Donor-Derived Squamous Cell Carcinoma after Allogeneic Bone Marrow Transplantation.

Long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT) develop solid tumors. Chronic graft-versus-host disease (GvHD) increases the risk of squamous cell carcinoma (SCC). Five of 24 patients with HSCT and SCC, had sex-mismatched HSCT. In 3 of them, tumor sex karyotype studied by combined XY FISH and double immunostaining on the same SCC section, with 3D Z-stack analysis, was compatible with a cancer originating from donor hematopoietic cells. After control by short tandem repeats analysis (PCR-STR) of laser micro-dissected tumor and normal epidermal cells from the recipient and donor or PCR-STR and FISH analysis of a tumoral cell line from one SCC, a recipient origin was found in one case but in the two other cases the donor genotype of the tumor was confirmed. In a third step, PCR-STR of laser micro-dissected tumor in 2 cases after sex-matched transplant proved SCC to be of the donor origin. We thus obtain conclusive evidence that 4 epithelial tumors among 8 studied arose from the engrafted donor cells. Tissue stem cells were proposed to exhibit an unexpected level of plasticity, although issues on cell fusions have lead to some controversies. Only transplantation experiments using genetically distinct recipients and donors can unequivocally demonstrate these changes in cell fate. We have analyzed a unique set of squamous cell carcinomas arising in long terms survivors of allogeneic stem cell transplantation. In these patients, chronic graft-versus host disease greatly favors development of solid tumors, possibly as a consequence of mucosal inflammation and immunosuppression. Thus, donor-derived hematopoietic stem cells recruited to sites of chronic inflammation yielded epithelial tumors.