High-grade endometrial cancers: serous, clear cell, carcinosarcoma
- Lesion
Three aggressive endometrial cancers of older women: they come from p53 damage rather than estrogen and spread to the abdomen early.
What it is
Serous carcinoma, clear cell carcinoma and carcinosarcoma are high-grade endometrial cancers of older women that do not follow the estrogen pathway. Serous carcinoma arises from serous intraepithelial carcinoma on an atrophic endometrium or polyp, carries TP53 mutation in nearly all cases, and can seed the peritoneum while still tiny in the uterus. Carcinosarcoma contains both malignant epithelium and malignant mesenchyme but is a single clone, essentially a carcinoma that has partly turned into sarcoma, and has a poor outlook.
Structure
- Serous: complex papillae with tufts, cells with large pleomorphic nuclei, frequent abnormal mitoses; usually ER-low; a subset has HER2 amplification.
- Clear cell: cells with glycogen-rich clear cytoplasm and hobnail nuclei bulging into lumens; Napsin A positive.
- Carcinosarcoma: a bulky, fleshy, necrotic and haemorrhagic polypoid mass that may protrude through the cervical os; a high-grade carcinoma intimately mixed with a high-grade sarcoma.
Step by step
- In an atrophic endometrium, a cell acquires a TP53 mutation.
- Genomic instability and copy-number changes follow rapidly.
- The surface lesion (serous intraepithelial carcinoma) sheds cells through the tubes onto the peritoneum.
- Invasive carcinoma develops; in carcinosarcoma part of the carcinoma undergoes epithelial-mesenchymal transition and becomes sarcoma.
Markers
- p53 aberrant
- p16 strong
- WT1 usually negative (helps separate from ovarian serous carcinoma)
- Napsin A (clear cell)
- HER2 (subset of serous)
Clinical notes
- Postmenopausal bleeding in an older woman, sometimes with ascites or an abdominal mass from early spread.
- Surgery includes omentectomy and peritoneal sampling because spread may be microscopic.
- Although uncommon, these tumours cause a disproportionate share of endometrial cancer deaths.
Test yourself
Think of the answer, then tap the question to see it.
Which gene is mutated in nearly all serous endometrial carcinomas?
TP53.
Why can a tiny serous endometrial carcinoma have a high stage?
Even serous intraepithelial carcinoma can shed cells to the peritoneum, so spread beyond the uterus is common when the uterine tumour is minimal.
Is carcinosarcoma a collision of two tumours?
No; it is monoclonal, a carcinoma in which part of the clone has become sarcomatous, and it behaves like a high-grade carcinoma.
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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Endometrial Cancer Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2026); Uterine Sarcoma Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2026).
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Representative model, for educational purposes only.