Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report.

Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.

Brain and/or Spinal Cord Tumors Accompanied with Other Diseases or Syndromes.

Several medical conditions that interest both the brain and the spinal cord have been described throughout the history of medicine. Formerly grouped under the term Phacomatosis because lesions of the eye were frequently encountered or genodermatosis when typical skin lesions were present, these terms have been progressively discarded. Although originally reported centuries ago, they still represent a challenge for their complexity of cure. Nowadays, with the introduction of advanced genetics and the consequent opportunity of whole-genome sequencing, new single cancer susceptibility genes have been identified or better characterized; although there is evidence that the predisposition to a few specific tumor syndromes should be accounted to a group of mutations in different genes while certain syndromes appeared to be manifestations of different mutations in the same gene adding supplementary problems in their characterization and establishing the diagnosis. Noteworthy, many syndromes have been genetically determined and well-characterized, accordingly in the near future, we expect that new targeted therapies will be available for the definitive cure of these syndromes and other gliomas (Pour-Rashidi et al. in World Neurosurgery, 2021). The most common CNS syndromes that will be discussed in this chapter include neurofibromatosis (NF) types 1 and 2, von Hippel-Lindau (VHL) disease, and tuberous sclerosis complex (TSC), as well as syndromes having mostly extra-neural manifestations such as Cowden, Li-Fraumeni, Turcot, and Gorlin syndromes.

Juvenile granulosa cell tumor associated with Ollier disease.

Prior case reports have described synchronous ovarian juvenile granulosa cell tumor (JGCT) and enchondromatosis in patients with Ollier disease and Maffucci syndrome. We present a case of a juvenile granulosa cell tumor with an IDH1 somatic mutation identified in the ovarian tissue in a 15-year-old female who presented with abnormal vaginal bleeding, several months of irregular menses, and a large multicystic adnexal mass. Multiple mixed lytic and sclerotic lesions were identified in the bones of the pelvis on imaging studies obtained during the work-up of her abdominal mass. Like previous reports in patients with undiagnosed enchondromatosis, these lesions were presumed to represent skeletal metastases; however, biopsy tissue revealed a hyaline cartilage neoplasm. Subspecialty review of the imaging findings revealed imaging features classic for Ollier disease involving the flat bones of the pelvis. It is important for radiologists to be familiar with the association between enchondromatosis and JGCT. When a female patient with enchondromatosis presents with a large, unilateral, mixed solid-cystic ovarian mass, the diagnosis of JGCT can be suggested. Alternatively, when a patient is diagnosed with JGCT, any skeletal lesions should be scrutinized for imaging features that suggest a hyaline cartilage neoplasm to avoid the misdiagnosis of skeletal metastases in a patient with previously undiagnosed Ollier disease or Maffucci syndrome. To our knowledge, this is the second reported confirmed case of an IDH1 somatic mutation identified in the ovarian tissue of a JGCT in a patient with Ollier disease.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

New bone formation accelerates during lower limb lengthening and deformity correction in children with Ollier's disease.

BACKGROUND: Ollier's disease can cause severe length discrepancy of the lower extremities and deformity in children. Osteotomy and limb lengthening with external fixation can correct the limb deformity. This study evaluated (1) whether the duration of external fixation was reduced in patients with Ollier's disease, and (2) the incidence of complications such as pin tract infection, external fixation loosening, and joint stiffness. METHODS: Two groups were compared with respect to age, angular correction (AC), lengthening gap (LG), distraction index (DI), lengthening length (LL), lengthening length percentage (L%), lengthening index (LI), bone healing index (BHI), and external fixation index (EFI). Group 1 (Ollier's disease) comprised nine patients undergoing 11 lower limb lengthening procedures using external fixators; group 2 (control, normal lengthened bone) comprised 28 patients undergoing 29 lengthening procedures with external fixators. RESULTS: In patients with Ollier's disease, full correction of the deformity and full restoration of length were achieved in all cases. In the femur, the mean AC (15.97° vs. 6.72°) and DI (1.11 mm/day vs. 0.78 mm/day) were significantly larger, while the LI (9.71 days/cm vs. 13.49 days/cm), BHI (27.00 days/cm vs. 42.09 days/cm), and EFI (37.86 days/cm vs. 56.97 days/cm) were all significantly shorter in group 1 than in group 2 (p < 0.05). In the tibia, the mean AC and L% were larger, while the LG, LI, BHI, and EFI were all shorter in group 1 than in group 2. There was no significant difference between the two groups in the incidence of complications. CONCLUSION: In children with Ollier's disease, new bone formation accelerated and the healing speed of the lengthened segments was faster throughout the whole lengthening period with external fixation, and full correction of the deformity and full restoration of length could be achieved.

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.

MRI features of low-grade and high-grade chondrosarcoma in enchondromatosis.

OBJECTIVE: To identify magnetic resonance imaging (MRI) features which aid differentiation of low-grade chondral tumours (LGCT-enchondroma and grade 1 chondrosarcoma) from high-grade chondral tumours (HGCT) in patients with enchondromatosis. MATERIALS AND METHOD: Approval from our local Research and Innovation Centre of The Institute of Orthopaedics was gained. Patients with enchondromatosis who had biopsy and/or resection of chondral lesions over a 13-year period were identified. The pre-biopsy MRI study was assessed by two experienced musculoskeletal radiologists for tumour origin (intramedullary or surface), cortical expansion, cortical destruction, bone marrow oedema, periosteal reaction, soft tissue mass and soft tissue oedema. MRI features were compared with the final histopathological diagnosis. RESULTS: The study group comprised 25 males and 16 females, with a mean age of 34.9 years (range 6-81 years). Fifty-nine lesions were assessed (12 patients had > 1 tumour treated), including 43 LGCT and 16 HGCT. Significant MRI features suggesting malignant transformation to HGCT for both observers included bone oedema (p = < 0.001 and 0.002), periosteal reaction (p = 0.01) and soft tissue oedema (p = 0.001 and 0.05). Cortical destruction and soft tissue mass were predictors of HGCT in major long bones, but no significant differentiating features were identified in the hands and feet. CONCLUSION: The presence of bone oedema, periosteal reaction and soft tissue oedema on MRI may indicate a high-grade malignant transformation of chondral tumours in patients with enchondromatosis.

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.

[Chondrosarcoma of the hand arising from multiple enchondromas: a case report]. / Chondrosarkom an der Hand bei multiplen Enchondromen: ein Fallbericht.

Malignancy occurs more often in multiple enchondromas than in solitary enchondromas. In the hands the rate is about 14%. We amputated the third ray of the hand in a young man with recurrence of an enchondroma. The histology showed a low grade chondrosarcoma. The patient had no tumour recurrence or metastasis in the following 5 years. We describe the evaluation as well as the treatment and outline the literature.

Limb lengthening for deformities in Ollier's disease: a systematic review.

BACKGROUND: The management of limb deformity, shortening, and bone defects in treatment of Ollier's disease is a major challenge. This study aims to summarize and compare the different surgical treatments, and to evaluate the outcome and possible prognostic factors of leg lengthening in these patients. MATERIALS AND METHODS: A systematic review of the literature from 1993 to 2017 was performed. Nineteen articles were found including a total of 121 patients with limb deformities because of Ollier's disease. The mean patients' age at the time of first surgery was 12 years. A total of 272 segments were surgically treated (14 segments in the upper limbs) with variable techniques including osteotomies and external fixation, intramedullary nails, as well as epiphysiodesis and lengthening over nail. We studied the bone healing index (BHI), distraction index (DI), distraction time, gained length, total treatment time, and complications. RESULTS: Available implants and techniques allowed correction of patients' deformities (lengthening and correction of angular defects) in most cases. External fixators, circular or monolateral frames were the most commonly used technique. The Ilizarov external fixator was the most commonly used frame (196 segments). The BHI was significantly better when the external fixation was combined with intramedullary nails. Epiphysiodesis was most likely to be more associated with the past than to the present. Joint stiffness, infection, early consolidation, pathological fracture, deformity recurrence, delayed union, non-union, neurapraxia, and overlengthening were the reported complications with an overall rate of 27.9%. CONCLUSIONS: There is no consensus for the optimal surgical technique and implants for correction of limbs deformities in patients with Ollier's disease. External fixators most commonly circular are the most commonly used implants; however, complications do occur.

Surgical Treatment of Enchondromas of the Hand During Childhood in Ollier Disease.

PURPOSE: The objective of the present study was to evaluate the outcome of surgical treatment of hand lesions in Ollier disease (OD) carried out during childhood. METHODS: A retrospective review was carried out of 10 pediatric patients with hand involvement of OD, who had undergone surgery for metacarpal or phalangeal enchondromas. The technique comprised curettage and cortical bone reconstruction with corticoplasty, to restore a near-normal phalangeal volume. The range of finger motion (pulp-to-palm distance), the shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire score, cosmetic improvement, radiological findings (according to Tordai's classification), and recurrence were recorded after a mean follow-up of 7.5 years (range, 4-11.3 years). RESULTS: The mean age at surgery was 10.7 years (range, 6-14 years). Curettage was performed on 35 enchondromas, and 9 cavities were filled with a bone graft. The mean pulp-to-palm distance was significantly lower after surgery (from 1.5 cm to 0.25 cm; P < .05). The mean QuickDASH score was 3.84 (range, 0-11.4). A marked cosmetic improvement was noted for 83% of the hands. Three enchondromas recurred in 1 patient, requiring a second curettage. Fifty-seven percent of the cavities were completely filled with bone (Tordai stage 1) at last follow-up. The outcome did not depend on the presence or absence of a bone graft. CONCLUSIONS: Our results suggest that early surgical treatment comprising curettage and corticoplasty leads to good clinical, cosmetic, and radiological outcomes. Early surgical treatment of well-developed and/or symptomatic enchondromas of the hand in OD should be considered. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Louis-Léopold-Xavier-Édouard Ollier (1830-1900): An Innovative Orthopedic Surgeon.

Louis-Léopold-Xavier-Édouard Ollier (1830-1900) was a pioneer in orthopedics considered as the founder of modern orthopedic surgery. He was a skillful and experimenter surgeon. He invented many new surgical techniques in orthopedic surgery and many new surgical instruments. His most known discovery is Ollier's disease.

Enchondroma of the Foot.

The present study is a review of 20 patients with enchondroma of the foot treated from January 2005 to March 2012. All patients were examined clinically, followed by an evaluation of their enchondroma of the foot radiographically and an assessment of the outcome of their surgical intervention. The patients' sex and age, enchondroma location, findings from imaging studies such as plain radiography, computed tomography, and magnetic resonance imaging, clinical findings, operative findings, and treatment outcomes were recorded. The average postoperative follow-up period was 24 months. Eighty percent of the tumors were located in the proximal phalanx and 14 (70%) patients presented with pathologic fracture. The plain radiographs and computed tomography findings revealed 13 (65%) cases of internal calcification and 11 (55%) with endosteal scalloping. A periosteal reaction was seen only in 4 (20%) cases. Magnetic resonance imaging of 11 (55%) patients showed low T1-weighted and high T2-weighted signal intensity in all cases. Internal septa and nodules with low T2-weighted signal intensity were observed in 9 (82%) out of 11 cases, and adjacent soft tissue edema was noted in 9 (82%). All patients underwent curettage of the tumor and bone grafting as their surgical treatment. No recurrence or postoperative complications were observed during the 24-month follow-up period. Enchondroma of the foot most frequently involves the proximal phalangeal bone and is often associated with pathologic fracture. The unique clinical signs and characteristic radiographic images are easily recognized, making this a relatively easy diagnosis. With appropriate treatment, a good surgical outcome can be expected.

Relapsing-Remitting Sixth Nerve Palsy in Association with Ollier's Disease.

Relapsing-remitting sixth nerve palsy is usually due to ophthalmoplegic migraine (recurrent cranial nerve palsy) in younger patients and microvascular disease in older patients. There have been isolated reports, however, of it occurring in the presence of a skull base tumour. We report a 20-year-old woman with Ollier's disease who presented with a relapsing-remitting sixth nerve palsy. Neuro-imaging revealed a skull base enchondroma.

Multiple enchondromas in Ollier's disease: A case report.

Ollier's disease is a rare sporadic nonhereditary condition associated with mutations in the IDH1 and IDH2 genes, that manifests in early age of life. It is characterized by widespread enchondromas, predominantly affecting one side of the body. Diagnosis is based on clinical and radiological evaluations, and interval assessment for Ollier's disease is important as enchondromas are at risk of malignant transformation into chondrosarcomas. This case report aims to discuss the role of bone scan and plain X-ray in managing multiple enchondromas of a 25-year-old male patient with swellings over the left chest wall and left acromial regions.

[Malignant transformation of Ollier disease-related multiple glioma with IDH1 p.R132C mutation].

A 21-year-old man who was diagnosed with Ollier disease at the age of 1 year developed incidental multiple gliomas at the age of 15 years. Subsequently, the multiple gliomas enlarged and the patient underwent three surgical removals. Genetic analysis revealed the IDH1 p.R132C mutation in the gliomas, and histopathology showed malignant transformation. Despite multimodality treatment, the gliomas could not be controlled, and the patient died at the age of 23 years. Ollier disease is a rare disease with IDH1/2 mutations and is often associated with gliomas. However, there are very few reports on genetic analysis of IDH1/2 mutations and long-term follow-up in Ollier disease-related gliomas. Genetic analysis of IDH mutations may contribute to the elucidation of its pathogenesis. The cross-departmental collaboration is required for long-term follow-up of Ollier disease-related gliomas.

Ollier Disease, Acute Myeloid Leukemia, and Brain Glioma: IDH as the Common Denominator.

Ollier disease (OD), acute myeloid leukemia (AML), and brain glioma (BG) are three apparently completely different neoplasms in terms of histopathology, clinic, natural history, and management, but they can affect the same patient. This study aimed to identify the common molecular pathways involved in the pathogenesis of all three diseases and discuss their current and potential role as therapeutic targets. A detailed and comprehensive systematic literature review according to PRISMA guidelines on OD patients harboring BG and/or AML was made. In addition, the unique case of a patient affected by all three considered diseases has been added to our case series. Demographic, pathological, treatment, and outcome data were analyzed and discussed, mainly focusing on the molecular findings. Twenty-eight studies reported thirty-three patients affected by OD and BG, and only one study reported one patient with OD and AML, while only our patient harbored all three pathologies. The IDH R132H mutation was the only genetic alteration shared by all three pathologies and was simultaneously detected in enchondromas and brain glioma in 100% (3/3) of OD patients with BG and also in the neoplastic blood cells of the single patient hosting all three diseases. The IDH1-R132H gene mutation is the etiopathogenetic common denominator among three apparently different tumors coexisting in the same patient. The adoption of mutant-specific IDH1 inhibitor molecules could represent a potential panacea for these conditions in the era of targeted therapies. Further studies with larger clinical series are needed to confirm our results and hypothesis.

Therapeutic effect of intramedullary reaming and nailing for long bones lengthening in children with Ollier disease and Maffucci syndrome on enchondromas: multicentric retrospective case series.

INTRODUCTION: Leg length discrepancy (LLD) and malalignment of long bones are frequent orthopedic problems encountered in Maffucci syndrome and Ollier disease (OD). Orthopedic surgeons used historically external fixators to address the deformities. In this multicentric case series, we propose the use of motorized intramedullary nails. METHODS: We retrospectively reviewed for 9 years, in four different centers, patients with OD and Maffucci's syndrome that had lengthening nails for LLD with or without associated deformities. The minimum follow-up period was 24 months. We reported complications, clinical tolerance of lengthening, lengthening rate and target, bone healing index, and EQ-5D-Y functional and visual analog scores (VAS). We also saw on X-rays the whole lengthened bone and its regenerate zone to assess the evolution of the enchondromas. RESULTS: we used the nailing technique in 8 femurs and 2 tibias in 8 patients (mean age: 13.3 years, range: 11-16, mean follow-up time: 53.8 months, range: 26-108). The mean correction amount was 6.44 cm for the femur over 76.8 days and 3.75 cm over 44 days for the tibia with a mean VAS score of 6.63/15 and mean EQ-5D-Y of 81/100. The lengthening goal was achieved in all patients. No mechanical complications were noted. The medullary canal of the operated bones showed improvement and healing in 8 out of 10 segments. DISCUSSION: Besides achieving the goals of surgery with good functional outcomes, lengthening nails has a therapeutic effect on enchondromas with fewer complications than traditional correction methods.

A Rare Ovarian Mixed Sex Cord Stromal Tumor in a Patient with Ollier Disease: A Case Report.

This is a case report of a 10-year-old with Ollier disease and an ovarian mass. Ollier disease, a rare disorder characterized by multiple enchondromas resulting in bone deformities, has been occasionally associated with ovarian juvenile granulosa cell tumor. This patient developed signs of precocious puberty and was found to have an ovarian tumor; however, pathology revealed a mixed sex-cord stromal tumor with components of juvenile granulosa and Sertoli-Leydig cell tumor. Tumor genomic testing revealed an IDH1 mutation. Mixed sex-cord stromal tumors of this type, also called "gynandroblastomas," have been associated with DICER1 mutations and DICER1 tumor predisposition syndrome but never with Ollier disease. Our findings expand the known spectrum of syndromic associations with this tumor type, with implications for tumor screening.