Combined tubular adenocarcinoma, neuroendocrine carcinoma and adenocarcinoma with enteroblastic differentiation arising in Barrett esophagus

Abstract

Adenocarcinoma (AC) with neuroendocrine carcinoma (NEC) or enteroblastic (ENT) differentiation rarely develops in Barrett’s esophagus (BE). A 76-year-old man was diagnosed with Barrett’s AC (cT1bN0M0) and underwent thoracoscopic esophagectomy. A type 0-IIc + 0-Is lesion measuring 26 × 21 mm was macroscopically observed on a background of long segment BE (pT1bN0M0). The tumor comprised three different histological types of carcinoma (NEC, AC with ENT differentiation and moderately differentiated AC). NEC showed positivity for synaptophysin, chromogranin A and insulinoma-associated protein 1 with a Ki-67 index of 60.6%. ENT tumors were immunopositive for AFP and sal-like protein 4, and focally immunopositive for human chorionic gonadotrophin. The amounts of NEC, ENT and AC were 40%, 40% and 20%, respectively. p53 expression was positive throughout the tumor. Rb expression was negative at the NEC, but positive at the ENT and AC. CD4 and CD8 densities were lower in the NEC segment than in the AC and ENT segments, and PD-L1 expression was negative throughout the tumor. Early cancer arising in BE with a combination of tubular AC, ENT tumors and NEC is very rare. Our observations might contribute to understanding the carcinogenetic pathways and tumor microenvironment of NEC and ENT tumors.

A case of pancreatic ductal adenocarcinoma with enteroblastic, neuroendocrine, and squamous differentiation with p53 overexpression and loss of Rb expression

“…Moreover, extragastric AED (EGAED) are much rarer than EGHAC and have not yet been listed in the WHO classification. We searched the PubMed database and found a few case reports or series of esophageal, colorectal, and biliary AED [ [11] , [12] , [13] , [14] , [15] ]; and only one case report of pancreatic AED that was written in Chinese [ 16 ]. However, there are tumors showing AED morphology in a case series of “hepatoid” tumor of the bile duct [ 8 ].…”

“…In our case, AED was mixed with conventional PDAC and NEC. Admixtures of both conventional adenocarcinoma and NEC have occasionally been reported in EGAED and pancreatic HAC [ 7 , 11 , 12 , 14 ]. As mentioned above, a mixed conventional adenocarcinoma component, suggesting that HAC/AED is transformed from conventional adenocarcinoma, is common in GHAC/AED.…”

“…These genetic findings suggest that non-neuroendocrine components have the potential to transform into NEC. In other mixed adenocarcinoma-AED-NEC cases, p53 overexpression in all components has also been frequently observed [ 11 , 13 , 14 ]; however, Rb status has not been well investigated, except in an esophageal case showing Rb loss only in the NEC component [ 14 ]. These findings differ from the findings in our case and suggest that Rb was lost during the transformation from adenocarcinoma or AED to NEC.…”