Case report: Donor cholangiocarcinoma in allograft liver (2023)

At time of transplant, the explant liver contained 9 hepatocellular carcinoma nodules with the largest 2.2 cm diameter. CT scans at 6 month intervals showed no tumor until 3 years and 5 months after transplant. CA19.9 and CEA were elevated, with normal alpha-fetoprotein and des-gamma-carboxy prothrombin. Biopsy confirmed (peripheral) cholangiocarcinoma. Although resection was planned, rapid tumor growth occurred and chemotherapy was given. However, the patient expired 4 months after start of treatment. The authors present this to underscore the fact that, although the vast majority of tumors that occur in this setting will represent recurrence of recipient HCC, the rare possibility of other tumors such as donor origin cancer should be kept in mind and the diagnosis should not be presumed. Several minor points in the Discussion merit comment. The authors state that the cutoff time for distinguishing donor-transmitted from donor-derived cancer is 6 weeks post-transplant, referencing a paper by Desai et al (Transplantation 2012;94:1200-7). However, that is a misreading, as that paper uses this time interval to separate early from late donor transmitted cancer, separate from "donor origin" cancers that are considered for all practical purposes not to be present at the time of transplant. Most would consider a 2-3 year posttransplant time interval as a reasonable approximation for separating those tumors present at the time of transplant (transmitted) from those arising de novo from donor cells in the posttransplant period (derived). However, since this is dependent on factors such as tumor doubling time, it is only an estimate, as later onset transmitted donor malignancies have been reported. Nevertheless, in this case, given the sudden appearance and rapid tumor growth, we would agree that this most likely represents a "donor-derived" tumor arising posttransplant. The second point they make is to consider the possibilty that the tumor represented a metastatic breast cancer from the donor, since pathologic studies showed the presence of the transcription factor GATA-3 in tumor cells. However, this marker is seen in approximately 5% of cholangiocarcinomas (and 16% of pancreatic ductal adenocarcinomas) (Agostini-Vulaj et al., Appl Immunohistochem Mol Morphol 2020;28:460-3) and is not specific for breast cancer. While this possiblity cannot be rigorously excluded, it appears highly unlikely.