Eosinophilic Granuloma

Key Points:

  • Eosinophilic granuloma is a benign, solitary tumor of bone.
  • Must rule-out multiple lesions and multi-system involvement (Langerhans-cell histiocytosis).
  • Common in the skull, mandible, spine, and long bones. Spine involvement may progress to vertebra plana deformity.
  • Treatment is varied, ranging from observation, biopsy with or without bone grafting, methylprednisolone injection, or internal fixation for impending fracture/deformity.

Description:

Langerhans-cell histiocytosis (LCH) includes a spectrum of diseases involving clonal proliferation of histiocytes, or dendritic cells and macrophages. The spectrum ranges from simple, solitary lesions of bone to leukemia-like disorders. Eosinophilic granuloma (EG) is the most common expression of LCH and is a benign, solitary lesion of bone. It can affect any bone, and is more common in the skull, mandible, spine, ribs, and long bones.  In long bones such as the femur, humerus and clavicle, EG often presents as a modestly destructive lytic lesion with a characteristic “punched out” appearance. (Herring, 2014)

Epidemiology:

EG represents 1% of all bone tumors, and consists of 60 to 80% of all cases of LCH, with 80 percent of cases affecting children and adolescents. (Angelini, 2017)

Clinical Findings:

Most EG lesions are identified incidentally.  Lesions are primarily asymptomatic but can occasionally be painful.  If present, symptoms may include fracture, pain, swelling, deformity, or soft tissue involvement (DiCaprio, 2014; Hoover, 2007). A low-grade fever and elevated erythrocyte sedimentation rate may also occur (Herring, 2014).

In the spine, 6.5-25% of bone tumors are EG.  In the spine, EG is most commonly located in the thoracic followed by the lumbar spine and constitutes 6.5 to 25% of all spine bone tumors. Depending on the location in the spine, symptoms can be severe, with the most common being pain, tenderness on palpation, restricted motion or torticollis. Neurologic symptoms and spinal instability are uncommon. (Angelini, 2017) 

A thorough exam including a complete neurologic exam is necessary, in patients with known or suspected cranial or spinal involvement. Laboratory studies are also important, including a basic laboratory panel, inflammatory markers, coagulation studies, and urinalysis in order to differentiate EG from infection and other causes of lytic bone lesions. (DiCaprio, 2014) 

On gross examination, EG lesions are typically filled with soft reddish-brown material with occasional hemorrhage or cysts.  Microscopically, EG lesions are characterized by histiocytes and often eosinophils, but plasma cells and Langerhans cells may also be present.  Langerhans cells are large mononuclear giant cells with indented nuclei and pale cytoplasm, containing the classic tennis racquet-shaped Birbeck granules visible on electron microscopy. (Herring, 2014)

Imaging Studies:

Radiographs demonstrate a solitary lytic lesion.  Classically, vertebral lesions in growing children are osteolytic and result in vertebra plana with sparing of the posterior elements and disc spaces. (Hoover, 2007)

Once a lesion has been identified, search for additional lesions should be undertaken. This may include a skeletal survey or bone scan; however skeletal survey is preferred as some lesions will not be visualized with scintigraphy. (Herring, 2014) CT may be helpful to confirm the diagnosis and determine the extent of cortical disruption. MRI may also be used, and is highly sensitive but nonspecific. (Hoover, 2007)

Etiology:

The pathogenesis of EG remains unclear, theories as to the etiology include an infectious, neoplastic, or even an autoimmune process (Hoover, 2007; DiCaprio, 2014; Angelini, 2017). However, the BRAF gene mutation has been discovered in over 50% of LCH cells, which is suggestive of a neoplastic process (DiCaprio, 2014). 

Treatment:

In children, EG is often observed to resolve spontaneously. Treatment may consist of observation alone or biopsy to confirm diagnosis (Angelini, 2017). Biopsy may be accompanied by curettage and/or autogenous bone grafting (Plasschaert, 2002). Spinal lesions at risk of instability or long bone lesions at risk of pathologic fracture may be an indication for internal fixation (Ghanem, 2003). In the spine, immobilization with a brace has been shown to be sufficient to allow remodeling and reconstitution of vertebral height (Plasschaert, 2002). Additionally, intralesional methylprednisolone is another option, and provides symptomatic relief and possibly inhibits IL-1-induced bone resorption (Angelini, 2017; Mavrogenis, 2012). 

Complications:

The primary complication is pathologic fracture.  There is a 100% survival rate and low rates of recurrence for patients with monostotic disease (DiCaprio, 2014).

References:

  1. Angelini, A; Mavrogenis, AF; Rimondi, E; Rossi, G; Ruggieri, P. Current concepts for the diagnosis and management of eosinophilic granuloma of bone. J Orthop Traumatol 2017; 18: 83-90
  2. DiCaprio, MR; Roberts, TT. Diagnosis and management of Langerhans cell histiocytosis. JAAOS 2014; 22: 643-652
  3. Ghanem, I; Tolo, VT; D’Ambra, P; Malogalowkin, MH. Langerhans cell histiocytosis of bone in children and adolescents. J Pediatr Orthop 2003; 23: 124-130
  4. Herring JA. Benign musculoskeletal tumors. In: Herring JA ed Tachdjian's Pediatric Orthopaedics. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:1083-1127
  5. Hoover, KB; Rosenthal, DI; Mankin, H. Langerhans cell histiocytosis. Skeletal Radiol 2007; 36: 95-104
  6. Mavrogenis, AF; Abati, CN; Bosco, G; Ruggieri, P. Intralesional methylprednisolone for painful solitary eosinophilic granuloma of the appendicular skeleton in children. J Pediatr Orthop 2012; 32: 416-422
  7. Plasschaert, F; Craig, C; Bell, R; Cole, WG; Wunder, JS; Alman, BA. Eosinophilic granuloma: a different behaviour in children than in adults. JBJS Br 2002; 84-B: 870-2

Top Contributors:

Eric Christianson MD
Karen Bovid MD