Hemophagocytic lymphohistiocytosis of indeterminate cause: a fatal adult case

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon life-threatening disorder characterized by wide spread non-neoplastic proliferation and inappropriate activation of mature macrophages resulting in hypercytokinemia. This uncontrollable and ineffective systemic immune response causes fever, hepatosplenomegaly, cytopenias and subsequently multiorgan failure. The authors report a case of a 41-year-old male patient with a 30-day history of weight loss, fever, icterus, hepatomegaly, and cytopenias. The diagnostic workup disclosed hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin. Bone marrow examination and clinical course raised the suspicion of HLH and treatment was started with high-dose corticosteroids and immune globulin. The patient underwent multi-organ failure and expired after 58 days of hospitalization. The autopsy finding included massive bone marrow infiltration by non-neoplastic histiocytes, many of them showing hemophagocytosis, which immunohistochemical study revealed diffuse CD68-positive histiocytes, which were negative for S100 protein. Hemophagocytosis was also observed in the lungs, lymph nodes and liver. The immediate cause of death was attributed to a massive intestinal bleeding due to extensive ischemic necrosis at the duodenum/jejunal transition area.

Hemophagocytic lymphohistiocytosis associated with hepatosplenic T-cell lymphoma: case report

“…This immune hyperactivity is postulated to be secondary to an increase in NK cell activity in response to EBV infection. A very similar phenomenon takes place in EBV-related lymphomas 6 , 10…”

“…However, it is believed that there is an overstimulation of the immune system, accompanied by oversecretion of cytokines, notedly tumor necrosis factor-alpha. In this setting, macrophages release ferritin, increase plasmin activity (leading to fibrinolysis, hepatomegaly, raised serum liver enzymes and bilirubin) and inhibit lipoprotein lipase (leading to hypertriglyceridemia) 9 , 10. This immune hyperactivity is postulated to be secondary to an increase in NK cell activity in response to EBV infection.…”

“…In this setting, macrophages release ferritin, increase plasmin activity (leading to fibrinolysis, hepatomegaly, raised serum liver enzymes and bilirubin) and inhibit lipoprotein lipase (leading to hypertriglyceridemia). 9 , 10 This immune hyperactivity is postulated to be secondary to an increase in NK cell activity in response to EBV infection. A very similar phenomenon takes place in EBV-related lymphomas.…”

Hemophagocytic lymphohistiocytosis presenting as acute coronary syndrome

“…Both of these evasive mechanisms can cause EBV-HLH. 1,4,8 Rare presentations, nonspecific symptoms, symptomatic overlap, and unexplained multiorgan failure require a high index of suspicion to diagnose HLH, which makes this disease particularly evasive of differential diagnoses and thereby particularly fatal. In 1991, the Histiocyte Society proposed a diagnostic criterion for the pediatric population, and this was widely used for adult or acquired HLH by the time it was revised in 2004.…”

In the pursuit of indexing

“…Many case reports published in Autopsy and Case Reports to date are accompanied by a literature review, providing the reader with an update on the issue at hand. Examples include the articles “Hemophagocytic lymphohistiocytosis of indeterminate cause: a fatal adult case,”6 and “Spindle-cell carcinoma of the prostate.”7 Although they do not have the obvious subtitle “case report and review of the literature,” they are, in fact, practical review articles, and could be classified as original articles according to current criteria. From the standpoint of an editor, here is the dilemma: should a systematic review in a case report be mandatory?…”