What is Hemophagocytic Lymphohistiocytosis (HLH)?
Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition characterized by a hyperinflammatory response due to excessive activation of
immune cells, particularly macrophages and lymphocytes. This uncontrolled immune response leads to severe tissue damage and multi-organ failure.
Histological Features of HLH
In the context of histology, HLH is identified by the presence of
hemophagocytosis, where activated macrophages engulf red blood cells, white blood cells, and platelets. This process can be observed in bone marrow, liver, spleen, and lymph nodes. The histological examination typically shows:
Causes and Risk Factors
HLH can be familial (genetic) or acquired. Familial HLH is often due to mutations in genes related to cytotoxic function of
Natural Killer (NK) cells and cytotoxic T lymphocytes. Acquired HLH can be triggered by infections, malignancies, autoimmune diseases, and certain medications. Common infectious triggers include
Epstein-Barr virus (EBV), cytomegalovirus (CMV), and HIV.
Clinical Presentation
Patients with HLH often present with a range of severe symptoms which may include prolonged fever, hepatosplenomegaly (enlarged liver and spleen), cytopenias (reduction in blood cell counts), hyperferritinemia (high levels of ferritin), and liver dysfunction. The excessive immune response can lead to significant tissue damage and organ failure.Diagnosis
The diagnosis of HLH requires a combination of clinical, laboratory, and histological findings. The
HLH-2004 criteria are often used, which include a set of diagnostic guidelines such as:
Fever
Splenomegaly
Cytopenias affecting at least two cell lineages
Hypertriglyceridemia and/or hypofibrinogenemia
Hemophagocytosis in bone marrow, spleen, or lymph nodes
Low or absent NK cell activity
Hyperferritinemia
Elevated levels of soluble CD25 (sIL-2R)
Histological Examination in Diagnosis
A bone marrow biopsy is often performed to observe hemophagocytosis. The presence of activated macrophages engulfing hematopoietic cells is a key histological feature. Liver biopsies can reveal lymphohistiocytic infiltrates and hemophagocytosis, while lymph nodes may show sinus histiocytosis.Treatment
Treatment of HLH involves immunosuppressive therapy to control the hyperactive immune response. Common treatments include corticosteroids, etoposide, and cyclosporine. Hematopoietic stem cell transplantation (HSCT) may be considered in familial cases or refractory cases not responding to initial treatment. Management also includes addressing the underlying trigger, such as treating infections or malignancies.Prognosis
The prognosis of HLH varies and depends on the underlying cause, the patient's response to treatment, and the timing of diagnosis. Early diagnosis and appropriate treatment are crucial for improving outcomes. Despite aggressive treatment, HLH remains a high-risk condition with significant morbidity and mortality.Conclusion
Histological examination plays a critical role in the diagnosis and understanding of HLH. Recognizing the histological features such as hemophagocytosis and lymphohistiocytic infiltrates is essential for timely diagnosis and initiation of treatment. Ongoing research is essential to further understand the pathophysiology of HLH and to develop more effective treatments.
