Status:
Ready to upload
Record number:
2347
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
Potential donors with WHO grade 3 astrocytomas can be accepted as organ donors. Transmission risk is considered low to intermediate for tumours without any risk factors (Council of Europe, 2022). Spontaneous extraneural metastases of grade 3 astrocytomas 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. A consistent relationship has emerged between mitotic activity and outcome; indeed, and on this basis, tumours are divided into CNS WHO grades 2 and 3. MAPK pathway gene aberrations, in particular BRAF V600E, as well as homozygous deletion of CDKN2A and/or CDKN2B, are central to the underlying genetics of PXA but are not associated with tumour grade or prognosis. TERT promoter alterations may be linked with a more aggressive phenotype and have been proposed as a marker of anaplastic transformation.
Time to detection:
Liver recipient: 56 d after transplant
Kidney recipient: 103 d after transplant
Kidney-Pancreas recipient: 120 d after transplant
Lung recipient: 49 d after transplant
Alerting signals, symptoms, evidence of occurrence:
Liver recipient: no signals and symptoms reported, liver biopsy performed
Kidney recipient: no signals and symptoms reported, graft nephrectomy performed
Kidney-Pancreas recipient: no signals and symptoms reported, a graft nephrectomy and a graft pancreatectomy with resection of the adjacent duodenum, an omentectomy, and biopsies of peritoneal and mesenteric nodules
were performed
Lung recipient: no signals and symptoms reported, a BRAF V600E–positive bronchiogenic carcinoma
Demonstration of imputability or root cause:
The cellular morphology of the recipient tumors shared similar features to those of the donor tumor. However, glial and neural markers, positively expressed by the donor cells were undetected in the recipient lesions. The genetic profiles of the tumors were used to track the lineage from the organ donor, to the participants. The genetic profile of a tumor includes both the DNA of the germline of the affected individual and the somatic mutations acquired over the development and expansion of the cancer. The germline sequence includes both common polymorphisms found in the general population and some rare and/or unique variation that may be specific to this individual. The mutations in BRAF, PIK3CA, SDHC, DDR2, and FANCD2, and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients’ lesions.
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Keywords:
References:
Suggest new keywords:
Malignancy
Pleomorphic xanthoastrocytoma
Deceased donor
Case Report
DNA typing
Whole exome sequencing
Central nervous system cancer
Astrocytoma (WHO grade 3)
Therapy not discussed
Reference attachment:
Suggest references:
Gingras MC, Sabo A, Cardenas M, Rana A, Dhingra S, Meng Q, Hu J, Muzny DM, Doddapaneni H, Perez L, Korchina V, Nessner C, Liu X, Chao H, Goss J, Gibbs RA. Sequencing of a central nervous system tumor demonstrates cancer transmission in an organ transplant. Life Sci Alliance. 2021 Jul 22;4(9):e202000941. doi: 10.26508/lsa.202000941. PMID: 34301805; PMCID: PMC8321656.
Note:
Please clone record for the following 3 organ recipients: Kidney, Kidney-Pancreas, Lung
Uploaded MN 6/19/23
Expert comments for publication:
The case is a donor with a grade 3 pleomorphic xanthoastrocytomawith transmission to 4 recipients (liver, kidney, pancreas and lung) detected from 49 to 120 d after transplantations. At procurement, computed tomography axial scans of the chest, abdomen, and pelvis without intravenous contrast did not detected signs of malignancy.
The presence of prior surgical treatment chemo-/radiotherapy increases the risk of transmission in grade 3 and 4 astrocytomas. Computed tomorgraphy axial scan with intravenous contrast can improve donor's assessment, at procurement.
The authors provide a detailed explanation of the logic behind the use of molecular genetic analysis to determine tumor origin that is worth reading. They also observe that the tumor in this case contained several mutations that have been associated with increased aggressiveness, and argue that whole genome studies in these cases could eventually help to clarify which CNS tumors are more likely to exhibit extraneural spread and increased transmission risk, thereby aiding in selecting or excluding patientd with CNS tumors as organ donors.