Donor-transmitted Melanoma Case Study

Donor-transmitted Melanoma Case StudyLakshmi Rangaswamy, D.O., Kim Jordan, MD., FACP, Ronald deAndrade, MDIntroductionOrgan channelise recipients are at an change magnitude risk of developing malignancy, estimated to occur in 15-20% of graft recipients after 10 years. Most malignancies occur de novo or as proceeds of previously treated disease, re noveld to immunosuppression and oncogenic viruses.Donor-transmitted tumors are rare. From 1994 2001, the US Transplant tumor registry reported 18 bestower-related cancers in 108,062 recipients.Case PresentationHistoryA 66-year-old female presents with abdominal fullness, fevers, chills and malaise for 1 weeks time. Admitted to transplant service to rule out rejection.Past Medical HistoryEnd award Renal Disease status post cadaveric renal transplant 3 months priorHypertensionDiabetes Mellitus Type 2 -Anemia of chronic disease affable HistoryNo tobacco, alcohol, or drug abuseMedications (do I really need strength and frequency?)Amlodipi ne 10 mg day-by-dayAspirin 81 mg dailyBactrim 160 mg dailyCarvedilol 25 mg twice dailyClotrimazole 10 mg troche three times dailyInsulin Lispro 10 units with mealsLantus 20 units in AMMyofortic 360 mg 2 tablets twice dailyPrednisone 10 mg dailyTacrolimus 2mg twice dailyValcyte 450 mg 2 tablets dailyPhysical examVITALS T 100.1, BP 133/60, HR 71, Resp 18, SpO2 99% on RA, nonoliguricNeck no lymphadenopathy, no carotid bruitsCardiovascular symmetric rate and rhythm, no clicks, gallops, rubs, no lower extremity edemaLungs clear to auscultation bilaterally, no rales or wheezesAbdomen soft, well healed Gibson incision in RLQ, no graft tenderness, no pipe organomegalySkin no rashes or lesions noted on skinLaboratory and Diagnostic Studies (insert images)WBC 3.94 K/mcl Hgb 9.8 g/dL (patients baseline) platelets 104 K/mclLDH 747 U/LCreatinine 1.72 mg/dL on the day of admission (baseline 1.02 two months prior, after transplant). During the hospital course, her renal failure worsened with cre atinine reaching 8.08 mg/dL and patient requiring intermittent hemodialysisCT of the abdomen with contrast and PET scanFindings compatible with metastatic disease to the liver, spleen, bones, and probably lungs.magnetic resonance imaging Abdomen/pelvisA few indeterminate T1 and T2 hyperintense lesions in the periphery of the transplant kidney, suspicious for neoplasm. Innumerable bone marrow and splenic lesions, suspicious for hemorrhagic metastasisMRI of brainDiffuse bony metastases, no signs of intraparenchymal metastasisPETPositive for multiple lesions in the transplant kidney, bone, and spleen.CT guided Bone marrow biopsymetastatic malignant neoplasm, quite consistent with metastatic malignant melanoma**Within days of patients admission, it was discovered that the recipient of the liver from the same donor developed melanoma within the transplanted liver and the recipient of the mate kidney had developed melanoma in the renal homograft.**The transplant center reported no cog nize history of donor melanoma and normal visual inspection of donor organs at time of transplant.Clinical CoursePatient elected to support allograft nephrectomy. Surgical pathology of removed donor kidney confirmed malignant melanoma that was BRAF-V600E mutation positive (insert histo slide of melanoma in kidney)Patient was taken morose of all immunosuppressive therapy and was started on chemotherapy with zelboraf and immunotherapy with ipilimumab (completed 4 months of zelboraf and 4 cycles of ipilimumab)Patient currently off of chemotherapy, and undergoes repeat imaging every month.At 6 months, CT proboscis from 6 months demonstrates basically stable disease.This patient is now undergoing hemodialysis for her end stage renal diseaseThe two other recipients died from metastatic melanoma bring in the transplanted liver and renal allograft this patient is the sole survivor of the transplanted melanoma.Transmission of melanoma by organ transplantation (VIPER)Not only is melanoma the most common fatal form of skin cancer, it is the most common tumor responsible for donor-derived malignancy.The late disease recurrence of melanoma is related to the quiescency of melanoma. Major theories for the dormancy of melanoma include kiosk-cycle arrest and blocked angiogenesis. Per Lancet article entitled Transmission of donor melanoma by organ transplantation, late recurrence of dormant melanoma can occur because of micrometastases or solitary dormant cells. Dormant micrometastasis occurs because of the inability for angiogenesis therefore there is an equilibrium between cell proliferation and apoptosis and thus an inability of malignant cell growth. In dormant solitary cells, there is an absence of proliferation or apoptosis, in essence a transgress in cell growth. Because of these theories, it is possible that these dormant cells stay latent in immunocompetent individuals for decades and even forever, but the immunosuppression of the organ recipient can reactivate the melanoma cells. transplantation for end-stage organ disease has become routine care with resultant increased demand for donor organs.With increased public awareness and donor pool expansion, numerous transplant programs are easing criteria for selection by accepting older donors and those with remote history of low-grade skin cancers and/or remote cured cancers.A recent study reported 23 disciplines of donor-transmitted melanoma from 12 separate donors between 1972 and 2006. Only 2 donors had known history of melanoma and one case of fatal melanoma occurred from a donor who had surgically removed melanoma sixteen years prior to donation.History of melanoma remains a contraindication to organ donation given melanoma high transmission rate of 74% and mortality of 58%.Treatment of donor-related melanoma involves withdrawing immunosuppression and allowing the body to reject the transplanted organ, followed by explantation of the allograft carrying the melanoma cells.SummaryMelanom a incidence in the general population is increasing, but whether this will translate into increased incidence of donor-transmitted melanoma and resultant increased mortality remains to be determined.Physicians must not only discuss risks of malignancy with transplant candidates, but also carefully question all donors and their family almost recent and remote malignancy, particularly melanoma, given its high transmission rate and mortality.Patients with any history of melanoma, whether it be in the early stages or cured, showed not be considered as organ donors.ReferencesGeller, A.,et al (2013). Melanoma Epidemic An Analysis of Six Decades of Data From the Connecticut Tumor Registry.Journal of Clinical Oncology,31, 4172-4178.Geller, A.,et al (2014). Screening and early maculation of melanoma. Retrieved January 1,2014, from http//www.uptodate.com/Morris-Stiff, G.,et al (2004). Transmission of Donor Melanoma to Multiple OrganTransplant Recipients.American Journal of Transplantation,1 0, 444-446.Strauss, D. (2010). Transmission of donor melanoma by organ transplantation. LancetOncology, 11, 790-796. Retrieved from www.thelancet.com/oncology