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BMC Urology Apr 2024Fasciitis ossificans is a rare subtype of nodular fasciitis, a benign soft tissue tumor with reactive characteristics. Due to its rapid growth, it is often misdiagnosed...
BACKGROUND
Fasciitis ossificans is a rare subtype of nodular fasciitis, a benign soft tissue tumor with reactive characteristics. Due to its rapid growth, it is often misdiagnosed as a malignant tumor. While fasciitis ossificans commonly originates from the subcutaneous tissue and can appear throughout the body, it may also arise from extraordinary sites.
CASE PRESENTATION
We report the first-ever documented case of fasciitis ossificans arising from the penis in a male patient who presented with a tumor on the glans penis. The tumor was surgically resected due to suspicion of penile cancer. Initial histopathological analysis led to a misdiagnosis of squamous cell carcinoma. However, pathological consultation ultimately confirmed the diagnosis of fasciitis ossificans of the penis originating from the glans penis by demonstrating ossification.
CONCLUSION
This case underscores the importance of considering fasciitis ossificans in the differential diagnosis of soft tissue tumors, even in unusual locations such as penile soft tissue.
Topics: Humans; Male; Ossification, Heterotopic; Pelvis; Diagnosis, Differential; Fasciitis; Penis; Penile Neoplasms
PubMed: 38594664
DOI: 10.1186/s12894-024-01475-y -
Bone Research Apr 2024Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral...
Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone, resulting in limited spinal mobility and nerve compression. Employing both bulk and single-cell RNA sequencing, we elucidate the molecular characteristics, cellular components, and their evolution during the OPLL process at a single-cell resolution, and validate these findings in clinical samples. This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo. Notably, our study identifies LOXL2 as a key regulator in this process. Through gain-and loss-of-function studies, we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells. It acts via the HIF1A pathway, promoting the secretion of downstream VEGFA and PDGF-BB. This function is not related to the enzymatic activity of LOXL2. Furthermore, we identify sorafenib, a broad-spectrum tyrosine kinase inhibitor, as an effective suppressor of LOXL2-mediated vascular morphogenesis. By disrupting the coupling between vascularization and osteogenesis, sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass. These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.
Topics: Animals; Longitudinal Ligaments; Osteogenesis; Sorafenib; Ossification of Posterior Longitudinal Ligament; Cell Differentiation
PubMed: 38594260
DOI: 10.1038/s41413-024-00327-7 -
Cell Reports Apr 2024Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues....
Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. While the effect of HO on blood vessels is well established, little is known about its impact on lymphatic vessels. Here, we use a mouse model of traumatic HO to investigate the relationship between HO and lymphatic vessels. We show that injury triggers lymphangiogenesis at the injury site, which is associated with elevated vascular endothelial growth factor C (VEGF-C) levels. Through single-cell transcriptomic analyses, we identify mesenchymal progenitor cells and tenocytes as sources of Vegfc. We demonstrate by lineage tracing that Vegfc-expressing cells undergo osteochondral differentiation and contribute to the formation of HO. Last, we show that Vegfc haploinsufficiency results in a nearly 50% reduction in lymphangiogenesis and HO formation. These findings shed light on the complex mechanisms underlying HO formation and its impact on lymphatic vessels.
Topics: Animals; Ossification, Heterotopic; Vascular Endothelial Growth Factor C; Lymphangiogenesis; Mice; Mesenchymal Stem Cells; Lymphatic Vessels; Cell Differentiation; Tenocytes; Osteogenesis; Haploinsufficiency; Mice, Inbred C57BL; Disease Models, Animal; Male
PubMed: 38573853
DOI: 10.1016/j.celrep.2024.114049 -
Journal of Orthopaedic Surgery and... Apr 2024The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR.
BACKGROUND
The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR.
METHODS
Aided by serial plain radiographs from recent cTDR cases (34 patients; 44 devices), a panel of experts assembled for the purpose of creating a classification system to aid in reproducibly and accurately identifying bony changes and assessing cTDR radiographic appearance. Subdividing the superior and inferior vertebral bodies into 3 equal sections, observed bone loss such as endplate rounding, cystic erosion adjacent to the endplate, and cystic erosion not adjacent to the endplate, is recorded. Determining if bone loss is progressive, based on serial radiographs, and estimating severity of bone loss (measured by the percentage of end plate involved) is recorded. Additional relevant bony changes and device observations include radiolucent lines, heterotopic ossification, vertebral body olisthesis, loss of core implant height, and presence of device migration, and subsidence.
RESULTS
Serial radiographs from 19 patients (25 devices) implanted with a variety of cTDR designs were assessed by 6 investigators including clinicians and scientists experienced in cTDR or appendicular skeleton joint replacement. The overall agreement of assessments ranged from 49.9% (95% bootstrap confidence interval 45.1-73.1%) to 94.7% (95% CI 86.9-100.0%). There was reasonable agreement on the presence or absence of bone loss or radiolucencies (range: 58.4% (95% CI 51.5-82.7%) to 94.7% (95% CI 86.9-100.0%), as well as in the progression of radiolucent lines (82.9% (95% CI 74.4-96.5%)).
CONCLUSIONS
The novel classification system proposed demonstrated good concordance among experienced investigators in this field and represents a useful advancement for improving reporting in cTDR studies.
Topics: Humans; Treatment Outcome; Diskectomy; Total Disc Replacement; Cervical Vertebrae; Neck; Intervertebral Disc Degeneration
PubMed: 38566203
DOI: 10.1186/s13018-024-04679-y -
Journal of Cancer Research and... Jan 2024Renal cell carcinoma (RCC) with heterotopic formation has been reported very rarely. We report this rare entity in a 33-year-old female patient who came to the...
Renal cell carcinoma (RCC) with heterotopic formation has been reported very rarely. We report this rare entity in a 33-year-old female patient who came to the out-patient department after complaining of pain in the lumbar region of the left side for 2 years. A computed tomography scan showed a heterogeneously enhancing lesion originating from the posterior cortex of the left kidney in the upper pole. It had many chunky calcification foci and was treated with left robotic partial nephrectomy. Histo-pathological examination revealed clear cell RCC with the heterotopic bone formation with a tumor size measuring 5 × 4 × 2.5 cm; the tumor was limited to the kidney, and the tumor resection margin were free of tumor, WHO/ISUP Grade 2. The pathological stage (AJCC 8th edition PTNM) was p T1b p NX p MX. The prognostic implications regarding calcification are poorly addressed in the literature. Patients suffering from osseous metaplasia are often in their early stages of the disease and have a favorable prognosis.
Topics: Adult; Female; Humans; Calcinosis; Carcinoma, Renal Cell; Kidney; Kidney Neoplasms; Nephrectomy; Ossification, Heterotopic
PubMed: 38554371
DOI: 10.4103/jcrt.jcrt_2085_22 -
Biomolecules Mar 2024Inflammation is a major driver of heterotopic ossification (HO), a condition of abnormal bone growth in a site that is not normally mineralized. (Review)
Review
BACKGROUND
Inflammation is a major driver of heterotopic ossification (HO), a condition of abnormal bone growth in a site that is not normally mineralized.
PURPOSE OF REVIEW
This review will examine recent findings on the roles of inflammation and the immune system in fibrodysplasia ossificans progressiva (FOP). FOP is a genetic condition of aggressive and progressive HO formation. We also examine how inflammation may be a valuable target for the treatment of HO. Rationale/Recent findings: Multiple lines of evidence indicate a key role for the immune system in driving FOP pathogenesis. Critical cell types include macrophages, mast cells, and adaptive immune cells, working through hypoxia signaling pathways, stem cell differentiation signaling pathways, vascular regulatory pathways, and inflammatory cytokines. In addition, recent clinical reports suggest a potential role for immune modulators in the management of FOP.
FUTURE PERSPECTIVES
The central role of inflammatory mediators in HO suggests that the immune system may be a common target for blocking HO in both FOP and non-genetic forms of HO. Future research focusing on the identification of novel inflammatory targets will help support the testing of potential therapies for FOP and other related conditions.
Topics: Humans; Myositis Ossificans; Ossification, Heterotopic; Cell Differentiation; Signal Transduction; Inflammation
PubMed: 38540775
DOI: 10.3390/biom14030357 -
Biomolecules Mar 2024Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as... (Review)
Review
Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.
Topics: Humans; Myositis Ossificans; Ossification, Heterotopic; Osteogenesis; Bone and Bones
PubMed: 38540768
DOI: 10.3390/biom14030349 -
Biomolecules Mar 2024Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder characterized by abnormal bone formation due to ACVR1 gene mutations. The identification of the...
Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder characterized by abnormal bone formation due to ACVR1 gene mutations. The identification of the molecular mechanisms underlying the ectopic bone formation and expansion in FOP is critical for the effective treatment or prevention of HO. Here we find that Hh signaling activation is required for the aberrant ectopic bone formation in FOP. We show that the expression of (), a Hh ligand, as well as downstream Hh signaling, was increased in ectopic bone lesions in ; mice. Pharmacological treatment with an Ihh-neutralizing monoclonal antibody dramatically reduced chondrogenesis and ectopic bone formation. Moreover, we find that the activation of Yap in the FOP mouse model and the genetic deletion of halted ectopic bone formation and decreased expression. Our mechanistic studies showed that Yap and Smad1 directly bind to the Ihh promoter and coordinate to induce chondrogenesis by promoting expression. Therefore, the Yap activation in FOP lesions promoted ectopic bone formation and expansion in both cell-autonomous and non-cell-autonomous manners. These results uncovered the crucial role of the Yap-Ihh axis in FOP pathogenesis, suggesting the inhibition of Ihh or Yap as a potential therapeutic strategy to prevent and reduce HO.
Topics: Mice; Animals; Hedgehog Proteins; Chondrogenesis; Osteogenesis; Ossification, Heterotopic; Myositis Ossificans; Mutation
PubMed: 38540766
DOI: 10.3390/biom14030347 -
Osteoarthritis and Cartilage Mar 2024Metabolic processes are intricately linked to the resolution of innate inflammation and tissue repair, two critical steps for treating post-traumatic osteoarthritis...
OBJECTIVE
Metabolic processes are intricately linked to the resolution of innate inflammation and tissue repair, two critical steps for treating post-traumatic osteoarthritis (PTOA). Based on lipolytic and immunoregulatory actions of norepinephrine, we hypothesized that intra-articular β-adrenergic receptor (βAR) stimulation would suppress PTOA-associated inflammation in the infrapatellar fat pad (IFP) and synovium.
DESIGN
We used the βAR agonist isoproterenol to perturb intra-articular metabolism 3.5 weeks after applying a non-invasive single-load compression injury to knees of 12-week-old male and female mice. We examined the acute effects of intra-articular isoproterenol treatment relative to saline on IFP histology, multiplex gene expression of synovium-IFP tissue, synovial fluid metabolomics, and mechanical allodynia.
RESULTS
Injured knees developed PTOA pathology characterized by heterotopic ossification, articular cartilage loss, and IFP atrophy and fibrosis. Isoproterenol suppressed the upregulation of pro-fibrotic genes and downregulated the expression of adipose genes and pro-inflammatory genes (Adam17, Cd14, Icam1, Csf1r, and Casp1) in injured joints of female (but not male) mice. Analysis of published single-cell RNA-seq data identified elevated catecholamine-associated gene expression in resident-like synovial-IFP macrophages after injury. Injury substantially altered synovial fluid metabolites by increasing amino acids, peptides, sphingolipids, phospholipids, bile acids, and dicarboxylic acids, but these changes were not appreciably altered by isoproterenol. Intra-articular injection of either isoproterenol or saline increased mechanical allodynia in female mice, whereas neither substance affected male mice.
CONCLUSIONS
Acute βAR activation altered synovial-IFP transcription in a sex and injury-dependent manner, suggesting that women with PTOA may be more sensitive than men to treatments targeting sympathetic neural signaling pathways.
PubMed: 38527663
DOI: 10.1016/j.joca.2024.03.109 -
International Journal of Surgery Case... Apr 2024Fibrodysplasia Ossificans Progressiva is an ultra-rare genetic disorder of progressive soft tissue ossification. Due to unawareness and poor clinical suspicion, the rate...
INTRODUCTION AND IMPORTANCE
Fibrodysplasia Ossificans Progressiva is an ultra-rare genetic disorder of progressive soft tissue ossification. Due to unawareness and poor clinical suspicion, the rate of misdiagnosis, delay in diagnosis, and unnecessary diagnostic procedures leading to permanent injury and lifelong disability is common. Here we report this rare genetic disorder in a six years old child who was initially misdiagnosed as multiple exostoses and operated on.
CASE PRESENTATION
A 6 year old child presented with swellings over the posterior neck and back for four years. The patient was misdiagnosed as a case of multiple exostoses and an excisional biopsy was done a year back. The swelling worsened after the excision; currently, she cannot move her neck from side to side, and flex and extend. Examination revealed multiple hard and slightly tender masses over the posterior neck, para scapular and thoracolumbar para spinal region. She also has hallux valgus deformity that had been present since birth. CT (computed tomography) scan confirmed extensive extra-skeletal soft tissue ossification.
CLINICAL DISCUSSION
The progression of heterotopic ossification is characteristically anatomic and orderly, typically initially involving the body's dorsal, axial, cranial, and proximal regions and later in the ventral, appendicular, caudal, and distal regions. Skeletal muscles of the tongue, diaphragm, extra-ocular muscles, cardiac muscles, and smooth muscles are inexplicably spared.
CONCLUSION
Early diagnosis prevents potentially harmful diagnostic and therapeutic procedures. The characteristic big toes malformation is the most important and best key for the early suspicion of the diagnosis.
PubMed: 38513414
DOI: 10.1016/j.ijscr.2024.109548