Histiocytic disorders: HLH and Langerhans cell histiocytosis
- Lesion
Two very different disorders of histiocytes: a reactive cytokine storm that eats blood cells, and a clonal tumour of Langerhans-type cells.
What it is
Haemophagocytic lymphohistiocytosis (HLH) is a reactive, life-threatening state in which macrophages and cytotoxic T cells are activated throughout the body; macrophages devour blood cells and a cytokine storm causes fever, cytopenias and organ failure. Langerhans cell histiocytosis (LCH) is a clonal neoplasm of immature dendritic cells, usually driven by MAPK pathway mutations such as BRAF V600E, that ranges from a single bone lesion to a fatal multisystem disease of infants.
Structure
- HLH marrow, spleen and liver: macrophages with engulfed red cells, platelets and leukocytes (haemophagocytosis), which is supportive but not required for diagnosis.
- LCH: sheets of cells with abundant pale cytoplasm and grooved, folded, coffee-bean nuclei, mixed with many eosinophils.
- Electron microscopy of LCH: rod-like Birbeck granules with a dilated end.
Step by step
- HLH: a trigger (EBV, other infection, lymphoma, autoimmune disease) meets cytotoxic cells that cannot kill infected cells efficiently.
- HLH: persistent T-cell and macrophage activation floods the body with interferon-γ, TNF, IL-6 and IL-12.
- HLH: macrophages eat blood cells; cytokines cause fever, liver injury, coagulopathy and shock.
- LCH: an acquired MAPK pathway mutation (often BRAF) arises in a myeloid dendritic precursor.
- LCH: the clone settles in bone, skin, pituitary, lung or liver and recruits eosinophils, causing lytic and destructive lesions.
HLH vs LCH
| Feature | HLH | LCH |
|---|---|---|
| Nature | Reactive (or inherited) immune hyperactivation | Clonal neoplasm of Langerhans-type dendritic cells |
| Key findings | Fever, cytopenias, hepatosplenomegaly, very high ferritin | Lytic bone lesions, skin rash, diabetes insipidus, lung cysts |
Markers
- CD1a
- Langerin (CD207)
- S-100
- BRAF V600E
- Ferritin
- Soluble IL-2 receptor
Clinical notes
- HLH should be suspected in any febrile patient with cytopenias and extreme ferritin; untreated it is often fatal.
- Smoking-related pulmonary LCH of adults causes nodules and cysts in the upper lobes.
Test yourself
Think of the answer, then tap the question to see it.
Which laboratory value is typically extremely high in HLH?
Serum ferritin, together with soluble IL-2 receptor.
Which ultrastructural finding identifies Langerhans cells?
Birbeck granules: pentalaminar rod-shaped structures with a dilated end, like a tennis racket.
What triad defines Hand–Schüller–Christian disease?
Calvarial bone defects, diabetes insipidus and exophthalmos.
Elsewhere in DurgiPedia
Connections
Microorganisms1
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Langerhans Cell Histiocytosis Treatment (PDQ®)–Patient Version (National Cancer Institute (NCI), 2026); Familial hemophagocytic lymphohistiocytosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.