Langerhans Histiocytosis
Eosinophilic Granuloma

General Considerations

• Also known as eosinophilic granuloma(tosis)
• Proliferative disorder of the Langerhans cells
• Normally found in the skin (and a few other organs) and serve as antigen-presenting cells
• Rare diseases, affecting neonates up to adults
• 2:1 male to female predominance
• Prognosis
• Mortality and morbidity are associated with the clinical presentation and age of onset of the disease
• Worst prognosis for neonates presenting with the disseminated form
• Upper lobe predominance in lung
• Small nodules which may contain cavities
• Cystic lesions of varying size, first thick walled, then thinner
• 25% pneumothorax

Three clinical forms

Acute disseminated langerhans cell histiocytosis (aka Letterer-Siwe disease)

• Occurs most frequently in infants 2 years of age or younger (and occasionally adults)
• Presents with multi system organ involvement
• Cutaneous lesions resembling seborrheic dermatitis involve the scalp, face, trunk and buttocks as the dominant clinical feature (nearly 80% of patient will have this)
• Infiltration of bone marrow and other organs lead to concurrent hepatosplenomegaly, lymphadenopathy, pulmonary lesions, anemia, thrombocytopenia, recurrent infections (otitis media)
• Eventually, there are destructive osteolytic bone lesions
• If untreated, this disease is rapidly fatal
• With chemotherapy, 5 year survival rate is approximately 50 percent

Unifocal langerhans cell histiocytosis (aka Eosinophilic granuloma or granulomatosis)

• Usually only affects the skeletal system of young adults
• Typically presents as an osteolytic lesion involving the
• Calvaria
• Vertebra
• Rib
• Mandible
• Femur
• Ilium
• Scapula
• Bony lesions are usually asymptomatic
• In some cases, can cause pain and even pathologic fractures
• Pulmonary lesions may be the only presenting symptom and organ involved, especially in adults
• Skeletal lesion is usually indolent in nature
• Can heal spontaneously or be cured by local excision or irradiation
• Pulmonary lesions are typically followed and treated with supportive care

Multifocal langerhans cell histiocytosis (aka Hand-Schuller-Christian disease)

• Triad
• Diabetes insipidus
• Exopthalmus
• Holes in the bone, usually the head (calvarium)
• Commonly affects children
• Can lead to
• Lymphadenopathy
• Hepatomegaly
• Splenomegaly
• Diabetes insipidus is secondary to infiltration of the posterior pituitary stalk by the Langerhans cell
• About a third of these patients will also display cutaneous lesions
• Some will experience spontaneous regression while others can be treated with chemotherapy

Quick Facts

Letterer-Siwe Disease

• 10% of histiocytosis X
• Acute disseminated, fulminant form
• Age at onset
• Several weeks after birth to 2 years
• Pathology
• May be confused with leukemia
• Symptoms
• Hemorrhage, purpura
• Severe anemia
• Fever
• Hepatosplenomegaly and lymphadenopathy
• Bone involvement in 50%
• Widespread lytic lesions
• Prognosis: 70% mortality rate

Hand-Schuller-Christian

• 15-40% of Histiocytosis X
• Triad of:
• Exopthalmus (33%)
• Diabetes insipidus (30-50%)
• Lytic skull lesions
• Pathology
• May simulate Ewing's sarcoma
• Age at onset
• 5-10 years
• Target organs
• Bone
• Lytic skull lesions with overlying soft tissue nodules
• Large geographic skull lesions
• "Floating teeth" with mandibular involvement
• Soft tissue
• Hepatosplenomegaly is rare
• Lymphadenopathy which may be massive
• Lung
• Cyst and bleb formation with spontaneous PTX
• Ill-defined diffuse nodular disease often leading to fibrosis and honeycombing
• Prognosis: spontaneous remissions and exacerbations

Eosinophilic granuloma

• In lung, usually smokers between 20 and 40 years of age
• Usually confined to bone
• Age at onset
• 5-10 years highest frequency
• Male predominance 3:2
• Location
  • Upper lobe predominance in lung
  • Small nodule which may contain cavities
  • Cystic lesions of varying size, first thick walled, then thinner
• Calvarium>mandible>spine>ribs>long bones
• Most are monostotic (50-75%)
• Target organs
• Skull (50%)
• Diploic space of parietal bone most often
• Round or ovoid punched out lesions with beveled edge
• Sclerotic margin during healing phase
• Beveled edge=hole-within-a-hole
• Button sequestrum- bony sequestrum within lytic lesion
• Axial skeleton (25%)
• "Vertebra plana"-"coin-on-edge"(Calve disease)=collapse of vertebral body, mostly thoracic
• Most common cause of vertebra plana in children
• Proximal long bones (15%)
• Expansile, lytic lesions, mostly diaphyseal
• Soft tissue mass
• Laminated periosteal reaction
• Lung (20%)
• Age peak between 20-40 years
• Multiple small nodules
• Predilection for apices
• Prototype for honeycomb lung
• Recurrent pneumothoraces (25%)
• Rib lesions with fractures common
• Nuclear Medicine
• Negative bone scans in 35%
• Bone lesions usually not Ga-67 avid
• Ga-67 may be helpful in detecting non-osseous lesions
• Prognosis: excellent

Eosinophilic granuloma of lung. Chest radiograph shows a large right-sided pneumothorax (white arrow) with a slight shift of the trachea to the left (yellow arrow). The partially collapsed right lung and left lung are abnormal, demonstrating an interstitial pattern of disease. An axial CT scan of the chest shows a smaller pneumothorax (white arrow) due to the interval introduction of a chest tube (blue arrow). There are multiple, small cysts of varying sizes with varying wall thicknesses in both upper lobes (red circles)
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Cotran, Kumar, Collins. Pathologic Basis of Disease, 6^th edition. Saunders, 1999.

EMedicine. Langerhans Cell Histiocytosis. A. Selim MD

Dhanert, 5^th Ed