Eosinophilic granuloma

Tumor biology

• Rare, benign, tumor-like disorder
• Belongs to a group of disorders of the reticuloendothelial system
• Also known as Histocytosis X, or Langerhan’s cell histiocytosis (LCH)
• Involves skeleton as either a solitary lesion or in multiple sites
• Generally active or aggressive in behavior

Age

• Most common from ages 5-10
• Rare after age 30

Gender

M:F = 2:1

Associated syndromes

• Hand-Schüller-Christian disease
• Letterer-Siwe disease

Presentation

• Pain most frequent presenting symptom
• Pediatric patient may present with limp, back pain, or scoliosis

Physical findings

• Palpable mass may be present (rare).
• Tenderness at site of symptomatic involvement
• Scoliosis or restricted motion common with spinal lesions

Plain films

• Single collapsed vertebra in children (vertebra plana)
• Lytic lesion of long bones or flat bones with variable degree of endosteal and periosteal response (may appear as permeative, aggressive, lytic lesion)
• Multiple lesions not uncommon

Site

• Skull, ribs, vertebrae, pelvis and long bones (femur and humerus mostly)
• Hands and feet almost never affected
• Ribs more commonly affected in adults; the long bones more commonly affected in children
• Lesions may be diaphyseal or metaphyseal

Size

Variable

Tumor effect on bone

• Variable
• Lytic
• Destruction can be patchy and uneven; more commonly geographic
• Rib lesions may expand bone as opposed to long bone lesions, where expansion is less common
• Pathologic fracture is common in the spine (vertebra plana)

Bone response to tumor

• Usually minimal metaphyseal sclerosis
• May be periosteal reaction in response to an endosteal erosive lesion
• Onion skinning may be present

Matrix

• Generally no matrix at presentation in symptomatic phase
• Can have a hazy matrix during the resolution phase; results from bone forming in lytic lesion

Cortex

• Cortex may be thinned, scalloped, or have an onion skinned appearance
• Differential diagnosis for such onion skinning includes eosinophillic granuloma, non-Hodgkin’s lymphoma, and Ewing sarcoma

Soft tissue mass

Rarely present

Differential diagnosis

• Unicameral bone cyst
  • More commonly larger, less painful, and located in the metaphysis of a bone; eosinophillic granuloma more commonly in diaphysis
• Osteomyelitis
• Primary osseous malignancy, such as Ewing sarcoma or lymphoma

Natural history

• Lesions can progress or disappear over time (can be a few months or longer)
• Most lesions require diagnostic biopsy, which stimulates resolution of lesion in some cases
• Persistent aggressive changes may be seen in patients with multiple lesions

Pathology

• Gross: Friable tan tissue
• Microscopic: Infiltrate of histiocytes, Langerhans’ cells, and inflammatory cells
  • Variable numbers of eosinophils present
  • Multinucleated giant cells are seen
• Langerhans’ cell is diagnostic cell
  • S100 positive on immunohistochemical staining
  • Contains characteristic Birbeck granules (tennis racket-shaped cytoplasmic inclusions) when examined by electron microscopy

Treatment

• Lesions typically observed because they often heal spontaneously
• Indications for surgery
  • Determine the diagnosis
  • Persistent pain
  • Prevention or treatment of pathologic fracture
• Curettage and bone graft especially indicated for lower extremity lesions; supplement with internal fixation if patient at risk for fracture
• Low-dose radiation effective in most lesions, but usually reserved for recalcitrant non-healing or recurrent lesions
• Multiple lesions or visceral involvement may respond to chemotherapy