(Subject review): Glioblastomas in organ transplant recipients (liver transplant)

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Record number: 
1947
MPHO Type: 
Estimated frequency: 
This Review covers only cases with events of Transmission of GBM to transplant recipients (11 studies, 11 cases: 3 liver recipients, 3 kidney recipients, 5 lung recipients). The paper includes cases already published in other reports. No controll Group provided with cases without Transmission events observed.
Time to detection: 
Time range from Transplantation to detection of glioma in 3 kidney recipients 17 to 18 months, 2 liver recipients 4 to 9 months, 3 lung recipients 3 to 15 months (other cases: no data). All 3 kidney recipients alive 32 to 33 months after transpaltantion, all 4 liver recipients died at 5 to 10 months after Transplantation, two lung recipients died at 3 and 16 months post Transplantation. Please note: in all cases the donor previous history of a GBM was known with a variable extend to exposure of risk factors for increased probability of tumour Transmission.
Alerting signals, symptoms, evidence of occurrence: 
Alerting singals were: space occupying lesion (SOL) in graft (n=6 of 11), SOL or lymph node enlargement outside graft (n=8 of 11); in lung pleural effusion (n=4 of 5) or SOL of mediastinum (n=3 of 5); please note mutliple counts are possible. Evidence of occurence was confirmed by histopathologic examination of the SOL etc. with cells positive for S100 and/or GFAP and/or CD56 markers for GBM and/or histomorphology -> wide range of yes/no for the items. Astrocytomas and Glioblastoma Multiforme (Council of Europe, 2018): Potential donors with pilocytic astrocytoma (WHO grade I) may be considered for organ donation with minimal risk of transmission. Extra-neural 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 more aggressive malignancy are ruled out. Since astrocytomas have a tendency to relapse with a histologically higher grade of malignancy, new histological examinations should be performed where relapse occurs to regrade the tumour. If the tumor 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 extra-neural metastases of anaplastic astrocytomas and glioblastoma multiforme are rare, but have been observed, and 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 multiforme (WHO grade IV) are considered intermediate to high risk for transmission depending on the 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.
Demonstration of imputability or root cause: 
Histologolgy (morphology or either one of the markers typical to confirm GBM was detected in SOL in recipients). Root cause: known risk associated to Transplantation for grafts procured from donors affected by GBM. Interestingly not all recipients of all donors developed GBM Transmission events. Risk of harm: selfspeaking.
Imputability grade: 
3 Definite/Certain/Proven
Groups audience: 
Suggest new keywords: 
Review article
Deceased donor
Kidney transplant/Kidney recipient/Kidney transplantation
Liver transplant/Liver recipient/Liver transplantation
Lung transplant/Lung recipient/Lung transplantation
Histologic analysis
Immunohistochemistry
Astrocytoma/glioblastoma multiform E. (WHO grade 4)
Malignancy
Suggest references: 
Jimsheleishvili S, Alshareef AT, Papadimitriou K, Bregy A, Shah AH, Graham RM, et al. Extracranial glioblastoma in transplant recipients. J Cancer Res Clin Oncol. Springer Berlin Heidelberg; 2014 May;140(5):801–7.
Note: 
Second review. KL 05/30/18
Expert comments for publication: 
Astrocytomas and Glioblastoma Multiforme (Council of Europe, 2018): Potential donors with pilocytic astrocytoma (WHO grade I) may be considered for organ donation with minimal risk of transmission. Extra-neural 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 more aggressive malignancy are ruled out. Since astrocytomas have a tendency to relapse with a histologically higher grade of malignancy, new histological examinations should be performed where relapse occurs to regrade the tumour. If the tumor 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 extra-neural metastases of anaplastic astrocytomas and glioblastoma multiforme are rare, but have been observed, and 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 multiforme (WHO grade IV) are considered intermediate to high risk for transmission depending on the 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.