Langerhans Cell Histiocytosis (LCH)

  • Used to be called Histiocytosis X or Class I
  • Usually pediatric
  • Dendritic cell origin and lineage (with Erdheim-Chester, JXG)
  • Clinical presentation in children
    • Skin
      • Polymorphic
      • Classic: recalcitrant seborrheic dermatitis with petechiae
        • Elementary lesion: micropapule, sometimes purpuric, covered with a scaly crust or eroded
        • “Erosive intertrigo with crusty edges” (Saurat)
      • Crusted papules, vesiculopustules, erosions, nodules, petechiae or purpura
      • Nails: oniycholysis, subungueal hyperkeratosis
    • Extra-cutaneous
      • Bone
        • Areas of osteolysis → “punch-out” lesions
        • Mainly cephalic and axial regions
      • Pituitary
        • Diabetes insipidus, bitemporal hemianopia, growth retardation
      • Liver, spleen
        • Hepatomegaly, hepatocellular insufficiency, portal hypertension
        • Sclerosing cholangitis and biliary cirrhosis
      • Hematopoietic, lymph nodes
        • Anemia, thombocytopenia, leukopenia, macrophage activation syndrome
      • Lung
        • Reticulonodular infiltrate → cysts and nodules
        • Dyspnea, cough, pneumothorax, pulmonary fibrosis → chronic respiratory failure and pulmonary arterial hypertension
      • Gastrointestinal
        • Polyps, extensive granulomatous lesions
  • Workup
    • Biopsy
    • Full physical exam, review of systems
      • Skin, lymph nodes, ears, mouth, skeletal, (lungs), thyroid, liver, spleen, CNS
    • CBC, LFT, electrolytes
      • Bone marrow biopsy & aspiration if cytopenia
    • Skeletal survey, CXR, US liver/spleen
    • Endocrine labs, brain MRI if polyuria, polydipsia (diabetes insipidus)
  • Risk stratification - determine indolent VS aggressive
      • notion image
    • Monosystem disease
      • Focal disease of bone, skin or lymph node
      • Multifocal disease of skeleton or lymph nodes
    • Multisystem disease
      • Low risk - age over 2, without involvement of liver, spleen or hematopoietic system
      • High risk - age under 2 and involvement of multiple organs, or age over 2 years and involvement of liver, spleen or hematopoietic system
  • Pathology
    • Langerhans cells in papillary dermis, bean-shaped nuclei, epidermotropism
      • Admixed inflammatory cells, including mast cells
      • Hashimoto-Pritzker: giant cells with eosinophilic or ground glass cytoplasm
      • Histology and immunohistochemistry indistinguishable from “congenital self-healing reticulohistiocitosis”
    • CD1a, CD207 (langerin), S100, MHC-II, peanut agglutinin positive
      • Some BRAF-V600E mutation (PCR) → higher risk but therapeutic implications
    • (Birbeck granules on electron microscopy obsolete)
      • Saurat “the only absolute diagnostic criterion is the detection of Birbeck granules in more than 50% of the infiltrate cells or testing for langerin
  • Treatment
    • Treatment based on organ systems affected
    • Localized skin disease
      • Observation, topical steroids, topical antimicrobials, topical nitrogen mustard, PUVA, nbUVB, imiquimod, MTX, AZA, 6-MP, oral retinoids
      • Follow closely for 5 years
    • Localized bone lesions
      • NSAIDs, IL steroids, curettage, XRT
    • Multisystem disease
      • Chemotherapeutics (vinblastine +/- other immunosuppressants like prednisone)
      • If Risk organs: liver, spleen, bone marrow
        • Cladribine and cytarabine
        • Bone marrow or solid organ transplant
        • Targeted BRAF inhibitors? Severe disease, low efficacy, many SEs
    • ALL and myelodysplastic syndrome can precede LCH, AMLand ALL can follow it
    • Advances/support - “Histiocyte Society”