Maffucci Syndrome Research Articles

Maffucci syndrome with unilateral limb: a case report and review of the literature.

Maffucci syndrome is a congenital, non-hereditary mesodermal dysplasia manifested by multiple enchondromas and hemangiomas. It is associated with diverse secondary musculoskeletal deformities, which is exceedingly rare. We report a case of hemangiomas and enchondromas localized in the unilateral limb in a patient with Maffucci syndrome. Treatment consists of orthopedic and surgical intervention to minimize deformities and for cosmetic purpose. Careful surveillance for malignant degeneration of both skeletal and non-skeletal tumors, especially in the brain and abdomen, is essential.

Achados Ultrassonográficos Inéditos Na Síndrome De Maffucci: Fístulas Arteriovenosas Unpublished Sonographic Findings in Maffucci Syndrome: Arteriovenous Fistulas

Maffucci Syndrome (MS) is a rare congenital mesodermal dysplasia characterized by the association of discondroplasias and vascular malformations. In the bones of the hands and feet and on the metaphysis of long bones, enchondromas that lead to pathologic fractures and deformities are frequently found. Vascular malformations are generally low-flow, venous ectasias forming lakes and eventually phleboliths.

Maffucci syndrome with the spindle cell hemangiomas in the mucosa of the lower lip: a rare case report and literature review

The presence of non-cutaneous vascular lesions in the syndrome of multiple enchondromas and subcutaneous hemangiomas, also named Maffucci syndrome, is exceedingly rare. Until now, non-cutaneous vascular lesions have been described in nine patients, while only three cases were present in the oral cavity; they were found in the tongue in two patients and in the lower lip in one patient. Herein, we report the second case of vascular lesions localized in the mucosa of lower lip in a patient with Maffucci syndrome. Histopathologic examination showed spindle cell hemangioma.

R132C IDH1 Mutations Are Found in Spindle Cell Hemangiomas and Not in Other Vascular Tumors or Malformations

Spindle cell hemangioma (SCH) is a rare, benign vascular tumor of the dermis and subcutis. The lesions can be multifocal and are overrepresented in Maffucci syndrome, in which patients also have multiple enchondromas. Somatic mosaic R132C IDH1 hotspot mutations were recently identified in Maffucci syndrome. We evaluated the presence of mutations in solitary and multiple SCHs in patients without multiple enchondromas and tested a range of other vascular lesions that enter into the differential diagnosis. The R132C IDH1 mutation was identified by hydrolysis probes assay and confirmed by Sanger sequencing in 18 of 28 (64%) SCHs; of the 10 negative cases, 2 harbored a mutation in IDH2 (R172T and R172M) by Sanger sequencing. None of 154 other vascular malformations and tumors harbored an IDH1 R132C mutation, and R132H IDH1 mutations were absent in all 182 cases. All 16 SCHs examined by immunohistochemistry were negative for expression of HIF-1α. In conclusion, 20 of 28 (71%) SCHs harbored mutations in exon 4 of IDH1 or IDH2. Given that mutations were absent in 154 other vascular lesions, the mutation seems to be highly specific for SCH. The mutation does not induce expression of HIF-1α in SCH, and therefore the exact mechanism by which mutations in IDH1 or IDH2 lead to vascular tumorigenesis remains to be established.

Staged endovascular and surgical treatment of slow-flow vulvar venous malformations

The objective of the study was to report our experience in a rare series of treated symptomatic slow-flow vulvar venous malformations (VVMs) using a staged, multidisciplinary approach. Consecutive patients with symptomatic lesions treated over a 7 year period (2005-2012) were followed up for technical success, resolution of symptoms, aesthetic outcomes, and complications. Direct endovenous sclerotherapy (DEVS) using sodium tetradecyl sulfate (STS) foam was performed in all patients under ultrasound and contrast-enhanced fluoroscopic guidance. Surgical excision and layered primary closure was performed within 24 hours after the last DEVS session. Eleven patients (mean age, 25 years; range, 4-43 years) were treated. Presenting symptoms included pain (n = 11), soft tissue swelling (n = 11), local heaviness (n = 11), dyspareunia (n = 2), and dysmenorrhea (n = 2). Most were isolated lesions (n = 8). There were 2 cases of Klippel-Trénaunay syndrome and 1 case of Maffucci syndrome. The latter required Nd:YAG laser photocoagulation prior to sclerotherapy. On average, approximately 3 DEVS sessions were required prior to surgical excision (range, 1-6). Mean estimated surgical blood loss was 130 mL (range, 20-400 mL). Mean follow-up was 23 months (range, 3-55 months). Elimination of pain and soft tissue redundancy was achieved in all patients with satisfactory aesthetic outcomes. All patients experienced minor pain and swelling after DEVS. Following surgical excision, there was 1 case of hematoma and wound dehiscence requiring surgical evacuation. No other reinterventions, endovascular or surgical, were required. VVMs require increased awareness and appropriate preoperative evaluation for proper identification and treatment. A multidisciplinary approach can provide improvement in clinical signs and symptoms with satisfactory cosmesis and minimal complications.

Enchondromas of the Hand: Factors Affecting Recurrence, Healing, Motion, and Malignant Transformation

Enchondromas represent the most common primary bone tumor in the hand. Despite their frequency, a standardized treatment protocol is lacking. This study examines the outcome of surgically treated enchondromas of the hand with regard to tumor location, graft choice, and presence or absence of fracture. We retrospectively reviewed 102 enchondromas in 80 patients, identified between 1991 and 2008, with a mean clinical follow-up of 38 months. We assessed the effects of age, tumor location, and graft choice on outcomes for all lesions. Patients presenting with Ollier disease, Maffucci syndrome, pathologic fractures, or recurrent disease were separated for additional analysis. Of the 102 lesions, 62 (61%) achieved complete radiographic healing in a median time of 6 months. Full range of motion was achieved following treatment of 68 lesions (67%) in a median time of 3 months. A total of 95 lesions (93%) remained recurrence free following surgery. One case of malignant transformation occurred in a patient with Maffucci syndrome. Tumor location and graft choice did not affect healing grade, time to healing, range of motion, or recurrence rate. Age at presentation greater than 30 was associated with more rapid healing. Monocentric, nonexpanding lesions were associated with improved postoperative range of motion. Patients with a diagnosis of multiple enchondromas had a higher rate of recurrence following surgery, and patients presenting with a recurrent lesion had a higher rate of complications. Following pathologic fracture, no differences in outcomes were observed when enchondromas were treated primarily or following fracture healing. Following surgical treatment of enchondromas in the hand, the majority of patients achieve complete bony healing and full range of motion, regardless of the graft material used. Malignant transformation is rare, and aggressive follow-up measures should be reserved for patients with a diagnosis of multiple enchondromas. Therapeutic IV.

Multifocal intracranial astrocytoma in a pediatric patient with Ollier disease

Ollier disease (OD) is a subtype of enchondromatosis. Historically, it has been distinguished from Maffucci syndrome (MS) by the presence of vascular malformations and nonskeletal neoplasms (NSN) in the latter. However, there is an increasing number of reports of NSN in OD, and this categorization is now being questioned. We report a case of OD complicated by multifocal astrocytoma in a young patient, once again pointing to a possible association between OD and NSN. We also review the available literature and examine the similarities between the reported cases.

Maffucci syndrome complicated with meningioma and pituitary adenoma

ejd.2011.1563 Auteur(s) : Sachiko Ono, Hideaki Tanizaki, Akihiro Fujisawa, Miki Tanioka mtanioka@kuhp.kyoto-u.ac.jp, Yoshiki Miyachi Department of Dermatology, Kyoto University, 54 Shogoin Kawaramachi Sakyo, Kyoto 606-8507, Japan Maffucci syndrome is a rare congenital, non-hereditary mesodermal dysplasia, characterized by a combination of multiple enchondromas and hemangiomas. There are only about 200 cases described in the literature to date [1]. Besides chondrosarcoma, the most common tumor, several [...]

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

Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p = 0.00l). Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with enchondromas located in long bones or axial skeleton, especially the pelvis, have a seriously increased risk of developing chondrosarcoma, and are identified as the population that needs regular screening on early detection of malignant transformation.

Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome

Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous IDH1 (R132C and R132H) or IDH2 (R172S) mutations in 87% of enchondromas, benign cartilage tumors, and in 70% of spindle cell hemangiomas, benign vascular lesions. In total, 35 of 43 (81%) patients with Ollier disease and 10 of 13 (77%) patients with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of sixteen patients displayed identical mutations in separate lesions. Immunohistochemistry for mutant R132H IDH1 protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors are associated with hypermethylation and downregulation of expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, enabling functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation.

Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2

Ollier disease and Maffucci syndrome are characterized by multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein. In 18 of 19 individuals with more than one tumor analyzed, all tumors from a given individual shared the same IDH1 mutation affecting Arg132. In 2 of 12 subjects, a low level of mutated DNA was identified in non-neoplastic tissue. The levels of the metabolite 2HG were measured in a series of central cartilaginous and vascular tumors, including samples from syndromic and nonsyndromic subjects, and these levels correlated strongly with the presence of IDH1 mutations. The findings are compatible with a model in which IDH1 or IDH2 mutations represent early post-zygotic occurrences in individuals with these syndromes.

Maffucci syndrome

Maffucci syndrome

Hemangioma related to Maffucci syndrome in a man: a case report

IntroductionMaffucci syndrome is a rare clinical entity (approximately 200 cases have been reported in the medical literature) with a combined occurrence of multiple enchondromas and vascular tumors.Case presentationThe case of a 43-year-old Japanese man with multiple chondromas and hemangiomas (Maffucci syndrome) is reported. One of the hemangiomas was removed and examined pathologically. The morphological picture was an admixture of cavernous hemangioma and spindle cell hemangioma without cytological atypia or mitosis. Sheets of vacuolated endothelial cells were also observed.ConclusionA rare case of hemangioma associated with Maffucci syndrome, focusing on the pathologic nature of the submitted tissue, is reported.

Maffucci syndrome: A genome-wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases

Ollier disease and Maffucci syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co-existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci syndrome is unknown. Here, we report the first genome-wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier-related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray-v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis.

Maffucci's syndrome and fibroadenoma of the breast: a case report

Maffucci's syndrome is a rare congenital non-hereditary condition that was initially described by Angelo Maffucci in 1881. It is characterised by multiple enchondromas and haemangiomas or lymphangiomas, however since the initial description associations with several other tumours, both benign and malignant, have been documented. These tumours include pituitary adenoma, uterine fibroids and polyps, intracranial chondrosarcoma and fibrosarcomas [1, 2]. The original description of Maffucci's syndrome suggested a unique malignant potential among the enchondromatoses; however, recent research has shown that this malignant potential is shared by Ollier's disease as well as others [2]. We present a case of a benign fibroadenoma of the breast in a patient with Maffucci's syndrome.

Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome

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.

Enfermedad de Ollier: tumores benignos con riesgo de malignización. Revisión de 17 casos

Aim To review Ollier disease, an uncommon disease, in order to understand the clinical symptoms, diagnosis, correct treatment, and risk factors in order to prevent malignant transformation. Materials and methods Seventeen cases of Ollier disease were treated between 1976 and 2006. The variables studied included: age at diagnosis and onset of malignant transformation, location of the lesion, family association with other tumours, radiological findings, treatment for the different lesions, metastatic lesions and survival. We excluded patients with Chondrosarcoma without previous diagnosis of Ollier disease. All malignant transformations were assessed by histopathology studies and radiological images. Results We include 16 cases of Ollier's and 1 of Maffucci's syndrome. The median age at diagnosis for patients having malignant transformation was 45 years, whereas the average age at diagnosis for patient without progression to malignancy was 11 years. Pathological fractures, dysmetria and deformities led to the diagnosis in young people. Benign lesions were treated with minor surgery. There were five malignancy transformations in four patients (23.5%), with the distal femur being the most frequent location for transformation to grade I chondrosarcoma. Surgery was the treatment in all of them. We found no family association with other tumours. Conclusions Multiple enchondromatosis is a benign disease with a high risk of malignant transformation above 40 years old. Bone scintigraphy is the best tool for detecting multiple lesions and malignant transformation. Radical surgery is the only way to improve survival, and this is the reason why early diagnosis is essential.

Maffucci′s syndrome associated with hyperparathyroidism

Maffucci's syndrome is a rare, congenital, nonhereditary, mesodermal dysplastic disease characterized by venous malformations and benign cartilaginous tumors. The occurrence of endocrine tumors in Maffucci's syndrome is very rare. We report a case of Maffucci's syndrome associated with hyperparathyroidism and multinodular goiter.

Gutartige Weichteiltumoren in der Orthopädie

For the most part soft tissue tumors are benign. However, the clinical presentation, including radiological aspects, is not always clear. Therefore, a biopsy is necessary in some cases to detect malignant tumors at an early stage. The course of even benign tumors is sometimes complicated. A not insignificant group of local, aggressive or intermediary tumors tend to recur and in exceptional cases can be fatal. Benign soft tissue tumors are subdivided according to the current WHO classification from 2002. They are classified by the tissue they mimick. In clinical practice they are additionally grouped according to aggressiveness. Some benign soft tissue tumors occur in the context of a syndrome, leading to multiple tumors. In these cases there is the threat of a tumor becoming malignant (neurofibromatosis, Maffucci syndrome).

Secondary Chondrosarcoma

Secondary chondrosarcoma is a distinctive type of tumor that originates from a preexisting cartilaginous lesion. Most commonly, it is associated with solitary or multiple osteochondromas. A fraction of cases arises from other conditions, such as Maffucci syndrome and Ollier disease. A sudden increase in the size of the cartilaginous cap of an osteochondroma is a sign of malignant transformation to secondary chondrosarcoma. However, there is no strict cutoff in terms of thickness of the cartilaginous cap that can be regarded as being pathognomonic of malignancy. Most cases of secondary chondrosarcoma are low to intermediate grade. Distant metastasis is uncommon, and the prognosis is good for most patients. Overall survival at 5 years is approximately 90%. Surgical resection with wide margins is the best treatment option, but local recurrence remains a significant problem in approximately 10% to 20% of patients. Patients with secondary chondrosarcoma of the pelvis are especially at risk for local recurrence.