Clinical overview
Endometrial carcinoma is the most common gynaecological malignancy in high-income settings and a rising problem in South Africa as obesity, type 2 diabetes and an ageing population converge. It is the cancer that announces itself early and loudly: roughly nine in ten women present with postmenopausal bleeding, and a small but important minority present with abnormal uterine bleeding in the perimenopause. That early symptom is the reason most endometrial cancers are diagnosed at FIGO stage I, while it is still confined to the corpus, and the reason the disease as a whole carries a comparatively good prognosis. The registrar's job is to take postmenopausal bleeding seriously every single time, because the symptom is shared by atrophic endometritis (benign and common) and by an aggressive serous carcinoma that will kill within two years if missed.
The pathology is what drives everything else — what the disease looks like grossly, down the microscope, and now at the molecular level. The field underwent a genuine paradigm shift over the last decade. The old binary of "type I oestrogen-driven endometrioid" versus "type II oestrogen-independent serous" is being replaced by a four-group molecular classification that is reproducible, prognostic and increasingly therapy-defining. Both frameworks matter, and so does how they relate, because the pathology connects directly to the molecular subgroups that FIGO 2023 and the ESGO–ESTRO–ESP 2025 guideline now place at the centre of staging and risk stratification. It is the pathology that predicts behaviour and dictates treatment.
Core knowledge
Precursor lesions
Figure D10.1 — The dualistic model: Type I endometrioid (oestrogen-driven, from atypical hyperplasia/EIN) vs Type II serous/clear-cell (non-oestrogen, aggressive), now refined by molecular class.
Most endometrioid carcinomas evolve from endometrial hyperplasia under sustained unopposed oestrogen. The current (WHO 2020) binary scheme divides hyperplasia into hyperplasia without atypia and atypical hyperplasia / endometrioid intraepithelial neoplasia (EIN). Hyperplasia without atypia carries a low (~1–3%) progression risk and is fundamentally a hormonal disturbance. Atypical hyperplasia/EIN is a true neoplastic precursor: progression to carcinoma is reported around 25–30% over follow-up, and crucially, when a hysterectomy specimen follows an atypical-hyperplasia biopsy, a concurrent carcinoma is found in up to 40% of cases. That 40% figure is what drives the surgical management of atypical hyperplasia. The serous lineage has a different precursor — serous endometrial intraepithelial carcinoma (SEIC) — typically arising in atrophic endometrium or an endometrial polyp, p53-mutant, and able to metastasise despite being intraepithelial.
Histological types (WHO 2020)
The WHO Classification of Tumours of the Female Genital Tract, 5th edition (2020) is the authoritative typing reference. The major endometrial carcinoma types are:
| Histotype | Approx. share | Key features |
|---|---|---|
| Endometrioid | ~75–80% | Gland-forming; oestrogen-related; usually low-grade; PTEN/PIK3CA/KRAS/CTNNB1 and MMR defects |
| Serous | ~5–10% | Papillary/glandular, marked nuclear atypia; TP53-mutant; aggressive |
| Clear cell | ~1–5% | Hobnail cells, clear cytoplasm; mixed molecular profile |
| Carcinosarcoma (MMMT) | ~2–5% | Biphasic carcinoma + sarcoma; now classed as a metaplastic/dedifferentiated carcinoma |
| Mixed / undifferentiated / dedifferentiated | small | Aggressive; undifferentiated component often MMRd |
The older terminology still circulates and is worth knowing: "type I" (endometrioid, low-grade, oestrogen-driven, good prognosis, obese/diabetic phenotype) versus "type II" (serous and clear cell, oestrogen-independent, high-grade, older atrophic uterus, poor prognosis). The dualistic model captures real biology but breaks down at the edges — some grade 3 endometrioid tumours behave like type II — which is exactly why the molecular classification was needed.
Gross (macroscopic) pathology
On opening the uterus, endometrioid carcinoma usually appears as an exophytic, shaggy, friable polypoid or sessile tan-grey mass filling the endometrial cavity, often with surface haemorrhage and necrosis. Myometrial invasion is assessed macroscopically: the tumour erodes into the myometrial wall, and the depth relative to the full wall thickness is estimated grossly and confirmed microscopically. A diffusely thickened endometrium, focal firmness, or a tumour reaching toward the serosa all matter. Lower uterine segment / cervical stromal involvement is sought because it upstages disease. Serous carcinomas may look deceptively bland or arise within a small polyp in an otherwise atrophic, often small uterus, which is a trap — minimal gross disease can already be metastatic.