Ollier Disease

Key Points:

  • Ollier disease is an asymmetric, multiple enchondromatosis usually confined to the appendicular skeleton
  • The most frequent anatomical locations for enchondromas are the phalanges and metacarpals 
  • The lesions of Ollier disease are classically lytic with well-defined, sclerotic margins and matrix containing punctate calcification visible on plain radiographs
  • Treatment is typically conservative unless lesions are symptomatic
  • Most common surgical treatments include curettage and bone grafting, internal fixation, or treatment for angular deformity or limb length discrepancy
  • Advanced imaging such as bone scintigraphy can help screen for malignant transformation of lesions
  • The risk for malignant transformation of a lesion ranges from 5-50%

Description:

  Ollier Disease, also commonly known as enchondromatosis, is classically defined by multiple enchondromas that present in an asymmetric distribution. The condition was described by Louis Xavier Édouard Léopold Ollier in 1889 who reported limb deformity related to abnormal growth of cartilage (Herring, 2014). Ollier Disease is also known as Spranger type I, based on the classification of multiple enchondromatosis (Kumar, 2015). Enchondromas are benign, slow-growing hyaline cartilage tumors that arise from the medullary canal (Lubahn, 2016).

Epidemiology:

Ollier Disease is found in approximately 1 in 100,000 people. It is twice as common in males as it is in females (Silve, 2006).

Clinical Findings:

  Clinical presentation of Ollier Disease is variable. The lesions can present in many different sizes, locations, and frequency.  The age of onset is also variable, although early onset is the classic presentation. Several key features of the disease include early childhood onset, radiologic changes in the ends of long bones, and the identification of cartilage in anatomic specimens from radiolucent enchondromas (Hunter, 1935). The enchondromas typically present as painless, firm masses of both short and long bones (e.g. phalanges and femur/tibia respectively). The lesions are usually found in the appendicular skeleton and are asymmetric in their distribution, although they can be found bilaterally. Classically, the lesions are not found in the vertebral column or craniofacial region; however, axial skeletal involvement does occur, most frequently in the pelvis, and can lead to scoliosis (Kumar, 2015). Patients can also present with bone shortening when the physis adjacent to an enchondroma is abnormal or the epiphyseal cartilage is tethered by a thick periosteal sleeve that forms in reaction to a nearby enchondromatous lesion (Shapiro, 1982).  The key distinguishing factor between Ollier disease and multiple hereditary exostosis (MHE) is the location of the lesions. In Ollier disease the enchondromas typically originate from the intramedullary canal but in MHE, osteochondromas are found at the cortices (Kumar, 2015).  
  Gross pathology demonstrates multiple areas of cartilage in the metaphysis and diaphysis.  Longitudinal columns of cartilage with intervening areas of bone extend distally from the physis through the metaphysis (Herring, 2014).  Histology is typically similar to solitary enchondromas consisting of cartilage cells lacking significant atypia.  However, increased cellularity is frequently found in Ollier Disease and may be difficult to differentiate from low grade sarcoma (Herring, 2014).  Papanicolaou stained smears show many fragments of cartilage with angular edges and scattered single, round cells (Kumar, 2015).  A more aggressive histology with increased cellularity will likely be interpreted as benign if it is found in the phalanges, versus malignant when obtained from the pelvis or large long bones because of the inherent increased risk of malignant transformation of lesions in these areas (Herring, 2014).

Imaging Studies:

  The diagnostic imaging standard is plain radiographs. These typically demonstrate osteolytic lesions that connect to the medullary canal with sclerotic margins with well-defined borders; endosteal erosion; and matrix that looks like ground glass. The lesions also usually contain small areas of stippled calcification, typical of cartilaginous matrix (Lubahn, 2016).  Columns of cartilage cells separated by ossification produce a classic fan-like appearance in the metaphysis of affected long bones (Herring, 2014).  CT is helpful in defining intralesional details, particularly in the pelvis. It also better evaluates the soft tissue component, if any, associated with the lesions (Khoo, 2008).  MRI may help characterize the lesion and further guide treatment, particularly when there is associated pathologic fracture. MRI with contrast will classically demonstrate central ring and arc enhancement with septal and peripheral rims of enhancement (Murphey 1998). Bone scintigraphy and PET/CT can be helpful to detect and screen for malignant transformation as chondrosarcomas typically reveal intense uptake on bone scan while enchondromas demonstrate only a mild to moderate uptake increase (Le, 2014; Kumar, 2015).

Etiology:

  The pathogenesis of Ollier Disease is not entirely understood, but it is believed to be related to an abnormality of limb bud development. One widely accepted theory states that the lesions are out of place groups of normal physeal cartilage cells (Jaffe 1943). There are several genetic mutations that are thought to contribute to Ollier Disease development, but it is classified as a non-hereditary disorder (Lubahn, 2016). Known genetic correlations include isocitrate dehydrogenase 1 or 2, but a genome-wide analysis predicted that small deletions, point mutations, and epigenetic mechanisms are primary factors in the genetic origin of the enchondromas in Ollier disease rather than large, inheritable genetic defects (Amary, 2011; Pansuriya, 2011).

Treatment:

  The mainstay of treatment remains supportive, unless complications of pain, limb length inequality, angular deformity, or malignant transformation arise (Lubahn, 2016). The goals of treatment are proper limb alignment, avoiding limb length discrepancy, and relieving pain.  Surgical treatment may include intralesional curettage with bone grafting or other artificial bone substitute, and possibly internal fixation. Epiphysiodesis, lengthening, or osteotomies may be used to treat limb length discrepancy and angular deformity. Ilizarov technique can be used to provide mechanical stability as distraction osteogenesis encourages transformation of abnormal cartilage into lamellar bone (Kumar, 2015). Nonoperative treatments such as ultrasound, cryotherapy, CO2 laser, stretching, active mobilization and coordination exercises have also been found to help improve patients’ functional ability (Kumar, 2015).  More definitive treatments include amputation or excision of lesions with subsequent reconstructive surgeries (Kumar, 2015; Lubahn, 2016). 

  Annual surveillance of patients is recommended, including intermittent imaging screening of the brain and abdomen for occult malignancies. Factors that indicate a worse prognosis in Ollier disease include early age of onset, gross asymmetrical distribution, repeated surgeries, and presence of malignant transformation (Kumar, 2015). Most enchondromas have a higher recurrence rate after surgery so close follow-up is needed for surgically treated patients (Sassoon, 2012).

Complications:

  Ollier Disease can cause limb deformities via asymmetric premature physeal arrest, nonuniform distribution of lesions, and pathologic fractures as the cortex thins over expanding lesions. The risk for malignant transformation of Ollier lesions ranges from 5-50% (Verdegaal, 2011). The most common malignancy is chondrosarcoma and is found in 25% of patients with Ollier Disease by age 40 years. The risk of malignant transformation is proportional to the amount of total abnormal tissue, taking into account both the size and number of individual lesions. Thus, when found in areas that accommodate larger lesions, such as in the pelvis and long bones, enchondromas have a higher risk for developing into chondrosarcomas (Kumar, 2015; Verdegaal, 2011). When lesions do malignantly transform, they are commonly found in the pelvis, shoulder, distal femur, and proximal tibia. Rarely do enchondromas of the hand transform into chondrosarcomas. The most common symptoms and signs of malignant transformation are pain, increasing size, and cortical thinning. Once a lesion transforms into a chondrosarcoma, it typically invades locally, recurs locally, and can metastasize distantly, most commonly to the lungs (Kumar, 2015).

References:

  1. Amary et al. Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nat Genet. 2011; 6:43(12): 1262-5. 
  2. Herring J. Benign Musculoskeletal tumors. In: Herring J. Tachdijan’s Pediatric Orthopaedics. 5th ed. Philadelphia, PA: Elsevier; 2014: 1107-1109.
  3. Hunter D, Wiles P. (Dyschondroplasias (Ollier’s disease): with report of a case. Br J Surg. 1935; 22: 507-519.
  4. Jaffe HL, Lichtenstein I. Solitary benign enchondroma of bone. Arch Surg. 1943; 46: 480-493.
  5. Khoo RN, Peh WC, Guglielmi G. Clinics in diagnostic imaging (124): multiple enchondromatosis in Ollier disease. Singapore Med J. 2008; 49(10) :841-845
  6. Kumar A, Jain VK, Bharadwaj M, Arya KR. Ollier Disease: Pathogenesis, Diagnosis, and Management. Orthopedics. 2015; 38(6): e497-506. 
  7. Le BB, Nguyen BD. Ollier Disease With Digital Enchondromatosis: Anatomic and Functional Imaging. Clinic Nucl Med. 2014; 39(8): e375-8.
  8. Lubahn JD, Bachoura A. Enchondroma of the Hand: Evaluation and Management. J Am Acad Orthop Surg. 2016; 24(9): 625-33.
  9. Murphey MD, et al. Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features. Radiographics. 1998: 18: 1213-1237.
  10. Pansuriya TC et al. Genome-wide analysis of Ollier disease: Is it all in the genes? Orphanet J Rare Dis. 2011; 14(6): 2.
  11. Sassoon AA, Fitz-Gibbons PD, Harmsen WS, Moran SI. Enchondromas of the hand: factors affecting recurrence, healing, motion, and malignant transformation. J Hand Surg Am. 2012; 37(6): 1229-1234. 
  12. Shapiro F. Ollier’s disease: an assessment of angular deformity, shortening, and pathological fracture in twenty-one patients. J Bone Joint Surg Am. 1982; 64: 95-103.
  13. Silve C, Juppner H. Ollier disease. Orphanet J Rare Dis. 2006; 1: 37.
  14. Verdegaal S, et al. Incidence, Predictive Factors, and Prognosis of Chondrosarcoma in Patients with Ollier Disease and Maffuci Syndrome: An International Multicenter Study of 161 patients. The Oncologist. 2011; 16: 1771-1779.

Top Contributors:

David Knowles MD
Karen Bovid MD