Incidence, predictive factors, and prognosis of chondrosarcoma in patients with Ollier disease and Maffucci syndrome: an international multicenter study of 161 patients

Abstract

Background: Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases.

Method: A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society.

Results: Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p = 0.00l).

Conclusions: Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with enchondromas located in long bones or axial skeleton, especially the pelvis, have a seriously increased risk of developing chondrosarcoma, and are identified as the population that needs regular screening on early detection of malignant transformation.

Figure 1.

Age when disorder was first discovered and a diagnosis of Ollier disease or Maffucci syndrome was made (n = 116). Twenty-three percent of the patients were diagnosed between age 0 and age 5 years and 45% were diagnosed before the age of 10 years. At 20 years of age, 75% of all patients had been diagnosed. Mean age at diagnosis, 13.38 years; standard deviation, 12.579 years.

Figure 2.

Distribution of age at first surgery for chondrosarcoma over time. Only 50% of the patients had their first event before the age of 35 years. Mean age at first event, 33.0 years; standard deviation, 13.2 years.

Figure 3.

Kaplan–Meier overall survival curves for group I (blue), group II (green), and group III (black) demonstrating excellent prognosis when enchondromas are restricted to the small bones of the hands and feet (group I). However, as soon as enchondromas are located in the long and flat bones, with or without disease in the small bones as well (group II and group III, respectively), the overall survival time is shorter. The difference between the curves is borderline significant (log-rank trend test, p = .08). Note that there are only zero, four, and seven events in the three groups, respectively, which explains the rather low power of the test. Point estimates (95% confidence intervals) at time = 40 years were: group II, 88% (75%–100%); group III, 85% (70%–100%).

Figure 4.

Survival analysis using a competing risk model. This analysis only aims at describing relative proportions (the composition of the study population) for specific patient ages. It therefore only pretends to give a (an unbiased) graphical description for each possible number of years since birth of how many patients at that moment were actually already dead or alive with enchondroma (EC) or chondrosarcoma (CHS) or alive without detection of EC or CHS. More precisely, at each point in time (patient age), it shows the relative proportion of study patients already dead without EC or CHS (the blue pattern); the proportion already dead after detection of EC or CHS (the red or inclining pattern); the proportion at that age alive with EC or CHS (the yellow or declining pattern); and the proportion alive at that age without EC or CHS. Note that the separation between the two shaded areas (red and orange) is in fact the overall survival duration of this group of patients; the border between the silver and the orange area is the survival interval free from EC and CHS. Again, the interpretation is a description of the age at onset of EC or CHS death among these specific patients; it is useful as a description of the population and gives insight into the interplay of the competing risks (dying versus acquiring EC or CHS). It is not a predictive model per se because this is not a cohort followed from birth but a set of patients defined retrospectively on the basis of the occurrence of disease.