Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological study of five cases

Abstract

Aims Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare malignancy, and its clinicopathological characteristics have not yet been fully elucidated. This study aimed to elucidate the clinicopathological features of CAED through immunostaining of enteroblastic lineage markers alpha‐fetoprotein (AFP), glypican‐3 (GPC3), and spalt‐like transcription factor 4 (SALL4). Methods and results We identified five CAED cases (0.3%) from 1666 colorectal carcinomas, analysed the clinicopathological characteristics and performed immunostaining for AFP, GPC3 and SALL4. Three patients were male and two were female. All cases were located in the sigmoid colon or rectum. Histologically, all cases showed adenocarcinoma composed of cuboidal or columnar cells, with clear cytoplasm resembling the primitive gut; one case exhibited a partial hepatoid pattern. The depth of invasion was T2 and T3 in two and three cases, respectively. Lymphatic/venous invasion was found in all cases (100%), lymph node metastases in four of five cases (80%) and distant metastases in three of five cases (60%) (liver, two cases; lung, one case). Two patients died as a result of their disease during follow‐up. Immunohistochemically, SALL4 and GPC3 were each positive in four of five cases, whereas one case with a hepatoid component was positive for AFP. All three CAED cases with distant metastases were GPC3‐positive. Conclusions CAED was frequently located in the sigmoid colon or rectum, showed aggressive behaviour, such as lymph node metastasis and distant metastasis, and had a dismal prognosis. In addition, CAED was immunoreactive to AFP, GPC3 or SALL4, indicating that these markers may be characteristic of CAED.

Molecular and clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation

“…Our group has previously reported five cases of pure CAED among 1666 CRC, 12 but this study did not include all the cases of CAED because these five cases were selected from electronic pathological case files by searching for keywords related to enteroblastic differentiation. In addition to the recently diagnosed cases of pure CAED between 2016 and 2018, 12 we have identified a further 10 cases of pure CAED. Among these, six cases had vascular invasion, six had lymph node metastasis and five had distant metastasis or peritoneal dissemination.…”

“…p53 overexpression was an adverse prognostic factor in the 42 cases of CAED ( Figure 2H,I), and this was in accordance with previous reports describing the prognostic value of TP53 status in conventional CRCs. 28,29 According to previous reports, 2,12,15 the existence of clear cytoplasm and the expression of at least one of the oncofetal proteins as enteroblastic markers are necessary for the diagnosis of gastrointestinal adenocarcinoma with enteroblastic differentiation. We have previously shown that there was no difference in clinicopathological and molecular characteristics based on the presence of tumour cells with clear cytoplasm in GAED, and we proposed that classical hepatoid adenocarcinoma could be grouped together as GAED based simply on the expression of enteroblastic markers, regardless of the presence of clear cytoplasm.…”

“…In addition, three patients who were diagnosed as CAED between 2016 and 2018 were included in these samples. 12 These three cases were included in our previous study, and contained clear cytoplasm. 12 This study was reviewed and approved by Juntendo University School of Medicine Institutional Review Board (no.…”

“…3,[6][7][8] However, the GAED counterpart, colorectal adenocarcinoma with enteroblastic differentiation (CAED), has been reported only in a single case or few cases. [9][10][11][12] CAED has been described as colorectal carcinoma (CRC) with clear cytoplasm and expression of enteroblastic markers, such as AFP, GPC3 and SALL-4. CAED has been shown to have aggressive behaviour and a poor prognosis.…”

“…CAED has been shown to have aggressive behaviour and a poor prognosis. 12 However, the clinicopathological and epidemiological features of CAED have not been fully elucidated because of its rarity.…”