Pediatric liver failure with massive sinusoidal infiltration of histiocytes

Histiocytic neoplasms, such as Langerhans cell histiocytosis (LCH) and disseminated juvenile xanthogranuloma (JXG), can involve the liver and sometimes cause liver failure. We aimed to classify non-LCH histiocytic proliferating disorders that do not exhibit typical disseminated JXG histology. We examined four pediatric patients who presented with liver failure and splenomegaly. Two patients with liver cirrhosis without cholestasis underwent liver transplantation (LT). The other two patients presented with giant cell hepatitis causing neonatal/infantile acute liver failure (ALF). The infantile ALF patient also underwent LT. Liver dysfunction developed after LT in all three transplant cases and the grafts exhibited massive sinusoidal infiltration of histiocytes with hemophagocytosis, similar to the native liver. The neonatal ALF patient was treated with an LCH-type chemotherapy regimen, and is alive and well at 18 months. Infiltrating histiocytes were positive for CD68 and CD163, and negative for CD1a, CD207, and S-100 protein. The BRAF V600E mutation was not present. Liver histological findings were not consistent with conventional disseminated JXG or LCH, although the histological findings in other organs overlapped those of well-known histiocytic neoplasms. The histological and immunohistochemical findings of infiltrating histiocytes suggest that these four cases constituted a disseminated JXG-like systemic disease.