes with recurrent TP53, RB1, ATRX and PTEN alterations; MED12 mutations are typical of leiomyoma and uncommon in leiomyosarcoma; a subset of myxoid leiomyosarcomas carries PLAG1 rearrangements.
- FH loss: seen in FH-deficient leiomyomas and occasional leiomyosarcomas; it should prompt evaluation for hereditary leiomyomatosis and renal cell carcinoma (HLRCC).
Differential diagnosis
| Mimic | Clues | Helpful tests |
|---|---|---|
| Low-grade ESS | Uniform small cells, arterioles, tongue-like permeation | CD10, ER, PR; JAZF1/PHF1 fusions |
| High-grade ESS | Uniform round high-grade cells, often with a low-grade component | Cyclin D1, BCOR; YWHAE, BCOR alterations |
| PEComa | Epithelioid clear to granular cells around vessels | HMB-45, melan-A, cathepsin K; TSC2 or TFE3 |
| Inflammatory myofibroblastic tumour | Myxoid, inflamed, often in younger women or pregnancy | ALK IHC; ALK rearrangement |
| SMARC-deficient sarcoma | Rhabdoid cells, sheets, young patients | Loss of BRG1 (SMARCA4) or INI1 |
| NTRK-rearranged spindle cell sarcoma | Fibrosarcoma-like spindle cells, often cervix | Pan-TRK IHC; NTRK fusion |
| Carcinosarcoma / undifferentiated carcinoma | Epithelial component or keratin-positive cells | Keratin, EMA, MMR, p53 |
Staging and prognosis
| FIGO stage (leiomyosarcoma and ESS) | Extent |
|---|---|
| IA | Limited to uterus, ≤5 cm |
| IB | Limited to uterus, >5 cm |
| II | Extends beyond the uterus, within the pelvis (adnexa or other pelvic tissue) |
| III | Infiltrates abdominal tissues (one site or more), or pelvic and/or para-aortic lymph nodes |
| IV | Invades bladder and/or rectum (IVA) or distant metastasis (IVB) |
Stage is the strongest prognostic factor. Even stage I tumours recur often, and 5-year survival for localised disease is only around 50–70%. Tumour size, mitotic count, morcellation and incomplete resection are adverse features.
Featured course · NEET-SS / DM Oncopathology
Leiomyoma, STUMP or leiomyosarcoma? Get the thresholds right on exam day.
Uterine smooth muscle tumours, ESS and the new molecularly defined sarcomas are favourite NEET-SS questions. The NEET-SS / DM Oncopathology course covers them with WHO-based notes, image MCQs and full-length mocks.
- WHO-based notes on gynaecological and soft tissue sarcomas
- Image-based and virtual slide MCQs with explanations
- System-wise tests and full-length NEET-SS mock tests
Test yourself: 10 MCQs
4 slide-based questions (H&E, h-caldesmon, Ki-67) plus 6 on WHO criteria, staging and mimics. Tap an answer for the explanation.
More practice: the full quiz is below, and the gynaecological pathology MCQ bank (WHO 6th edition) →
More practice: uterine leiomyosarcoma quiz
Exam pearls and key takeaway
- Spindle LMS = 2 of 3; epithelioid and myxoid need only 1 worrisome feature (myxoid also needs an infiltrative border).
- Atypia plus tumour cell necrosis is enough for spindle LMS even with fewer than 10 mitoses per 10 HPF.
- Thresholds: ≥4/mm² spindle, ≥1.6/mm² epithelioid, >0.4/mm² myxoid.
- No stain separates leiomyoma, STUMP and leiomyosarcoma; stains exclude mimics (ESS, PEComa, IMT, SMARC-deficient and NTRK sarcomas).
- WHO 6th edition: one Mesenchymal tumours chapter; subtypes and criteria of leiomyosarcoma carry over.
- Key takeaway: sample well, separate tumour cell from infarct-type necrosis, count mitoses per mm² in hot spots, apply the subtype-specific rule, and exclude molecularly defined mimics.
Go further
Prepare for NEET-SS Oncopathology
Online course, mock tests and printed notes by practising pathologists.
RECOMMENDEDNEET-SS / DM Oncopathology Online CourseWHO-based notes, image and virtual slide MCQs, system-wise tests and full-length mocks across every oncopathology system.View course →The Pathology MCQ app
A slide and an MCQ every day
Daily MCQ with streaks, pinch-zoom virtual slides with annotations, and your courses in one place.
Related reads: Gynaecological pathology MCQs (WHO 6th edition) → · p57 in molar pregnancy → · ICCR uterine sarcoma dataset →
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