Subtitle: Diagnostic criteria for uterine leiomyosarcoma (WHO 2020 Female Genital Tumours): spindle, epithelioid and myxoid subtypes, tumour cell vs hyaline necrosis, STUMP and leiomyoma variants, IHC and molecular features, annotated virtual slides and 8 MCQs.
Author: PathologyMCQ Editorial Board
Category: Gynaecological Pathology
Last Updated: October 2026
Read Time: 6 minutes
At-a-Glance
- Three features: atypia, tumour cell necrosis, mitoses.
- Spindle LMS: ≥2 of 3 (mitoses ≥10/10 HPF, ≥4/mm²).
- Epithelioid LMS: ≥1 (mitoses ≥4/10 HPF, ≥1.6/mm²).
- Myxoid LMS: ≥1 (mitoses ≥1/10 HPF, ≥0.4/mm²) or infiltrative borders.
- Not meeting criteria but worrying: STUMP.
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These criteria follow the WHO Classification of Female Genital Tumours (5th edition, 2020), which uses the Stanford criteria. Mitotic counts are given per 10 high-power fields and per mm²; count in the most active area, and count only unequivocal mitotic figures.
Conventional (Spindle Cell) Leiomyosarcoma
Two or more of the following:
- Diffuse moderate-to-severe cytological atypia.
- Tumour cell (coagulative) necrosis.
- Mitotic count ≥10 per 10 HPF (≥4 per mm²).
Epithelioid Leiomyosarcoma
One or more of the following:
- Moderate-to-severe cytological atypia.
- Tumour cell necrosis.
- Mitotic count ≥4 per 10 HPF (≥1.6 per mm²).
Myxoid Leiomyosarcoma
One or more of the following:
- Moderate-to-severe cytological atypia.
- Tumour cell necrosis.
- Mitotic count ≥1 per 10 HPF (≥0.4 per mm²).
- Infiltrative (irregular) borders into the myometrium.
Myxoid leiomyosarcoma is often hypocellular and deceptively bland; the infiltrative margin is the clue, so sample the interface generously.
Tumour Cell vs Hyaline Necrosis
| Feature | Tumour cell (coagulative) necrosis | Hyaline (infarct-type) necrosis |
|---|---|---|
| Interface | Abrupt transition from viable to necrotic cells | Zonal: necrosis, then granulation tissue or hyalinised rim, then viable tumour |
| Pattern | Perivascular cuffs of viable cells; ghost cells with preserved outlines | Uniform, often central; haemorrhage and fibrosis |
| Meaning | Counts as a criterion for malignancy | Seen in leiomyomas, torsion, after GnRH agonists or embolisation; not a criterion |
STUMP and Leiomyoma Variants
| Diagnosis | Atypia | Tumour cell necrosis | Mitoses (per 10 HPF) |
|---|---|---|---|
| Leiomyoma | None | Absent | <5 |
| Mitotically active leiomyoma | None | Absent | 5–20 (no other worrying feature) |
| Leiomyoma with bizarre nuclei | Focal or multifocal, may be marked | Absent | <10 (<4/mm²) |
| Cellular leiomyoma | None | Absent | Low; mimics endometrial stromal tumour |
| STUMP | Any combination that falls short of LMS criteria yet raises concern, e.g. diffuse atypia with 5–9 mitoses, or necrosis of uncertain type | Uncertain | Variable |
| Leiomyosarcoma | See criteria above |
IHC and Molecular
- Smooth muscle markers (desmin, SMA, h-caldesmon) are positive in benign and malignant tumours; they do not grade.
- Supportive of LMS: diffuse p16, aberrant p53 (overexpression or null), high Ki-67; ATRX loss in a subset.
- Molecular: complex karyotype with TP53, RB1, PTEN and ATRX alterations. Leiomyomas carry MED12 mutations or HMGA2 rearrangement; FH-deficient leiomyomas show eosinophilic nucleoli with perinucleolar halos and loss of FH / 2SC positivity.
- Mimics: endometrial stromal sarcoma (CD10+, JAZF1::SUZ12), inflammatory myofibroblastic tumour (ALK), PEComa (HMB45, cathepsin K).
Virtual Slides
An oral cavity leiomyosarcoma with annotated H&E and immunostains: apply the same atypia, mitosis and necrosis assessment, and confirm smooth muscle differentiation.
What to look for
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Question
Which of the following is true of uterine leiomyosarcomas? A. The mitotic threshold for epithelioid LMS is >5/10 HPF · B. The mitotic threshold for myxoid LMS is ≥1/10 HPF · C. The mitotic threshold for spindle cell LMS is >4/10 HPF
Show answer
B. Myxoid LMS needs only ≥1 mitosis per 10 HPF (with atypia, necrosis or infiltrative borders counting too). Epithelioid LMS uses ≥4/10 HPF and spindle cell LMS ≥10/10 HPF.
Test Yourself: 8 MCQs
Leiomyosarcoma: 8 MCQs
Diagnostic criteria, necrosis, STUMP, IHC and molecular, with instant explanations.
More practice: the question banks →
Exam Pearls
- Spindle: 2 of 3, mitoses ≥10. Epithelioid: 1 of 3, mitoses ≥4. Myxoid: 1 of 4, mitoses ≥1 or infiltrative borders.
- Tumour cell necrosis = abrupt interface; hyaline necrosis does not count.
- Mitoses alone = mitotically active leiomyoma. Focal atypia alone = bizarre-nuclei leiomyoma. Not sure = STUMP.
- p16, p53, Ki-67 help; desmin and caldesmon only confirm lineage.
- FH-deficient leiomyoma: think hereditary leiomyomatosis and RCC.
For more concise notes like these, see the Histopathology Notes, volumes 1 and 2 →
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Related reads: Giant-cell-rich bone lesions → · Bethesda cervical cytology →
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References
- WHO Classification of Tumours Editorial Board. Female Genital Tumours. 5th ed. IARC; 2020.
- Bell SW, Kempson RL, Hendrickson MR. Problematic uterine smooth muscle neoplasms: a clinicopathologic study of 213 cases. Am J Surg Pathol. 1994;18:535–58.
- Ip PPC, Cheung ANY, Clement PB. Uterine smooth muscle tumors of uncertain malignant potential (STUMP). Am J Surg Pathol. 2009;33:992–1005.
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