Multiple Enchondromatosis Research Articles

Rare radiological manifestation of enchondromatosis in children: Columnar pattern: A retrospective cohort study.

The columnar cartilage pattern is characterized by parallel aligned cartilage tissue columns related to the physis without matrix calcification separated by the surrounding osseous tissue. Usually, it is seen in patients with multiple enchondromas. The objective of this study was to elucidate the clinical and radiological features of this rare radiological pattern in the physis, which remains unfamiliar to most physician. We retrospectively evaluated the clinical features and imaging findings of 15 patients (9 men and 6 women) who have a columnar pattern with varied spectrum of enchondromatosis. On X-ray and computed tomography (CT) examination, all these lesions were seen as vertical or oblique oriented tubular zones, which have relatively low radiologic density compared with normal bone. The lesions have similar signal characteristics relative to epiphyseal cartilage plates, on T1W and T2W magnetic resonance images. Columnar pattern was observed in different appearances from one single column in one physis to multiple columns in multiple physis. The mean follow-up was 62 months (range: 36-96 months). The mean age was 9.7 (range: 4-14) years at the initial admission. Eight patients had 3 or less affected physis. Five patients had only one affected physis. We defined these patients' group who had up to 3 affected physis as "limited enchondromatosis with columnar pattern (LE-CP)." We observed that most of the columnar cartilage was turning into the normal bone via endochondral ossification. Based on our observations, the columnar pattern is a rare manifestation of the enchondromas. Columnar pattern, along with the related physis, acts as a normal endochondral ossification process, and surgery is not necessary unless there is a risk of fracture or severe deformity. Further awareness of this unique subset of patients may improve our understanding of the disease and lead to better patient outcomes. We have modified non-hereditarily enchondromatosis into 2 categories: limited enchondromatosis with the columnar pattern and multiple enchondromatosis. We believe that LE-CM reflects a developmental anomaly of the physis rather than a true neoplasia, and it acts as a normal endochondral ossification process. Level IV (case series).

Blau syndrome with incidental multiple enchondromatosis

Blau syndrome with incidental multiple enchondromatosis

Extended oligoarticular juvenile idiopathic arthritis with multiple enchondromatosis: A case report

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. Since there is no pathognomonic diagnostic criterion, the diagnosis is made by excluding other arthritis in childhood. Multiple Enchondromatosis, also known as Ollier’s disease, is an ossification disorder often seen in the metaphyseal and diaphyseal regions of long bones or the metaphyseal regions of tubular bones in the hands and feet. Pain, shortening, deformity, fracture, and transformation into malignancy may appear. Here we report a case with extended oligoarticular juvenile idiopathic arthritis (oligo JIA) who developed enchondromatosis during clinical follow-up. While the patient was in remission without medication, he presented with swelling in the hand fingers and enchondromatosis lesions with expansile lytic characteristics were seen on the radiograph. Comorbid diseases can be added in the clinical follow-up of JIA patients. Physical examination is important in terms of added comorbid disease. Our case report is important because it is the first case in which these two diseases are seen together in the literature.

Intracranial Metastasis of Extracranial Chondrosarcoma: Systematic Review With Illustrative Case.

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. 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. 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, p<0.05) and grade (low grade 54±16.7 months vs. high-grade 10±6.4 months, p<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, p=0.017; radiation: HR 0.31, 95% CI 0.091-1.072, p=0.064). 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.

Haploinsufficiency of EXT1 and Heparan Sulphate Deficiency Associated with Hereditary Multiple Exostoses in a Pakistani Family.

Background and Objectives: 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 (EXT1 and EXT2) 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. Materials and Methods: Genotyping of eight members of the family by amplifying microsatellite markers, tightly linked to the EXT1 and EXT2 genes. Results: The study revealed linkage of the HME family to the EXT1 locus 8q24.1. Sanger sequencing identified a heterozygous deletion (c.247Cdel) in exon 1 of EXT1, 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. Conclusion: Consequently, haploinsufficiency could be the cause of HME in the investigated family as the mutated copy of EXT1 is ineffective for EXT-1/2 complex formation. The predicted ORF3 protein could be of great significance in understanding several aspects of HME pathogenesis.

Ollier´s disease: Multiple enchondromatosis

Ollier disease is a rare condition involving the development of intraosseous benign tumors known as enchondromas. These are usually formed during early stages of growth when the cartilage or growth plate is still biologically active. Once the patient matures, these tumors cause dysmorphic deformities and fragile bone fractures in adulthood. It is important to search for cutaneous vascular tumors in order to differentiate with Maffuci syndrome. Malignization of the enchondromas is also a severe complication. Regular control of the patients is key to detect malignant transformations and stablish an early treatment. Malignant transformation involves the development of increased vascular structures around the tumor, thus gammagraphic imaging is key to control the disease. Literature describing this disease is rare and treatment options are limited. Surgical treatment is often required when the osteochondromas transform or become very symptomatic; causing pain and articular malfunction. Our report describes a case of Ollier disease diagnosed in our center and discusses the core concepts of the disease and therapeutic management.

Chondromas and multiple enchondromatosis

Introduction The chondromas are a cartilaginous proliferation of mature appearance and moderate size, reason why these tumors are regarded more like hamartomas than real benign tumor. Chondromas represent 10 to 12 % of benign bone tumors. Any bone of an enchondral ossification may be involved. Several bones can be involved, and the disease is called “chondromatosis”. In the review we describe clinical and radiological findings of this pathology as well as indications for reconstructive surgery. Material and methods The review is dedicated to isolated chondromas, periosteal and extraskeletal chondromas, chondromatosis. Results The aspects of epidemiology, clinical presentation, radiology, MRI, prognosis, indications and methods of surgical treatment have been described in the article for each types of chondroma and enchondromatosis. Conclusion Chondromas are benign bone tumors which may be responsible of pathologic fractures. Their surgical treatment consists in curettage and bone grafting or bone-cement filling with or without osteosynthesis. Multiple enchondromatosis should be considered as an osteochondrodysplasia. Its treatment is not the treatment of the multiple chondromas themselves, but of the bone deformities and length discrepancy induced by the disorder. The transformation of some tumors in chondrosarcomas in adolescence or adulthood needs a strict follow up of these patients.

Ollier disease: A case report and literature review

Ollier disease, also known as multiple enchondromatosis, is a rare congenital disease of unknown etiology. The main manifestation of this disease is a non‑ossifying chondrocyte mass or hamartomatous growth of a chondrocyte in the metaphysis. A few cases can develop into chondrosarcoma or osteosarcoma. The present study describes the case of a 37‑year‑old male patient with left hip pain and dyskinesia diagnosed with Ollier disease, according to clinical features and findings of imaging analysis. In general, the incidence of Ollier disease is low, and thus, it is not well‑known among orthopedic surgeons. However, due to its malignant transformation rate, medical practitioners should encourage patients to undergo regular follow‑up examinations. In an aim to provide some insight into this disease, the present study begins by describing the case of an affected patient case and subsequently presents a review of the relevant literature in order to guide the clinical diagnosis and treatment of the disease.

The investigation and management of common polyostotic bone conditions

Polyostotic bone diseases can present with skeletal lesions in multiple bones, or at several locations within the same bone. They consist of a small number of conditions, which includes both benign and malignant pathologies. The treatment and prognosis of polyostotic bone diseases varies hugely, which makes a methodical approach to their investigation essential. The most commonly encountered polyostotic bone diseases include multiple enchondromatosis, hereditary multiple exostoses (HME), fibrous dysplasia, Paget's disease (osteitis deformans), skeletal metastases and multiple myeloma. The aim of this article is to provide an overview of each of these conditions, discussing their presentation, pathophysiology and the principles behind their management.

Multiple Hereditary Exostoses: Genetics, Multimodality Imaging Features, Complications, Differential Diagnosis, and Treatment

Osteochondromas are a common type of benign bone tumor that occur during childhood. Osteochondromas can be solitary or multifocal as a part of a syndrome, known as multiple hereditary exostoses (MHE). This differentiation was first discovered in 1786 by John Hunter, a famous Scottish surgeon. In 1814, MHE was found to have a familial association. Later, in the 1900s, MHE was differentiated from other disorders, such as Ollier disease (multiple enchondromatosis) and Trevor disease (dysplasia epiphysealis hemimelica). MHE is known by other names including hereditary multiple osteochondromas, diaphyseal aclasis, hereditary deforming chondrodysplasia, and Ehrenfried disease. MHE occurs more frequently in males than in females (1.5–2:1) and whites. Males also tend to be more severely affected. In patients with MHE, the mean number of osteochondromas is typically 15 to 18. Osteochondromas typically occur within the first decade of life (80%) and continue to increase in size until physeal closure. Osteochondromas are most commonly asymptomatic, although they can present with various symptoms including pain and limb length discrepancies. Osteochondromas have key imaging characteristics that help to differentiate them from other types of skeletal lesions and to characterize malignant potential.1

Multiple Enchondromas of the Hand in Children: Long-Term Follow-Up of Mean 15.4 Years.

Multiple enchodromatosis of bone, termed Ollier's disease, or Maffucci syndrome when associated with hemangiomas, is a rare disease that can affect the pediatric hand. This condition often causes a finger mass, deformity, pain and possible pathologic fractures, and has been associated with malignant transformation to chondrosarcoma. The aim of our study is to describe the long-term sequela of multiple enchondromatosis of the hand in the pediatric population, specifically the rates of malignant transformation, tumor recurrence, rates of pathologic fracture, and phalangeal growth arrest. We examined 15 pediatric patients who were treated in our institute with a total of 127 phalanges and metacarpals lesions. Only patients with follow-up of at least 4 years were included. We retrospectively reviewed patients' chart and hand radiograph for symptoms including pathologic fractures, indications for surgery, and postoperative complications including tumor recurrence, and malignant transformation. We assessed phalangeal growth arrest with radiographs and normalized phalangeal growth charts. Mean age of diagnosis was 5.8 years and mean follow-up time was 15.4 years. Pathologic fractures were common at 46% of pediatric patients, but ceased to occur once reaching adulthood. Outcomes of pathologic fractures were excellent, regardless of treatment. Malignant transformation occurred in 1 patient and did not occur during childhood. A total of 80% of patients and 29% of lesions underwent surgical treatment of curettage and bone graft for the lesion, yet recurrence was common and affected 33% of treated patients. Phalangeal growth arrest was the most common long-term sequela and affected 11% of phalanxes and metacarpals. This sequela was significantly more prevalent in patients who had surgical excision of the tumor. Our findings reassure that malignant transformation of enchodromatosis of the hand is unlikely in the pediatric population. Pathologic fracture is common, but has excellent outcomes. When considering surgery, parents should be counseled about the possibility of phalangeal growth arrest and recurrence of the lesion. Level IV-therapeutic.

The association of enchondromatosis with malignant transformed chondrosarcoma and ovarian juvenile granulosa cell tumor (Ollier disease)

ObjectiveOvarian juvenile granulosa cell tumor has an interesting association with multiple enchondromatosis (Ollier disease and Maffucci syndrome) and should be considered a leading diagnosis when an ovarian mass is found in young patients with these conditions. Besides the association with nonskeletal malignancies, there is a high risk of malignant transformation of enchondroma in chondrosarcoma as was also the case in this instance. Case ReportThe report uses multiple images to document the representative and characteristic markers of multiple enchondromas in a 22-year-old patient with Ollier disease complicated by malignant transformation of chondrosarcoma and in whom the disease is associated with ovarian juvenile granulosa cell tumor of the right ovary. ConclusionIt is important to recognize that when the female patient presents with enchondromatosis and a large unilateral multilocular-solid ovarian mass, the specific diagnosis of granulosa cell tumor can be made with high accuracy.

Tibia deformity correction by circular external fixator in multiple enchondromatosis

Objective To discuss the outcomes of tibia varum and shorting deformity correction by circular external fixator in multiple enchondromatosis. Methods Thirty-one tibias treated with varum and shorting deformity correction by circular external fixator in multiple enchondromatosis were statistically analyzed. Of 31 tibias (28 cases), 12 were from boys, and 19 from girls, with an average age of 12.3 years. After open tibia and fibula osteotomy through small incision, all tibia varum and shorting deformity were corrected slowly by circular external fixator. The patients were followed up for 1, 2, 3, 6, 12, 24 and 36 months after the operation. Preoperative and postoperative data at 12th and 36th month about tibia shorting deformity, angle of varus knee, medial proximal tibial angle, lateral distal tibial angle, the maximum length and width of the tumors which had been gone through by stainless steel needles were analyzed. Results As compared with the preoperative group whose tibia shorting deformity was (35.16±8.62) mm, postoperative tibia shorting deformity at 12th and 36th month was (16.04±2.73) mm and (6.99±1.93) mm respectively, the difference between the two groups had statistical significance (t=15.927, P=0.000; t=20.814, P=0.000). As compared with the preoperative group whose angle of varus knee was (25.0±7.9)°, postoperative angle of varus knee at 12th and 36th month was (2.1±0.9)° and (5.0±1.1)° respectively, the difference between the two groups had statistical significance (t=15.955, P=0.000; t=13.843, P=0.000). As compared with the preoperative group whose medial proximal tibial angle was (70.6±3.0)°, postoperative medial proximal tibial angle at 12th and 36 month was (88.7±1.6)° and (87.6±1.4)° respectively, the difference between the two groups had statistical significance (t=-26.806, P=0.000; t=-28.591, P=0.000). As compared with the preoperative group whose lateral distal tibial angle was (131.5±2.9)°, postoperative lateral distal tibial angle at 12th and 36th month was (88.9±1.9)° and (89.3±1.8)° respectively, the difference between the two groups had statistical significance (t=78.459, P=0.000; t=71.467, P=0.000). As compared with the preoperative group whose the maximum length of the tumors was (46.2±23.7) mm, postoperative maximum length of the tumors at 12th and 36th month was (47.2±24.0) mm and (46.6±24.1) mm respectively, the difference between the two groups had no statistical significance (t=-1.808, P=0.081; t=-0.741, P=0.464). As compared with the preoperative group whose maximum width of the tumors was (33.9±5.0) mm, postoperative the maximum width of the tumors at 12th and 36th month was (34.6±6.3) mm and (35.1±5.1) mm respectively, the difference between the two groups had no statistical significance (t=-1.014, P=0.319; t=-1.910, P=0.066). All patients were not diagnosed with osteomyelitis and had no symptoms of nerve and vascular injury. Conclusion It demonstrates that tibia deformity correction by circular external fixator in multiple enchondromatosis is safe and effective. Tumors being gone through by stainless steel needles have no growth rapidly in a short time. But the higher probability of malignant change is necessitating lifelong follow-up. Key words: Multiple enchondromatosis; Tibia; Circular external fixator

Enchondroma of the Hand: Evaluation and Management

Enchondroma is the most common primary bone tumor of the hand. This benign, cartilaginous tumor often presents as a pathologic fracture. When hand enchondroma is suspected, less common conditions, such as multiple enchondromatosis syndromes and benign and malignant lesions, should be ruled out. Surgical management with curettage is the standard of care for symptomatic lesions. However, controversy surrounds the timing of surgery for pathologic fractures and the use of surgical adjuncts and postcurettage void management. Microscopically distinguishing hand enchondroma from low-grade hand chondrosarcoma is a diagnostic challenge for pathologists, but the primary surgical treatment for both conditions is curettage because the latter has a low metastatic potential. Postoperative complications are typically joint stiffness and soft-tissue[FIGURE DASH]related deformities, whereas recurrence and malignant degeneration of solitary lesions are much less common. Most patients return to full function after surgery.

Encondromatosis múltiple, enfermedad de Ollier

Multiple enchondromatosis (Ollier's disease) is a rare disease characterized by widespread enchondromas with a unilateral predominance, especially in fingers in early childhood. In general, the short tubular bones of the hand are involved, with progressive lesions resulting in cosmetic problems and functional deformities. Herein, we, describe two cases of Ollier's disease diagnosed on X-ray of hands followed by MRI. There was no evidence of cortical disruption or periosteal reaction associated in either case. The bone lesions revealed cartilaginous matrix. MRI using conventional T1W and T2W sequences and STIR showed expansile lesions within the metacarpals and phalanges of both hands with cartilaginous matrix.

Ollier Disease: Pathogenesis, Diagnosis, and Management.

Ollier disease (Spranger type I) is a rare bone disease that is characterized by multiple enchondromatosis with a typical asymmetrical distribution and confined to the appendicular skeleton. The pathogenesis of enchondromatosis is not clearly understood. Recently, heterozygous mutations of PTHR1, IDH1 (most common), and/or IDH2 genes have been suggested by various authors as genetic aberrations. Genomic copy number alterations and mutations controlling many vital pathways are responsible for the pathogenesis of Ollier disease. A comprehensive description of all genetic events in Ollier disease is presented in this article. Clinically, Ollier disease has a wide variety of presentations. This article describes the plethora of clinical features, both common and rare, associated with Ollier disease. Multiple enchondromas are most commonly seen in phalanges and metacarpals. Radiologically, Ollier disease presents with asymmetrical osteolytic lesions with well-defined, sclerotic margins. In this article, various radiological features of Ollier disease, including radiographs, computed tomography, and magnetic resonance imaging, are also discussed. Gross pathology, cytological, and histological features of both Ollier disease and its malignant transformation are outlined. Although treatment is conservative in most cases, different possible treatment options for difficult cases are discussed. In the literature, there is a paucity of data about the disease, including diagnosis, management, prognostication, and rehabilitation, necessitating a comprehensive review to further define all of the possible domains related to this disease.

Limb reconstruction in Ollier's disease.

We present our experience of lengthening and correction of complex deformities in the management of patients with Ollier’s dysplasia (multiple enchondromatosis) from 1985 and 2002. All patients were under 18 years with a minimum follow-up time of 2 years (mean 9.6 years, range 2–15 years). There were a total of ten patients of which seven were male and three female. The mean age at presentation was 10.7 years (range 5–17 years; SD 3.7 years). The total length gain was 42.3 mm (range 30–110 mm; SD 28.9 mm). The number of days in external fixation was 164.8 days (range 76–244 days; SD 42.9 days). The bone healing index was 32.5 days/cm (18–50 days/cm; SD 10.3 days/cm). Patients with Ollier’s disease have limb length inequality and angular deformities and require multiple reconstructive procedures owing to a high incidence of recurrence. We identified a tendency for the osteotomy to prematurely consolidate and advise the latency period after surgery to be 4–5 days and for distraction to proceed at a faster rate.

Correction of Length Discrepancy of Radius and Ulna with Distraction Osteogenesis: Three Cases.

Objectives. The aim of the study was to investigate the results of patients with isolated length discrepancy between ulna and radius who underwent distraction osteogenesis with unilateral external fixator. Material and Methods. A patient with ulna shortening due to multiple enchondromatosis, a patient with ulna shortening due to ulnar club hand, and a patient with radial shortening due to radial club hand were included in the study. The patients underwent ulna and radial distraction osteogenesis with unilateral external fixator. Range of wrist and forearm motion, deformities, and length discrepancy of ulna and radius were compared at preoperative and postoperative. Results. Duration of external fixation and followup were 2.6 and 23.3 months, respectively. Mean distraction osteogenesis was 1.66 cm. No patient reached the length of normal side. Range of rotation of forearm was increased by 15°. Range of ulnar-radial deviation was increased by 21.6°. Deformity of 15° at patient with multiple enchondromatosis was corrected. Conclusion. Isolated ulna or radius shortening may reduce with distraction osteogenesis by unilateral external fixator to prevent serious deformity.

Growth hormone deficiency and multiple Enchondromatosis (Ollier disease) in a boy with short stature

We present a boy diagnosed and treated with growth hormone (GH) for isolated GH deficiency. During 2 year follow up he did not catch up in both height and weight. Although there was no skeletal disproportionality, nor any other complaints, his walk began changing and lower limbs deformity appeared (genua vara). Extensive skeletal radiological survey found multiple enchondromatosis (knees, iliac bones) and Ollier disease was diagnosed. There is no specific treatment for this condition, but its presence questions future GH therapy. The poor response to growth hormone treatment and the risk of developing malignant transformation in the future raises the important questions of the real benefits and the possible harms of its maintenance.

Chondrosarcoma of the Proximal Humerus Secondary to Ollier Disease: An 8-Year Follow-Up of Successful Resection of the Tumor With Endoprosthetic Replacement of the Proximal Humerus

We present a 25-year-old male patient with a diagnosis of multiple enchondromatosis, who developed chondrosarcoma on the proximal humerus of the right upper limb. The patient had the pre-existing lesions of Ollier’s disease discovered during his childhood. The patient underwent wide resection of the sarcoma with a prosthetic replacement of the proximal humerus. So far we have followed up the patient for 8 years with no evidence of local recurrence and/or metastasis. The therapeutic results have been satisfied with a good functional recovery of the treated limb, enabling the patient to return to the pre-disease daily living and occupational activities. The reconstructive procedures represent an effective surgical strategy for limb salvage in the treatment of large segmental defects after resection of humeral tumors, substantially solving the functional and esthetic problems due to such a wide resection, and significantly improving the quality of life for the patient.