Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality following bone marrow transplantation (BMT). GVHD occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient. GVHD, which can present either acutely or chronically, typically involves the skin, gastrointestinal tract, and liver. In contrast, GVHD involving other organs such as the heart and kidney is highly uncommon and involvement of the central nervous system has only very rarely been described in the literature. We report an unusual case of GVHD that involved the heart, kidney, adrenals, and the brain in a deceased patient that received a dual haploidentical stem cell transplant for myelodysplastic syndrome. Pre-mortem, the patient had experienced biopsy proven GVHD of the skin and liver. The clinical course was also complicated by fungal infection (Rhizopus). There was no histologic evidence of viral infection pre or post-mortem. Pre-mortem PCR analysis of nasopharyngeal swabs was negative for respiratory viruses. PCR also failed to identify BK virus or CMV from blood or urine. GVHD of the CNS was characterized by a lymphocytic leptomeningitis with few perivascular multinucleated giant cells. Immunohistochemical studies demonstrated both CD8+ and CD4+ lymphocytes in the leptomeninges and the brain parenchyma with a marked predominance of CD8+ lymphocytes. CD20 and VZV immunohistochemistry was negative. Post-mortem PCR analysis of short tandem repeat (STR) polymorphisms demonstrated a range of ~20-50% of both donors’ cells in multiple organs, likely lymphocytes, based on the H&E examination. However, due to prolonged formalin fixation, no PCR signal could be detected in the brain. GVHD of the CNS is rare but may be underreported due to the declining autopsy rate and a lack of recognition of the salient histologic features.
Recommended CitationYoo, Janet; Simon, Lindsay; Wang, PhD, Zi-Xuan; and Kenyon, Lawrence C., "Graft Versus Host Disease of the Brain Following Allogeneic Stem Cell Transplant for Myelodysplastic Syndrome" (2012). Department of Pathology, Anatomy and Cell Biology Faculty Papers. Paper 91.