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Brain Tumor Research and Treatment Apr 2023Cerebral chondrosarcoma metastases are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment,...
BACKGROUND
Cerebral chondrosarcoma metastases are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. We further present the first case with Maffucci syndrome.
METHODS
Three databases, PubMed, Embase, and Google Scholar, and crossed references were queried for cerebral chondrosarcoma metastases. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analyses were performed.
RESULTS
Fifty-six patients were included from 1,489 literature results. The average age at brain metastasis was 46.6±17.6 years and occurred at a median of 24±2.8 months from primary diagnosis. Primary tumor histology (dedifferentiated 5.0±1.5 months, mesenchymal 24±3.0 months, conventional 41±7.4 months, <0.05) and grade (low grade 54±16.7 months vs. high-grade 10±6.4 months, <0.001) correlated with time interval until brain metastasis. A multiple enchondromatosis syndrome occurred in 13.2% of cases. At time of brain metastases diagnosis, extracranial metastases were identified in 76.2% of cases. Median survival after the development of brain metastasis was 2.0±0.78 months with a 1-year survival of 10.0%. On regression analysis, surgery reduced brain metastasis mortality risk and radiation trended towards reduced mortality risk (surgery: hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.064-0.763, =0.017; radiation: HR 0.31, 95% CI 0.091-1.072, =0.064).
CONCLUSION
We present a systematic review of cerebral chondrosarcoma metastases. Primary tumor histology and grade correlate with time until cerebral metastasis. Following cerebral metastasis, these tumors have poor prognosis and modestly benefit from surgery.
PubMed: 37151152
DOI: 10.14791/btrt.2023.0003 -
European Journal of Vascular and... Jul 2023
Topics: Humans; Enchondromatosis; Vascular Malformations; Vascular Diseases; Cardiovascular Abnormalities
PubMed: 37054874
DOI: 10.1016/j.ejvs.2023.04.005 -
Neuropathology : Official Journal of... Oct 2023Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman...
Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.
Topics: Female; Humans; Young Adult; Adult; Oligodendroglioma; Enchondromatosis; Brain Neoplasms; In Situ Hybridization, Fluorescence; Isocitrate Dehydrogenase; Glioma; Astrocytoma; Mutation
PubMed: 36942363
DOI: 10.1111/neup.12902 -
Medicina (Kaunas, Lithuania) Dec 2022: Hereditary multiple exostoses (HME) is a disease characterized by cartilage-capped bony protuberances at the site of growth plates of long bones. Functional mutations...
: Hereditary multiple exostoses (HME) is a disease characterized by cartilage-capped bony protuberances at the site of growth plates of long bones. Functional mutations in the exostosin genes ( and ) are reported to affect the hedgehog signalling pathways leading to multiple enchondromatosis. However, the exact role of each EXT protein in the regulation of heparan sulphate (HS) chain elongation is still an enigma. In this study, a Pakistani family with HME is investigated to find out the genetic basis of the disease. : Genotyping of eight members of the family by amplifying microsatellite markers, tightly linked to the and genes. : The study revealed linkage of the HME family to the locus 8q24.1. Sanger sequencing identified a heterozygous deletion () in exon 1 of , segregating with the disease phenotype in the family. In silico analysis predicted a shift in the frame causing an early stop codon (p.R83GfsX52). The predicted dwarf protein constituting 134 amino acids was functionally aberrant with a complete loss of the catalytic domain at the C-terminus. Interestingly, an alternative open reading frame 3 (ORF3) caused by the frame shift is predicted to encode a protein sequence, identical to the wild type and containing the catalytic domain, but lacking the first 100 amino acids of the wild-type EXT1 protein. : Consequently, haploinsufficiency could be the cause of HME in the investigated family as the mutated copy of is ineffective for complex formation. The predicted ORF3 protein could be of great significance in understanding several aspects of HME pathogenesis.
Topics: Humans; Exostoses, Multiple Hereditary; Haploinsufficiency; Pakistan; Hedgehog Proteins; Mutation; N-Acetylglucosaminyltransferases; Heparitin Sulfate; Amino Acids
PubMed: 36676722
DOI: 10.3390/medicina59010100 -
European Journal of Medical Genetics Mar 2023Mosaic variants of IDH1 (isocitrate dehydrogenase-1) R132 and IDH2 (isocitrate dehydrogenase-2) R172 loci were detected in most of the bone cysts of Ollier and Maffucci...
Mosaic variants of IDH1 (isocitrate dehydrogenase-1) R132 and IDH2 (isocitrate dehydrogenase-2) R172 loci were detected in most of the bone cysts of Ollier and Maffucci series and in the blood and tissue samples of metaphyseal enchondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA) patients. We aimed to report an intermediate phenotype comparing with the reported cases. The proband was a 9-year-old boy with widespread metaphyseal enchondromatosis involving metaphyses of long tubular bones, iliac bones and tubular bones of both hands and feet and sparing spine and flat and short bones. He underwent quad whole exome sequencing (index-both parents-healthy sibling). Sanger sequencing was performed for confirmation and segregation purposes. Heterozygous IDH1 R132H (c.395G > A) variant was detected in his blood via whole exome sequencing and Sanger analysis in mosaic state, 22% of the reads and Sanger signal. He had no D-2-hydroxyglutaric aciduria in urinary organic acid analysis. Our case is unique with the presence of IDH1 R132H variant in blood with metaphyseal enchondromatosis without D-2-hydroxyglutaric aciduria. It was a transitional phenotype. With his phenotype, we expand the IDH1/IDH2 related enchondromatosis phenotypes.
Topics: Humans; Enchondromatosis; Isocitrate Dehydrogenase; Mutation; Phenotype; Male; Child
PubMed: 36649847
DOI: 10.1016/j.ejmg.2023.104697 -
PLoS Genetics Dec 2022Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies,...
Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it.
Topics: Humans; Enchondromatosis; Chondrosarcoma; Sequence Analysis, DNA; Hypoxia-Inducible Factor 1, alpha Subunit; Vascular Diseases; Bone Neoplasms
PubMed: 36480544
DOI: 10.1371/journal.pgen.1010504 -
Vascular and Endovascular Surgery Apr 2023Here, we report our experience treating a patient with Maffucci syndrome and evaluate the outcomes resulting from surgical management combined with sclerotherapy in the...
PURPOSE
Here, we report our experience treating a patient with Maffucci syndrome and evaluate the outcomes resulting from surgical management combined with sclerotherapy in the treatment of head and neck venous malformations (VMs). A 19-years-old woman with multiple enchondromas and heterauxesis complained of masses in the oral cavity that had gradually increased in size and eventually affected her daily life. A tracheotomy was performed followed by traditional sclerotherapy to treat the oropharyngeal VMs. Next, we surgically excised the VMs of the oral cavity and maxillofacial skin.
RESULTS
Magnetic resonance imaging indicated that the oral VMs were nearly eradicated and the oropharyngeal VMs had stabilized. The patient's appearance and normal maxillofacial region function were restored.
CONCLUSION
In summary, local resection combined with sclerotherapy facilitated timely and efficient VMs removal from the head and neck region of a patient with Maffucci syndrome.
Topics: Humans; Female; Young Adult; Adult; Sclerotherapy; Enchondromatosis; Treatment Outcome; Neck; Veins; Vascular Diseases; Vascular Malformations
PubMed: 36453211
DOI: 10.1177/15385744221140687 -
Diagnostics (Basel, Switzerland) Nov 2022This study aims to investigate isocitrate dehydrogenase gene mutations in patients with the non-hereditary skeletal disorders of Ollier disease and Maffucci syndrome,...
Mutations Are Potentially the Intrinsic Genetic Link among the Multiple Neoplastic Lesions in Ollier Disease and Maffucci Syndrome: A Clinicopathologic Analysis from a Single Institute in Shanghai, China.
BACKGROUND
This study aims to investigate isocitrate dehydrogenase gene mutations in patients with the non-hereditary skeletal disorders of Ollier disease and Maffucci syndrome, particularly in the extraosseous tumours.
METHODS
A total of 16 tumours from three patients with Ollier disease and three patients with Maffucci syndrome were collected. Sanger sequencing was applied to determine the hotspot mutations of and genes in multiple neoplastic tissues.
RESULTS
A majority of the tumours displayed an mutation (p.R132C in 11 tumours including the paediatric ovarian tumour from one patient with Ollier disease, 4 cutaneous haemangiomas from three patients with Maffucci syndrome, 5 enchondromas and 1 chondrosarcoma; p.R132H in 2 cartilaginous tumours from one patient).
CONCLUSIONS
mutations were demonstrated in multiple cartilaginous tumours and extraskeletal neoplasms in this case series. Specifically, identical mutations were confirmed in the separate lesions of each patient. These results are in concordance with findings that have been reported. However, here, we additionally reported the first case of Ollier disease with an ovarian tumour, which harboured the identical mutation with the corresponding cartilaginous tumour. We further provided evidence that mutations are the potential genetic links among the multiple neoplastic lesions of Ollier disease and Maffucci syndrome.
PubMed: 36428825
DOI: 10.3390/diagnostics12112764 -
The Journal of Allergy and Clinical... Apr 2023In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of...
BACKGROUND
In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.
OBJECTIVE
This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.
METHODS
We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3.
RESULTS
Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate.
CONCLUSION
STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.
Topics: Child; Humans; Autoimmunity; Cohort Studies; Gain of Function Mutation; Immune System Diseases; Immunologic Deficiency Syndromes; Mutation; STAT3 Transcription Factor; Cell Proliferation; Lymphocytes
PubMed: 36228738
DOI: 10.1016/j.jaci.2022.09.002 -
Radiographics : a Review Publication of... Oct 2022Vascular anomalies encompass a spectrum of tumors and malformations that can cause significant morbidity and mortality in children and adults. Use of the International...
Vascular anomalies encompass a spectrum of tumors and malformations that can cause significant morbidity and mortality in children and adults. Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system is strongly recommended for consistency. Vascular anomalies can occur in isolation or in association with clinical syndromes that involve complex multifocal lesions affecting different organ systems. Thus, it is critical to be familiar with the differences and similarities among vascular anomalies to guide selection of the appropriate imaging studies and possible interventions. Syndromes associated with simple vascular malformations include hereditary hemorrhagic telangiectasia, blue rubber bleb nevus syndrome, Gorham-Stout disease, and primary lymphedema. Syndromes categorized as vascular malformations associated with other anomalies include Klippel-Trenaunay-Weber syndrome, Parkes Weber syndrome, Servelle-Martorell syndrome, Maffucci syndrome, macrocephaly-capillary malformation, CLOVES (ongenital ipomatous vergrowth, ascular malformations, pidermal nevi, and coliosis, skeletal, and spinal anomalies syndrome, Proteus syndrome, Bannayan-Riley-Ruvalcaba syndrome, and CLAPO (apillary malformations of the lower lip, ymphatic malformations of the face and neck, symmetry of the face and limbs, and artial or generalized vergrowth) syndrome. With PHACES (osterior fossa malformations, emangiomas, rterial anomalies, ardiac defects and/or coarctation of the aorta, ye abnormalities, and ternal clefting or supraumbilical raphe) syndrome, infantile hemangiomas associated with other lesions occur. Diagnostic and interventional radiologists have important roles in diagnosing these conditions and administering image-guided therapies-embolization and sclerotherapy, and different ablation procedures in particular. The key imaging features of vascular anomaly syndromes based on the 2018 ISSVA classification system and the role of interventional radiology in the management of these syndromes are reviewed. RSNA, 2022.
Topics: Adult; Child; Hemangioma; Humans; Klippel-Trenaunay-Weber Syndrome; Musculoskeletal Abnormalities; Radiology, Interventional; Vascular Malformations
PubMed: 36190850
DOI: 10.1148/rg.210234