Adverse Occurrence type:
Most recent risk assessment for astrocytoma and glioblastoma (Council of Europe, 2022): Potential donors with pilocytic astrocytoma (WHO grade I) may be considered for organ donation with minimal risk of transmission. Extraneural metastases from low-grade astrocytomas (WHO grade II) are rare and have been associated with resection and ventriculo-peritoneal shunts. In the absence of these risk factors, the donor may be considered minimal risk. Risk may increase with the extent of performed interventions. A complete histological examination of the tumour should be performed so that areas of transformation into a more aggressive malignancy can be ruled out. Since astrocytomas tend to relapse with a histologically higher grade of malignancy, new histological examinations to regrade the tumour should be performed where relapse occurs. If the tumour co-exists with histological areas of greater malignancy or is very invasive locally, it should be considered high-grade and will be associated with an increased risk of transmission. Spontaneous extraneural metastases of anaplastic astrocytomas and glioblastoma are rare, but such metastases have been observed, and seem to occur more frequently when associated with prior surgical treatment and/or ¬ventriculo-peritoneal drainage, or chemo-/radiotherapy. Potential donors with anaplastic astrocytomas (WHO grade III) can be accepted as organ donors. Transmission risk is considered low to intermediate for tumours without any risk factors. Potential donors with glioblastoma (WHO grade IV) are considered intermediate to high risk for transmission, depending on different national recommendations, which are expected to be adjusted with increasing evidence. The transmission risk is increased (high risk) in all cases with previous interventions such as tumour resection, ¬ventriculo-peritoneal/-atrial drainage and/or cranial chemo-/radiotherapy.
Time to detection:
Alerting signals, symptoms, evidence of occurrence:
Rapid clinical deterioration resulting in death, five months after liver transplantation. Necropsy shows multiple intrahepatic, adrenal gland, lymph node, and leptomeningeal metastases of a gliomatous tumor.
Demonstration of imputability or root cause:
Condition known in the donor. Frontal lobe glioma removed 4 months before death with local recurrence and death following a second surgery. Two kidneys and liver were transplanted. No evidence of malignant disease in the two kidney recipients 2 months after transplantation. So only one recipient affected. Histopathological examination of the primary and recurrent brain tumour and of all metastatic lesions showed the classic features of glioblastoma multiforme (GBM). The primary GBM was the only lesion to express glial fibrillary acidic protein (GFAP). Loss of GFAP expression during disease progression coincided with the less differentiated histological appearance of the locally recurrent and metastatic lesions and is directly associated with glioma dissemination. Microsatellite DNA fingerprinting revealed identical allele patterns in all brain tumour and metastatic lesions, thus identifying all metastases as donor related. In addition, DNA sequencing of the p53 tumour suppressor gene showed a C→T transition changing aminoacids from histidine to tyrosine at codon 179 in all lesions. Alternatively spliced variants of the CD44 cell adhesion molecule expressed by both the recurrent brain tumour and its metastatic lesions were linked with the unusual metastatic phenotype of a GBM and, in addition, support the previously proposed metastasis model.
Suggest new keywords:
Central nervous system
Astrocytoma/glioblastoma multiform E. (WHO grade 4)
Expert comments for publication:
Lliver recipient developed tumor; both kidney recipients from same donor alive without tumor at 52 month followup.