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Bulletin of the Hospital For Joint... Dec 2015Maffucci syndrome, a rare sporadic form of enchondromatosis, is characterized by hemangiomas and multiple enchondromas, benign cartilaginous tumors that arise near... (Review)
Review
Maffucci syndrome, a rare sporadic form of enchondromatosis, is characterized by hemangiomas and multiple enchondromas, benign cartilaginous tumors that arise near growth plates. Previous studies demonstrate that individuals diagnosed with Maffucci syndrome have approximately 100% lifetime risk of malignant transformation. Identification of Maffucci syndrome by surgical excision and pathological diagnosis can be life-saving due to its high malignant potential relative to other subtypes of enchondromatosis such as Ollier's disease. We report a case of a 58-year-old man with enchondromatosis who experienced malignant transformation of the enchondroma in his distal femur into a chondrosarcoma. He underwent a right distal femoral replacement without complications. Two years later, new masses were identified in his left hand and excised following progressive growth, pain, and functional limitation. Pathology confirmed these to be hemangiomas, and he was diagnosed with Maffucci syndrome. At last follow-up, patient reported additional nodular tumor growths occurring unilaterally on the left side. For patients with Maffucci syndrome, continual follow-up and careful surveillance of these masses is crucial as these lesions can cause fractures, deformities, pain, and undergo malignant transformation. Our report reviews the literature and outlines the treatment and management plans for patients with this rare and potentially dangerous disorder.
Topics: Biopsy; Cell Transformation, Neoplastic; Chondrosarcoma; Enchondromatosis; Femoral Neoplasms; Femur; Humans; Male; Middle Aged; Predictive Value of Tests; Radiography; Recurrence; Reoperation; Treatment Outcome
PubMed: 26630472
DOI: No ID Found -
Experimental and Therapeutic Medicine Sep 2023Maffucci syndrome is an extremely rare disease which can manifest symptoms as early as childhood. It is estimated that there have been <300 cases reported globally;...
Maffucci syndrome is an extremely rare disease which can manifest symptoms as early as childhood. It is estimated that there have been <300 cases reported globally; however, this number is likely to be an underestimate. Maffucci syndrome is characterized by multiple enchondromas and soft tissue hemangiomas, which can cause growth and developmental malformations. In addition to bone deformities, pathological fractures and a loss of mobility, patients with Maffucci syndrome may develop secondary central chondrosarcoma and have a higher risk of developing non-skeletal malignant tumors, such as gliomas and mesenchymal ovarian tumors. The present study provides information for clinicians about this disease through the use of imaging, physical examinations, clinical manifestations and the treatment strategy used. There is need to summarize the existing cases of this disease around the world and produce an effective framework for the diagnosis, treatment and prevention of Maffucci syndrome, in order to better understand this disease. The present study reports on a 15-year-old male diagnosed with Maffucci syndrome. . Due to the risk of malignant tumor development in the absence of effective treatment, regular and careful observation through monitoring of tumor markers and imaging studies is important for patients with Maffucci syndrome. As cases of this disease are rare and case data is limited, it is difficult to create a clear treatment plan. There is an urgent need to establish a case database of Maffucci syndrome patients and explore its pathogenesis for early diagnosis, treatment and prevention of disease.
PubMed: 37602309
DOI: 10.3892/etm.2023.12134 -
Radiology Case Reports Oct 2022Maffucci syndrome is a non-hereditary congenital condition that affects the skin and skeleton. Enchondromas (benign cartilage enlargements), bone abnormalities, and...
Maffucci syndrome is a non-hereditary congenital condition that affects the skin and skeleton. Enchondromas (benign cartilage enlargements), bone abnormalities, and venous anomalies (hemangiomas) are all symptoms. Enchondromas occur as a result of mesodermal dysplasia and have the potential to become cancerous. They are most commonly found on the phalanges and long bones. Venous abnormalities commonly manifest themselves as soft lumps or tumors on the distal extremities. A 19-year-old boy presented with swellings on his fingers and left foot since the age of 5, along with a few bluish soft tissue swellings on his left heel. Multiple expansile lytic lesions and soft tissue swellings with phleboliths were seen on X-ray. Histology confirmed the diagnosis of hemangiomas and enchondromas. Soft tissue swellings were found to have hyper echoic areas, as well as modest marginal blood flow on Doppler, which could indicate hemangiomas. Maffucci syndrome was identified, and treatment with a multidisciplinary approach was initiated. Maffucci syndrome is a rare genetic illness reported in the literature less than 200 times. The enchondromas and hemangiomas have a strong link to malignant changes, with chondrosarcomas accounting for 30% of the associated malignancies. On X-ray, enchondromas are easily identified as osteolytic lesions with cortex thinning and endosteal scalloping while color Doppler ultrasound detects the presence of hemangiomas. Phleboliths are easily identified as small calcifications on X-rays. Radiographic examinations should be considered in patients presenting with bone or soft tissue swellings for an early diagnosis of Maffucci syndrome.
PubMed: 35936883
DOI: 10.1016/j.radcr.2022.07.008 -
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 -
Indian Journal of Dermatology,... 2019Maffucci syndrome is a rare nonhereditary disorder comprising of lymphovascular malformations and multiple enchondromas, which may be associated with several internal...
Maffucci syndrome is a rare nonhereditary disorder comprising of lymphovascular malformations and multiple enchondromas, which may be associated with several internal malignancies. This report describes a new association of Maffucci syndrome with pedal synovial sarcoma. Our case is also remarkable as lymphangioma circumscriptum is the sole lymphovascular component, which has been rarely reported. The aim of this report is to generate awareness about this rare condition and also highlight the importance of screening for malignancies in this disorder.
Topics: Enchondromatosis; Humans; Male; Middle Aged; Sarcoma, Synovial
PubMed: 29667613
DOI: 10.4103/ijdvl.IJDVL_547_17 -
Indian Journal of Otolaryngology and... Oct 2019Maffucci syndrome is an extremely rare sporadic disease, characterized by multiple enchondromas and associated with multiple hemangiomas and/or lymphangiomas. First case...
Maffucci syndrome is an extremely rare sporadic disease, characterized by multiple enchondromas and associated with multiple hemangiomas and/or lymphangiomas. First case was reported in 1881, and fewer than 200 case have been reported to date. Potential sarcomatous malignant transformation have been noticed in previous cases. This report describes the case of 21 years-old male complain of right sided nasal obstruction for 10 months, and right sided aural fullness. Examination revealed multiple asymptomatic nodules in both hands since childhood, that have not been investigated and a large nasopharyngeal mass. Computed tomography, showed a 36 mm in 30 mm diameter lesion extending from the inferior aspect of the clivus and basisphenoid into the nasopharynx, which did not seems to be highly vascular with angiogram. Incidental radiological findings of multiple bubbly lytic bony lesions. Endoscopic sinus surgery and clival lesion excision was performed. Pathology confirmed diagnosis of clival enchondroma with clinical and radiological features consistent with Maffucci syndrome. Clear etiology have not been established yet. Mutations in gene encoding parathyroid hormone receptor 1 found in 10% of enchondromatosis. Mutations in gene encoding isocitrate dehydrogenase 1 and 2 (IDH 1&2) occur in some enchondromas and spindle cell hemangiomas. Maffucci syndrome usually presents with asymmetrical distribution of multiple enchondromas. Malignant transformation is the most concerning potential sequel. Many studies have shown sarcomatous degeneration of enchondromas to chondrosarcomas in average of 25% of cases. Patient counselling and education are crucial in the management. Surgical excision usually for symptomatic patients and suspicious lesions. Nevertheless, all patient of Maffucci syndrome will require a long term follow up and surveillance for the lifelong risk of malignant transformation. Maffucci syndrome diagnosis based on clinical presentation, radiological and histopathological findings. Surgical excision offered for symptomatic patients and for suspicious lesions. Lifelong risk of sarcomatous malignant transformation necessitate a long term surveillance.
PubMed: 31742037
DOI: 10.1007/s12070-018-1463-8 -
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 -
Laboratory Investigation; a Journal of... Apr 2018The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has... (Review)
Review
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate. In contrast, SDH and FH act as tumor suppressors and genomic inactivation results in succinate and fumarate accumulation, respectively. SDH deficiency may result from germline SDHA, SDHB, SDHC, or SDHD mutations and is found in autosomal-dominant familial paraganglioma/pheochromocytoma and Carney-Stratakis syndrome, describing the combination of paraganglioma and gastrointestinal stromal tumor (GIST). In contrast, patients with the non-hereditary Carney triad, including paraganglioma, GIST, and pulmonary chondroma, usually lack germline SDH mutations and instead show epigenetic SDH complex inactivation through SDHC promoter methylation. Inactivating FH germline mutations are found in patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome comprising benign cutaneous/uterine leiomyomas and renal cell carcinoma. Mutant IDH, SDH, and FH share common inhibition of α-ketoglutarate-dependent oxygenases such as the TET family of 5-methylcytosine hydroxylases preventing DNA demethylation, and Jumonji domain histone demethylases increasing histone methylation, which together inhibit cell differentiation. Ongoing studies aim to better characterize these complex alterations in cancer, the different clinical phenotypes, and variable penetrance of inherited and sporadic cancer predisposition syndromes. A better understanding of the roles of metabolic enzymes in cancer may foster the development of therapies that specifically target functional alterations in tumor cells in the future. Here, the physiologic functions of these metabolic enzymes, the mutational spectrum, and associated functional alterations will be discussed, with a focus on mesenchymal tumor predisposition syndromes.
Topics: Animals; Fumarate Hydratase; Fumarates; Glutarates; Humans; Isocitrate Dehydrogenase; Mixed Function Oxygenases; Neoplasms; Proto-Oncogene Proteins; Succinate Dehydrogenase; Succinic Acid
PubMed: 29339836
DOI: 10.1038/s41374-017-0003-6 -
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 -
Medicina (Kaunas, Lithuania) May 2023: Maffucci syndrome is a rare genetic disorder associated with the development of multiple enchondromas and soft tissue cavernous hemangiomas, as well as an increased...
: Maffucci syndrome is a rare genetic disorder associated with the development of multiple enchondromas and soft tissue cavernous hemangiomas, as well as an increased risk of malignant tumors. : Here we report a case of Maffucci syndrome in a patient who presented with a giant left frontal lobe tumor. Molecular genetic analysis of the tumor revealed an isocitrate dehydrogenase (IDH) mutation p.R132H (c.395C>A) mutation in the IDH1 gene and a heterozygous duplication of the CDKN2A genes. : The presence of an IDH1 mutation is notable because this mutation is frequently seen in glial tumors and other neoplasms, and its co-occurrence with Maffucci syndrome may represent a novel risk factor for the development of gliomas. This case underscores the importance of genetic testing in patients with Maffucci syndrome who present with central nervous system tumors, as well as the need for further research to understand the relationship between IDH1 mutations and the development of gliomas in this population.
Topics: Humans; Enchondromatosis; Mutation; Astrocytoma; Genetic Testing; Isocitrate Dehydrogenase; Brain Neoplasms
PubMed: 37374260
DOI: 10.3390/medicina59061056