Case report: Breast carcinoma transmission to 4 recipients (lung transplant) (2018)

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Estimated frequency: 
Most recent risk assessment for breast cancer (Council of Europe, 2022): Newly diagnosed invasive breast cancer is an unacceptable risk for organ donation. Organs from donors with invasive breast cancer might be accepted in selected cases after full treatment, complete remission and stringent follow-up for > 5 years, depending on the initial stage and E/P and HER2/neu receptor expression, always bearing in mind the risk of transmission due to possible late metastases. Breast cancer stage 1 (AJCC, 8th edition) [18] with curative surgery and cancer-free period > 5 years seems to be associated with low to intermediate risk for transmission. All other invasive breast cancer stages are considered high-risk for transmission, independent of the presumed recurrence-free survival and treatment.
Time to detection: 
Double lung recipient: 16 mo; Left kidney recipient: 6 years 1 mo; Liver recipient: 4 years 5 months; Right kidney recipient: 4 years 3 months
Alerting signals, symptoms, evidence of occurrence: 
Lung recipient (first patient to develop tumor): Chest X-ray performed during allograft dysfunction 16 months after transplant showed mediastinal lymphadenopathy, biopsy showed tumor; FES-PET and CT revealed lung and bone metastases; reduction of immunosuppression; recipient died 12 months after detection of first metastases (28 months after transplant). Left kidney recipient: CT performed after being informed of lung recipient status was negative for tumor, 5 years later patient devleoped hypercalcemia, malaise and weight loss, CT showed multiple liver lesions and biopsy showed tumor; recipient died 2 months after detection of first metastases (6 years and 3 months after transplant). Right kidney recipient: Screening performed after being informed of lung recipient status was negative for tumor, 18 months later a biopsy performed for nephrotic range proteinuria thought due to antibody mediated rejection showed tumor, with masses confirmed by CT. Transplantnephrectomy without ability to resect the complete widespread tumor (including local iliac growth), cessation of immunosuppression and chemotherapy followed; complete remission after 13 months; recipient was still alive without signs for recurring malignancy at the time of case publication 10 years after transplant. Liver recipient: Alerting signs not listed; tumor detected in liver graft 4 years and 5 months after transplant and biopsy showed carcinoma. Recipient refused the offered retransplantation; extracorporeal proton radiation was performed and showed signs of complete response; extrahepatic tumor progression was detected 7 years after transplant; recipient died 3 years and 1 month after detection of transmitted tumor (7 years and 6 months after transplant). The heart recipient died of sepsis 5 months after transplant. At this time, neither the donor tumor nor the other recipients' metastases had been detected. Therefore, no information about a possible tumor transmission in the heart recipient is available.
Demonstration of imputability or root cause: 
The ER+/PR+ tumor in the lung recipient was shown to be of donor origin by DNA microsatellite analysis; tumors in all other recipients were also ER+/PR+ except for the liver recipient, in which only the ER is listed and is positive.
Imputability grade: 
3 Definite/Certain/Proven
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Suggest new keywords: 
case report
deceased donor
kidney transplant
liver transplant
lung transplant
DNA typing
microsatellite analysis
breast cancer
Suggest references: 
Matser YAH, Terpstra ML, Nadalin S, Nossent GD, de Boer J, van Bemmel BC, et al. Transmission of breast cancer by a single multiorgan donor to 4 transplant recipients. Am J Transplant. 2018;18(7):1810-4.
Please clone record for lung and liver recipients (I listed kidney transplant in this record). Also, I think we should split the breast cancer category into "Breast cancer, not further specified" and "Breast cancer, other". The not further specified category would include the "garden variety" ductal and lobular cancers, ie the breasst carcinomas, whereas the other would include rare types such as sarcomas. Leading off with the word "other" suggests that we are listing unusual tumors only in this category, in my opinion (MN) Thannk you, nothing to add (CLFF) Further review done by Kerstin and addition of some information of recipient´s course of events (Oct 21, 2018).
Expert comments for publication: 
Interesting case report documenting multiple transmission of breast carcinoma from a single donor to 4 recipients, with disease manifesting at different times between 16 months and 6 years after transplantation. The donor cancer was unknown at time of transplant, implying that either it was clinically inapparent (likely) or was present and missed by physical examination (unlikely). The donor underwent complete physical examination and chest X-ray, although it is not specifically mentioned if breast examination was performed. Regardless, the presence of donor malignancy presenting in 3 of the 4 affected recipients at times between 4-6 years post-transplant proves that late arising cancers can be of donor origin. (At present, the term "donor origin" tumor is applied to late arising tumors, almost always in reference to isolated renal cell cancers arising within allograft kidneys). This report shows that it is prudent to consider donor origin tumor in any unusual late-arising tumor in a transplant recipient and, if possible, take steps to confirm the suspicion (e.g. DNA microsatellite analysis that can be performed on routine surgical pathology specimens) in order to provide warning for other potential recipients from that donor. The authors also point out that removal of the graft and restoration of immunosuppression can cause complete tumor remission. This is not a new observation; unfortunately it is not a uniform outcome and at present there is no way to predict who will or will not respond to this intervention. Finally, the authors note that a breast examination should be part of the routine donor physical examination.