Enchondromatosis is a non-hereditary disease, characterised by the presence of multiple enchondromas. While Ollier Disease is typified by multiple enchondromas, in Maffucci Syndrome they are combined with haemangioma.

Due to the rarity of these diseases, systematic studies on clinical behaviour providing information how to treat patients are lacking.

This study intends to answer the following questions: What are predictive factors for developing chondrosarcoma? When is extensive surgery necessary? How often patients die due to dedifferentiation or metastasis?

Twelve institutes in eight countries participated in this descriptive retrospective EMSOS-study. 118 Patients with Ollier Disease and 15 patients with Maffucci Syndrome were included. Unilateral localization of disease was found in 60% of Ollier patients and 40% of patients with Maffucci Syndrome.

One of the predictive factors for developing chondrosarcoma is the location of the enchondromas; the risk increases especially when enchondromas are located in the scapula (33%), humerus (18%), pelvis (26%) or femur (15%). For the phalanges, this risk is 14% in the hand and 16% in the feet. The decision whether or not to perform extensive surgery is difficult, especially in patients who suffer multiple chondrosarcomas.

Malignant transformation was found in fourty-four patients with Ollier Disease (37%) and eight patients with Maffucci Syndrome (53%). Multiple synchronous or metachronous chondrosarcomas were found in 15 patients.

Nine patients died (range 21–54 yrs). Seven of them died disease related due to pulmonary metastasis (2 humerus, 2 pelvis, 3 femur). Two patients died from glioma of the brain.

In conclusion, one important predictive factor for developing chondrosarcoma is the location of the enchondromas; interestingly, only patients with chondrosarcoma outside the small bones died of their disease. In this series, no dedifferentiation of chondrosarcoma was seen. A first design flow-chart how to approach chondrosarcoma in patients with Ollier Disease and Maffucci Syndrome is in preparation.

Ollier disease is a rare skeletal disorder. It is characterized by the occurrence of multiple enchondromas with a marked unilateral predominance mainly affecting medulla of the metaphyses and diaphyses of the short and long tubular bones of the limbs, especially the hands and feet. The risk of malignant transformation is suggested to be up to 35%. We hypothesise that Ollier disease is a mosaic condition as it is polyostotic and because of its unilateral predominance. Here we aimed to identify molecular defects in Ollier disease related enchondromas and chondrosarcomas using high resolution single nucleotide polymorphism (SNP) array approach. Affymetrix SNP 6.0 was performed on 67 samples which include 10 blood samples and 3 matched blood-saliva samples as a control; 13 enchondromas and 26 chondrosarcomas of different grades from 30 Ollier patients and normal DNA from 12 Ollier patients for paired comparison.

All samples were divided into three groups: normals, enchondromas and chondrosarcomas. The number of numerical genomic changes in the chromosomes were not different for the enchondromas (p=0.36) while large genomic aberrations were seen in chondrosarcomas as compared to normals (p=0.01). Copy number variation (CNV) analysis showed 95K amplification at 4q13 in 5 out of 13 enchondromas and a 2K deletion at 14q11 in 6 out of 13 enchondromas. Paired loss of heterozygosity (LOH) analysis failed to show LOH in 5 enchondromas at higher resolution. Paired LOH was observed at 3q, 5p, 6p, 6q, 7q, 9p, 12p, 13p and 13q in 7 high grade chondrosarcomas associated with loss of chromosomes.

The results of this study indicate involvement of chromosomes 4 and 14 for the development of enchondromas. We were unable to detect LOH in enchondromas at 1Mb resolution containing approximately 500 SNP probes. High grade chondrosarcomas showed LOH at different chromosomes. In future, we will study LOH and CNV changes at gene level and select candidate genes.