[Clincopathological analysis of 171 patients with osteochondroma and malignant transformation in maxillofacial bone].

PURPOSE: To investigate the clinical and pathological features of osteochondroma in maxillofacial region, and to summarize the clinicopathological features of rare osteochondroma malignant transformation in order to provide clinical guidance. METHODS: From January 2018 to September 2023, a total of 171 patients with osteochondroma were retrospectively collected in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Their preoperative CT and clinicopathological features were analyzed. RESULTS: Of the 171 patients with osteochondroma in maxillofacial bone, 66%（113/171） were females and 34% were male. Their age ranged from 11-76 with an average age was 44 years old. Of the 171 cases, 95.3%（163/171）in mandible condyle, 4%(7/171) in mandible processus coronoideus, and 0.5%（1/171） in zygomatic arch. The imaging findings showed that the thickness of cartilaginous cap was less than 1 cm in 98%（159/161） cases with condyle lesions. Only 2 cases(2/171, 1.1%) had malignant transformation. One was diagnosed with secondary chondrosarcoma, another developed low-grade osteosarcoma. CONCLUSIONS: Osteochondroma in maxillofacial region mostly occurs in females, and most commonly located in condylar process, with a malignant change rate of 1.1%, which is similar to that of other parts of the body. Imaging findings have important guiding significance for the diagnosis of osteochondroma malignant change.

Bizarre parosteal osteochondromatous proliferation in the distal ulna where the lesion is continuous with the medullary cavity: a case report.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign bone tumor, it is also called "Nora's lesion". The lesion is characterized by heterotopic ossification of the normal bone cortex or parosteal bone. The etiology of BPOP is unclear and may be related to trauma. In most BPOPs, the lesion is not connected to the medullary cavity. Here we report an atypical case, characterized by reversed features compared to the typical BPOP, which demonstrated continuity of the lesion with the cavity. CASE PRESENTATION: An 11-year-old female child had a slow-growing mass on her right wrist for 8 months with forearm rotation dysfunction. Plain X-rays showed an irregular calcified mass on the right distal ulna, and computed tomography (CT) showed a pedunculated mass resembling a mushroom protruding into the soft tissue at the distal ulna. The medulla of this lesion is continuous with the medulla of the ulna. A surgical resection of the lesion, together with a portion of the ulnar bone cortex below the tumor was performed, and the final pathology confirmed BPOP. After the surgery, the child's forearm rotation function improved significantly, and there was no sign of a recurrence at 1-year follow-up. CONCLUSION: It is scarce for BPOP lesions to communicate with the medullary cavity. However, under-recognition of these rare cases may result in misdiagnosis or inappropriate treatment thereby increasing the risk of recurrence. Therefore, special cases where BPOP lesions are continuous with the medulla are even more important to be studied to understand better and master these lesions. Although BPOP is a benign tumor with no evidence of malignant transformation, the recurrence rate of surgical resection is high. We considered the possibility of this particular disease prior to surgery and performed a surgical resection with adequate safety margins. Regular postoperative follow-up is of utmost importance, without a doubt.

Analysis of the Actions of RARγ Agonists on Growing Osteochondromas in a Mouse Model.

The actions of the retinoic acid nuclear receptor gamma (RARγ) agonist, palovarotene, on pre-existing osteochondromas were investigated using a mouse multiple osteochondroma model. This approach was based on the knowledge that patients often present to the clinic after realizing the existence of osteochondroma masses, and the findings from preclinical investigations are the effects of drugs on the initial formation of osteochondromas. Systemic administration of palovarotene, with increased doses (from 1.76 to 4.0 mg/kg) over time, fully inhibited tumor growth, keeping the tumor size (0.31 ± 0.049 mm3) similar to the initial size (0.27 ± 0.031 mm3, p = 0.66) while the control group tumor grew (1.03 ± 0.23 mm3, p = 0.023 to the drug-treated group). Nanoparticle (NP)-based local delivery of the RARγ agonist also inhibited the growth of osteochondromas at an early stage (Control: 0.52 ± 0.11 mm3; NP: 0.26 ± 0.10, p = 0.008). Transcriptome analysis revealed that the osteoarthritis pathway was activated in cultured chondrocytes treated with palovarotene (Z-score = 2.29), with the upregulation of matrix catabolic genes and the downregulation of matrix anabolic genes, consistent with the histology of palovarotene-treated osteochondromas. A reporter assay performed in cultured chondrocytes demonstrated that the Stat3 pathway, but not the Stat1/2 pathway, was stimulated by RARγ agonists. The activation of Stat3 by palovarotene was confirmed using immunoblotting and immunohistochemistry. These findings suggest that palovarotene treatment is effective against pre-existing osteochondromas and that the Stat3 pathway is involved in the antitumor actions of palovarotene.

Bizarre parosteal osteochondromatous proliferation (Nora lesion) involving the spine: a case report and systematic review.

Bizarre parosteal osteochondromatous proliferation (BPOP), also termed Nora lesion, is a rare, benign tumor most often located in the hands and feet. We herein present the second reported case of BPOP affecting the spine, an uncommon location. One year after surgical excision, the patient was pain-free and showed no evidence of recurrence. We reviewed a total of 323 cases of BPOP among 101 articles, providing the first systematic update on the latest knowledge of BPOP. The age of patients with BPOP ranges from 3 months to 87 years, peaking in the second and third decades of life. The hands are the most common location of BPOP (58.39%), followed by the feet (20.81%). Imaging features play a key role in the diagnosis of BPOP, but histopathologic diagnosis remains the gold standard. Differential diagnosis of BPOP should be based on the epidemiologic and clinical features as well as clinical examination findings. Surgical resection is the most extensively used treatment for BPOP. Recurrence is common (37.44%) and can be treated with re-excision. This article can deepen our understanding of BPOP and will be helpful for the diagnosis and treatment of BPOP in clinical practice.

The Role of Routine Pathologic Assessment After Pediatric Osteochondroma Excision.

BACKGROUND: Osteochondromas are benign osseous lesions often excised for pain, growth abnormalities, and aesthetic concerns. While characteristic clinical and radiographic features leave little diagnostic ambiguity in most cases of osteochondroma, pathologic analysis to confirm the diagnosis and screen for malignancy is routinely performed following surgical excision. The purpose of this study was to determine the clinical and economic value of routine pathologic analysis after osteochondroma excision in a pediatric population. METHODS: A retrospective review of clinical records from 2 pediatric orthopaedic hospitals (St. Louis Children's Hospital and Shriner's Hospital for Children, St. Louis) identified 426 osteochondroma lesions surgically resected from 201 patients. Patients with solitary and multiple lesions were included. Clinical, radiographic, and surgical data were recorded for each resection surgery. Pathologic reports were evaluated. Costs incurred for routine pathologic assessment was also noted. RESULTS: Totally, 132 patients were treated with surgical resection of a solitary osteochondroma lesion, while an additional 291 lesions were resected from 69 patients with multiple lesions. Average age at the time of surgical resection was 13.0 years (2.1 to 17.9). The most common anatomic locations of excised lesions included the distal femur (110, 25.8%), proximal tibia/fibula (95, 22.3%), and distal radius/ulna (58, 13.6%). All resected specimens were sent for pathologic analysis. The average size of the resected lesions was 19.9 mm 3 (0.02 to 385.0 mm 3 ). In all cases, the histologic diagnosis confirmed benign osteochondroma. The total charges of pathologic analysis including processing and interpretation fees was ∼$755.00 for each lesion assessed, for a total cohort charge of $321,630. CONCLUSION: We propose that in most cases of pediatric osteochondroma excision procedures, postoperative histologic analysis is not strictly indicated as it rarely, if ever, alters diagnosis or management. We suggest using a "gross only" analysis in these cases. However, we do believe that with preoperative diagnostic ambiguity, or if patients present with concerning features such as rapidly expansile lesions or cortical destruction, have axial skeleton or pelvic involvement, or enlarged cartilaginous caps, full histologic evaluation of the excised lesions will continue to be prudent. LEVEL OF EVIDENCE: Level IV-case series.

Subungual Osteochondroma of the Great Toe: A Case Report.

Bony outgrowths of the distal phalanx of the great toe have been described in the literature but rarely. These subungual bony outgrowths can be caused by subungual exostosis or subungual osteochondromas. Both of these abnormalities are bony outgrowths with differences in the cartilage cap wherein the exostoses have fibrocartilage, and osteochondromas have hyaline cartilage. The subungual exostosis and osteochondroma that are protruding present symptoms of pain, redness, and deformed nail bed, whereas the nonprotruding osteochondromas have only a lump as the presenting symptom. In both conditions, excision of the lesion and curettage of the base helps prevent a recurrence. Curettage at the end of the excision of the bony outgrowth is required to avoid recurrence. After excision, the specimen should be sent for histopathologic examination to differentiate between the exostosis and osteochondromas, which are underreported in subungual locations, and to rule out malignant transformation. We present a 13-year-old girl with an isolated subungual nonprotruding exostosis of the great toe that was treated by excisional biopsy. The histopathologic examination confirmed it as osteochondroma, which is underreported.

Osteochondrolipoma of the foot treated by surgical excision: a case report and literature review.

BACKGROUND: Osteochondromas, classified as a new benign subtype of lipomas and characterised by chondroid and osseous differentiation, are rare lesions that have been infrequently reported in previous literature. The maxillofacial region was reported as the most frequent localization, with infrequent occurrence in the lower limb. This paper represents the first documented case report of osteochondrolipoma in the foot. CASE PRESENTATION: A 51-year-old male patient presented with a chief complaint of right foot pain at the plantar aspect, accompanied by the observation of swelling between the first and the second metatarsal shafts. His complaint of pain and swelling started 10 and 4 years prior, respectively. Since their onset, both symptoms have progressed in nature. Imaging revealved a large mass exhibiting a nonhomogenous composition of fibrous tissue and bony structures. Surgical intervention through total excision was indicated. CONCLUSION: Osteochodrolipoma is a benign lesion that can affect the foot leading to decreased functionality of the foot due to the pain and swelling. Surgical excision is the recommended approach for this lesion, providing both symptomatic relief and confirmation of the diagnosis through histopathological examination.

Bizarre parosteal osteochondromatous proliferations of the temporal region: a case report.

Bizarre parosteal osteochondromatous proliferations (BPOPs) are distinct clinical-pathological entities that demonstrate combinations of atypical-appearing osseous and chondromatous tissues. These lesions are usually reactive in nature. Histopathologically, 'bizarre' cartilage is a characteristic feature of this lesion. BPOPs usually represent slow-growing painless bony hard protuberances that arise from the surface of affected bone cortices, typically the metacarpals, metatarsals, and phalanges. The occurrence of these lesions in the skull and jaws is sporadic. This case report highlights the clinical presentation, histopathological characteristics, and management of BPOP arising from the supraorbital rim in a 61-year-old female patient.

Secondary peripheral chondrosarcoma in multiple osteochondromas: a retrospective single-institution case series.

BACKGROUND: Multiple osteochondromas is genetic disorder characterized by the formation of multiple benign cartilage-capped bone tumors, named osteochondromas, during skeletal development. The most feared complication is the secondary peripheral chondrosarcoma, a malignant cartilaginous neoplasm that arises from the chondroid cap of pre-existent osteochondromas. We conducted a retrospective cohort study on patients diagnosed and followed up from 1960 to 2019 to describe the clinical and pathological features of individuals affected by peripheral chondrosarcoma in multiple osteochondromas, to evaluate follow up information and individual outcome and to compare the results with literature. Data, including age, gender, site, histological grade, cartilage cap thickness, surgical treatments, surgical margins, genotype mutational status as well as treatment details were captured from the hospital electronic health records and from Registry of Multiple Osteochondromas. In addition, a complete histological review of all hematoxylin and eosin (H&E)-stained sections has been performed by expert pathologists. RESULTS: One hundred five of the screened cases were included in the present study. The age at diagnosis of SPC ranges from 13 to 63, with median age at diagnosis of 34 years. The site most frequently affected by malignant degeneration was the pelvis (46 patients, 44%) with higher incidence in male patients (32 males vs.14 females). The second one was lower limbs (including femur, fibula, or tibia), identified in 35 patients. Histological information - available for 103 patients - showed: 59 patients with grade 1; 40 patients had a grade 2 and 4 patients had a grade 3. The most common surgical treatment was the complete resection, followed by debulking, amputation and partial resection. Most of cases did not have recurrence of the disease. Outcome in disease-free survival highlights that a worse course of the disease was associated with histological grade 2 or 3, and partial resection surgery. In most of analyzed cases (94%) a pathogenic variant was identified. CONCLUSIONS: In conclusion, the present study gives an overview of the secondary peripheral chondrosarcomas, confirming that this disease represents an impacting complication for multiple osteochondromas patients and suggests that malignant transformation can occur also in younger patient, in a not irrelevant number of cases.

Robotic resection of a second rib osteochondroma.

A 43-year-old man presented with a several-month history of worsening left shoulder pain. On imaging, he was found to have an osseous mass arising from his left second rib and protruding into the soft tissues of his chest. The mass had radiographic characteristics consistent with those of an osteochondroma. He had point tenderness over the mass, and the area of point tenderness was consistent with his description of the location of his pain over the past several months. Based on his symptoms, he was taken to the operating room for robotic excision of this mass. He was placed in a right lateral decubitus position, and three robotic ports were inserted. The mass was identified based on landmarks and was dissected free. The bony attachment of the mass to the second rib was transected using a Kerrison rongeur. The mass was delivered into the chest and removed using an endobag. The patient was discharged the following day after removal of his Blake drain. His pain had completely resolved at the postoperative follow-up examination, and his final pathological report confirmed the benign diagnosis of osteochondroma.

Isolated Dysplasia Epiphysealis Hemimelica (Trevor Disease) of the Acetabulum: Literature Review.

Dysplasia epiphysealis hemimelica (DEH), also known as Trevor disease, is a rare pathologic proliferation of cartilage with unknown etiology creating cartilaginous osteochondroma exostoses intra-articularly or juxta-articularly. Herein, we reviewed the literature about acetabular osteochondroma in children and report a case of a 9-year-old boy who presented to the orthopaedic clinic with complaints of gait disturbance, right hip discomfort, and with increasing severity and frequency of hip subluxation episodes over the course of a year. Imaging studies revealed dysplasia of the right hip with subluxation secondary to acetabular lesion. The patient underwent surgical hip dislocation to facilitate surgical excision of the lesion and reduce hip, and pathology confirmed osteochondroma with chondromatosis. We report the early follow-up for this patient and discuss the value of surgical hip dislocation to manage intra-articular bone or cartilage lesions.

Solitary osteochondromas in paleo-oncology: A case report from 4th-century BCE Pontecagnano (southern Italy).

OBJECTIVE: This study presents a new case of solitary osteochondroma (SOC) identified on the proximal tibia of a 4th-century BCE individual from Pontecagnano (Salerno, Italy) with an aim to contribute to differential diagnosis of bone tumors in archeological contexts. MATERIALS: Paleopathological assessment of a male individual with an estimated age-at death of 45.9-62.9 years brought to light during the archaeological excavations in the funerary sector of 'Sica de Concillis' within the necropolis of Pontecagnano. METHODS: Macroscopic and radiographic analyses were performed for diagnostic purposes. RESULTS: The proximal portion of the right tibia exhibited a large exophytic bone formation extending from the anteromedial to the posteromedial portion of the diaphysis. The x-ray confirmed the lesion being characterized by regular trabecular bone tissue with cortico-medullary continuity. CONCLUSIONS: The lesion observed is diagnostic of sessile SOC, a neoplasm that must have had aesthetic and, possibly, neurovascular complications due to its large size. SIGNIFICANCE: By offering a detailed description of a case of tibial osteochondroma and discussing the possible complications the individual might have experienced during life, this study highlights the role and importance of benign bone tumors in paleo-oncology. LIMITATIONS: Histological analysis was not carried out in order to preserve the integrity of the affected tibia. SUGGESTIONS FOR FURTHER RESEARCH: More attention should be devoted to benign tumors in paleopathology as their occurrence and manifestations in the past will lead to a better understanding of their impacts on the quality of life of affected individuals and to greater knowledge of their natural history.

Sacroiliac joint involvement in osteochondromatosis: identifying its prevalence and characteristics from cross-sectional imaging

PURPOSE: Apart from a few case reports, sacroiliac joint (SIJ) involvement in osteochondromatosis has not been studied. We aimed to determine the prevalence and characteristics of such involvement using cross-sectional imaging. METHODS: In this retrospective study, three observers (one junior radiologist and two musculoskeletal radiologists) independently reviewed computed tomography (CT) or magnetic resonance imaging (MRI) of patients in our database who had osteochondromatosis (≥2 osteochondromas across the skeleton) for SIJ involvement. The final decision was reached by the consensus of the two musculoskeletal radiologists in a later joint session. RESULTS: Of the 36 patients with osteochondromatosis in our database, 22 (61%) had cross-sectional imaging covering SIJs (14 females, 8 males; age range 7-66 years; mean age 23 years; 13 MRI, 9 CT). Of these, 16 (73%) had intra-articular osteochondromas. For identifying SIJ osteochondromas on cross-sectional imaging, interobserver agreement was substantial [κ = 0.67; 95% confidence interval (CI): 0.34, 1.00] between the musculoskeletal radiologists and moderate (κ = 0.59; 95% CI: 0.23, 0.94) between the junior radiologist and the final consensus decision of the two musculoskeletal radiologists. In the cohort with cross-sectional imaging, the anatomical variations of the accessory SIJ (n = 6, 27%) and iliosacral complex (n = 2, 9%) were identified in six different patients with (n = 2) and without (n = 4) sacroiliac osteochondromas. CONCLUSION: Cross-sectional imaging shows frequent (73%) SIJ involvement in osteochondromatosis, which, although a rare disorder, nevertheless needs to be considered in the differential diagnosis of such SIJ anatomical variants as the accessory SIJ and iliosacral complex. Differentiating these variants from osteochondromas is challenging in patients with osteochondromatosis.

A possible case of "kissing" osteochondroma and multiple enchondromas in a medieval skeleton from the church of Sant' Agostino in Caravate (Northern Italy).

This work presents the neoplastic bone changes found in the lower limb of a medieval skeleton from the church of Sant' Agostino in Caravate (Northern Italy). After briefly assessing the individual's overall pathological picture, a differential diagnosis for the neoplastic changes is now proposed. These changes were analysed macroscopically and radiographically and subsequently evaluated considering the paleopathological and clinical literature available. The differential diagnosis allowed us to recognize a tibiofibular osteochondroma and some enchondromas in the medullary cavity of the tibia. The results presented here highlight the importance of radiological analyses in the recognition and study of bone neoplasms in the paleopathological field, further contributing to our knowledge of the presence of neoplasms in Medieval Northern Italy.

Regulatory role of human fibrocartilage stem cells in condyle osteochondroma.

OBJECTIVE: Osteochondroma is a common benign skeletal disorder for which different molecular and histological features of long bones have been reported. We investigated cell-of-origin and molecular mechanisms of a rare condylar osteochondroma (CO). METHODS: Human fibrocartilage stem cells (hFCSCs) isolated from CO and normal condyle tissue were used for RNA sequencing, real-time PCR, Western Blotting, immunohistology, flowcytometry, as well as for chondrogenic differentiation, proliferation, and apoptosis detection assays. RESULTS: HFCSCs were fewer in number with weaker proliferative capacity and higher apoptosis ratio in the CO group. During the chondrogenic inducing process, hFCSCs from CO were prone to form more mature and hypertrophic cartilage. The result of RNA sequencing of hFCSCs from CO and normal condyle revealed a correlation between the PI3K/AKT signalling pathway and CO. Activated PI3K/AKT signalling might lead to functional changes in hFCSCs by enhancing cell apoptosis in the developmental process of CO. Increased expression of BCL2-like protein 11 (BIM) in CO tissue also supports this conclusion. Furthermore, the activation of the PI3K/AKT pathway in TMJ of mice induced histological disorder and increased apoptosis in condylar cartilage. CONCLUSION: We conclude that the activation of PI3K/AKT signalling in hFCSCs of CO suggests a new hypothesis for the cell-of-origin of human CO and another possible target to treat it.

Characterization of primary fibular bone tumors and post-surgical clinical and functional outcomes.

OBJECTIVES: In this study, we present the characterization of tumors located in the fibula, which is a rare site for tumors, and the clinical and functional results of patients with fibular tumors that we operated in our clinic. PATIENTS AND METHODS: Between February 2008 and December 2018, a total of 104 patients (58 males, 46 females; mean age: 26±18 years; range, 3 to 78 years) who were operated for tumor located in the fibula were retrospectively analyzed. Demographic data, histopathological diagnosis, tumor localization, surgical method and postoperative complications, metastases, follow-up time, and functional results of the patients were recorded. The fibula was divided into three groups as proximal, diaphysis and distal one-third. RESULTS: The mean follow-up was 56±25.3 (range, 24 to 108) months. Eighty (76.9%), seven (6.7%) and 17 (16.3%) patients were located proximal, diaphysis and distal to the fibula, respectively. The number of patients with malignant tumors located in the fibula was 26 (25%), the tumor was benign in 54 (51.9%) patients and 24 (23%) tumors were borderline. The most common tumor localized to the fibula was osteochondroma with 28 (26.9%) patients. The most common malignant tumors located in the fibula were Ewing sarcoma and osteosarcoma in 11 patients each. The most common surgical method was curettage in 44 (42.3%) patients. Distant organ metastases were present in 18 (17.3%) patients. The Musculoskeletal Tumor Society score of 17 patients who underwent resection of the proximal fibula were 87%. CONCLUSION: Fibula is a rare location for tumors and fibula tumors tend to be located more proximal. Tumors located in the fibula have good functional outcomes after surgery.

Expression pattern and clinical significance of ß-catenin gene and protein in patients with primary malignant and benign bone tumors.

This study is aimed to unravel the status of local and circulating ß-catenin in different primary bone tumors and its relevance to tumor types, severity, and chemotherapy. The ß-catenin mRNA expression level and the expression of the protein (intensity level) were evaluated in tumor tissue and peripheral blood mononuclear cells of 150 patients with different types of primary bone tumors (78 malignant and 72 benign tumors) using Real-Time PCR and immunohistochemistry. The ß-catenin mRNA expression level and the expression of the protein were increased in bone tumors which was positively correlated with the tumor malignancy. Amongst osteosarcoma, Ewing's Sarcoma, chondrosarcoma, osteochondroma, Giant Cell Tumor, and exostosis tumors, the osteosarcoma, and Giant Cell Tumor groups showed the highest level of ß-catenin expression. The ß-catenin expression in malignant bone tumors was significantly correlated with tumor grade, size, metastasis, tumor recurrent, and the level of response to chemotherapy. A similar pattern of ß-catenin gene expression and its association with tumor characteristics was detected in the patient's peripheral blood cells. The simultaneous increase in the expression of the ß-catenin gene and protein in tumor tissue and in circulating blood cells and its relationship with tumor severity indicates the possible promoting role of ß-catenin in primary bone tumor pathogenesis.

Rapidly Growing Solitary Osteochondroma in the Adult Finger A Case Report.

Osteochondromas are common benign bone tumors that are most commonly found in children and adolescents. They are usually slow-growing and located at the metaphysis of the long bones. When present in adults in atypical locations or with concerning features, such as thickened cartilage cap and rapid growth, osteochondromas warrant imaging to assess the risk of malignant transformation into chondrosar- coma and may require surgical excision. Here, we describe the unusual case of an adult male with a rapidly growing osteochondroma of the proximal phalanx that subsequently underwent surgical excision.

Secondary peripheral chondrosarcoma arising in solitary osteochondroma: variables influencing prognosis and survival.

BACKGROUND: Secondary peripheral chondrosarcomas arising in solitary osteochondromas is an unusual complication, reported in small series. In this study, we aimed to present our experience with this rare variant of chondrosarcoma and compare results with already published data in order to determine prognostic factors for overall and disease-free survival. METHODS: The case study includes retrospective data from patients diagnosed at a single institution from 1943 to 2019. Clinical data were collected reviewing all available medical records from first to last follow-up visits. To exclude the presence of the Multiple Osteochondroma Hereditary Syndrome, few patients, with a suspect of a familial form of the disease, were evaluated for the presence of germline heterozygous variants in EXT1 and EXT2 genes. Results were summarized using descriptive statistics and statistical analysis were performed to reveal associations between variables. RESULTS: Two hundred and fourteen secondary peripheral chondrosarcomas that arose exclusively from solitary osteochondromas diagnosed in a multidisciplinary setting at the IRCCS Istituto Ortopedico Rizzoli were retrospectively identified, 66.4% males and 33.6% females with a median age at diagnosis of 38 years. The local recurrence rate was 17.3%, while the metastases one was 5.1%. Besides age, a high histologic grade is the only factor associated with worse 5-year and 10-year overall survival (log-rank p = 0.0005, HR = 3.74; 95% CI 1.69-8.26). Moreover, high histological grade (HR = 3.75; 95% CI = 1.69-8.34; p = 0.001) and surgical debulking (HR = 3.71; 95% CI = 1.57-8.79; p = 0.003) were associated with a significantly worse disease-free survival. CONCLUSIONS: Our study confirm the low-grade behavior of secondary peripheral chondrosarcomas and demonstrate that the best choice of treatment for those arising in solitary osteochondromas is the wide surgical excision, when possible. Location per se is not a factor that affects prognosis, while the accurate histological grade assessment is correlated with the tumor aggressiveness and a long term follow up is necessary for this rare variant of chondrosarcoma.

Osteochondroma formation is independent of heparanase expression as revealed in a mouse model of hereditary multiple exostoses.

Hereditary multiple exostoses (HME) is a rare, pediatric disorder characterized by osteochondromas that form along growth plates and provoke significant musculoskeletal problems. HME is caused by mutations in heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. Seemingly paradoxically, osteochondromas were found to contain excessive extracellular heparanase (Hpse) that could further reduce HS levels and exacerbate pathogenesis. To test Hpse roles, we asked whether its ablation would protect against osteochondroma formation in a conditional HME model consisting of mice bearing floxed Ext1 alleles in Agr-CreER background (Ext1f/f ;Agr-CreER mice). Mice were crossed with a new global Hpse-null (Hpse-/- ) mice to produce compound Hpse-/- ;Ext1f/f ;Agr-CreER mice. Tamoxifen injection of standard juvenile Ext1f/f ;Agr-CreER mice elicited stochastic Ext1 ablation in growth plate and perichondrium, followed by osteochondroma formation, as revealed by microcomputed tomography and histochemistry. When we examined companion conditional Ext1-deficient mice lacking Hpse also, we detected no major decreases in osteochondroma number, skeletal distribution, and overall structure by the analytical criteria above. The Ext1 mutants used here closely mimic human HME pathogenesis, but have not been previously tested for responsiveness to treatments. To exclude some innate therapeutic resistance in this stochastic model, tamoxifen-injected Ext1f/f ;Agr-CreER mice were administered daily doses of the retinoid Palovarotene, previously shown to prevent ectopic cartilage and bone formation in other mouse disease models. This treatment did inhibit osteochondroma formation compared with vehicle-treated mice. Our data indicate that heparanase is not a major factor in osteochondroma initiation and accumulation in mice. Possible roles of heparanase upregulation in disease severity in patients are discussed.