81 A recent study conducted by a team of international researchers has brought attention to an uncommon and underrecognised subtype of bile duct cancer, known as enteroblastic cholangiocarcinoma. This rare form of cancer, which originates in the biliary tract, has largely escaped the notice of the medical community until now due to its unusual presentation and rarity. The study, published in Human Pathology, involved a detailed examination of four cases, shedding light on the clinical and pathological characteristics of this elusive malignancy. Cholangiocarcinoma is a type of cancer that forms in the bile ducts, the slender tubes that carry bile, a digestive fluid, from the liver to the gallbladder and small intestine. Within this broad category, enteroblastic cholangiocarcinoma stands out as a particularly rare variant. This subtype is marked by clear cancer cells with a unique chromatin pattern called “blastic”. It is linked to high levels of alpha-fetoprotein (AFP), a protein that is normally made during foetal development. Although AFP-producing cancers have been observed in other organs, such as the stomach and pancreas, their occurrence in the bile ducts is extremely rare. The research team, comprising experts from institutions in the UK, South Korea, and Japan, analysed four cases of enteroblastic cholangiocarcinoma. The patients, three men and one woman, ranged in age from 48 to 82 years. Two of the cases involved tumours located within the liver, while the other two were found in the common bile duct, which lies outside the liver. Notably, both of the cases that happened inside the liver happened in people who had a history of primary sclerosing cholangitis (PSC), a long-term liver disease that makes the bile ducts swell and scar. The study found that enteroblastic cholangiocarcinoma is similar to other types of cholangiocarcinoma in some ways. For example, it has cancer cells that are cube-shaped or polygonal and are arranged in patterns like papillary, micropapillary, tubular, or solid. But its hallmark feature is the clear cytoplasm and the distinctive subnuclear vacuolation observed in the cancer cells. These cells closely resemble those found in the foetal gut epithelium, hence the designation “enteroblastic”. Immunohistochemical analysis showed that all four cases had AFP, GPC3, and SALL4 markers. SALL4 was the most consistently present marker. Interestingly, while SALL4 is known to be associated with foetal gut differentiation, its presence in cholangiocarcinoma is particularly unusual, further emphasising the unique nature of this cancer subtype. Despite the aggressive nature of many AFP-producing tumours, the outcomes for the patients in this study were varied. One patient succumbed to the disease 17 months after surgery, while another remained alive with the disease eight months post-diagnosis, having received chemotherapy. The remaining two patients were alive and free of the disease at 14 and 18 months following surgical resection.