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The Pan African Medical Journal 2022
Topics: Bone Neoplasms; Humans; Osteochondroma; Ribs
PubMed: 35949455
DOI: 10.11604/pamj.2022.42.59.35217 -
The American Journal of Pathology Dec 2021Osteochondromas are cartilage-capped tumors that arise near growing physes and are the most common benign bone tumor in children. Osteochondromas can lead to skeletal... (Review)
Review
Osteochondromas are cartilage-capped tumors that arise near growing physes and are the most common benign bone tumor in children. Osteochondromas can lead to skeletal deformity, pain, loss of motion, and neurovascular compression. Currently, surgery is the only available treatment for symptomatic osteochondromas. Osteochondroma mouse models have been developed to understand the pathology and the origin of osteochondromas and develop therapeutic drugs. Several cartilage regulatory pathways have been implicated in the development of osteochondromas, such as bone morphogenetic protein, hedgehog, and WNT/β-catenin signaling. Retinoic acid receptor-γ is an important regulator of endochondral bone formation. Selective agonists for retinoic acid receptor-γ, such as palovarotene, have been investigated as drugs for inhibition of ectopic endochondral ossification, including osteochondromas. This review discusses the signaling pathways involved in osteochondroma pathogenesis and their possible interactions with the retinoid pathway.
Topics: Animals; Bone Neoplasms; Disease Models, Animal; Humans; Mice; Osteochondroma; Retinoids; Signal Transduction
PubMed: 34809786
DOI: 10.1016/j.ajpath.2021.08.003 -
Indian Pediatrics Feb 2021
Topics: Bone Neoplasms; Exostoses; Humans; Nail Diseases; Osteochondroma; Toes
PubMed: 33632969
DOI: No ID Found -
Indian Journal of Dermatology,... 2017
Topics: Bone Neoplasms; Child; Exostoses; Female; Humans; Nail Diseases; Osteochondroma
PubMed: 28474643
DOI: 10.4103/ijdvl.IJDVL_931_16 -
Orphanet Journal of Rare Diseases Feb 2008Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is... (Review)
Review
Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15-18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5-5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection of malignancy seems justified. For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed.
Topics: Adult; Animals; Bone Neoplasms; Cell Transformation, Neoplastic; Child; Chondrosarcoma; Diagnosis, Differential; Exostoses, Multiple Hereditary; Female; Genetic Counseling; Humans; Male; Mutation; N-Acetylglucosaminyltransferases; Prognosis; Sex Factors
PubMed: 18271966
DOI: 10.1186/1750-1172-3-3 -
Archives of Pathology & Laboratory... Jan 2022A number of fibro-osseous and osteocartilaginous lesions, especially common in the small bones of the hand and feet, pose a diagnostic challenge and have historically... (Review)
Review
CONTEXT.—
A number of fibro-osseous and osteocartilaginous lesions, especially common in the small bones of the hand and feet, pose a diagnostic challenge and have historically been thought to be reactive lesions. However, modern molecular techniques when supplementing clinical, radiographic, and histologic evaluation suggest they may, in fact, be neoplasms.
OBJECTIVE.—
To review the clinical presentation and histopathologic, molecular, and radiologic features of selective bone lesions, focusing most specifically on subungual exostosis, florid reactive periostitis, and bizarre periosteal osteochondromatous proliferation.
DATA SOURCES.—
Literature review and personal experience are the sources of this review.
CONCLUSIONS.—
Some lesions previously thought to be reactive are locally aggressive and demonstrate reproducible molecular abnormalities, and thus may be neoplasms. Although most common in the bones of the fingers and toes, these lesions also occur in long and other bones. The clinical presentations, radiologic appearances, and histopathologic features often overlap, making the diagnosis challenging, and these lesions may require molecular evaluation to maximize accurate prognostication.
Topics: Bone Neoplasms; Diagnosis, Differential; Exostoses; Hand; Humans; Osteochondroma; Periostitis
PubMed: 33946096
DOI: 10.5858/arpa.2020-0817-RA -
Matrix Biology : Journal of the... Oct 2018Heparan sulfate (HS) is an essential component of cell surface and matrix proteoglycans (HS-PGs) that include syndecans and perlecan. Because of their unique structural... (Review)
Review
Heparan sulfate (HS) is an essential component of cell surface and matrix proteoglycans (HS-PGs) that include syndecans and perlecan. Because of their unique structural features, the HS chains are able to specifically interact with signaling proteins -including bone morphogenetic proteins (BMPs)- via their HS-binding domain, regulating protein availability, distribution and action on target cells. Hereditary Multiple Exostoses (HME) is a rare pediatric disorder linked to germline heterozygous loss-of-function mutations in EXT1 or EXT2 that encode Golgi-resident glycosyltransferases responsible for HS synthesis, resulting in a systemic HS deficiency. HME is characterized by cartilaginous/bony tumors -called osteochondromas or exostoses- that form within perichondrium in long bones, ribs and other elements. This review examines most recent studies in HME, framing them in the context of classic studies. New findings show that the spectrum of EXT mutations is larger than previously realized and the clinical complications of HME extend beyond the skeleton. Osteochondroma development requires a somatic "second hit" that would complement the germline EXT mutation to further decrease HS production and/levels at perichondrial sites of osteochondroma induction. Cellular studies have shown that the steep decreases in local HS levels: derange the normal homeostatic signaling pathways keeping perichondrium mesenchymal; cause excessive BMP signaling; and provoke ectopic chondrogenesis and osteochondroma formation. Data from HME mouse models have revealed that systemic treatment with a BMP signaling antagonist markedly reduces osteochondroma formation. In sum, recent studies have provided major new insights into the molecular and cellular pathogenesis of HME and the roles played by HS deficiency. These new insights have led to the first ever proof-of-principle demonstration that osteochondroma formation is a druggable process, paving the way toward the creation of a clinically-relevant treatment.
Topics: Animals; Bone Morphogenetic Proteins; Disease Models, Animal; Exostoses, Multiple Hereditary; Heparitin Sulfate; Humans; Mice; Mutation; N-Acetylglucosaminyltransferases; Signal Transduction
PubMed: 29277722
DOI: 10.1016/j.matbio.2017.12.011 -
RoFo : Fortschritte Auf Dem Gebiete Der... Mar 2021Chondrogenic tumors are the most frequent primary bone tumors. Malignant chondrogenic tumors represent about one quarter of malignant bone tumors. Benign chondrogenic... (Review)
Review
BACKGROUND
Chondrogenic tumors are the most frequent primary bone tumors. Malignant chondrogenic tumors represent about one quarter of malignant bone tumors. Benign chondrogenic bone tumors are frequent incidental findings at imaging. Radiological parameters may be helpful for identification, characterization, and differential diagnosis.
METHODS
Systematic PubMed literature research. Identification and review of studies analyzing and describing imaging characteristics of chondrogenic bone tumors.
RESULTS AND CONCLUSIONS
The 2020 World Health Organization (WHO) classification system differentiates between benign, intermediate (locally aggressive or rarely metastasizing), and malignant chondrogenic tumors. On imaging, typical findings of differentiated chondrogenic tumors are lobulated patterns with a high signal on T2-weighted magnetic resonance imaging (MRI) and ring- and arc-like calcifications on conventional radiography and computed tomography (CT). Depending on the entity, the prevalence of this chondrogenic pattern differs. While high grade tumors may be identified due to aggressive imaging patterns, the differentiation between benign and intermediate grade chondrogenic tumors is challenging, even in an interdisciplinary approach.
KEY POINTS
· The WHO defines benign, intermediate, and malignant chondrogenic bone tumors. · Frequent benign tumors: osteochondroma and enchondroma; Frequent malignant tumor: conventional chondrosarcoma. · Differentiation between enchondroma versus low-grade chondrosarcoma is challenging for radiologists and pathologists. · Pain, deep scalloping, cortical destruction, bone expansion, soft tissue component: favor chondrosarcoma. · Potential malignant transformation of osteochondroma: progression after skeletal maturity, cartilage cap thickness (> 2 cm adult; > 3 cm child). · Potentially helpful advanced imaging methods: Dynamic MRI, texture analysis, FDG-PET/CT.
CITATION FORMAT
· Engel H, Herget GW, Füllgraf H et al. Chondrogenic Bone Tumors: The Importance of Imaging Characteristics. Fortschr Röntgenstr 2021; 193: 262 - 274.
Topics: Adult; Bone Neoplasms; Child; Chondroma; Chondrosarcoma; Humans; Osteochondroma; Positron Emission Tomography Computed Tomography
PubMed: 33152784
DOI: 10.1055/a-1288-1209 -
Journal of the American Veterinary... Feb 2018
Topics: Animals; Bone Neoplasms; Cervical Vertebrae; Diagnosis, Differential; Dog Diseases; Dogs; Fatal Outcome; Female; Magnetic Resonance Imaging; Osteochondroma; Pain; Spinal Cord Compression
PubMed: 29393733
DOI: 10.2460/javma.252.4.423 -
Journal of Orthopaedic Research :... Oct 2022Hereditary multiple exostoses (HME) is a rare, pediatric disorder characterized by osteochondromas that form along growth plates and provoke significant musculoskeletal...
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 (Ext1 ;Agr-CreER mice). Mice were crossed with a new global Hpse-null (Hpse ) mice to produce compound Hpse ;Ext1 ;Agr-CreER mice. Tamoxifen injection of standard juvenile Ext1 ;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 Ext1 ;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.
Topics: Animals; Bone Neoplasms; Child; Disease Models, Animal; Exostoses, Multiple Hereditary; Glucuronidase; Heparitin Sulfate; Humans; Mice; Mutation; N-Acetylglucosaminyltransferases; Osteochondroma; Retinoids; Tamoxifen; X-Ray Microtomography
PubMed: 34996123
DOI: 10.1002/jor.25260