Ollier's Disease

Synonyms: Multiple endochondromatosis, dyschondroplasia, endochondromatosis

Enchondromas are common intraosseous, usually benign cartilaginous tumours, that develop in close proximity to growth plate cartilage. When multiple enchondromas are present, the condition is called enchondromatosis also known as Ollier's disease (WHO terminology).¹ When it is associated with haemangioma it is called Maffucci Disease. A major cause for concern is the risk of malignant change to osteosarcoma, chondrosarcoma or other bone tumours.

• Ollier disease (and Maffucci syndrome) are usually non-familial disorders. Both disorders thus appear to occur spontaneously and are not inherited.¹
• Although an identical heterozygous mutation in the PTHR1 gene has been identified other mutations in this gene were not identified in additional patients with this disorder. These studies suggest that the cause of Ollier disease is heterogenous and raise the possibility that two (or more) genetic mutations are required to develop the disease. The development of enchondromas could thus be caused by a germ line mutation associated with a somatic mosaic mutation.¹
• Additional mutational events may underly progression from enchondromas to tumors.¹

• Ollier's disease is very rare. The estimated prevalence of Ollier disease is 1/100,000.¹
• Maffucci disease is even rarer.
• Solitary endochondromas are most commonly discovered between 20 and 40 years of age but Ollier's disease tends to present before 10 years old.
• Boys are affected twice as often as girls.

There are 6 types of enchondromatosis but 3 are more common.

• In Ollier's disease there are multiple enchondromas that are mostly unilateral or unevenly distributed throughout the metaphases of the long bones, sparing the cranium and spine.
• In Maffucci's disease the enchondromas occur with multiple cutaneous haemangiomas that appear as soft tissue calcifications or phleboliths on x-ray.
• If there is symmetrical involvement throughout the body including the cranium, hands and feet, it is known as generalised enchondromatosis.

The lesions of Ollier's disease tend to be bilateral but to predominate on one side. Enchondromas usually occur in the short tubular bones of the hands and feet as well as long bones of upper and lower extremities. Palpable masses develop that may cause angular deformity and asymmetrical growth. The masses increase in size as the child grows along with asymmetrical shortening of a limb and either genu varus or genu valgus deformities. Varus deformity is very common.²

The differential diagnosis may include:

• Hereditary multiple endochondromatosis (HME) HME is an autosomal dominant disorder characterised by multiple bone tumors capped by cartilage, that occur mostly in the metaphyses of long bones.¹
• Other rare forms of chondromatosis (which include metachondromatosis, spondyloenchondroplasia and genochondromatosis type I and II)¹
• Polyostotic fibrous dysplasia
• Diaphyseal aclasis
• Kaposi sarcoma
• Klippel-Trenaunay-Weber Syndrome

• The basic investigation is x-ray. Most cases have diaphyseal or metaphyseal lesions which do not cross the growth plate until after it has closed. Sometimes enchondromatosis will affect the metaphyseal and epiphyseal regions. When enchondromas cross the growth plate they cause severe limb length deformities and angular deformities.
• CT or MRI may be required as may bone scans.They are indicated for the evaluation and surveillance of lesions that become symptomatic (pain, increase in size).¹
• Biopsy of suspicious lesions may be required.

Distortion of knees and unequal length of legs may require serial surgery.^2,3,4,5,6

As well as the problem of asymmetrical growth there can be pathological fracture and malignant change.

In Ollier's disease about 25% of patients will have had malignant change by the age of 40.⁷ In Maffucci's disease it is almost inevitable. A study from the Mayo Clinic reviewed 55 cases between 1907 and 1985.⁸ Such numbers from such a centre of excellence shows how rare is the condition. Of the 55 patients, 16 had malignant bone neoplasms of which 12 were chondrosarcomas, 2 dedifferentiated chondrosarcomas, 1 chordoma, and 1 osteosarcoma. One patient had a chondrosarcoma in two different bones. This suggests that approximately 30% of patients with Ollier's disease will develop a malignant bone neoplasm, most probably chondrosarcoma.

• The prognosis for Ollier disease is difficult to assess.
• As is generally the case, forms with an early onset appear more severe.¹
• The prognosis for most patients is good and 5 of the 16 patients survived more than 13 years after treatment.
• The reported incidence of malignant transformation is variable and estimated to occur in 5–50%.¹

Despite the universal acceptance that Ollier's disease carries a high risk of malignant change there is very little in the literature about systematic screening for early diagnosis. One paper stated, "We concluded that periodic surveillance of the brain and abdomen for occult malignant lesions is indicated in patients who have enchondromatosis"⁷ but failed to be more specific about the recommended frequency of screening. Another stated, "It is associated with an increased risk of malignancy including intracranial chondrosarcomas. Early diagnosis is crucial; screening patients with Ollier's disease is recommended."⁹ Again there is no guidance as to frequency or technique. It did state that the treatment of choice for intracranial cartilaginous tumours is complete surgical excision but this is often difficult to achieve due to difficult access and relationships with neurovascular structures. An alternative treatment is proton-beam therapy.

Louis Xavier Édouard Léopold Ollier was a French surgeon who was born in 1830 and died in 1900. He was an intern of Lyon Hospital in 1851, graduated in medicine with distinction in 1856, and in 1857 obtained his doctorate at Paris with a dissertation based on histological studies of 400 malignant neoplasms. His most notable work was in bone and joint surgery. In 1877 a new medical faculty was established in Lyon and he was appointed professor of clinical surgery.

Angelo Maffucci was an Italian pathologist who was born in 1847 and died in 1903. He graduated in Naples in 1872. In 1882 he became head of general pathology at Messina University and the following year he received the chair of anatomical pathology at Catania. In 1884 he was appointed to the chair of pathological anatomy in Pisa, where he died in 1903. He made considerable contributions that were poorly recognised outside Italy.