Histiocytosis

Question 1

What are histiocytes? (2 main groups)

Answer 1

• APCs - dendritic cells
  
  • Langerhan’s cells (skin), interdigitating reticulum cells (nodes), dendritic reticulum cells (nodes)
• Antigen Processing Cells - phagocytosis
  
  • Tissue macrophages, monocytes, tingible body macrophages (nodes), sinusoidal histiocytes, epithelioid histiocytes

Question 2

Langerhan Cell Histiocytosis

Answer 2

• Most common histiocytic disorders
• Usually seen in childhood (median - 30 mo) but can occur in adults
• BRAF kinase mutation in 57% of cases
• Bone lesions due to histiocyte infiltration +/- organ involvement (younger pts have more organ involvement while adults more bone alone)

Question 3

Langerhan Cell Immunophenotype

Answer 3

FcIgG, HLA-DR, ++S100, ++Langerin, ++CD1a and +/- CD4

Question 4

Langerhan Cell Histiocytosis Tx

Answer 4

DEP ON RISK

• Restricted - skin only or 1 + bone lesions only (LOW RISK)
  
  • Tx - minimal; topical steroids for skin, corticosteroid injections; low-dose radiation
  • Most pts do well
• Extensive (multi-system) - visceral organ involvement w/ or w/o dysfunction of lung, liver, etc (HIGH RISK)
  
  • Tx - multiagent chemo (do well if respond to tx)

Question 5

Hand-Schuller-Christian Disease

Answer 5

• Langerhand histio syndrome

- lytic lesions in skull + diabetes insipidus + exopthalmos (chronic and recurring)

Question 6

Letterer-Siwe Disease

Answer 6

• Langerhand histio syndrome

- infants w/ failure to thrive + hepatosplenomegaly + lymphadenopathy + anemia/cytopenia (FATAL)

Question 7

Hematophagocytic Syndrome Dx

Answer 7

• Dx (5/8)
  
  • Fever (high and long duration)
  • Enlarged spleen +/- liver
  • Heme - anemia, thrombocytopenia, low neutrophils
  • High triglycerides
  • High ferritin (almost pathopneumonic)
  • Inc sCD25
  • Dec or absent NK cell activity
  • Hematophagocytosis in BM, spleen, nodes (very common but not requirement)

Question 8

Farquar’s Disease

Answer 8

Familial Hematophagocytosis

• Septic infants w/ high fever and hepatosplenomegaly
• Almost always diagnosed in first yr
• Rapidly fatal w/o tx
• Perforin gene mutation is most common –> defective cytotoxicity –> inc cytokine levels (interferon-gamma, TNF, PGF2alpha, IL-2 receptor)
• Interferon-gamma - Activation of histiocytes and hematophagocytosis
• TNF - fever, pancytopenia
• PGF2alpha - fever and hyperlipidemia
• sIL2 receptor - hematophagocytosis
• Tx - calm cytokines (decadron, cyclosporin A, methotrexate, etoposide), BM transplant is curative

Question 9

Secondary Hematophagocytosis

Answer 9

(viral-associated or reactive)

• Immunosuppressed child w/ fever, hepatosplenomegaly, pancytopenia
• Not same mortality rate as familial
• Tx - treat specific infection; remove immunosuppressive agents; aggressive chemo if needed
  - Does not require BM transplant
• Most common causes - EBV, but also bacteria, fungal, parasite, etc