Chapter 1: Histopathology of gynaecological cancers
Uterine corpus tumours – Epithelial tumours
The majority of malignant uterine corpus tumours are carcinomas, which are classified as endometrioid, serous, clear cell, mixed type or other, rarer subtypes.
Endometrial cancers (ECs) are broadly divided into oestrogen-dependent (endometrioid) and oestrogen independent (non-endometrioid), though mixed and hybrid forms exist.
The most common predisposing genetic condition for developing EC is Lynch syndrome, in which mutations occur in mismatch repair (MMR) genes (Figure 1.10).
Figure 1.10: Lynch syndrome cancer risk at 75 years
Credit: Ryan NA, et al. Obstet Gynaecol 2021;23:9-20
Endometrioid endometrial carcinoma (EEC) is the only EC histotype that is graded. Low-grade tumours generally have good prognosis and high-grade tumours often behave aggressively.
EEC has frequent loss of the PTEN tumour suppressor and often expresses hormone receptors, whereas aberrant p53 and diffuse p16 staining pattern is associated with clinically aggressive tumours.
The Cancer Genome Atlas (TCGA) classification is central to molecular risk assessment in EEC and other histotypes, with a surrogate test based on p53, MMR IHC and POLE (polymerase epsilon) mutation analysis (Figure 1.11).
Figure 1.11: Molecular classification of EC
Abbreviations: dMMR, MMR-deficient; EC, endometrial carcinoma; MMR, mismatch repair; NSMP, no specific molecular profile; p53-abn, p53 abnormal; POLE, polymerase epsilon; POLEmut, POLE-ultramutated.
Credit: Casey L, Singh N. Int J Gynecol Pathol 2021;40:5-16
Other histotypes: Serous carcinomas are aggressive tumours characterised by TP53 mutations; serous endometrial intraepithelial carcinoma (SEIC) is a preinvasive precursor (Figure 1.12).
Figure 1.12: Serous carcinoma
Abbreviations: SEIC, serous endometrial intraepithelial carcinoma.
Credit: Courtesy of the authors
CCCs are rare when diagnosed based on strict criteria, often carry ARID1A mutations, overexpress HNF1β and are hormone receptor-negative.
Rare EC histotypes include carcinosarcoma, mesonephric like carcinoma, mucinous carcinoma of intestinal type and squamous cell carcinoma (SCC).
Revision Questions
- Which genetic syndrome is associated with increased risk for developing EC?
- Which ancillary tests are applied to the molecular classification of EC?
- What is the precursor of uterine serous carcinoma?
