Donor-Derived Testicular Germ Cell Cancer in a Heart Transplant Recipient

Heart transplantation (HTx) is considered the gold standard therapy for selected patients with end-stage heart failure, significantly improving survival and quality of life in comparison to medical therapy (1). Necessary immunosuppression results in an increased risk of malignancy, but transmission of donor-derived solid tumors is rare due to stringent criteria in donor selection (2). Testicular germ cell cancer (TGCC) is a highly treatable solid neoplasm; high cure rates can be obtained with cytotoxic chemotherapy. However, metastases of TGCC to the heart are very rarely detected in clinical practice (3). Here, we present a case of transplanted germ cell cancer after HTx, detected by endomyocardial biopsy.

the risk of transmission of TGCC, given the significant shortage of donor hearts and relatively high waiting list mortality. Additional irrigation of the heart was performed to remove as many intravascular cells as possible. Implantation of the donor heart was uneventful. Immunosuppression was started as usual-tacrolimus, mycophenolate mofetil (MMF), and prednisolone-in combination with increased oncological surveillance.
Temporary venoarterial extracorporeal membrane oxygenation support because of RV failure and hemofiltration was necessary for 3 days. The patient was extubated on day 6 and then transferred to the cardiology ward on day 9 postoperatively. He recovered quickly and had normal cardiac function and rhythm.
Routine endomyocardial biopsy on days 16 and 23 showed 1R cellular rejection, for which prednisolone tapering was deferred, and he remained at a dose of 20 mg/day. Thereafter, endomyocardial biopsy normalized and surveillance for clinical stage 1 TGCC was initiated by the oncologist. Two months after HTx, serum tumor markers (aFP and hCG) were normal. Computed tomography (CT) of the chest and abdomen did not show any metastases, and ultrasound of the testes was normal as well. After discussions with patient, family, and experts in the field of TGCC, it was decided to start cytotoxic chemotherapy consisting of a 5-day regimen of cisplatin and etoposide. The dose of MMF was reduced to 250 mg twice daily, and target tacrolimus levels were reduced to 5 mg/l. Continuous heart rate monitoring during treatment did not show any abnormalities, and the patient was discharged on day 6 without signs of heart failure or other toxicities.
Ten days post-chemotherapy, he experienced diarrhea without fever, and loperamide was started. The next day, however, he arrested, and the first registered rhythm was asystole. After successful resuscitation, the patient was transported to a nearby hospital. Echocardiography showed a normal LV and RV function without pericardial effusion. A CT scan was performed, which showed bilateral infiltrates in the lungs and signs of cure rates can be obtained with cytotoxic chemotherapy, even with metastatic TGCC (9). Despite the use of tacrolimus and MMF, regression of the pulmonary metastases was observed on CT. Although a switch to sirolimus was considered given its potentially antineoplastic properties, 2 important arguments were raised against its use: 1) its efficacy in TGCC is questionable (10); and 2) sirolimus clearance is increased when dexamethasone (as an antiemetic drug) is added, leading to an unstable immunosuppressive state and unacceptable risk of graft rejection.
The presented patient died acutely of toxicities such as neutropenia and mucositis, but with a primary cause of death being the cardiac arrest and its sequelae. It can certainly not be excluded that necrosis in the cardiac tumor was the trigger for cardiac arrhythmias, although not observed during chemotherapy administration. In summary, we report the case of a patient in whom a heart and a potentially curable tumor were transplanted.
Unfortunately, the recipient of each died.

FUNDING SUPPORT AND AUTHOR DISCLOSURES
The authors have reported that they have no relationships relevant to the contents of this paper to disclose. ADDRESS FOR CORRESPONDENCE: Dr. Marish Oerlemans, Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, the Netherlands. E-mail: m.oerlemans@umcutrecht.nl.