section name header

Information

Bone and Soft-Tissue Disorders

= 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

Histo:

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

Langerhans cell:

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!

Localized Langerhans Cell Histiocytosis (70%)!!navigator!!

= Eosinophilic Granuloma

= localized often solitary bone lesion as the most benign variety of LCH

Age: 5–10 years (highest frequency); range 2–30 years; <20 years (in 75%); M÷F = 3÷2

Path: bone lesion arises within medullary canal (RES)

Histo: considerable number of eosinophils in addition to the dominant Langerhans cell constituent

  • painful tender bone lesion + soft-tissue swelling (may be misdiagnosed as local trauma / seborrhoic skin lesion)
  • fever, leukocytosis, elevated sedimentation rate
  • eosinophilia in blood + CSF

Location: limited to single / few bones (in children); may involve lung (in adults)

Sites: monostotic involvement in 50–75%;

  1. flat bones: calvarium >mandible >ribs >pelvis >vertebrae (rarely posterior elements)
  2. long bones: diaphyseal (58%) + metaphyseal (28%) + metadiaphyseal (12%) + epiphyseal (2%) in humerus, femur, tibia

X-ray:

  • osteolytic bone lesions 1–15 cm in diameter:
    • geographic / permeative / moth-eaten configuration
    • well- / poorly defined borders
    • ± sclerosis

DDx: neuroblastoma metastasis, leukemia, lymphoma

CT:

  • moderately to markedly enhancing soft-tissue mass with bone erosion

MR:

  • low to intermediate SI on T1WI + hyperintense T2WI
  • diffuse avid contrast enhancement (fat suppression!)
  • depicts intracranial extension of LCH
  • Skull (40–50%)
    Site: diploic space of parietal bone >temporal bone (petrous ridge, mastoid)
    • round / ovoid punched-out lytic lesion:
      DDx: venous lake, arachnoid granulation, parietal foramen, epidermoid cyst, hemangioma
      • beveled edge / “hole-within-hole” appearance ← asymmetric destruction of inner + outer tables
      • sharply marginated without sclerotic rim (DDx: epidermoid with bone sclerosis)
      • sclerotic margin during healing phase (50%)
    • “button sequestrum” = remnants of bone as a central bone density within a lytic lesion ← erosive accumulation of histiocytes
    • soft-tissue mass overlying the lytic process in calvarium (often palpable)
  • CNS involvement (4%)
    Site: predilection for hypothalamic pituitary axis
    • diabetes insipidus (in 5 –50%)
    • thickening of the infundibular stalk >3 mm
    • isodense markedly homogeneously enhancing mass in superior aspect of stalk / hypothalamus
    • absence of posterior pituitary “bright spot” on T1WI
    • partially / completely empty sella
    • threadlike narrowing of infundibulum (<1 mm)
  • Orbit
    • ptosis, palpebral and periocular erythema, enlargement of associated palpebral fissure
      Site: superior / superolateral orbital region
    • osseous destruction + soft-tissue mass extending into orbit / temporal fossa / forehead / face / epidural space
  • Mastoid process
    • intractable otitis media with chronically draining ear (in temporal bone involvement)
    • destructive lesion near mastoid antrum
      DDx: otomastoiditis, cholesteatoma, metastasis
      Cx: extension into middle ear may destroy ossicles leading to deafness
  • Jaw
    • gingival + contiguous soft-tissue swelling
    • “floating” teeth = destruction of alveolar bone
    • mandibular fracture
  • Axial skeleton (8–25%)
    • pain, rapidly subsiding after bed rest
    • mild hyperpyrexia, mild ↑ ESR, slight eosinophilia, slight leukocytosis
    • rarely mild neurologic complications
      Site: vertebral body >posterior elements
    • “vertebra plana” = “coin on edge” = Calvé disease (6%) = collapse of vertebra (most commonly thoracic):
      • Most common cause of vertebra plana in children!
      • pertinent negatives:
        • increased opacity in collapsed vertebral body
        • absence of osteolysis
        • preserved disk space + pedicles
        • rare involvement of posterior elements
        • no kyphosis
        • absence of adjacent paravertebral soft-tissue
    • lytic lesion in supraacetabular region
      Prognosis: reconstitution of vertebral height is usual
  • Rib (9–15%)
    • rib lesions with fractures (common)
    • ± perilesional edema, especially in early phase
  • Proximal long bones (15–33%)
    Site: mostly diaphyseal; epiphyseal lesions are uncommon
    • expansile lytic lesion with ill-defined / sclerotic edges
    • endosteal scalloping, widening of medullary cavity
    • cortical thinning, intracortical tunneling
    • erosion of cortex + soft-tissue mass
    • laminated periosteal reaction (frequent), may show interruptions
    • may appear rapidly within 3 weeks
    • lesions respect joint space + growth plate
  • Lung involvement (20%)
  • GI tract
    Location: terminal ileum (most commonly)
    • diarrhea, protein-losing enteropathy, malabsorption
    • diffuse concentric bowel wall thickening
  • Skin involvement (up 50%)
    • erythematous papules + plaques → become eroded + develop serous / hemorrhagic crust

    Frequently accompanied by: petechiae / purpura
    Location: scalp, perinasal + preauricular areas of face, flexural areas

NUC:

  • negative bone scans in 35% (radiographs more sensitive)
  • bone lesions generally not 67Ga avid
  • 67Ga may be helpful for detecting nonosseous lesions

Prognosis: excellent with spontaneous resolution of bone lesions in 6–18 months

Chronic Disseminated LCH (20%)!!navigator!!

= HAND-SCHÜLLER-CHRISTIAN DISEASE

[Alfred Hand (1868–1949), American pediatrician at University of Pennsylvania, Philadelphia]

[Artur Schüller (1874–1957), neurologist, psychiatrist and neuroradiologist in Vienna, Austria and Melbourne, Australia]

[Henry Asbury Christian (1876–1951), American pathologist and first physician in chief at Peter Bent Brigham Hospital, Boston]

= chronic disseminated form of LCH characterized by CLASSIC triad (in 10–15%) of

  1. Exophthalmos (mass effect on orbital bone)
  2. Diabetes insipidus (basilar skull disease / direct infiltration of posterior pituitary gland)
  3. Destructive bone lesions (often of calvaria)

Path: proliferation of histiocytes, may simulate Ewing sarcoma

Age at onset:<5 years (range from birth to 40 years); M÷F = 1÷1

  • diabetes insipidus (30–50%) often with large lytic lesion in sphenoid bone / panhypopituitarism
  • otitis media with mastoid + inner ear invasion
  • exophthalmos (33%), sometimes with orbital wall destruction
  • generalized eczematoid skin lesions (30%)
  • ulcers of mucous membranes (gingiva, palate)

Sites: bone, liver, spleen, lymph nodes, skin

  • Bone
    • osteolytic skull lesions with overlying soft-tissue nodules
    • “geographic skull” = ovoid / serpiginous destruction of large area
    • “floating teeth” with mandibular involvement
    • destruction of petrous ridge + mastoids + sella turcica
  • Orbit
    • diffuse orbital disease with multiple osteolytic bone lesions
  • Liver
    • hepatosplenomegaly (rare)
    • scattered echogenic / hypoattenuating liver granuloma
    • lymphadenopathy (may be massive)
    • gallbladder wall thickening (from infiltration)
  • Lung
    • cyst + bleb formation → spontaneous pneumothorax (25%)
    • ill-defined diffuse nodular infiltration often progressing to fibrosis + honeycomb lung
  • Thymus
    • enlarged thymus + punctate calcifications

Prognosis: spontaneous remissions + exacerbations; fatal in 15%

Fulminant Disseminated LCH (10%)!!navigator!!

= LETTERER-SIWE DISEASE

= acute disseminated fulminant form of LCH characterized by wasting, pancytopenia (from bone marrow dysfunction), generalized lymphadenopathy, hepatosplenomegaly

Frequency: 1÷ 2,000,000

Age: several weeks after birth to 2 years

Path: generalized involvement of reticulum cells; may be confused with leukemia

  • hemorrhage, purpura ← coagulopathy
  • severe progressive anemia / pancytopenia
  • intermittent fever
  • failure to grow / malabsorption + hypoalbuminemia
  • skin rash: scaly erythematous seborrhea-like brown to red papules

Location: especially pronounced behind ears, in axillary, inguinal, and perineal areas

Sites: liver, spleen, bone marrow, lymph nodes, skin

  • hepatosplenomegaly + lymphadenopathy (most often cervical)
  • obstructive jaundice
  • Bone involvement (50%):
    • widespread multiple lytic lesions; “raindrop” pattern in calvarium

Prognosis: rapidly progressive with 70% mortality rate

Outline