Xanthomatous Cells in Cutaneous Graft-Versus-Host Disease Biopsies: A Clue for the Diagnosis of Hepatic Graft-Versus-Host Disease

Abstract

Graft-versus-host disease (GVHD) is one of the most common and serious complications of hematopoietic stem-cell transplantation that mainly affects the skin, gastrointestinal tract, and liver. Hepatic GVHD is associated with high morbidity and mortality, and its diagnosis can be especially challenging because of nonspecific clinical signs and symptoms. It must be suspected in patients with elevated liver enzymes and cholestasis, especially in those with a history of preceding skin rash and diarrhea. We describe 3 patients with cutaneous and hepatic GVHD that presented with severe hypercholesterolemia and hypertriglyceridemia, and no xanthomatous macular lesions, in which cutaneous biopsies revealed the presence of xanthomatous dermal histiocytes. We propose that the presence of these xanthomatous cells in skin biopsies from patients with cutaneous GVHD could be a dermatopathological clue for the diagnosis of hepatic GVHD.

Foamy Macrophages in a Case of Mononucleosis With Amoxicillin-Induced Rash, Hyperlipidemia, and Hemophagocytic Lymphohistiocytosis

“…The finding of xanthomatous cells, on the other hand, was observed in skin biopsies of 3 patients with acute graft-versus-host disease (GVHD) with liver involvement, and these cells were suggested to represent a clue to the presence of liver involvement in the disease. 6 The biopsy findings in these 3 cases were remarkably similar to those observed in our case, showing a superficial perivascular infiltrate with interface dermatitis and the presence of foamy macrophages in the upper dermis. A similar case of GVHD with severe liver involvement and foamy histiocytes in the papillary dermis was presented by one of us (L.C.)…”

“…10 This may explain its tendency to accumulate in macrophages in the skin, thus giving rise to the development of planar xanthomas in cholestasis. 8 In this context, accumulation of lipoprotein X in dermal macrophages may also be responsible for the presence of foamy macrophages in the cases of acute GVHD with hepatic involvement described by Gamé et al 6 as well as in our case of IM with antibiotic-induced exanthema and associated acute liver disease.…”

“…at a dermatopathology meeting in France in 2010. Our particular case of mononucleosis and the 3 cases described by Gamé et al 6 had in common the presence of underlying cholestatic hepatopathy with mixed hyperlipidemia.…”