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Transmission of Donor-Derived Small-Cell Carcinoma Cells by a Nontumor-Bearing Allograft

2005; Wolters Kluwer; Volume: 80; Issue: 4 Linguagem: Inglês

10.1097/01.tp.0000168489.71242.fd

1534-6080

Christian Morath, Peter Rohmeiss, Vedat Schwenger, R. Waldherr, Eberhard Ritz, Martin Zeier, Christine Fallsehr, Matthias Kloor, Magnus von Knebel Doeberitz, Joachim Andrassy, W. Huckenbeck, Markus B chler, Gerhard Opelz,

Polyomavirus and related diseases

Transmission of cancer by a tumor-bearing allograft is rare. Transmission of isolated tumor cells had only been reported for Kaposi sarcoma and acute promyelocyte leukemia. The following observation documents that such transmission may also occur with solid tumors. A 40-year-old white female received a first renal transplant on December 31, 2001. The donor was a 63-year-old otherwise healthy man (75 kg/175 cm) who died from traumatic intracerebral bleeding. He was a heavy smoker (about 80 packyears) with no evidence of malignancy. A chest x-ray and an abdominal ultrasound at the time of organ harvesting were unremarkable. Only the kidneys were allowed to be removed (the recipient of the second kidney is doing well with no signs of malignancy on a triple-drug regimen with cyclosporine A, mycophenolate mofetil and methylprednisolone); autopsy was not permitted. Renal function in the recipient started immediately postoperatively and no rejection episodes were noted. Immunosuppression consisted of cyclosporine A, mycophenolate mofetil (discontinued in March 2002 due to urosepsis), and methylprednisolone. In October 2002, she experienced back pain of increasing intensity, followed by hypercalcemia (2.70 mmol/l). An x-ray showed destruction of the 10th thoracic vertebra and three osteolytic lesions of the skullcap. Five masses were found in the liver by magnetic resonance imaging. A percutaneous biopsy of one liver tumor disclosed infiltration by spindle-shaped tumor cells with scant cytoplasm, numerous mitoses, focal necrosis, and occasional rosette formation. The tumor cells stained positive for cytokeratins, synaptophysin, and NSE. Thus, light microscopic diagnosis of small-cell carcinoma (probably metastasis) could be confirmed by immunohistology. Extensive clinical evaluation disclosed no malignancy of the lungs, abdomen, skin, and renal transplant. Because the patient’s clinical course deteriorated rapidly, immunosuppression was discontinued and the renal allograft was removed. Macroscopically no tumor mass was noted and microscopically no tumor cells were present upon complete lamellation of the kidney and on more than 100 histological sections. To exclude donor origin of the malignancy, DNA fingerprinting analysis was performed. Y-chromosomal sequences were amplified from the tumor tissue DNA in the female patient. Additionally, the malignancy displayed an allele pattern consisting of alleles from both the female recipient and the male donor as determined from the renal allograft (Table 1).TABLE 1: DNA fingerprinting analysisA preproGRP-specific product (sensitive marker for circulating small cell lung carcinoma cells in humans) was still amplifiable from peripheral blood of the recipient two months after transplant nephrectomy and cessation of immunosuppression but absent at 4 months (Fig. 1), indicating that malignant cells had disappeared from systemic circulation. These changes were paralleled by a dramatic improvement of the patient’s condition. After 18 months of follow-up metastases, the malignancy had either disappeared or shrunken significantly. Rejection of the malignant cells expressing HLA class I antigens (as shown by staining for MHC class I heavy-chain and beta-2 microglobulin) is a plausible explanation for these findings because no cancer therapy was administered in this patient.FIGURE 1.: PreproGRP RT-PCR for detection of circulating tumor cells in peripheral blood. Columns 1-4: Positive controls for preproGRP RNA in small cell lung cancer cell lines (SCLC). Column 5: Peripheral blood lymphocytes of a healthy individual (N_PBL). Column 6: Amplification of a preproGRP specific product from patient’s blood sample 2 months after transplant nephrectomy (PBL 1). Column 7: absent preproGRP PCR product 4 months after explantation of the allograft and cessation of immunosuppression (PBL 2) indicating the disappearance of tumor cells from circulation. NC, negative control. All PCR reactions were performed at least in duplicate from two independent cDNA preparations.What is striking in this case is that no tumor cell infiltration could be found in the renal allograft. We propose that transmission of the tumor was due to release of tumor passenger cells present in the allograft at the time of transplantation. This observation is supported by an observation of Lacroix et al. (1) who documented exfoliated small cell lung cancer cells in peripheral blood (13/26) of tumor-bearing patients. In conclusion, we report the transmission of a donor-derived solid organ tumor by a nontumor-bearing renal allograft by the transplantation procedure. In the future, strategies to minimize the risk of tumor transmission with solid organ allografts are clearly indicated in view of an aging donor population. Christian Morath Peter Rohmeiss Vedat Schwenger Rüdiger Waldherr Eberhard Ritz Martin Zeier Department of Nephrology University of Heidelberg Heidelberg, Germany Christine Fallsehr Matthias Kloor Magnus von Knebel Doeberitz Institute of Molecular Pathology University of Heidelberg Heidelberg, Germany Joachim Andrassy Department of Surgery University of Wisconsin Madison, WI Wolfgang Huckenbeck Department of Legal Medicine University of Düsseldorf Düsseldorf, Germany Markus Büchler Department of Transplant Surgery University of Heidelberg Heidelberg, Germany Gerhard Opelz Department of Transplant ImmunologyUniversity of Heidelberg Heidelberg, Germany