Langerhans Cell Histiocytosis

(Histiocytosis X)

 

Epidemiology:

    • Multifocal multisystem Langerhans cell histiocytosis (Letterer-Siwe disease):
      • Before 2y usually
    • unifocal lesions (eosinophilic granuloma):
      • older children or adults
    • multifocal unisystem Langerhans cell histiocytosis:
      • young children
    • Pulmonary Langerhans cell histiocytosis
      • Adult smokers

 

Common sites:

    • Unifocal and multifocal unisystem Langerhans cell histiocytosis (Eosinophilic granuloma):
      • Medullary cavities of bones usually
        • calvarium
        • ribs
        • femur
        • any bone can be involved
      • skin
      • lungs (smokers)
      • stomach
    • multifocal unisystem Langerhans cell histiocytosis:
      • involvement of the posterior pituitary stalk causing diabetes insipidus (50%)

 

Gross features:

    • Multifocal multisystem Langerhans cell histiocytosis (Letterer-Siwe disease):
      • Cutaneous lesions resembling a seborrheic eruption over the front and back of the trunk and on the scalp
      • Hepatosplenomegaly
      • Lymphadenopathy
      • Pulmonary lesions
      • Destructive osteolytic bone lesions
    •  

 

Histologic feature: s

    • Unifocal and multifocal unisystem Langerhans cell histiocytosis (Eosinophilic granuloma):
      • Expanding, erosive accumulations of Langerhans cells
      • Histiocytes, eosinophils, lymphocytes, plasma cells, neutrophils
        • eosinophilic infiltrate usually prominent
    • abundnant, often vacuolated cytoplasm
      • Birbeck granules are characteristic
    • vesicular nuclei with linear grooves or folds
      • larger than histiocyte nucleus

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 HLA-DR

 

 

S100

 

 

CD1a

 

 

langerin

 

 

 

Molecular features:

    • clonal (shown by X-linked androgen receptor gene assay)
      • except in some adult pulmonary lesions
    • no consistent molecular genetic defect

 

Other features:

    • neoplastic
    • EM – Birbeck granules (not seen in all tumour cells)– penalaminar, rodlike, tubular appearance
      • Sometimes a dilated end (tennis-racket appearance)
    • Likely dendritic cells are attracted by aberrent chemokine receptors (CCR7)
    • Multifocal multisystem Langerhans cell histiocytosis (Letterer-Siwe disease):
      • Anemia
      • Thrombocytopenia
      • Recurrent infections
      • Rapidly fatal course untreated
    • unifocal lesions (eosinophilic granuloma):
      • indolent
      • cured by local excision or irradiation
      • 99% survival
    • multifocal unisystem Langerhans cell histiocytosis:
      • Hand-Schuller-Christian triad:
        1. calvarial bone defects
        2. diabetes insipidus
        3. exophthalmos
      • spontaneous regression in many; others need chemotherapy
      • 66% survival in those who do not respond promptly to therapy
    • Pulmonary Langerhans cell histiocytosis
      • May regress spontaneously on smoking cessation
      • Reactive (polyclonal)

 

References:

    • Robbins 2005
    • WHO blue book (2008)