Ollier's Disease Research Articles

Impact of Patient and Tumor Characteristics on Range of Motion and Recurrence Following Treatment of Enchondromas of the Hand

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. 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. 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). 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. Therapeutic IV.

Сонографічна діагностика акроформи хвороби Ольє у дітей

Вступ. Хвороба Ольє, відома також під назвами «дисхондроплазія», «множинний енхондроматоз», є порушенням хондрогенезу, при якому спотворюється енхондральне окостеніння, що призводить до розвитку внутрішньокісткових хрящових осередків. Мета даної роботи: удосконалити діагностику акроформи хвороби Ольє шляхом встановлення та висвітлення ультрасонографічних особливостей проявів перебігу акроформи дисхондроплазії. Результати. За нашими даними, інформативність поєднання ультразвукової діагностики з традиційною рентгенографією була вищою на 1/3 порівняно із застосуванням виключно рентгенівського методу. Тому основним завданням було обговорення й аналіз результатів ультразвукового дослідження акроформи хвороби Ольє. Встановлено характерні сонографічні прояви акроформи дисхондроплазії: випуклі, щільні, нерівні, хвилясті контури утворення, з неправильною формою та неоднорідною структурою. Ультрасонографічно діагностовано 61 патологічний осередок, серед яких 18 (29,5 %) не було виявлено на первинних рентгенограмах, це пояснюється їх незначними розмірами в поєднанні з відсутністю візуальних деформацій на початкових стадіях уражень та проекційними похибками при рентгенографії. Висновки. Ультрасонографія є перспективним і пріоритетним методом діагностики у хворих з акроформою дисхондроплазії, інформативність якого вища, ніж у виключно рентгенологічного методу, на 29,5 %. За даними ультразвукової діагностики, акроформа дисхондроплазії характеризується наявністю в кістках кистей патологічних хрящеподібних утворень з нерівними контурами, неправильної форми та неоднорідною ехоструктурою. Застосування ультразвукової діагностики при акроформі хвороби Ольє в комбінації з рентгенографією сприяє більш ранньому виявленню клінічно безсимптомних хрящових осередків у кістках кистей, дозволяє проводити моніторинг їх розвитку, своєчасно виявляти загрозу росту патологічного вогнища за межі кортікального шару в суміжні тканини, що є підґрунтям для хірургічного видалення вищевказаних уражень Ольє.

Ollier's disease associated with ovarian juvenile granulosa cell tumor and triple X syndrome: A letter to the editor.

Ollier's disease associated with ovarian juvenile granulosa cell tumor and triple X syndrome: A letter to the editor.

OD121 - Organ dose evaluation in radiological monitoring of paediatric Ollier disease

OD121 - Organ dose evaluation in radiological monitoring of paediatric Ollier disease

Proton Radiation Therapy for Pediatric Skull Base Chondrosarcomas

<h3>Purpose/Objective(s)</h3> Skull base chondrosarcomas are extremely rare tumors, accounting for 6% of skull base (BOS) neoplasms and 0.15% of all intracranial tumors. There are very few studies discussing chondrosarcomas in pediatric population. We report outcomes for children and young adults with BOS chondrosarcomas treated with proton radiotherapy (PRT). <h3>Materials/Methods</h3> Between 1984 and 2018, pediatric patients were treated with PRT or combined proton/photon RT (comboRT) at a single institution. The primary endpoints were overall survival (OS) and progression free survival (PFS). Univariable analysis was used to identify prognostic factors for PFS. Cox proportional hazards regression and Kaplan Meier estimates were used for survival analyses. <h3>Results</h3> 65 patients were identified [37 females (57%) and 28 males (43%)]. Median age at diagnosis was 18 years (range, 6 -21). 3 patients presented with Ollier's disease. 63 patients (97%) were diagnosed with low-grade (grade 1-2/3) chondrosarcoma and 2 patients (3%) with a grade 3 chondrosarcoma. The majority of the patients (n = 42, 65%) had a mixed hyaline and myxoid chondrosarcoma, 10 (15%) were diagnosed with a myxoid subtype, 4 (6%) with a hyaline one, and 4 (6%) patients had a mesenchymal chondrosarcoma. All patients underwent surgical resection (range, 1-6). 7 patients (6%) underwent gross total resection, 51 patients (78%) underwent STR while 7 patients (6%) had biopsy only. 3 patients (4%) received pre-RT chemotherapy. All patients received post-operative radiation therapy. 22 (34%) patients developed progressive disease prior to RT. The median time from the time of diagnosis to RT was 8.6m (range, 1.2 - 113.7). 22 patients (34%) were treated with PRT and 43 (66%) patients received comboRT. Median prescription dose was 70 Gy (RBE) (range, 55.8 – 76.3) delivered in 1.8 - 2 Gy (RBE) fractions. The median maximum dose to the brainstem was 66.3 Gy (RBE) (range, 26 – 74.6). The median maximum dose to the optic chiasm was 62.5 Gy (RBE) (range, 3.8 – 66.1). At a median follow-up of 10 years (range, 0.6 –33.7) from the date of diagnosis, 8 patients recurred (4 local, 2 distant, 2 both local and distant). 4 patients died of disease. 4 patients died of other causes The 10-year OS and PFS rates were 91.9% (95% CI: 79.4 – 97.0) and 84.9% (95% CI: 70.2-92.7), respectively. On univariate analysis, high grade, mesenchymal chondrosarcoma, pre-RT chemo and larger tumor size were worse prognostic factors for PFS. RT was well tolerated, with most acute side effects limited to moderate erythema and epilation, otitis media, and nausea. Late toxicities include 1 case of RT-induced GBM of the brainstem, 1 case of radiation necrosis, 2 cases of RT-related vascular malformations, 4 cases of temporal lobe injury, and 1 case of RT ocular neuromyotonia. <h3>Conclusion</h3> This is the largest cohort of pediatric BOS chondrosarcomas in the literature to date. High dose PRT following surgical resection achieves excellent disease control with minimal toxicity.

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.

Update on the imaging features of the enchondromatosis syndromes

Ollier disease and Maffucci syndrome are the commonest enchondromatosis subtypes, arising from non-hereditary mutations in the IDH1 and IDH2 genes, presenting in childhood and being characterised by multiple enchondromas. Maffucci syndrome also includes multiple soft tissue haemangiomas. Aside from developing bony masses, osseous deformity and pathological fracture, ~ 40% of these patients develop secondary central chondrosarcoma, and there is increased risk of non-skeletal malignancies such as gliomas and mesenchymal ovarian tumours. In this review, we outline the molecular genetics, pathology and multimodality imaging features of solitary enchondroma, Ollier disease and Maffucci syndrome, along with their associated skeletal complications, in particular secondary chondrosarcoma. Given the lifelong risk of malignancy, imaging follow-up will also be explored. Metachondromatosis, a rare enchondromatosis subtype characterised by enchondromas and exostoses, will also be briefly outlined.

Ollier disease and neurological complications—a clinical case

Ollier disease, also known as enchondromatosis, is a rare skeletal disease with an estimated prevalence of about 1/100,000. It is characterized by the presence of multiple intraosseous, usually benign cartilage tumors, enchondromas, showing a risk of malignant transformation. The latter is very likely in patients with Maffucci syndrome, where, in addition to enchondromatosis, multiple hemangiomas are observed. Cases of the disease with involvement of the skull bones and intracranial tumor masses have been described in the literature. According to some authors, the treatment of intracranial enchondromes is surgical, aiming at a complete removal. According to others, emphasis should be placed on monitoring, as lesions may remain asymptomatic and surgical resection may lead to additional complications. This article presents the case of a woman with known Ollier disease, hospitalized because of severe headache and blurred vision, presenting with limited mobility of the eyeballs inwards and upwards, with computed tomography data for tumor formation on the right parasellar with multiple cell calcifications interpreted as related to the underlying disease. Some diagnostic and therapeutic challenges in this rare pathology have been discussed.

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.

Liver Mass in a Young Male With Ollier Disease

Question: A 29-year-old Asian man with a history of Ollier disease (OD) presented to an outside medical center with right upper quadrant abdominal pain. He underwent a computed tomography (CT) scan of the abdomen and pelvis, which showed multiple bilateral hypodense lesions in the liver. A CT-guided liver mass biopsy was performed and was interpreted as hepatocellular carcinoma (HCC), nuclear grade II/III. He was discharged with consideration of participation in an immunotherapy-based clinical trial for unresectable HCC.

Cancer surveillance in children with Ollier Disease and Maffucci Syndrome

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Polyostotic Fibrous Dysplasia With Extensive Cartilaginous Differentiation: A Rare Case Clinically Mimicking Ollier Disease

Abstract Fibrous dysplasia is a dysplastic disorder of bone caused by missense mutations of the GNAS1 gene. Fibrocartilaginous dysplasia (also known as fibrochondrodysplasia or fibrous dysplasia with extensive cartilaginous differentiation) is a rare variant of fibrous dysplasia with extensive cartilaginous differentiation that shows a predilection for the lower extremities and can affect one or multiple bones. Although benign, this entity causes progressively expansile lesions that can lead to deformity and ultimately pathologic fracture. On imaging, this entity can show features consistent with a variety of benign and malignant cartilage-forming tumors. We present the case of a 16-year-old male patient who presented with clinical history of Ollier disease and multiple presumed enchondromas. He underwent below-the-knee amputation for progressive tibial deformity, pathologic fracture, and pain. Microscopic examination of multiple lower-extremity bones revealed a fibro-osseous lesion with massive cartilaginous differentiation consistent with fibrocartilaginous dysplasia.

Diffuse Astrocytoma and Ollier’s Disease

Several syndromes are associated with an increased incidence of intracranial tumors. Among these is enchondromatosis. It is a rare, nonhereditary condition. The common subtypes of enchondromatosis are Ollier’s disease (OD) and Maffucci syndrome. It has been distinguished between them by the presence of vascular malformation and non-skeletal neoplasm in Maffucci syndrome. The emergence of malignant neoplasms, including gliomas is a well-recognized complication in Maffucci syndrome, but over the past few years there has been an increasing number of reported cases of patients with intracranial tumors and OD. In our case report we discuss a 23-year-old female recently diagnosed with World Health Organization (WHO) grade II diffuse astrocytoma and found to have OD. J Neurol Res. 2020;10(6):240-244 doi: https://doi.org/10.14740/jnr580

Abstract 5909: IDH mutations in G2-3 conventional chondrosarcoma of bone: a mono institutional experience

Abstract Purpose: 5-years overall survival (OS) in high grade conventional chondrosarcoma is about 50%. Grade has been identified as the main prognostic factor. Heterozigous isocitrate dehydrogenase (IDH) mutations are present in about half of conventional chondrosarcomas, with higher frequency in low grade lesions. IDH prognostic role is not fully understood. Aim of this study is to assess the frequency of IDH mutations in high grade chondrosarcoma, their relationship with clinical characteristics, and their prognostic role. Methods: patients who underwent surgery at Rizzoli between 2002 and 2012 with a diagnosis of G2- G3 conventional chondrosarcoma and fresh frozen tissue available were selected from archives. DNA extraction was performed with commercial kit. PCR amplification of exon 4 of IDH1 and IDH2 genes, and sequencing analysis with Sanger was performed. Results: 54 patients identified:18 (33%) were male, 36 (67%) female; median age was 62 (range 17-85 years). 40 (74%) patients had localized tumor, and 14 (26%) presented with metastases. Tumor was in the extremities in 25 (46%) patients. 41 (76%) of the cases were G2, 13 (24%) G3. 4 patients had a genetic predisposition (1 Maffucci syndrome and 3 Ollier disease). IDH mutation was detected in 26 (48%) of the patients (20 IDH1, 4 IDH2, and 2 patients both IDH1 and 2). Frequency of mutation was 17 (65%) in G2, and 9 (35%) in G3. 4/4 chondrosarcomas in with a syndrome presented a mutation. Gender, site and stage were not significantly different by mutational status. After a median follow-up of 124 months (range 1-166) the 5-year OS was 51% (95% CI:36-64), with no difference according to mutational status (5-year OS IDHmut 54% vs IDHwt 48%, p=0.45), and better survival for localized vs metastatic pts (68% vs 7%, p&amp;lt;0.001), and for grade G2 vs G3 (59% vs 22%, p=0.0031). No difference in survival was observed for gender and site. In 25/27 patients with histological confirmation of recurrence/progression (21 cases G2, 4 G3), 27% of G2, IDHwt chondrosarcomas at initial diagnosis acquired higher grade in the recurrence, as compared with 50% in G2 IDHmut tumors. Conclusions: IDH mutations had higher frequency in G2 chondrosarcomas as compared to G3. No difference in OS according to mutational status was demonstrated. IDH mutated tumors had higher rate of grade progression at relapse, as compared to IDHwt. Confirmation of our results is needed in a larger series. Citation Format: Elisabetta Setola, Stefania Benini, Alberto Righi, Gabriella Gamberi, Sofia Avnet, Elisa Carretta, Cristina Ferrari, Emanuela Palmerini, Pier Luigi Lollini, Marilena Cesari, Anna Paioli, Alessandra Longhi, Davide Maria Donati, Nicola Baldini. IDH mutations in G2-3 conventional chondrosarcoma of bone: a mono institutional experience [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5909.

Gene of the month: IDH1

Isocitrate dehydrogenase 1 (IDH1) encodes a protein which catalyses the oxidative decarboxylation of isocitrate to α-ketoglutarate. Mutant IDH1 favours the production of 2-hydroxyglutarate, an oncometabolite with multiple downstream effects which...

Single-Bone Forearm as a Salvage Procedure in Recalcitrant Pediatric Forearm Pathologies

To report on the outcome of single-bone forearm reconstruction (SBFR) as a salvage procedure in pediatric forearm pathologies. Twenty-eight forearms in 27 patients (median age, 9.6 years; range, 3.4-29.7 years) treated with SBFR at a pediatric referral center were included in the study. Records and radiographs were retrospectively analyzed. Median follow-up was 84 months (range, 24-261 months). The most common underlying condition was multiple hereditary exostoses (MHEs) (17 of 28), followed by brachial plexus birth injury (5 of 28), Ollier disease (2 of 28), congenital radial head dislocation (2 of 28), and others (2 of 28). By 4 months (range, 2-10 months) after surgery, 21 of 28 forearms had united. Median resting postoperative forearm rotation was 10° pronation (range, neutral to 25° pronation). Before surgery, pain was present in 23 of 28 forearms. At the latest follow-up, pain was present in 5 of 28 forearms. In three of the 5 forearms with residual pain, this was attributed to ulnohumeral degenerative changes that existed prior to SBFR. Following SBFR, elbow flexion-extension range was maintained. In the subgroup with MHEs, radial articular angle was maintained (median, 37°-30°) and carpal slip percentage improved significantly (median, 40%-12%). Complications occurred in 8 forearms: 3 cases of nonunion in older patients (age, 30, 20, and 14 years), 2 cases of traumatic juxtaimplant fractures following successful union, 1 case of infection, 1 case of compartment syndrome, and 1 case of persistent radiocapitellar impingement. All complications were successfully treated. When stratified by age, none of the patients in the younger group (16 forearms, age < 12 years) had nonunions or pain at latest follow-up. The SBFR is an old, but generally reliable, option as a single-stage salvage procedure for a number of recalcitrant pediatric forearm pathologies. Success rate may be higher in younger patients. Therapeutic IV.

Physical Therapy Management in Femoral Ollier Disease

Introduction: Ollier disease (OD) is a non-hereditary, an uncommon bone disorder that typically presented by multiple or unilateral enchondromatosis associated with the deformity of the extremities. This article describes a case of a patient with OD that contribute endochondral ossification of the femoral bone and the physical therapy management.Case Description: An eight years old female patient referred to physical therapy unit after resection of right femur enchondroma, had undergone surgery for bone lengthening with external fixation. Further, the patient has been undergone surgical intervention for the tibial enchondromatosis. Physical therapy management aimed to improve the range of motion, pain, gait pattern, and activity of daily living. After three sessions of intervention, the patient reported the improvement in the pain and range of motion of the right lower limb.Conclusion: The physical therapy management might improve the pain and lower limb range of motion after the surgical intervention in femoral OD.

Multiple hereditary exostoses and enchondromatosis.

Multiple hereditary exostoses (MHE) and enchondromatosis are rare multifocal benign disorders usually causing skeletal deformities appearing already in childhood. MHE is a dominant autosomal inherited disorder characterized by multiple osteochondromas (exostoses) growing outward from the metaphyses of long bones as well as from flat bones. They may cause reduced joint motion and pain due to tendon, muscle, and nerve compression. Enchondromatosis (or Ollier's disease) is a noninherited disorder characterized by the presence of multiple intraosseous enchondromas located asymmetrically in the skeleton and with a wide variation regarding location, size, and number ranging from the involvement of a single hand to the involvement of the entire skeleton. It can occur together with soft-tissue hemangiomas in Maffucci's syndrome. Clinical problems caused by the enchondromas are mainly related to skeletal deformities causing malalignment and restricted motion of joint. In both disorders, there is a risk of malignant transformation as well as secondary degenerative joint changes.

Natural history of Ollier disease and Maffucci syndrome: Patient survey and review of clinical literature.

Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant in 8.5% of cases. OD is characterized by multiple enchondromas, typically unilateral in distribution with a predilection for the appendicular skeleton. MS is characterized by multiple enchondromas bilaterally distributed in most of the cases. Both disorders feature multiple swellings on the extremity, deformity around the joints, limitations in joint mobility, scoliosis, bone shortening, leg-length discrepancy, gait disturbances, pain, loss of function, and pathological fractures. About 50% of patients with OD or MS develop a malignancy, such as chondrosarcoma, glioma, and ovarian juvenile granulosa cell tumor. To better understand the natural history of OD and MS, we reviewed 287 papers describing patients with OD and MS. We also created a survey that was distributed directly to 162 patients through Facebook. Here, we compare the review of the cases described in the literature to the survey's responses. The review of the literature showed that: the patients with OD are diagnosed at a younger age; the prevalence of chondrosarcomas among patients with OD or MS was ~30%; in four patients, vascular anomalies were identified in internal organs only; and, the prevalence of cancer among patients with OD or MS was ~50%. With these data, health care providers will better understand the natural history, severity, and prognosis of these diseases and the prevalence of malignancies in these patients. Here, we recommend new guidelines for the care of patients with OD and MS.

Differential Diagnosis of Cartilaginous Lesions of Bone.

Cartilaginous tumors represent one of the most common tumors of bone. Management of these tumors includes observation, curettage, and surgical excision or resection, depending on their locations and whether they are benign or malignant. They can be diagnostically challenging, particularly in small biopsies. In rare cases, benign tumors may undergo malignant transformation. To review common cartilaginous tumors, including in patients with multiple hereditary exostosis, Ollier disease, and Maffucci syndrome, and to discuss problems in the interpretation of well-differentiated cartilaginous neoplasms of bone. Additionally, the concept of atypical cartilaginous tumor/chondrosarcoma grade 1 will be discussed and its use clarified. PubMed (US National Library of Medicine, Bethesda, Maryland) literature review, case review of archival cases at the Massachusetts General Hospital, and personal experience of the authors. This review has examined primary well-differentiated cartilaginous lesions of bone, including their differential diagnosis and approach to management. Because of the frequent overlap in histologic features, particularly between low-grade chondrosarcoma and enchondroma, evaluation of well-differentiated cartilaginous lesions should be undertaken in conjunction with thorough review of the imaging studies.