Hemophagocytic Syndromes

 Autosomal recessive inheritance

image 1 in 50,000 live births

• Reactive hemophagocytic syndrome (secondary HLH)
image Infections, malignancies, autoimmune diseases

• Hyperproduction of cytokines and chemokines due to T-cell dysregulation that causes “cytokine storm” with proliferation and activation of macrophages

Clinical Issues

• Presentation
image FHL typically seen in infants and young children

image Secondary HLH typically seen in adolescents and adults

• Laboratory tests
image Hypertriglyceridemia, hyperferritinemia, hypofibrinogenemia

image Cytopenia affecting ≥ 2 of 3 lineages in peripheral blood

image Abnormal liver tests

• Prognosis
image FHL invariably fatal if untreated, with median survival of 2-6 months after diagnosis

image Varied outcomes for secondary HLH, but full recovery can be achieved


• Kupffer cell hyperplasia and hypertrophy
image Cytoplasmic engulfment of erythrocytes, leukocytes, and platelets, as well as cell fragments

• Features of underlying diseases, such as EBV hepatitis

Ancillary Tests

• Bone marrow biopsy and aspirate

• Molecular genetic testing for FHL

This liver biopsy shows sinusoidal dilatation with prominent Kupffer cells image. Many Kupffer cells have abundant cytoplasm that contain engulfed lymphocytes. In situ hybridization is positive for EBV RNA in scattered lymphocytes, confirming a diagnosis of EBV hepatitis.

Hypertrophic Kupffer cells image in dilated sinusoids contain engulfed red cells in the cytoplasm image, which can be easily overlooked. Focal cholestasis image is noted in this case.

CD163 Immunostain
Immunohistochemical stains using histiocytic markers, such as CD163, can highlight hyperplastic and hypertrophic Kupffer cells, but the stains do not help in the recognition of hemophagocytosis.

Bone Marrow Aspirate
Compared to that in liver biopsy, hemophagocytosis is easier to recognize on a Wright-Giemsa bone marrow smear, which shows a macrophage image containing phagocytosed red cells, platelets, and leukocyte debris.



• Hemophagocytic lymphohistiocytosis (HLH), familial HLH (FHL2)


• Hemophagocytic syndrome


• Proliferation and activation of macrophages with hemophagocytosis in reticuloendothelial system


Primary or Familial HLH

• Autosomal recessive inheritance
• 5 subtypes based on causative genes

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Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Hemophagocytic Syndromes

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