Chapter 1 - Histopathology of Gynaecological Cancers
In the uterine corpus there are three major categories of cancer: (1) epithelial, (2) mesenchymal and (3) mixed epithelial and mesenchymal.
Uterine leiomyosarcoma (LMS) is the most common type of mesenchymal malignant tumour; microscopic features of LMS include cytological atypia, mitotic activity and necrosis. They are aggressive also when Stage 1.
Endometrial stromal sarcoma is less frequent than LMS. Most are low-grade tumours and the stage is prognostically relevant; few are high grade. They show typical genetic anomalies.
FIGO staging of endometrial carcinoma: Stage I: limited to the corpus; Stage II: infiltration of the cervical stroma; Stage III: metastases to adnexa, vagina and retroperitoneum; and Stage IV: metastases to bladder, rectum and distant organs.
There are two stereotypes of endometrial carcinoma.
Type 1 (75%), or low-grade endometrioid carcinomas, present at low stage in perimenopause and are associated with unopposed oestrogen stimulation, obesity and infertility. Prognosis depends on depth of myometrial invasion and stage. Grading is mixed, architectural and nuclear. Molecular changes include microsatellite instability, mutations of p-TEN, k-RAS, and β-catenin.
Type 2 (10%), or serous carcinoma, arises in atrophic endometrium in postmenopausal women and is more aggressive. p53 mutations and genetic instability are characteristic.
A third minor type, clear cell carcinoma, shows intermediate features.
An integrated genomic characterisation of endometrial carcinoma identified four different prognostic subgroups: POLE ultramutated, microsatellite instability hypermutated, copy number low and copy number high. This may impact postsurgical treatments for aggressive tumours.
Revision Questions
- What are the diagnostic histological features of uterine LMS?
- What are the clinical features of Type 1 and Type 2 endometrial carcinomas?
- What are the molecular features of Type 1 and Type 2 endometrial carcinomas?