Langerhans histiocytosis

Clinical features

  • Localized forms have a good prognosis whereas multiorgan disease, especially in younger than 2 years, have poor outlook.
  • Congenital cases and familial cases have been rarely reported
  • Three entities are recognized:
    • Letterer-Siwe´s disease:
      • Children from 3months-3 years
      • Hepatosplenomegaly, lymphadenopathy and cutaneous lesions
      • Skin lesions on the scalp, face, mouth, neck, trunk and buttocks
    • Hand-Shüller-Christian disease:
      • Children from 2-6 years
      • Otitis media, diabetes insipidus, cranial bone defects, exophthalmia and cutaneous lesions.
      • Skin lesions on chest, axillae and groin
    • Eosinophilic Granuloma:
      • Accounts for 60% of the cases
      • Affects mainly skeleton (monostotic or polyostotic)
      • Bones, specially long bones, are the most common location of involvement
      • Radiologically lytic with punched out appearance
      • 50% in spine, skull, pelvis, ribs and mandibula
      • Children from 2-5 years
      • Osteolytic, pulmonary, cutaneous and occasional cranial lesions
      • Skin lesions on the scalp, face, oral cavity and groin

 

Fig 60 - Langerhans Histiocytosis - Cellular smears with multiple single Langerhans cells. These cells have convoluted nuclei and prominent grooves and fine vesicular chromatin. Eosinophils in the background (H&E)
Fig 61- Langerhans Histiocytosis –Nuclear details -convoluted aspects of Langerhans nuclei (H&E)
Fig 62 - Langerhans Histiocytosis – CD1a immunostaining showing intense cytoplasmic positivity

 

  • Cellular smears with discohesive cells.
  • Large cells with convoluted nuclei and prominent grooves.
  • Fine vesicular chromatin.
  • Bi/multinucleation frequent.
  • Abundant pale or granular cytoplasm with well-defined borders
  • Macrophages with phagocytosis can be a feature.
  • Mitosis are rare
  • Eosinophils and other inflammatory cells.
  • Necrosis can be seen-(eosinophilic micro abscesses)

 

Special Stains and Immunocytochemistry

  • CD1a: Positive  (essential for diagnosis)
  • S100-protein: Positive
  • CD68: Positive ( 96% of the cases)
  • CD21: Negative
  • CD 35:Negative

 

Differential Diagnosis

  • Hemophagocytic syndromes
  • Reactive processes with histiocytic proliferation
  • Rosai-Dorfman
    • Affects mainly adults
    • Emperipolesis
    • CD11c: Positive
    • CD68: Positive
    • S100-protein: Positive
    • CD1a Negative
  • Juvenile xanthogranuloma
    • Located in soft tissue
    • Touton cells
    • CD68: Positive
    • XIIIa: Positive
    • CD1a: Negative
  • Malignant Histiocytosis

 

Main Points

  • Letterer-Siwe´s disease: Mortality in one year
  • Hand-Shüller-Christian disease: Poor prognosis -50% mortality rate
  • Eosinophilic Granuloma : Benign
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