Hepatic sinusoidal hemophagocytosis with and without hemophagocytic lymphohistiocytosis

Abstract

Background/purpose: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life threatening hyperinflammatory syndrome. Sinusoidal hemophagocytosis is occasionally observed on liver biopsy in patients who do not have clinical suspicion of HLH. We aimed at comparing the clinical characteristics and outcomes of patients with signs of hemophagocytosis on liver biopsy meeting and not meeting the HLH diagnostic criteria.

Methods: We reviewed the clinical, laboratory features and outcomes of all adult patients consecutively admitted in our center between 08/2011 and 08/2017 presenting with liver histology showing sinusoidal hemophagocytosis and of critically ill patients presenting with severe liver disease in whom hemophagocytosis was histologically confirmed. The characteristics of patients fulfilling and not fulfilling the diagnostic criteria of HLH were compared.

Results: We identified 12 cases (58% male, median age 61, 75% with a chronic underlying disease) with liver histology showing sinusoidal hemophagocytosis. All had at least some of the clinical features typically associated with HLH. Six were critical ill patients. In 4 cases with insufficient laboratory and clinical criteria, liver biopsy allowed to confirm the HLH diagnosis. Six patients died, of which four met the diagnostic criteria for HLH. Two patients with chronic liver disease died despite not fulfilling the diagnostic criteria of HLH.

Conclusion: Hemophagocytosis on liver biopsy may contribute to confirming a diagnosis of HLH in suspected cases with indeterminate clinical and laboratory findings. Sinusoidal hemophagocytosis in patients with cirrhosis was associated with bad outcome.

Fig 1. Liver biopsy showing signs of sinusoidal hemophagocytosis (arrows).

Panel A and Panel B: HE (100x) patient with HLH syndrome. Panel C: HE (100x) patient fulfilling 3 diagnostic criteria of HLH syndrome. Panel D. IHC for CD68 (20x) showing multiple cells expressing CD68.

Fig 2. Correlation of AST and number of sinusoidal hemophagocytosis foci; observed at 20x on liver biopsy (Spearman’s Rho r = 0.773, p = 0.015).