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Cancers Jul 2022Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is... (Review)
Review
Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is the only curative treatment for primary disease and its complications. Patients with OD are at risk of malignant transformation of enchondromas and of occurrence of other neoplasms. A wide literature review disclosed thirty cases of glioma associated with OD, most of them belonging to the pre-molecular era. Our own case was also included. Demographic, clinical, pathologic, molecular, management, and outcome data were analyzed and compared to those of sporadic gliomas. Gliomas associated with OD more frequently occur at younger age, present higher rates of multicentric lesions (49%), brainstem localizations (29%), and significantly lower rates of glioblastomas (7%) histotype. The IDH1 R132H mutation was detected in 80% of gliomas of OD patients and simultaneously in enchondromas and gliomas in 100% of cases. The molecular data suggest a higher risk of occurrence of glioma in patients with enchondromas harboring the IDH1 R132H mutation than those with the IDH1 R132C mutation. Thus, we suggest considering the IDH1 R132H mutation in enchondromas of patients with OD as a predictive risk factor of occurrence of glioma.
PubMed: 35884525
DOI: 10.3390/cancers14143464 -
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 -
Anatolian Journal of Cardiology Apr 2022
Topics: Cardiology; Cardiovascular System; Hospitals; Humans; India; Italy
PubMed: 35435846
DOI: 10.5152/AnatolJCardiol.2021.960 -
Journal of Orthopaedic Case Reports Nov 2021Enchondromas are benign lesion of cartilaginous origin seen in early childhood. Multiple enchondromatosis is also known as Ollier's disease which involves the...
INTRODUCTION
Enchondromas are benign lesion of cartilaginous origin seen in early childhood. Multiple enchondromatosis is also known as Ollier's disease which involves the appendicular skeleton with multiple site involvement. We present a rare case of appendicular as well as axial skeleton involvement in a case of Ollier's disease.
CASE REPORT
A 13-year-old male with multiple enchondromas including all the appendicular skeleton along with ribs and cervical spine. Patient was evaluated with X-rays and non-contrast computerized tomography and is on conservative treatment and on regular monthly follow-up with no neurological deficit and no respiratory complications till now. Further evaluation for deformity correction if required, will be considered after skeletal maturity.
CONCLUSION
Ollier's disease is a rare presentation with multiple enchondromas in the appendicular skeleton. Current case is further rare presentation of the Ollier's disease with involvement of cervical spine and ribs as well.
PubMed: 35415112
DOI: 10.13107/jocr.2021.v11.i11.2504 -
The Journal of Hand Surgery May 2023The approach to the treatment of enchondromas of the hand is varied, and there is no clear consensus on graft source, fixation, or need for intraoperative adjuvant... (Review)
Review
PURPOSE
The approach to the treatment of enchondromas of the hand is varied, and there is no clear consensus on graft source, fixation, or need for intraoperative adjuvant therapy. We reviewed a cohort of patients who underwent curettage and bone grafting with cancellous allograft chips without internal fixation or adjuvant therapy and reported on postoperative range of motion (ROM) and recurrence rates.
METHODS
We performed a retrospective review of patients who underwent surgical treatment for hand enchondroma over a 23-year period. We collected information on demographics and presenting enchondroma characteristics, including Takigawa classification and presence of pathologic fracture or associated syndromes. Patients were treated with open biopsy with curettage and grafting with cancellous allograft chips. Postoperative ROM, complications, and recurrences were recorded.
RESULTS
Our series included 111 enchondromas in 104 patients. Seventeen of 104 patients (16%) had a diagnosis of Ollier disease. Average length of follow-up was 3.1 years. Eighty-one percent of patients achieved full ROM. Treatment of patients who presented with preoperative pathologic fracture resulted in a greater frequency of reduced postoperative ROM at 28% (9/32) compared to 15% (11/72) of those patients who did not present with preoperative pathologic fracture. Local recurrence developed in 5 of 50 (10%) patients with a minimum of 2 years of follow-up. Local recurrence occurred at higher-than-average rates in patients with giant form Takigawa classification (43%, 3/7) and Ollier disease (23%, 3/13).
CONCLUSIONS
Treatment of enchondromas with biopsy, curettage, and allograft results in full ROM in 81% of patients. Patients with preoperative pathologic fracture should be advised of a greater risk of postoperative extension deficit. Recurrence remains rare and is associated with syndromic presentation and giant form lesions.
TYPE OF STUDY/LEVEL OF EVIDENCE
Therapeutic IV.
Topics: Humans; Fractures, Spontaneous; Bone Neoplasms; Enchondromatosis; Curettage; Chondroma; Postoperative Complications; Range of Motion, Articular; Retrospective Studies; Treatment Outcome
PubMed: 35115192
DOI: 10.1016/j.jhsa.2021.11.027 -
Hereditas Jan 2022Maffucci syndrome (MS, OMIM 166000) is an extremely unusual, nonhereditary, multisystemic disorder that is characterized with multiple enchondromas and vascular lesions,...
Maffucci syndrome (MS, OMIM 166000) is an extremely unusual, nonhereditary, multisystemic disorder that is characterized with multiple enchondromas and vascular lesions, most of which are spindle cell hemangiomas. Complications of MS, such as bone deformities and dysfunction caused by enchondromas, usually increase during childhood and adolescence. Malignant transformation of enchondromas and other malignancies are the most severe complications. MS is caused by somatic mosaic IDH1/2 mutations, 65% of which are the IDH1 p.Arg132Cys variant. Due to its rarity, there is no international consensus for the most appropriate treatment option of MS.Here, we report a case of a female patient presenting with multiple enchondromas and spindle cell hemangiomas (SCHs) on bilateral hand and feet diagnosed as MS. A detailed clinical, pathological and genetic diagnosis of MS was rendered. Integrative Genomics Viewer (IGV) visualization of next-generation sequencing (NGS) data revealed the consistent detection of the low-frequency somatic IDH1 p.Arg132Cys mutation between SCH tissue and cystic blood-derived cfDNA. This is the first successful molecular diagnosis of MS complicated with SCH utilizing minimally invasive cfDNA techniques. We suggest that cfDNA sequencing could potentially be used as an alternative, reliable and sensitive method to identify molecular information for genetic diagnosis and for future targeted therapies of MS.
Topics: Cell-Free Nucleic Acids; Enchondromatosis; Female; Hemangioma; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 35042566
DOI: 10.1186/s41065-022-00223-2 -
Frontiers in Endocrinology 2021Maffucci's syndrome is characterized by the coexistence of multiple enchondromas and soft-tissue hemangiomas. It has been clear that somatic mosaic isocitrate...
BACKGROUND
Maffucci's syndrome is characterized by the coexistence of multiple enchondromas and soft-tissue hemangiomas. It has been clear that somatic mosaic isocitrate dehydrogenase type 1 (IDH1) or isocitrate dehydrogenase type 2 (IDH2) mutations are associated with Maffucci's syndrome and Ollier disease, but the mechanisms underlying hemangiomas of the Maffucci's syndrome is still obscure. This study aimed to determine the mechanism of hemangiomas in Maffucci's syndrome.
METHODS
We received a 26-year-old female patient with typical Maffucci's syndrome, and exome sequencing was conducted using DNA from her peripheral blood and enchondroma tissues. Somatic mutations were characterized by a comparative analysis of exome sequences and further confirmed by the sequencing of PCR products derived from original blood and tissue samples. The mutations of an additional 69 patients with Ollier disease were further tested. The functional impacts of these somatic mutations on Maffucci's syndrome, especially the development of hemangiomas, were evaluated.
RESULTS
We reported a typical case of Maffucci's syndrome, which was confirmed by both imaging findings and pathology. Through exome sequencing of this patient's DNA samples, we identified an R132C mutation in the isocitrate dehydrogenase type 1 (IDH1) gene and an L309I mutation in the ELKS/RAB6-interacting/CAST family member 2 (ERC2) gene in this patient. Approximately 33.3% of the clones were positive for the IDH1 R132C mutation, and 19.0% of the clones were positive for the ECR2 L309I mutation. The IDH1 R132C mutation was detected in most of the patients with Ollier disease (51/69 patients), and the mean frequency of this mutation was 63.3% in total sequence readouts, but the ECR2 L309I mutation was absent in all of the patients with Ollier disease. experiments confirmed that the IDH1 R132C mutation promotes chondrocyte proliferation, and the ERC2 L309I mutation enhances angiogenesis.
CONCLUSIONS
Our results suggest that while IDH1 is a known pathogenic gene in enchondromatosis, ERC2 is a novel gene identified in Maffucci's syndrome. The somatic L309I mutation of ERC2 contributes to the pathogenesis of hypervascularization to facilitate the development of hemangiomas in Maffucci's syndrome. The combination of the IDH1 R132C and ERC2 L309I mutations contributes to the development of Maffucci's syndrome, and these results may enable further research on the pathogenesis of Maffucci's syndrome.
Topics: Adaptor Proteins, Signal Transducing; Adult; Cytoskeletal Proteins; Enchondromatosis; Female; Humans; Isocitrate Dehydrogenase; Mutation; Exome Sequencing
PubMed: 34790172
DOI: 10.3389/fendo.2021.763349 -
Journal of Pediatric Genetics Mar 2024Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short...
Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in , playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old. He had short stature, platyspondyly, metaphyseal changes, intracranial calcification, spastic paraparesis, and mild intellectual disability. He also had recurrent pneumonia attacks. The clinical diagnosis of SPENCD was confirmed by sequencing of the gene, and a homozygous c.155A > C (p.K52T) variation was found, which was reported before as pathogenic. In conclusion, in early onset chronic autoimmune cytopenias an immune dysregulation may often have a role in the etiology. Associating findings and immunologic functions should be carefully evaluated in such patients in the light of the literature. The present case shows the importance of multisystemic evaluation for the detection of SPENCD that has a monogenic etiology.
PubMed: 38567175
DOI: 10.1055/s-0041-1736560 -
Case Reports in Oncology 2021Maffucci syndrome is characterized by multiple hemangiomas and enchondromas. Somatic mutations in and are associated with the development of Maffucci syndrome, and...
Maffucci syndrome is characterized by multiple hemangiomas and enchondromas. Somatic mutations in and are associated with the development of Maffucci syndrome, and these patients develop various malignant nonskeletal tumors in addition to malignant skeletal tumors. We report a case of Maffucci syndrome with mutation complicated by intrahepatic cholangiocarcinoma. The patient was a 35-year-old woman who was diagnosed with Maffucci syndrome in childhood. She was referred to our department because of a large hepatic tumor. Serum carcinoembryonic antigen was 27.1 ng/mL upon laboratory examination. CT scanning showed a large low-density tumor (90 × 70 mm) in the right lobe of the liver, and MRI revealed a multilobulated and fibrous tumor, which was observed as high signal intensity on T2- and diffusion-weighted images and low signal intensity on T1-weighted images. Positron emission tomography-CT revealed peritoneal dissemination and cancer spread to the muscles of the back. Finally, she was diagnosed with intrahepatic cholangiocarcinoma with dissemination and metastases. We performed a tumor biopsy to determine a treatment plan for chemotherapy. Sanger sequencing of a tumor biopsy identified a mutation in at c.394C>T (R132C), but the patient died of rapid cancer progression before the chemotherapy could be initiated. Although rare, malignant tumors can develop in patients with Maffucci syndrome; therefore, it is necessary to monitor these tumors through careful and periodic observation.
PubMed: 34720940
DOI: 10.1159/000515779 -
Cold Spring Harbor Molecular Case... Dec 2021Maffucci syndrome is a rare, highly variable somatic mosaic condition, and well-known cancer-related gain-of-function variants in either the or genes have been found...
Maffucci syndrome is a rare, highly variable somatic mosaic condition, and well-known cancer-related gain-of-function variants in either the or genes have been found in the affected tissues of most reported individuals. Features include benign enchondroma and spindle-cell hemangioma, with a recognized increased risk of various malignancies. Fewer than 200 affected individuals have been reported; therefore, accurate estimates of malignancy risk are difficult to quantify and recommended surveillance guidelines are not available. The same gain-of-function and variants are also implicated in a variety of other benign and malignant tumors. An adult male presented with several soft palpable lesions on the right upper limb. Imaging and histopathology raised the possibility of Maffucci syndrome. DNA was extracted from peripheral blood lymphocytes and tissue surgically resected from a spindle-cell hemangioma. Sanger sequencing and droplet digital polymerase chain reaction (PCR) analysis of the gene were performed. We identified a somatic mosaic c.394C > T (p.R132C) variant in exon 5 of , in DNA derived from hemangioma tissue at ∼17% variant allele fraction. This variant was absent in DNA derived from blood. This variant has been identified in the affected tissue of most reported individuals with Maffucci syndrome. Although this individual has a potentially targetable variant, and there is a recognized risk of malignant transformation in this condition, a decision was made not to intervene with an IDH1 inhibitor. The reasons and prospects for therapy in this condition are discussed.
Topics: Adult; Enchondromatosis; Hemangioma; Humans; Isocitrate Dehydrogenase; Male; Mutation
PubMed: 34588213
DOI: 10.1101/mcs.a006127