Incidence, Predictive Factors, and Prognosis of Chondrosarcoma in Patients with Ollier Disease and Maffucci Syndrome: An International Multicenter Study of 161 Patients

Verdegaal, S.H.M.; Bovée, Judith V.M.G.; Pansuriya, Twinkal C.; Grimer, R. J.; Özger, Harzem; Jutte, Paul C.; Julián, Mikel San; Biau, David; Geest, I.C.M. van der; Leithner, Andreas; Streitbürger, Arne; Klenke, Frank M.; Gouin, F.; Campanacci, Domenico Andrea; Marec‐Bérard, Perrine; Hogendoorn, Pancras C.W.; Brand, Ronald; Taminiau, A. H. M.

doi:10.1634/theoncologist.2011-0200

Cited by 181 publications

(145 citation statements)

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“…Malignant transformation in enchondromatosis is estimated to occur in 25-30% of the patients [2,20], in a recent study up to 40% [15]. In our reported literature it was between 20% and 45.8% in pre-existing enchondromatosis, and ranged between 52% and 57.1% in patients with a Maffucci syndrome (Table 1).…”

mentioning

confidence: 74%

“…Of all patients diagnosed with Ollier disease, malignant transformation is believed to occur in 10-20% [14] and a recent study recorded the development of one or more chondrosarcomas in 40% of patients with Ollier diseases and Maffucci syndrome, respectively [15].…”

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confidence: 99%

“…Recently, mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) and IDH2 were detected in solitary cartilaginous tumors as well is in patients with multiple enchondromas [15,37]. These mutations might represent early postzygotic genetic events and account for the initiation of the disease process [15,37].…”

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confidence: 99%

“…These mutations might represent early postzygotic genetic events and account for the initiation of the disease process [15,37]. Furthermore, rearrangements of chromosome 6 and the long arm of chromosome 12 (particularly q13q15) seem to be recurrent in chondromas, also including soft tissue chondromas [38].…”

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confidence: 99%

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Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up

Herget¹,

Strohm²,

Rottenburger³

et al. 2014

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confidence: 74%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up

Herget¹,

Strohm²,

Rottenburger³

et al. 2014

neo

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“…Clinical problems caused by enchondromas include pain, fractures, and skeletal deformity. There is a potential for malignant progression to chondrosarcoma that may be greater than 50% in some cases of multiple enchondromatosis (i.e., Maffucci syndrome) (3)(4)(5)(6)(7). Many chondrosarcomas are thought to derive from enchondromas, and such sarcomas are termed central chondrosarcomas (3).…”

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confidence: 99%

Mutant IDH is sufficient to initiate enchondromatosis in mice

Hirata

Sato

Cairns

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

112

118

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Enchondromas are benign cartilage tumors and precursors to malignant chondrosarcomas. Somatic mutations in the isocitrate dehydrogenase genes (IDH1 and IDH2) are present in the majority of these tumor types. How these mutations cause enchondromas is unclear. Here, we identified the spectrum of IDH mutations in human enchondromas and chondrosarcomas and studied their effects in mice. A broad range of mutations was identified, including the previously unreported IDH1-R132Q mutation. These mutations harbored enzymatic activity to catalyze α-ketoglutarate to D-2-hydroxyglutarate (D-2HG). Mice expressing Idh1-R132Q in one allele in cells expressing type 2 collagen showed a disordered growth plate, with persistence of type X-expressing chondrocytes. Chondrocyte cell cultures from these animals or controls showed that there was an increase in proliferation and expression of genes characteristic of hypertrophic chondrocytes with expression of Idh1-R132Q or 2HG treatment. Col2a1-Cre;Idh1-R132Q mutant knock-in mice (mutant allele expressed in chondrocytes) did not survive after the neonatal stage. Col2a1-Cre/ERT2;Idh1-R132 mutant conditional knock-in mice, in which Cre was induced by tamoxifen after weaning, developed multiple enchondroma-like lesions. Taken together, these data show that mutant IDH or D-2HG causes persistence of chondrocytes, giving rise to rests of growth-plate cells that persist in the bone as enchondromas.isocitrate dehydrogenase | cartilage tumor | hedgehog E nchondromas, one of the most common benign tumors occurring in bone, are present in more than 3% of the population (1, 2). They are composed of cells derived from chondrocytes and occur as solitary lesions or multiple lesions in enchondromatosis syndromes (Ollier disease or Maffucci syndrome-in the latter, enchondromas are associated with vascular malformations). Clinical problems caused by enchondromas include pain, fractures, and skeletal deformity. There is a potential for malignant progression to chondrosarcoma that may be greater than 50% in some cases of multiple enchondromatosis (i.e., Maffucci syndrome) (3-7). Many chondrosarcomas are thought to derive from enchondromas, and such sarcomas are termed central chondrosarcomas (3).The hedgehog (Hh) signaling pathway is constitutively active in enchondromas and chondrosarcomas (8,9). Hh is important in growth-plate chondrocyte differentiation, where it cooperates with parathyroid hormone-like hormone in a negative feedback loop to inhibit the differentiation of proliferative growth-plate chondrocytes (6,(10)(11)(12)(13)(14). Disruption of this feedback loop can result in either skeletal dysplasias with abnormal bone growth or enchondromas; 5% of enchondromas harbor mutation in parathyroid hormone-like hormone receptor (PTHR1), resulting in activation of Hh signaling (6,(10)(11)(12)(13)(14), and expression of a mutant PTHR1 or overexpression of the Hh-regulated transcription factor Gli2 under the Col2a1 promoter causes enchondroma-like cartilage lesions to develop adjacent to the growth-plate ...

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Natural history of Ollier disease and Maffucci syndrome: Patient survey and review of clinical literature

Abiad

Robbins

Cohen

et al. 2020

American J of Med Genetics Pt A

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Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant in 8.5% of cases. OD is characterized by multiple enchondromas, typically unilateral in distribution with a predilection for the appendicular skeleton. MS is characterized by multiple enchondromas bilaterally distributed in most of the cases. Both disorders feature multiple swellings on the extremity, deformity around the joints, limitations in joint mobility, scoliosis, bone shortening, leg-length discrepancy, gait disturbances, pain, loss of function, and pathological fractures. About 50% of patients with OD or MS develop a malignancy, such as chondrosarcoma, glioma, and ovarian juvenile granulosa cell tumor. To better understand the natural history of OD and MS, we reviewed 287 papers describing patients with OD and MS. We also created a survey that was distributed directly to 162 patients through Facebook. Here, we compare the review of the cases described in the literature to the survey's responses.The review of the literature showed that: the patients with OD are diagnosed at a younger age; the prevalence of chondrosarcomas among patients with OD or MS was~30%; in four patients, vascular anomalies were identified in internal organs only; and, the prevalence of cancer among patients with OD or MS was~50%. With these data, health care providers will better understand the natural history, severity, and prognosis of these diseases and the prevalence of malignancies in these patients.Here, we recommend new guidelines for the care of patients with OD and MS.

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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.

Cited by 181 publications

References 32 publications

Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up

Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up

Mutant IDH is sufficient to initiate enchondromatosis in mice

Natural history of Ollier disease and Maffucci syndrome: Patient survey and review of clinical literature

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