Endometrial Carcinomas with Intestinal-Type Metaplasia/Differentiation: Does Mismatch Repair System Defects Matter? Case Report and Systematic Review of the Literature

Abstract

Background: Intestinal metaplasia/differentiation in primary endometrial carcinomas is an uncommon phenomenon, with only few cases described.

Material and methods: We performed a systematic review of endometrial carcinomas with intestinal metaplasia/differentiation interrogating the electronic databases Pubmed, Web of Science, and Scopus, and we reported an additional case arising in a 49-year-old woman.

Results: We identified only eight patients diagnosed with endometrial carcinomas exhibiting intestinal metaplasia/differentiation, and additionally our case. Endometrial carcinomas with intestinal-type features can present in pure or mixed forms in association with usual-type endometrioid carcinomas; in mixed forms, the two neoplastic components may derive from a common neoplastic progenitor, as evidenced by the concomitant loss of MSH2 and MSH6 protein expression in our case. Disease recurrences occur in a significant fraction of the cases, including patients diagnosed in low-stage disease.

Conclusions: Endometrial carcinomas with intestinal metaplasia/differentiation are rare and they may represent a more aggressive tumor variant, thus requiring a proper treatment despite the low-tumor stage. The ProMise classification should be performed also in these unusual tumors, since they can be associated with mismatch repair system defects.

Keywords: endometrial carcinoma; goblet cells; intestinal; metaplasia; mismatch repair; mucinous.

Figure 1

Histological features of Endometrial Carcinoma showing intestinal-type features. (a) Endometrial carcinoma showing mixed endometrioid (right half) and intestinal-type mucinous (left half) features (H&E). (b) Single tumor gland showing concomitant endometrioid and intestinal-type differentiation (H&E). (c,d) Morphological details of the endometrioid component, composed by glands lined by columnar cells with scant cytoplasm (c), and foci of squamous differentiation (d) (H&E). (e) Morphological details of the intestinal-type component composed by enterocyte-like cells with apical brush border and goblet cells (H&E). (f) PAS-D istochemical stain highlighting the presence of intracytoplasmic mucin in the goblet cells of the intestinal-type tumor component (PAS-D stain).

Figure 2

Immunohistochemical features of Endometrial Carcinoma showing intestinal-type features. (a) Representative H&E section of the endometrial carcinoma showing two tumor components, the intestinal differentiated one in the upper half and the endometrioid one in the lower half. (b–e) Immunohistochemical stainings for CK20 (b), CDX2 (c), PAX8 (d) and ER (e); the intestinal differentiated component (upper half) is positive for CK20 (b) and CDX2 (c) while negative for PAX8 (d) and (ER); the endometrioid component (lower half) shows opposite profile with positivity for PAX8 (d) and ER (e) and negativity for CK20 (b) and CDX2 (c). Immunohistochemical staining for MSH6 showing protein loss of expression in the intestinal (f) and endometrioid (g) tumor components.

Figure 3

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart with summary of search results.