IMP3, CDK4, MDM2 and ß-catenin expression in Enchondroma and Central Chondrosarcoma: Diagnostic and prognostic utility.

INTRODUCTION: The role of IMP3, CDK4, MDM2 and ß-catenin proteins in Enchondroma and Central Chondrosarcoma is not totally understood. The aim of this study is to evaluate the immunoexpression of these proteins, associating histological grade, clinical data and prognosis to these tumors. METHODS: This is a retrospective-analytical study of 32 Enchondroma and 70 Central Chondrosarcoma. RESULTS: IMP3, CDK4, MDM2 and ß-catenin expression was observed in 22.82 %, 13.82 %, 17.17 % and in 8.8 % of cases, respectively. All Enchondromas positive for these immunomarkers were located in short tubular bones. The positivity for these antibodies is directly proportional to Chondrosarcoma's histological grade increase. No difference was found between Enchondroma and Chondrosarcoma, Grade 1 for IMP3, CDK4 and ß-catenin positivity. Significant metastasis outcome was observed for IMP3, CDK4, MDM2 and death for MDM2 expression. CONCLUSION: IMP3, CDK4, MDM2 and ß-catenin expression in Enchondromas of short bones phenotypically characterizes these tumors. Their expression has not proven to be useful either as diagnostic markers of these neoplasms or in distinguishing between Enchondroma and Chondrosarcoma, Grade 1. The significant immunoexpression of IMP3, CDK4 and MDM2 in metastatic Chondrosarcoma and the lower survival in those with positivity for MDM2 suggest a possible association of these proteins with tumor aggressiveness.

Clinical and radiological response of Maffucci related enchondromas to mutant IDH1 inhibitor Ivosidenib.

Ollier Disease (OD) and Maffucci syndrome (MS) is a rare bone disorder that affects the growth and development of the bones, with an estimated prevalence of 1 in 100,000 people. It is associated with somatic mosaicism of isocitrate dehydrogenase-1 (IDH1) or 2 (IDH2) pathogenic variants. Ivosidenib is indicated for the treatment of acute myeloid leukemia and locally advanced or metastatic cholangiocarcinoma and is currently investigated in low-grade glioma with a susceptible isocitrate dehydrogenase-1 (IDH1) pathogenic variant, but its effects in patients with OD or MS are unknown. We here report the first case of a patient with MS who was treated with Ivosidenib for recurrent IDH-1 mutated glioma. Besides the stabilization of the tumor size, the patient observed significant improvement in his enchondromas that became stiffer, with reduced pain, and significant modification of the mineralization of the enchondromas observed on X-rays. This first case report provides hope for the medical management of patients suffering because of OD or MS. Future clinical research is urgently needed to evaluate long-term benefit risk profile of IDH inhibitors in these rare diseases.

CT radiomics-based machine learning model for differentiating between enchondroma and low-grade chondrosarcoma.

It may be difficult to distinguish between enchondroma and low-grade malignant cartilage tumors (grade 1) radiologically. This study aimed to construct machine learning models using 3D computed tomography (CT)-based radiomics analysis to differentiate low-grade chondrosarcoma from enchondroma. A total of 30 patients with enchondroma and 26 with chondrosarcoma were included in this retrospective study. Tumor volume segmentation was manually performed by 2 musculoskeletal radiologists. In total, 107 radiomic features were obtained for each patient. The intraclass correlation coefficient was used to assess interobserver reliability and estimate the absolute agreement between the 2 radiologists. Algorithm-based information gain was used as a feature reduction method, and the 5 most important features were detected. For classification, 7 machine learning models were utilized. Classification was carried out using either all features or 5 features. There was good to excellent agreement between the 2 radiologists for the 107 features of each patient. Therefore, a dataset containing 107 features was used for machine learning classification. When assessed based on area under curve (AUC) values, classification using all features revealed that naive Bayes was the best model (AUC = 0.950), while classification using 5 features revealed that random forest was the best model for differentiating chondrosarcoma from enchondroma (AUC = 0.967). In conclusion, machine learning models using CT-based radiomics analysis can be used to differentiate between low-grade chondrosarcoma and enchondroma.

Extraskeletal chondroma of the toe in a child with DICER1 tumor predisposition syndrome: support for a dominant negative mechanism.

DICER1 tumor predisposition syndrome is a pleiotropic disorder that gives rise to various mainly pediatric-onset lesions. We report an extraskeletal chondroma (EC) of the great toe occurring in a child who, unusually, carries a germline "hotspot" missense DICER1 variant rather than the more usual loss-of-function (LOF) variant. No heterozygous LOF allele was identified in the EC. We demonstrate this variant impairs 5p cleavage of precursor-miRNA (pre-miRNA) and competes with wild-type (WT) DICER1 protein for pre-miRNA processing. These results suggest a mechanism through which a germline RNase IIIb variant could impair pre-miRNA processing without complete LOF of the WT DICER1 allele.

SPECT/CT Radiomics for Differentiating between Enchondroma and Grade I Chondrosarcoma.

This study was performed to assess the value of SPECT/CT radiomics parameters in differentiating enchondroma and atypical cartilaginous tumors (ACTs) located in the long bones. Quantitative HDP SPECT/CT data of 49 patients with enchondromas or ACTs in the long bones were retrospectively reviewed. Patients were randomly split into training (n = 32) and test (n = 17) data, and SPECT/CT radiomics parameters were extracted. In training data, LASSO was employed for feature reduction. Selected parameters were compared with classic quantitative parameters for the prediction of diagnosis. Significant parameters from training data were again tested in the test data. A total of 12 (37.5%) and 6 (35.2%) patients were diagnosed as ACTs in training and test data, respectively. LASSO regression selected two radiomics features, zone-length non-uniformity for zone (ZLNUGLZLM) and coarseness for neighborhood grey-level difference (CoarsenessNGLDM). Multivariate analysis revealed higher ZLNUGLZLM as the only significant independent factor for the prediction of ACTs, with sensitivity and specificity of 85.0% and 58.3%, respectively, with a cut-off value of 191.26. In test data, higher ZLNUGLZLM was again associated with the diagnosis of ACTs, with sensitivity and specificity of 83.3% and 90.9%, respectively. HDP SPECT/CT radiomics may provide added value for differentiating between enchondromas and ACTs.

Nasal chondrogenic tumors: Case reports of primary chondroma and recurrence of atypical cartilaginous tumor (chondrosarcoma grade I) with review of the literature.

Nasal chondromas and nasal atypical cartilaginous tumors (or chondrosarcoma grade 1) are very rare chondrogenic tumors. Approximately 150 cases of nasal chondroma and fewer than 50 cases of nasal atypical cartilaginous tumors have been described. We reported a case with nasal chondroma in the right ethmoid area and a case with a nasal atypical cartilaginous tumor of the anterior septum. No chondroma recurrence was noted for 17 years after endoscopic resection. Recurrence was noted for the nasal atypical cartilaginous tumor 36 months after wide surgical excision via midfacial degloving. Revision surgery was performed again via midfacial degloving. Recurrences of nasal chondroma and atypical cartilaginous tumors are extremely rare. The current data indicate adequate surgical excision, in some cases even radical, as the most important parameter to avoid recurrence. For inoperable recurrent cases of atypical cartilaginous tumors, observation may be followed.

Active surveillance of atypical cartilaginous tumours of bone: short term quality of life measurements.

BACKGROUND: In the recent years active surveillance has been introduced for atypical cartilaginous tumours (ACT). This is the first study on the impact of this new treatment approach on patients' quality-of-life. We evaluated general health-related quality of life (HRQL) in patients diagnosed with enchondroma or ACT. METHODS: In this prospective study, patients recently diagnosed with enchondroma and ACT of the long bones were asked to participate. Health-related quality of life (HRQL) was assessed at diagnosis and at six month follow-up, using the 36-item Short Form Health Survey (SF-36) and Numeric Pain Rating Scale (NRS). HRQL of the active surveillance group was compared to the Dutch population and a Dutch sample with locoregional cancer. RESULTS: In total, 45 patients were included in the study, of which four patients underwent curettage and cryosurgery, 41 patients were under active surveillance. The HRQL of the active surveillance group seemed lower compared to the Dutch population, but similar to patients suffering locoregional cancers. No comparison between the surgery and the active surveillance group could be made. In the active surveillance group no statistical difference was found between baseline and six months follow-up regarding HRQL and pain during rest and activities. CONCLUSION: Patients diagnosed with non-malignant chondroid tumours have lower HRQL compared to the healthy population. Active surveillance had no adverse effect on patients well-being, after six months active surveillance the HRQL remained unchanged. Interestingly, in our study no impact on mental health was seen, implicating that diagnosed but untreated chondroid tumours do not seem to influence patients anxiety.

Simple curettage and allogeneic cancellous bone chip impaction grafting in solitary enchondroma of the short tubular bones of the hand.

Enchondroma is the most common bone tumor in the hand. While standard surgical procedure is intra-lesional excision and bone grafting, there is a dispute between allogeneic bone, autogenous bone, and synthetic bone substitute grafting. Diverse adjuvant treatments have been introduced to reduce recurrence, but results are mixed with controversies. Meanwhile, whether existing descriptive classification could predict treatment outcome remains unclear. Thus, we reviewed patients with solitary enchondroma of the hand who underwent simple curettage followed by allogeneic cancellous bone chip impaction grafting. Eighty-eight patients with more than 5 years of follow-up were enrolled. Demographic data, local recurrence, and complications were reviewed. Duration of consolidation and the difference according to Takigawa classification were assessed. Range of motion (ROM), and functional scores were also evaluated. There were 51 women and 37 men, with a mean age of 37.9 years. Mean follow-up was 10.2 years. Recurrence occurred only in one patient. There was no complication. Mean postoperative total active motions of fingers and thumb were 239° and 132.9°. Mean modified Disabilities of the Arm, Shoulder, Hand score, and Musculoskeletal Tumor Society Score were 1.63, and 99.2 at the last follow-up. Consolidation, ROM, and functional scores according to Takigawa classification showed no significant differences. This study suggests that simple curettage with impaction grafting of allogeneic cancellous bone chip is a feasible method for treating solitary enchondromas involving short tubular bone of the hand with good long-term outcomes. Postoperative recurrence and complication rates were very low. Radiographic and clinical results were good regardless of the previous radiological classification.

Osteoscopic versus open surgery for the treatment of enchondroma in the foot.

INTRODUCTION: The conventional treatment of enchondromas is the open surgery with curettage of lesions. Osteoscopic surgery is a minimally invasive endoscopic approach for lesions inside bone. The aim of this study was to evaluate the feasibility of the osteoscopic surgery in comparison with the conventional open surgery for patients with foot enchondromas. MATERIALS AND METHODS: A retrospective cohort study comparing patients with foot enchondromas treated with osteoscopic or open surgery from 2000 to 2019. Functional evaluations were based on both the AOFAS score and the Musculoskeletal Tumor Society (MSTS) functional rate. Complication and local recurrence were evaluated. RESULTS: Seventeen patients underwent endoscopic surgery, and eight patients underwent open surgery. The AOFAS score was higher in the osteoscopic group than the open group at 1 and 2 weeks after surgery (mean, 89.18 vs 67.25 [p = 0.001], 93.88 vs 79.38 [p = 0.004]). The MSTS functional rate was also higher in the osteoscopic group than the open group at 1 and 2 weeks after surgery (mean, 81.96 vs 59.58% [p = 0.00], 90.98 vs 75.00% [p = 0.02]). No statistical differences were found after 1-month of surgery. The osteoscopic group had lower complication rate than the open group (12 vs 50%; p = 0.04). No local recurrence was found in any groups. CONCLUSION: The osteoscopic surgery is feasible to provide earlier functional recovery and fewer complications than the open surgery.

Concurrent intraosseous cartilaginous lesions in patients with multiple osteochondromas identified on total-body MR imaging.

PURPOSE: To assess the prevalence of intraosseous cartilaginous lesions in patients with multiple osteochondromas based on total-body (TB) MRI examinations, used for screening purposes. SUBJECTS AND METHODS: Between 2013 and 2020, TB-MRI examinations were performed in 366 patients with proven multiple osteochondromas syndrome, to rule out malignant progression. For this study, presence, or absence of intraosseous central or eccentrical chondroid lesions, defined as lobulated lesions with low signal intensity on T1-weighted images, replacing bone marrow and high signal intensity equal to fluid on T2-weighted images in the bone marrow of the meta-diaphysis of (one of) the long bones, were recorded in the long bones as part of a TB-MRI protocol. RESULTS: In 62 patients out of the 366 MO patients (17%), one or more intraosseous chondroid lesions (either enchondroma or atypical cartilaginous tumor) were detected. The age of the patients at time of diagnosis ranged from 17 to 61 years (mean, 36). Size of the lesions varied from 4 to 69 mm (mean, 16.3 mm). The most common location was the proximal femur (n = 29), followed by the distal femur and proximal humerus (n = 18 and n = 10, respectively). In nine of the patients with an intraosseous chondroid lesion, a second and/or third TB-MRI were available during the period of evaluation (mean interval, 2.7 years between the exams). In none of these patients increase of these intraosseous lesions was noticed. CONCLUSION: Intraosseous chondroid lesions (enchondroma and ACT) appear to occur more frequently in MO patients than in the general population. TB-MRI allows to detect these, besides the identification of OC with suspicious features.

Chondroma of the urinary bladder: A case report.

RATIONALE: Chondromas are benign tumors comprising cartilaginous tissue that commonly occur in the small bones of the hands and feet. Chondromas are extremely rare in extraskeletal soft tissues, and only six cases of bladder chondromas have been reported thus far. PATIENT CONCERNS: A 75-year-old woman presented with abdominal pain and urinary symptoms, including increased frequency and a weak stream. DIAGNOSIS: Cystoscopy revealed a well-defined bladder mass over the anterior bladder wall. The pathology report showed neoplastic chondrocytes within the hyalinized and focal myxoid matrix, and immunopositivity for S-100, leading to the seventh known diagnosis of bladder chondroma. INTERVENTIONS: The tumor was endoscopically resected. The postoperative stay was uneventful, and 5 days later, the patient was discharged after the removal of the urinary catheter. OUTCOMES: One month after surgery, repeated cystoscopy showed no recurrence of the bladder tumor, and the patient reported improvement in urinary symptoms and relief of lower abdominal pain. LESSONS: Chondromas of the urinary bladder can present as urinary symptoms and abdominal pain in older patients. Transurethral resection is the treatment of choice.

Rare Presentation of Pediatric Multiple Enchondromatosis Limited to Single Ray or Single Nerve Distribution in the Hand: A Multicenter Case Series.

BACKGROUND: Multiple enchondromas in the pediatric hand is a relatively rare occurrence and the literature regarding its incidence and treatment is sparse. Within this rare subset of patients, we identified a unique cohort in which lesions are confined to multiple bones in a single ray or adjacent rays within a single nerve distribution. We review the clinical and pathologic characteristics and describe the indications for and outcomes of treatment in this unique subset of patients as well as offer conjectures about its occurrence. METHODS: Institutional review board (IRB)-approved retrospective multicenter study between 2010 and 2018 identified subjects with isolated multiple enchondromas and minimum 2-year follow-up. Data analyzed included demographics, lesion quantification and localization, symptoms and/or fracture(s), treatment of lesion(s), complications, recurrence, and presence of malignant transformation. RESULTS: Ten patients were evaluated with average age at presentation of 9 years (range: 4 to 16) and mean clinical follow-up of 6 years (range: 2.8 to 8.6). Five subjects had multiple ray involvement in a single nerve distribution and 5 had single ray involvement with an average of 4 lesions noted per subject (range: 2 to 8). All children in the study had histopathologic-proven enchondromas and underwent operative curettage±bone grafting. Indications for surgical intervention included persistent pain, multiple prior pathologic fractures, impending fracture and deformity. During the study period three subjects experienced pathologic fracture treated successfully with immobilization. Recurrence was noted in 40% at an average of 105 weeks postoperatively (range: 24 to 260) and appears higher than that reported in the literature. No case of malignant transformation was observed during the study period. CONCLUSIONS: A rare subset of pediatric patients with multiple enchondromas of the hand is described with lesions limited to a single ray or single nerve distribution. Further awareness of this unique subset of patients may increase our understanding of the disease and improve patient outcomes. LEVEL OF EVIDENCE: Level IV-therapeutic (case series).

[Soft tissue tumours with FN1 (Fibronectin 1) fusion gene]. / Tumeurs des tissus mous avec fusion du gène FN1 (Fibronectine 1).

Translocations involving FN1 gene have been described in several tumours, which share the presence of a cartilaginous matrix with or without calcifications and a good prognosis. They encompass: soft tissue chondroma, synovial chondromatosis, calcifying aponeurotic fibroma, phosphaturic mesenchymal tumour and a new spectrum of tumours: "the calcified chondroid mesenchymal neoplasms". We review all the clinical, histopathological and molecular data of these tumours and discuss the differential diagnoses.

Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.

Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant, respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tumors with IDH mutations. Using genetic and pharmacological approaches, we demonstrated that glutaminase-mediated glutamine metabolism played distinct roles in enchondromas and chondrosarcomas with IDH1 or IDH2 mutations. Glutamine affected cell differentiation and viability in these tumors differently through different downstream metabolites. During murine enchondroma-like lesion development, glutamine-derived α-ketoglutarate promoted hypertrophic chondrocyte differentiation and regulated chondrocyte proliferation. Deletion of glutaminase in chondrocytes with Idh1 mutation increased the number and size of enchondroma-like lesions. In contrast, pharmacological inhibition of glutaminase in chondrosarcoma xenografts reduced overall tumor burden partially because glutamine-derived non-essential amino acids played an important role in preventing cell apoptosis. This study demonstrates that glutamine metabolism plays different roles in tumor initiation and cancer maintenance. Supplementation of α-ketoglutarate and inhibiting GLS may provide a therapeutic approach to suppress enchondroma and chondrosarcoma tumor growth, respectively. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).