Intestinal differentiated mucinous adenocarcinoma of the endometrium with sporadic MSI high status: a case report

Abstract

BackgroundIntestinal differentiation of primary mucinous adenocarcinoma of the uterine corpus is exceedingly rare in comparison to the approximately 25% rate in endocervical and ovarian mucinous carcinoma. Additionally, little is known about the related genetic and epigenetic alterations, even though large-scale molecular characterisation of the different types of endometrial cancer took place in the TCGA project along the entities defined by the recent WHO classification.Case presentationWe present a 62-year-old patient harbouring a primary mucinous carcinoma of the uterine corpus with a morphological resemblance to mucinous colorectal adenocarcinoma. The intestinal differentiation was substantiated by CDX2 and CK20 positivity in the absence of PAX8, p16, WT1, p53, ER, PgR, AFP, SALL4 and Glypican3. A high MSI status with MLH1 hypermethylation was revealed by molecular testing.ConclusionIntestinal differentiation of mucinous adenocarcinoma of the endometrium is a unique observation. Besides morphology, it obviously can share molecular features of sporadic MSI colorectal cancers. It can be speculated that either CDX2 positive morula formation or intestinal metaplasia of the endometrium as rare conditions might be the origin of carcinogenesis for this type II endometrial cancer. Both conditions were not detectable in this case. Of note, categorising endometrial cancers in genetic subgroups like MSI high cancers alone might lead to the integration of likewise morphologically different tumours like the case presented here with intestinal differentiation. Hence, careful genotype-phenotype correlations are warranted for studies of mucinous adenocarcinoma of the endometrium.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-017-0629-0) contains supplementary material, which is available to authorized users.

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

“…IM/diff can manifest in ECs with a wide spectrum of morphological features, ranging from the presence of sole goblet cells to the association of goblet cells with additional gastrointestinal-type cells, such as enterocyte-like cells, neuroendocrine cells, and Paneth-like cells. Histological presentation similar to colic mucinous adenocarcinoma [9] or as pseudo-myxomatous lakes containing strips of atypical glands can also happen [14]. Besides intestinal-type features, most of the reported tumors showed immunohistochemical positivity for gastrointestinal markers (CK20, CK7, CDX2, villin, MUC6, and/or MUC2); PAX8, ER, and PR were usually negative, focally/weakly expressed or with positivity confined in tumor components lacking IM/diff features.…”

“…Evaluation of clinical features points out that even if the majority of the patients were diagnosed with stage I disease, a significant fraction presented at advanced stage (stage III or IV), including our case. Furthermore, follow-up data (available for five patients) showed three disease recurrences; interestingly, two of them occurred in patients presenting with stage IA disease [9,13], including one carcinoma leading to patient's death after 21 months of follow-up. However, the extent of IM/diff areas required to increase the aggressiveness of an EC is unknown; in the majority of papers, it was unclear if IM/diff features were focal or diffuse.…”

“…We performed a systematic review of the English Literature in multiple databases and identified only eight previous cases of EC with IM/diff, arising in patients of 49 to 81 years of age (Table 2) [9][10][11][13][14][15][16]. IM/diff can manifest in ECs with a wide spectrum of morphological features, ranging from the presence of sole goblet cells to the association of goblet cells with additional gastrointestinal-type cells, such as enterocyte-like cells, neuroendocrine cells, and Paneth-like cells.…”

“…Finally, seven studies were included in the review, for a total of nine patients diagnosed with EC with IM/diff including the case reported by us. Table 2 summarizes the clinical and pathological features, treatment modalities, and outcomes of all published cases of primary ECs with IM/diff [9][10][11][13][14][15][16]. Mean and median age were respectively 64 and 62 years (range 49-81 years).…”

“…Rare variants of mucinous differentiation were described in ECs, including gastric-type and intestinal-type [8,9]. Gastric (gastrointestinal)-type differentiation in malignant ECs has been recently elucidated by Wong and Colleagues who proposed diagnostic criteria for its recognition.…”