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World Journal of Surgical Oncology Jun 2022Maffucci syndrome (MS) is a rare, nonhereditary congenital mesodermal dysplasia characterized by multiple enchondromas and hemangiomas, associated with an increased risk...
BACKGROUND
Maffucci syndrome (MS) is a rare, nonhereditary congenital mesodermal dysplasia characterized by multiple enchondromas and hemangiomas, associated with an increased risk of developing malignant tumors. Given their rarity, the pathogenesis of these tumors has not been clarified, and there is no standard treatment.
CASE PRESENTATION
We present a case of a 45-year-old man with MS to supplement the clinical manifestations and explore the molecular mechanism of MS. The patient underwent amputation surgery to inhibit tumor development and was diagnosed with MS with 1-2 grade giant chondrosarcoma in the left ankle. In addition, the whole exon analysis results revealed isocitrate dehydrogenase 1 (IDH1) R132C mutation in chondrosarcoma lesions but not in blood DNA.
CONCLUSIONS
This case report showed MS complicated by giant chondrosarcoma in the left ankle with an IDH1 R132C mutation, which is appropriate to monitor the development of MS pathology and other concomitant lesions.
Topics: Ankle; Bone Neoplasms; Chondrosarcoma; Enchondromatosis; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation
PubMed: 35765075
DOI: 10.1186/s12957-022-02686-z -
Human Molecular Genetics Sep 2008PTHR1-signaling pathway is critical for the regulation of endochondral ossification. Thus, abnormalities in genes belonging to this pathway could potentially participate...
PTHR1-signaling pathway is critical for the regulation of endochondral ossification. Thus, abnormalities in genes belonging to this pathway could potentially participate in the pathogenesis of Ollier disease/Maffucci syndrome, two developmental disorders defined by the presence of multiple enchondromas. In agreement, a functionally deleterious mutation in PTHR1 (p.R150C) was identified in enchondromas from two of six unrelated patients with enchondromatosis. However, neither the p.R150C mutation (26 tumors) nor any other mutation in the PTHR1 gene (11 patients) could be identified in another study. To further define the role of PTHR1-signaling pathway in Ollier disease and Maffucci syndrome, we analyzed the coding sequences of four genes (PTHR1, IHH, PTHrP and GNAS1) in leucocyte and/or tumor DNA from 61 and 23 patients affected with Ollier disease or Maffucci syndrome, respectively. We identified three previously undescribed missense mutations in PTHR1 in patients with Ollier disease at the heterozygous state. Two mutations (p.G121E, p.A122T) were present only in enchondromas, and one (p.R255H) in both enchondroma and leukocyte DNA. Assessment of receptor function demonstrated that these three mutations impair PTHR1 function by reducing either the affinity of the receptor for PTH or the receptor expression at the cell surface. These mutations were not found in DNA from 222 controls. Including our data, PTHR1 functionally deleterious mutations have now been identified in five out 31 enchondromas from Ollier patients. These findings provide further support for the idea that heterozygous mutations in PTHR1 that impair receptor function participate in the pathogenesis of Ollier disease in some patients.
Topics: Adolescent; Adult; Animals; CHO Cells; COS Cells; Child; Chlorocebus aethiops; Chondroma; Cohort Studies; Cricetinae; Cricetulus; Cyclic AMP; Enchondromatosis; Female; Humans; Male; Middle Aged; Molecular Sequence Data; Mutation, Missense; Parathyroid Hormone; Protein Binding; Protein Structure, Tertiary; Receptor, Parathyroid Hormone, Type 1; Signal Transduction
PubMed: 18559376
DOI: 10.1093/hmg/ddn176 -
BMC Musculoskeletal Disorders Apr 2017Enchondroma, a subtype of chondroma, originates from the medullary cavity of the bone and produces an expansile growth pattern. Enchondroma located in the spine is rare... (Review)
Review
BACKGROUND
Enchondroma, a subtype of chondroma, originates from the medullary cavity of the bone and produces an expansile growth pattern. Enchondroma located in the spine is rare and a few cases of large thoracic enchondroma have been reported. The authors document a rare case of large enchondroma in the thoracic spine of a 49-year-old woman, and discuss its clinical, radiological and histopathological characteristics.
CASE PRESENTATION
The patient presented with rapidly progressive and severe pain on her upper back. Magnetic resonance imaging revealed an expansile lesion at the posterior elements of T3 that was hypointense on T1-weighted images and mixed iso- to hyperintense on T2-weighted images. Administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) resulted in heterogeneous enhancement. During surgery, a large tumor of 4.2cm × 4.7cm × 2.1cm was resected along with the lamina and spinous process. Histological examination revealed that the tumor consisted of mature hyaline cartilage with typical chondrocytes, indicating that it was an enchondroma.
CONCLUSIONS
Despite its benign-growing nature, enchondroma should be examined closely for signs of enchondromatosis and enchondrosarcoma. Complete surgical resection is the treatment of choice for immediate relief of symptoms and avoidance of recurrence.
Topics: Back Pain; Chondroma; Contrast Media; Female; Gadolinium DTPA; Humans; Hyaline Cartilage; Magnetic Resonance Imaging; Middle Aged; Neoplasm Recurrence, Local; Orthopedic Procedures; Osteolysis; Radiography, Thoracic; Spinal Neoplasms; Thoracic Vertebrae; Tomography, X-Ray Computed
PubMed: 28407736
DOI: 10.1186/s12891-017-1519-z -
Cureus Aug 2023Ollier disease is a rare skeletal dysplasia characterized by the formation of multiple enchondromas (enchondromatosis), typically in the long bones of the extremities....
Ollier disease is a rare skeletal dysplasia characterized by the formation of multiple enchondromas (enchondromatosis), typically in the long bones of the extremities. These tumors are benign but can become complicated by the development of pathologic fractures, limb deformity, and malignant transformation to chondrosarcoma. Ollier disease has a highly variable presentation and is associated with a range of presenting findings; however, the most common presentation is a pathologic fracture. Surgical options include curettage and grafting of the enchondromas and, when displaced, fracture reduction and fixation. Of note, these fractures will heal without surgery. Regardless, all patients must be routinely monitored with yearly radiographs in order to detect malignant transformation as early as possible. In this report, we describe the case of an 11-year-old female who presented to her physician with pain and swelling of her right ring and small fingers after playing in a swimming pool with no obvious mechanism of trauma. A routine, plain radiographic evaluation of her hand revealed the presence of multiple enchondromatosis. We hope to use this case to highlight the surgical management options for young patients with Ollier disease and discuss circumstances in which surgical management may not be indicated.
PubMed: 37731444
DOI: 10.7759/cureus.43815 -
Indian Journal of Dermatology,... 2015
Topics: Child; Diagnosis, Differential; Enchondromatosis; Female; Finger Phalanges; Forearm; Hand; Humans; Metacarpal Bones; Radiography
PubMed: 25994886
DOI: 10.4103/0378-6323.157451 -
PLoS Genetics Apr 2011Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from...
Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a "second hit," that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome.
Topics: Chromosomes, Human; DNA Copy Number Variations; Enchondromatosis; Exons; Exostoses, Multiple Hereditary; Gene Deletion; Genetic Linkage; High-Throughput Nucleotide Sequencing; Humans; Loss of Heterozygosity; Mutation; Pedigree; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Sequence Analysis, DNA
PubMed: 21533187
DOI: 10.1371/journal.pgen.1002050 -
Revue de Chirurgie Orthopedique Et... Dec 1999Several studies have demonstrated better prognosis of chondrosarcomas arising in hereditary multiple exostosis or Ollier's disease. The aim of this study was to evaluate... (Review)
Review
PURPOSE OF THE STUDY
Several studies have demonstrated better prognosis of chondrosarcomas arising in hereditary multiple exostosis or Ollier's disease. The aim of this study was to evaluate their clinical, radiological and histological features and compare their prognosis with other chondrosarcomas.
MATERIAL AND METHODS
We reviewed twenty nine secondary chondrosarcomas among seventeen patients with osteochondroma (group A), and eight with Ollier's disease (group B). These tumors represented 12 p. 100 of all chondrosarcomas treated between 1950 and 1994 in Cochin Hospital. Two group B patients successively developed three multicentric chondrosarcomas. Twenty six resections (eight intra and eighteen extra-lesional), two disarticulations and one amputation were performed as primary treatment. The average follow-up of the study was 10.5 years. The results were evaluated by means of survival curves. The significance of the difference between the curves was determined by the log-rank test.
RESULTS
The mean age of malignant change was 36 years old. The most frequent tumoral site was the innominate bone for group A and the femur for group B. In three cases, radiographs showed no malignant features. All chondrosarcomas were classified as grade 1 or 2. The ten-year survival rate was 82 p. 100 with no significant difference between the two groups. The survival rates were significantly different after carcinologic surgery (extra-lesional resection or amputation) and contaminated surgery (intralesional resection), with 5 and 88 p. 100 of local recurrences respectively.
DISCUSSION AND CONCLUSION
These secondary chondrosarcomas represent about 10 p. 100 of all chondrosarcomas. They appear 15 years earlier. According to O'Neal and Ackerman classification, most of the tumors are well-differentiated (60 p. 100 grade I, 39 p. 100 grade II and 1 p. 100 grade III). Carcinologic surgery is generally curative. Ten-year survival rate is 94 p. 100. With equivalent grade and surgery, their prognosis is better as compared to primary chondrosarcomas.
Topics: Adult; Bone Neoplasms; Chondrosarcoma; Enchondromatosis; Female; Humans; Male; Middle Aged; Prognosis
PubMed: 10637885
DOI: No ID Found -
Radiology Case Reports Oct 2023Ollier disease is an uncommon disease characterized by several enchondromas and an asymmetric distribution of cartilage lesions, which can vary significantly in size,...
Ollier disease is an uncommon disease characterized by several enchondromas and an asymmetric distribution of cartilage lesions, which can vary significantly in size, location, age, and gender. The primary symptom of this condition is a nonossifying chondrocyte mass or hamartomatous chondrocyte growth in the metaphysis of a short or long bone. Specific cases can progress to chondrosarcoma or osteosarcoma. X-ray is the most fundamental diagnostic technique for skeletal illnesses. In this article, we present a case of Ollier disease from Mother and Child Hospital IBN SINA, Rabat, Morocco.
PubMed: 37593331
DOI: 10.1016/j.radcr.2023.07.042 -
Orphanet Journal of Rare Diseases Jan 2011Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within...
BACKGROUND
Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown.
METHODS
We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis using Affymetrix SNP 6.0 array on 37 tumours of 28 Ollier patients in combination with expression array using Illumina BeadArray v3.0 for 7 ECs of 6 patients.
RESULTS
Non-recurrent EC specific copy number alterations were found at FAM86D, PRKG1 and ANKS1B. LOH with copy number loss of chromosome 6 was found in two ECs from two unrelated Ollier patients. One of these patients also had LOH at chromosome 3. However, no common genomic alterations were found for all ECs. Using an integration approach of SNP and expression array we identified loss as well as down regulation of POU5F1 and gain as well as up regulation of NIPBL. None of these candidate regions were affected in more than two Ollier patients suggesting these changes to be random secondary events in EC development. An increased number of genetic alterations and LOH were found in Ollier CS which mainly involves chromosomes 9p, 6q, 5q and 3p.
CONCLUSIONS
We present the first genome-wide analysis of the largest international series of Ollier ECs and CS reported so far and demonstrate that copy number alterations and LOH are rare and non-recurrent in Ollier ECs while secondary CS are genetically unstable. One could predict that instead small deletions, point mutations or epigenetic mechanisms play a role in the origin of ECs of Ollier disease.
Topics: Chondrosarcoma; Enchondromatosis; Genome-Wide Association Study; Humans; Immunohistochemistry; Loss of Heterozygosity; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 21235737
DOI: 10.1186/1750-1172-6-2 -
Actas Dermo-sifiliograficas Nov 2017
Topics: Adult; Enchondromatosis; Hand; Humans; Male; Musculoskeletal Abnormalities
PubMed: 27939020
DOI: 10.1016/j.ad.2016.05.021