Presentation
Obese woman presented to her family doctor with a history 'menorrhagia' (of uncertain duration). Transvaginal ultrasound showed a mildly thickened endometrium but was essentially unhelpful. She proceeded to a uterine curettage, which yielded 18 grams of hemorrhagic tissue.
Patient Data
H&E Sections
There is no normal endometrium within these images.
Most of the specimen is composed of endometrial tissue displaying tightly packed, back-to-back, complex glands with scant intervening stroma that contains occasional clusters of foamy histiocytes. Cells lining these glands show mild cytological atypia with nuclear stratification, mildly enlarged hyperchromatic nuclei and scattered mitotic figures.
A smaller component of the specimen, however, is composed of solid sheets and occasional glands within a desmoplastic stroma, showing prominent necrosis and apoptotic debris. Tumor cells in these areas are display marked cytological atypia, with large vesicular, pleomorphic nuclei, prominent nucleoli, scant cytoplasm and abundant mitotic figures. There is focal necrosis.
Images, in order, show:
20x H&E: Low-power image showing an increased gland-to-stroma ratio, with closely packed, irregular and complex glands.
20x H&E: Low-power image showing both better differentiated adenocarcinoma glands and smaller component of high grade carcinoma displaying a solid architectural growth pattern. Focal necrosis can also be seen in several fragments.
100x H&E: Well-differentiated, grade 1 component, with closely packed, complex glands and prominent collections of stromal foamy macrophages. Tumor cells show mild atypia with nuclear stratification.
400x H&E: High-power view of grade 1 component.
40x H&E: Poorly differentiated grade 3 tumor with areas of necrosis and displaying high grade cytological atypia.
400x H&E: High-power view of poorly differentiated, grade 3 component, showing severe atypia with marked pleomorphism, increased nuclear to cytoplasmic ratios, loss of glandular architecture and prominent mitotic activity.
Immunohistochemistry
Immunohistochemistry was performed on a section containing poorly differentiated areas with the following results:
- Broad spectrum cytokeratin AE1/AE3: Positive
- ER and PR: Negative
- CK5: Focal, weak
- P53: Weak, patchy
- Chromogranin and Synaptophysin: Negative
Case Discussion
Poorly differentiated areas made up less than 5% of the overall specimen examined. An undifferentiated component was considered, however, these areas retained focal glandular architecture and displayed strong cytokeratin positivity; similarly, P53 staining showed a negative result (i.e. weak and patchy staining), rendering 'serous adenocarcinoma' a less likely diagnosis.
Overall, whilst this is an uncommon finding, this case was thought best considered to represent a predominantly Grade 1 endometrioid adenocarcinoma (villoglandular pattern), with very focal high grade areas (Grade 3).
Other sections, in this case, showed endometrial fragments displaying proliferative endometrium with complex atypical hyperplasia, which is in keeping with the hyperplasia/atypia to carcinoma tumor pathway seen in endometrioid adenocarcinoma.