A Donor-Derived Tongue Squamous Cell Carcinoma After Allogeneic Peripheral Blood Stem Cell Transplantation.

Abstract 4510

Recently the increasing number of cases of solid malignancies developed in recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has attracted more attention while less donor-derived solid malignancies after allo-HSCT have been found. We describe here a case of donor-derived tongue squamous cell carcinoma (SCC) in a young adult patient who had undergone allogeneic peripheral stem cell transplantation for acute leukemia 2 years ago. The female patient had a history of acute lymphoblastic leukemia (ALL-L2) at 20 years of age in July 2004 and received a successful busulfan and cyclophosphamide (BU/CY2) myeloablative allografting (allogeneic peripheral blood stem cells) from a HLA-matched unrelated male donor in August 2006. Acute graft versus host disease (GVHD) prophylaxis consisted of cyclosporine A 2.5 mg/kg/day, methotrexate 10 mg on day 1,3,6, and mycophenolate mofetil 0.5 g/day. However, on day 12 the patient developed skin grade II acute GVHD. Subsequently, she complicated with intestinal grade II acute GVHD characterized by recurrent diarrhea on day 49. 2 mg/kg/day of methylprednisolone and 4 mg/kg/day of cyclosporine A were given. 7 days later acute GVHD was controlled gradually. After that, grade II chronic GVHD with skin rash and oral mucositis accompanied by leukoplakia occurred after 5 months post engraftment. Prolonged immunosuppressive agents containing prednisolone and cyclosporine A were administered. In April 2008 (20 months post engraftment), the patient presented with symptoms of pain in the tongue which worsened in the following 2 months. A firm mass was seen in the tongue which was highly suspicious for malignancy. The histology of the puncture biopsy showed a well-differentiated SCC. The neoplastic cells were pleomorphic and prominent nucleoli. Cell nests and keratinous pearls could be seen clearly. Then she was treated with mass excision in addition to supraomohyoid neck dissection immediately. At the same time peripheral blood STR analysis showed full donor's chimerism, and bone marrow aspiration as well as minimal residual disease with FACS indicated complete remission of the primary disease. The patient is now under follow-up with no recurrence or metastasis. Further investigation of the tissue specimens by fluorescent in situ hybridization (FISH) (X,Y probes) combined with double-SP immunohistochemical staining (CD45, Pan-cytokerin) revealed the presence of one Y chromosome-specific signal and one × signal within most of the neoplastic cells which was identified as pan-cytokerin (+), CD45(-) cells and this suggested that donor-derived stem cells might transform into malignancies in the recipient by several potential mechanisms (Hu YX et al, Onkologie 2010). Till now about 13 cases developing donor-derived solid malignancies including oral SCC (Janin A et al, Blood 2009; Tomihara K et al, Head Neck 2009), colonic adenoma (Cogle CR et al, Stem cells 2007), breast adenoma (Golfinopoulos V et al, Breast Cancer Res Treat 2009), gastric adenoma (Arai Y et al, AM J Transplant 2006), larynx squamous cell carcinoma (Avital I et al, Stem cells 2007), Kaposi's sarcoma (Avital I et al, Stem cells 2007), lung adenoma (Avital I et al, Stem cells 2007) and glioblastoma multiforme (Avital I et al, Stem cells 2007) have been reported post-HSCT. The presence of donor-derived solid malignancies suggests that human bone marrow-derived stem cells have a role in the carcinogenesis of solid organ cancer especially in the organ with inflammation. But which kind of bone marrow derived stem cells transformed into solid malignancies and its mechanisms need further investigation.