= LCH = HISTIOCYTOSIS X (former name)

[Paul Langerhans (1847–1888), German pathologist, physiologist, and microscopist in Berlin, close friend of Virchow, discoverer of dendritic cells in the skin and islet cells of the pancreas]

= poorly understood group of disorders characterized by abnormal nonmalignant proliferation of monoclonal Langerhans cells within one / multiple organ systems

• Leading (most common) dendritic cell disorder apart from
  1. Erdheim-Chester disease
  2. Juvenile xanthogranuloma
  3. Rosai-Dorfman disease
  4. Hemophagocytic lymphohistiocytosis

Histo:

granuloma contains Langerhans cells (= large histiocyte of bone marrow origin), foamy histiocytes, lymphocytes, plasma cells, eosinophils

Langerhans cell:

• dendritic cell found in basal layer of skin + in liver (Kupffer cell), lymph nodes, spleen, bone marrow, lung (detects + phagocytizes pathogenic organisms and presents their surface antigens to T and B lymphocytes)
• contains unique mostly pentalaminar rods / “tennis racket”-shaped cytoplasmatic inclusion bodies known as Birbeck granules (identifiable by electron microscopy)
• stains positive for S100, CD1a, CD207
• proliferation triggers release of chemokines + proteases + enzymatic reactions → production of damaging free radicals → destruction of lung architecture → airway fibrosis + failed wound healing

Cause: uncertain (? primary proliferative disorder possibly due to defect in immunoregulation; neoplasm; virus)

Prevalence: 1÷2,000,000 children per year

Path: influx of eosinophilic leukocytes simulating inflammation; reticulum cells accumulate cholesterol + lipids (= foam cells); sheets or nodules of histiocytes may fuse to form giant cells, cytoplasm contains (? viral) Langerhans bodies

Age: any age, mostly presenting at 1–4 years; adults affected in <30%; <30 years in 80%; M÷F = 1÷1

Location: bone + bone marrow, lymph nodes, thymus, ear, liver and spleen, gallbladder, GI tract, endocrine system; multifocal (10–20%)

DDx: osteomyelitis, Ewing sarcoma, leukemia, lymphoma, metastatic neuroblastoma

Clinical manifestations:

1. Localized LCH (70%) = eosinophilic granuloma
2. Disseminated LCH (30%)
   1. Chronic disseminated LCH (20%) = Hand-Schüller-Christian disease
   2. Fulminant disseminated LCH (10%) = Letterer-Siwe disease

formerly: Histiocytosis X = eosinophilic granuloma / Letterer-Siwe disease / Hand-Schüller-Christian syndrome

◊Names should be disregarded as they were thought of formerly as different diseases!

• Bone (80%)
  • bone lesions: in 80% (most common radiographic manifestation)
  
  Location: predilection for flat bones (skull >mandible >rib >pelvis >spine) especially in adults
  • Skull:
    • asymptomatic/ focal pain
    • soft-tissue swelling in scalp
    • well-defined lytic “punched-out” lesion of skull
    • CHARACTERISTIC beveled edge = asymmetric destruction of inner + outer cortices
    • geographic skull = skull lesions may grow in size and coalesce
    
    N.B.: calvarial disease lacks periosteal reaction
    DDx for single lesion: epidermoid / dermoid cyst, osteomyelitis
    DDx for multiple lesions: lymphoma, leukemia, multiple myeloma, metastases
    • Mastoid bone
      • swelling, dizziness, vertigo, otorrhea
      • soft-tissue component : T1-isointense + T2-hyperintense + enhancement; isoechoic on US
    • Mandible
      • gingival bleeding + facial swelling
      • “floating teeth” = destruction of alveolar ridge
  • Vertebral body
    • pain, substantial neurologic defects
    • lytic lesion in early disease
    • vertebra plana = symmetric uniform vertebral collapse + preservation of intervertebral disk spaces
      DDx: leukemia, metastatic neuroblastoma, aneurysmal bone cyst, Ewing sarcoma
  • Long bone: most commonly femur, humerus, tibia
    • asymptomatic / focal pain + swelling
      Site: intramedullary lesion of diaphysis / metaphysis
    • lytic expansile aggressive lesion (in early disease)
    • cortical thickening, smooth periosteal reaction
    • extramedullary soft-tissue component with decreased T1 + increased T2 signal intensity
    • increased radiotracer uptake on bone scan; may be falsely negative (not uncommon)
    • lesion resolution turning sclerotic ← periosteal new bone + sharply defined sclerotic margin (in chronic mature lesion)
    
    DDx: chondromyxoid fibroma, plasmacytoma, metastasis, unicameral cyst, aneurysmal bone cyst
• Liver (15%)
  • hepatic dysfunction
  • hepatomegaly + focal solid / cystlike lesions
  • hypoattenuating, hypoechoic, hypointense T1 and T2 signal along biliary tracts + portal triads= periportal fibrosis
    Cx: progressive sclerosing cholangitis
  • Involvement indicates a worse prognosis
• Spleen (<15%)
  • splenomegaly → hypersplenism → cytopenias
  • Involvement indicates a worse prognosis
• Lymph Nodes (20%)
  Location: predominantly in neck
  • hard / soft matted groups of nodes → lymphedema
• CNS (~16%)
  • ataxia, cognitive dysfunction ← neurodegeneration (with T2-hyperintense lesions in cerebellum + basal ganglia)
  • growth hormone deficiency (later in life)
  • diabetes insipidus (most common) ← decreased secretion of antidiuretic hormone ← infiltration of posterior pituitary gland
  • loss of normal posterior pituitary bright spot
  • thickening of pituitary stalk (~70%) on CEMR
    DDx: germinoma, craniopharyngioma, tuberculosis, sarcoidosis, lymphocytic hypophysitis
  • leukoencephalopathy-like white matter changes
  • lesions in meninges + choroid plexus
• Lung (~10%)
  Age: more common in adults + almost always associated with smoking
  • shortness of breath, nonproductive cough
  • fever / weight loss (sometimes)
  • centrilobular micronodules
    Distribution: bilateral symmetric upper- to mid-lung with sparing of costophrenic angles
    DDx: metastases, miliary tuberculosis, sarcoidosis, silicosis
  • usually <1 cm cysts ± confluence to bulla formation → recurrent spontaneous pneumothorax
  • pleural effusion + enlarged hilar lymph nodes (rare)
    DDx: lymphangioleiomyomatosis, lymphocytic interstitial pneumonia, bullous emphysema