Status:
Ready to upload
Record number:
1857
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
Most recent risk assessment for neuroendocrine tumors (including high grade neuroendocrine carcinomas, low(er) grade neuroendocrine tumors, carcinoid tumors, pheochromocytomas and paragangliomas) (Council of Europe, 2022):
Due to their potential for undetected metastasis, high-grade neuro-endocrine carcinomas are an unacceptable risk for organ donation. Insufficient information exists to guide practice for neuro-endocrine tumours, carcinoid tumours, phaeochromocytomas and paragangliomas. In the case of critically ill recipients, these tumours might be acceptable after a careful individual risk–benefit analysis. Neuro-endocrine tumours in the donor history: No data are available from the literature. Due to this and their potential for undetected metastasis, treated high-grade neuro-endocrine neoplasms in the donor history are classified as high risk for organ donation. In the case of a previous history (> 5 years) of neuro-¬endocrine tumours (carcinoid tumours, phaeochromocytomas and paragangliomas) without any kind of disease recurrence or progression, donors should be considered high risk in the absence of sufficient information to guide practice.
Time to detection:
5 years after first OLT. Retransplant performed for NET therapy one year later (no other treatments performed), recurrence of donor-derived NET in second liver transplant after 2 years with no other visible metastatic sites, pancreas metastases detected 3 months later.
Alerting signals, symptoms, evidence of occurrence:
First diagnosis of NET in the transplant liver was made incidentally in the annual follow-up MRI imaging at year 5 with three hepatic lesions (largest 2.4cm). Biopsy showed poorly differentiated NET, strongly positive for synaptophysin,chromogranin, TTF-1, CK7 with a Ki67 index of 4%. Extensive diagnostics in the recipient did not reveal a primary extrahepatic source. The organ donor had no suspicion for malignancy but DNA analysis confirmed donor-derived NET. After retransplant one year later, MRI follow-up was conducted at 6 and 12 months with no sign for malignancy. The routine MRI at 24 months showed incidental hepatic lesions. Biopsy including DNA analysis confirmed the same NET as in the first biopsy from the first liver donor, indicating that occult donor NET must have existed outside the liver at the time of the second transplantation as source for the recurrent tumor. Despite radioembolization of the selective liver segment artery, reduction of the immunosuppressive therapy and treatment with systemic sunitinib and octreotid, the disease progressed, the recipient finally died 9 years after his first OLT and 3 years after his second OLT. No autopsy was performed. No other recipients received organs from the first organ donor.
Demonstration of imputability or root cause:
DNA comparison of donor liver and tumor (first and second liver graft) showed an identical pattern in all 15 short tandem repeats (STR) and amelogenin which was consistent with donor-derived NET.
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Keywords:
References:
Suggest new keywords:
Malignancy
Case report
Liver transplant
DNA typing
Microsatellite analysis
STR (short tandem repeat) analysis
neuroendocrine tumor
NET
Reference attachment:
Suggest references:
Al-Azzawi Y, Stein LL, Shrestha R, Bhasin D, Citron SJ, Rubin RA. Donor-Derived Hepatic Neuroendocrine Tumor: Pause Before Proceeding With Liver Retransplantation. Transplant Direct. 2016;2(7):e88.
Note:
First review done on June 16, 2018 (Kerstin), second reviwe done on June 16, 2018 (Carl-Ludwig - did read paper before)
Of note: Carl-Ludwig: in 2011 we had also a case with NET in the liver graft occuring 4 months post transplant, checked recipient and did retransplant & reciepient died of metastasis of NET recurrence within less than one year. In that case kidney recipients of same donor were put on surveillance - a few months late also NET in graft + NET metastatsis - there nephrectomy&cehmotherapy&stop of immunosuppression -> both free of cancer and alive (2017). Unfrotunately not published.
Expert comments for publication:
The authors conclude that redo OLT as first-line treatment for donor-derived hepatic NET might not be a favourable option even with favourable prognostic markers as in this case (disease seemed to be limited to the liver, low Ki67 index). Additionally they show US-data of 185 liver recipients who were transplanted for their own hepatic NET and which had a 5-year survival 10-15% lower than recipients transplanted for other etiologies and death from NET recurrence in 50%. Interestingly, the immunosuppression of the recipient in this case was switched to an mTOR-inhibitor (Sirolimus) mono therapy one year after every transplantation. The possible and often discussed ability to reduce tumor growth remains unclear in this case.