8. Immunohistological study at 24 years of the skin of the first bilateral human hand allograft

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Introduction: The first bilateral human upper extremity transplantation (UET) was performed in our hospital on January 10, 2000. The patient is a 33-year-old man with traumatic amputation at the level of the forearms who received a bilateral UET. The maintenance immunosuppressive treatment (IST) included prednisone (10 mg/d), tacrolimus (serum trough levels 5-10 microg/L) and mycophenolate mofetil (2 g/d). We report here the (immuno)histological study of the skin of this allograft, 24 years post-graft. Methods: Punch-skin biopsies were obtained under local anesthesia from the allografted forearm at various times post-graft, the latest one at the 24-year follow-up. Formalin-fixed, paraffin-embedded tissue sections were examined after routine (hematoxylin-eosin-affron) staining and immunohistochemically with a panel of antibodies recognizing various skin cell types. Results: During the first post-transplant months, the patient developed some episodes of acute graft rejection that were reversed with a temporary increase of the systemic IST and the addition of local immunosuppressants (clobetasol & tacrolimus ointments). Motor and sensitivity recovery were rapid and satisfactory. The patient is in good condition and his grafts are currently functioning. Over the years he developed some cutaneous infections (tinea versicolor, warts, scabies) that were easily and successfully treated. At 24 years post-graft, the skin maintains macroscopically a normal appearance, its sensitivity is normal and the growth of skin adnexa uneventful, even though the nails progressively thinned. Microscopically, the skin has a normal appearance, containing its essential cell types, such as cycling epidermal keratinocytes (Ki67+), Langerhans cells (CD1a+), Merkel cells (K20+), melanocytes (MART-1+), dermal dendrocytes (fact. XIIIa/CD163+), blood and lymphatic vessels containing endothelial cells (CD34+/podoplanin+, respectively), nerve fibers (CD56+/prot. S100+), adipocytes (S100 prot.+), pilosebaceous follicles and eccrine sweat glands. A sparse inflammatory perivascular inflitrate made of T CD3+ T-cells and some CD20/CD79a+ B-cells was present in the deep dermis in the latest biopsy. Conclusions: These results show that, despite the chronic IST, the allografted skin maintains in the long-term a normal cellular and architectural structure, which is a prerequisite to its normal function. The presence of a minimal inflammation, consistent with a smoldering rejection process, highlights the necessity of a long-term maintenance IST.

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