Multiple Skin Cancers Arising in Bone Marrow Transplant Recipients Can Exhibit a Donor Origin
RW Lamberts, RS Ritzlin, K Yearsley, SH Barsky. University of Nevada School of Medicine, Reno, NV; The Ohio State University College of Medicine, Columbus, OH; Nevada Cancer Institute, Las Vegas, NV
Background: Multiple skin cancers (basal cell carcinomas, squamous cell carcinomas and melanomas) and their precursor lesions often arise in bone marrow transplant recipients months to years after the transplant for reasons that are not understood. Approximately half of these patients receive a transplant from a sex-mismatched donor. We exploited this fact to gain insights into the nature of the skin carcinogenesis process in these transplant recipients.
Design: We studied 100 sex-mismatched transplant recipients who developed multiple (at least 5) skin cancers or precursor lesions over a period of months to years following successful transplant for diseases like relapsed lymphoma or leukemia. We created a tissue microarray (TMA) consisting of the secondary skin cancers or precursor lesions, the adjacent normal tissues and control skin cancers arising in non-transplant patients. We initially conducted X and Y chromosome FISH on this TMA. In selected cases we supplemented our FISH studies with studies that utilized informative but stable polymorphic microsatellite loci which could reliably distinguish donor from recipient; in other studies, we investigated possible donor lymphocytic or macrophage fusion with recipient stem cells by conducting gene rearrangement and ploidy studies in the skin cancers.
Results: Approximately 20% of the secondary skin cancers that developed were of donor origin. This was seen in both female as well as male recipients. The numbers may actually have been higher than observed because some skin cancers of male origin spontaneously lost the Y chromosome. This observation, not withstanding, cancers with the Y chromosome arising in females and cancers with XX signals arising in males supported their donor origin. Microsatellite marker studies further confirmed their donor origin. In these cases, there was no significant ploidy or immunoglobulin / T cell receptor monoclonal gene rearrangements, which excluded cell fusion or donor-recipient chimerism as mechanisms to explain the findings. Evidence of donor origin was seen in all of the histological types of skin cancers studied including their precursor lesions.
Conclusions: Our studies suggest that skin carcinogenesis arising in the transplant setting can take origin from pluripotent stem cells of bone marrow donor origin. These pluripotent stem cells first migrate into the skin where they subsequently transform.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 71, Monday Morning