Chapter 1: Histopathology of gynaecological cancers
Tubo-ovarian tumours – Epithelial tumours
Tubo-ovarian carcinomas consist of high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), clear cell carcinoma (CCC), endometrioid ovarian carcinoma (EOC) and mucinous carcinoma (MC).
These five histotypes are five different diseases, each with its own pathogenesis, morphology, immunohistochemistry (IHC) profile, genetic features, prognosis and clinical response to chemotherapy (ChT) and targeted therapy (Figure 1.7).
Figure 1.7: Tubo-ovarian carcinoma genetic heterogeneity
Abbreviations: HGSC, high-grade serous carcinoma; STIC, serous tubal intraepithelial carcinoma.
Credit: Courtesy of the authors.
Borderline tumours are tumours of low malignant potential that can be precursors of LGSC, CCC, EOC and MC, often carrying mutations related to the corresponding carcinoma.
HGSC is the most common extra-uterine carcinoma histotype (70%); the majority develop from serous tubal intraepithelial carcinoma (STIC) in the fimbrial region, and harbour universal TP53 mutations, BRCA1/2 mutations in 15%–30% of cases (Figure 1.8).
Figure 1.8: STIC and HGSC
Abbreviations: HGSC, high-grade serous carcinoma; STIC, serous tubal intraepithelial carcinoma.
Credit: Courtesy of the authors
The majority express the female genital marker PAX8 and the serous marker WT1, and have an aberrant (diffusely positive, entirely negative or cytoplasmic) p53 staining pattern.
It is a clinically aggressive tumour often diagnosed at an advanced stage. Debulking to no macroscopic disease, ChT and PARP (poly [ADP-ribose] polymerase) inhibition are mainstays of therapy.
Other histotypes: LGSCs develop from serous borderline tumours, stain for PAX8 and WT1, have wild-type p53 and are characterised by KRAS/NRAS/BRAF mutation.
EOC and CCC are endometriosis-associated tumours harbouring mutations in phosphatase and tensin homologue (PTEN) and CTNNB1 (mainly EOC) and ARID1A and PIK3CA (both); hepatocyte nuclear factor 1 beta (HNF1β) is often overexpressed; both are PAX8-positive (Figure 1.9).
Figure 1.9: EOC and CCC
Abbreviations: CCC, clear cell carcinoma; EOC, endometrioid ovarian carcinoma.
Credit: Courtesy of the authors
MCs develop from mucinous borderline tumours or mature teratomas, have an expansile (indolent) or infiltrative (aggressive) pattern and harbour KRAS and TP53 mutations and ERBB2 amplification.
Revision Questions
- What are the five tubo-ovarian carcinoma histotypes?
- What is the name of the preinvasive lesion from which HGSC develops?
- Which carcinomas are associated with endometriosis?
