Answer to the Letter to the Editor

The growing success of transplantation medicine increases the demand for donor organs, especially during infancy and early childhood. This was the reason to ask the parents of the 1 year patient for organ donation dying postoperatively by brain swelling after resection of a large brain tumor of the fossa posterior [6]. Due to the cystic non-malignant appearance of the tumor, the lack of tumor cells in the cerebrospinal fluid and no clinical evidence for distant metastases as well as the fact that no shunt had been inserted we considered this case to be of low risk for transmission. Up to now, the three recipients of the organs are free of malignant disease for more than 2 years.

Unfortunately, it was impossible to establish a tumor diagnosis by histology because of the fluid like texture of the resected tumor. In respect to age of the patient, tumor location, imaging and macroscopic feature a medulloblastoma seemed most likely. The uncertainty of the clinical diagnosis was one reason to present this case because the metastatic potential of a malignant tumor is related to the histology respectively to the tumor biology.

Therefore Dr. Schiff discussed the impact of primitive neuroectodermal tumors encompassing very different entities like medulloblastoma, pineoblastoma or retinoblastoma as well as glioblastoma. In his letter he mentioned three adults dying by transmitted glioblastoma after bilateral lung transplantation. Furthermore he pointed out that there is occurrence of bone metastases in adults with medulloblastoma. However, glioblastoma of the fossa posterior is very unusual, especially in infancy [4] [9]. Moreover, some organs (e. g. lungs) may confer an increased risk for transmission of malignancy: The United Network for Organ Sharing UNOS recommends that lungs and livers from high grade CNS tumors should be avoided as they are much more common sites of metastases compared to hearts and kidneys [2].

There is ongoing research on molecular markers with the aim to predict each individual's risk for metastatic disease: e.g. expression of selectins is an important factor for tumor metastasis as shown in patients with colon carcinoma [3]. Probably histone deacetylases 5 and 9 are more important in medulloblastomas [5]. Future identification of biological and genetic markers such as selectin or histone deacetylases 5 and 9 expression in the organ from a donor with a malignancy may help to differentiate which organs may be transplantable and which carry an increased risk of transmission.

In the situation of uncertain histology we discussed the possible role of physical risk factors like tumor cells in the cerebrospinal fluid, open surgery or insertion of a device. We agree with Dr. Schiff that the available data are not very convincing [1] [8]. In addition it is unclear at which time point of the disease extraneural spread of metastases occurs. In the German multicentre trials medulloblastomas, supratentorial peripheral neuroectodermal tumors (PNET), ependymomas are followed prospectively in the HIT 2000 trial, high grade malignant gliomas including glioblastomas and pontine gliomas in the HIT GBM trial [7] [9]. In each trial more than 1000 cases are followed. There was one case of extraneural metastases in the HIT 2000 trial (Bone, Bone marrow in a 3-year-old) and not a single case in the HIT GBM trial (personal communication S. Rutkowski, C. Kramm).

One aim of our publication was to stimulate discussion about donors with brain tumors and potential risk-factors. We therefore gratefully acknowledge the letter by Dr. Schiff regarding our publication. To achieve more data on possible and definite risk factors all patients transplanted with donor organs of a brain tumor patient should be registered into an international registry in a prospective and standardised manner.

J. W. Rey, T. Niehues

References

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