Dedifferentiated Endometrial Carcinoma: A Rare Aggressive Neoplasm-Clinical, Morphological and Immunohistochemical Features

Abstract

Dedifferentiated endometrioid adenocarcinoma is characterised by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma. The low-grade component in this subtype of endometrial carcinoma is Grade 1 or 2 according to the Federation of Gynaecology and Obstetrics (FIGO) grading system. The coexistence of low-grade endometrial carcinoma and solid undifferentiated carcinoma can cause diagnostic problems on histological examination. In fact, this combination can often be mistaken for a more common Grade 2 or Grade 3 endometrial carcinoma. Therefore, this subtype of uterine carcinoma can often go under-recognised. An accurate diagnosis of dedifferentiated endometrial carcinoma is mandatory because of its poorer prognosis compared to Grade 3 endometrial carcinoma, with a solid undifferentiated component that can amount to as much as 20% of the entire tumour. The aim of this review is to provide clinical, immunohistochemical, and molecular data to aid with making an accurate histological diagnosis and to establish whether there are any findings which could have an impact on the prognosis or therapeutic implications of this rare and aggressive uterine neoplasm.

Keywords: DNA Polymerase Epsilon (POLE); Switch/Sucrose Non-Fermentable (SWI/SNF) complex; Tp53 mutations; endometrial dedifferentiated/undifferentiated carcinoma; immune checkpoint inhibitors; mismatch repair (MMR) gene mutations; the Cancer Genome Atlas (TCGA) Research Network.

Figure 1

Example of Grade 3 endometrial carcinoma in endometrial curettage specimens, showing in solid component diffuse nuclear positivity to PAX-8 ((A) ×100), positivity to cytokeratin ((B) ×200), positivity to EMA ((C) ×200) and ER ((D) ×100). Note the same positivity in the glandular component and the solid component).

Figure 2

Dedifferentiated rhabdoid variant of EDC with rhabdoid cells and glandular component ((A): haematoxylin-eosin ×40, arrowheads: rhabdoid component. Arrows: glandular component). At higher magnification, note the eccentrically located nuclei, prominent nucleoli, and abundant and eosinophilic cytoplasm of the rhabdoid cells ((B): haematoxylin-eosin ×200).

Figure 3

Schematic and simplified representation of the steps of molecular classification of endometrial carcinoma using immunohistochemical and Sanger sequencing techniques and the impact of therapeutic strategies. (MMR: mismatch repair, POLE: polymerase ε, IHC: immunohistochemistry, EDM: exonuclease domain mutations, Tp53: tumour protein p53).