STUDY DESIGN: Retrospective single institutional observational study. PURPOSE: Segmental spinal dysgenesis (SSD), a complex spinal dysraphic state caused by notochord malformation disorders, is named after its morphological presentation where a spine segment is dysgenetic, malformed or absent. This study’s objective was to examine and reassess SSD imaging findings and correlate them with an embryological explanation. OVERVIEW OF LITERATURE: Scott and his colleagues defined SSD as segmental agenesis or dysgenesis of the lumbar or thoracolumbar vertebrae and underlying spinal cord. Tortori-Donati and his colleagues defined it as a morphologic continuum ranging from hypoplasia to an absent spinal cord segment. METHODS: Fifteen children, whose imaging findings and clinical features were consistent with SSD, were included in the study. Magnetic resonance imaging (MRI) was performed per institutional spine protocol. RESULTS: Five children (33.3%) presented with a high-ending bulbous cord with no caudal segment, six (40%) presented with a dorsal or lumbar segmental dysgenetic cord with a low-lying, bulky caudal cord but without significant spinal canal narrowing, and four (26.6%) presented with segmental caudal dysgenesis with severe kyphoscoliosis, gibbus deformity, and spinal canal narrowing with a normal distal segment (normal or low-lying). CONCLUSIONS: SSD is a complex spinal anomaly in children requiring clinical-radiological assessment followed by multidisciplinary management based on the extent and severity of the dysgenetic cord and the type of SSD. MRI plays a crucial role in both diagnosing and classifying SSD prior to surgical treatment to prevent further impairment.
Child ; Congenital Abnormalities ; Humans ; Magnetic Resonance Imaging ; Notochord ; Observational Study ; Retrospective Studies ; Scoliosis ; Silver Sulfadiazine ; Spinal Canal ; Spinal Cord ; Spine

BACKGROUND: Chordomas are aggressive bone tumors that have a predilection for the axial skeleton including the skull base and spinal/sacral bones. However, the histopathological and clinical differences between skull base chordoma (SBC) and sacral/spinal chordoma (SC) are unclear as previous studies have been focused on patient prognosis and treatment outcome. This study aimed to evaluate the clinicopathologic features and prognosis of chordoma according to its location. METHODS: Patients with chordomas were enrolled, and the histopathologic features were compared according to the tumor location. RESULTS: A total of 52 patients were enrolled. SBCs had more abundant chondroid matrix and diffuse growth pattern, while SCs had non-chondroid, myxoid matrix and a lobulating pattern, typical of chordoma. Old age and residual tumors were risk factors for shorter overall survival in SBCs. The chondroid matrix was an independent risk factor for shorter disease-free survival in the overall population. CONCLUSION: Chordomas have different histopathologic features depending on the anatomical location.
Bone Neoplasms ; Brain Neoplasms ; Chordoma ; Disease-Free Survival ; Humans ; Neoplasm, Residual ; Notochord ; Prognosis ; Risk Factors ; Skeleton ; Skull Base ; Skull Base Neoplasms ; Soft Tissue Neoplasms ; Treatment Outcome

Skull base chordomas are rare, malignant tumors arising from primitive notochord remnants of the axial skeleton and comprise approximately 25–35% of all chordoma cases. Nasal endoscopy in previous case reports has characterized nasopharyngeal chordomas as firm, semi-translucent masses protruding from the posterior nasopharyngeal wall with a pink, “meaty” appearance. However, the nasopharyngeal chordoma in the present case had a soft, cystic appearance, unlike the tumors previously described. Herein, an unusual case of an incidentally discovered nasopharyngeal chordoma is reported in a patient with papillary thyroid cancer; the discovered chordoma had a benign cystic appearance with no abnormal positron emission tomography-computed tomography (PET-CT) uptake.
Chordoma ; Cranial Fossa, Posterior ; Electrons ; Endoscopy ; Humans ; Notochord ; Skeleton ; Skull Base ; Thyroid Gland ; Thyroid Neoplasms

STUDY DESIGN: In vitro cell culture model. PURPOSE: To investigate the effects of RNA interference (RNAi) on p75 expression and viability of rat notochordal cells treated with serum deprivation. OVERVIEW OF LITERATURE: RNAi enables the inhibition of specific genes by sequence-specific gene silencing using a double-stranded RNA. METHODS: Notochordal cells were isolated, cultured, and placed in 10% (control) or 0% (apoptosis-promoting) fetal bovine serum (FBS) for 48 hours. The expression of p75, apoptosis, and cell proliferation were determined. To suppress p75 expression, a small interfering RNA (siRNA) was synthesized against p75 (p75 siRNA) and transfected into cells. The suppression of p75 mRNA expression was investigated using the reverse transcription-polymerase chain reaction. The degree of p75 suppression was semiquantitatively analyzed using densitometry. The effect of p75 siRNA on apoptosis and proliferation of cells was determined. Solutions of an unrelated siRNA and transfection agent alone served as controls. RESULTS: Serum deprivation significantly increased apoptosis by 40.3%, decreased proliferation of notochordal cells by 45.3% (both, p<0.001), and upregulated p75 expression. The p75 siRNA suppressed p75 expression in cells cultured in 0% FBS. The rate of suppression by p75 siRNA of p75 mRNA was 72.9% (p<0.001). Suppression of p75 expression by p75 siRNA inhibited apoptosis by 7% and increased proliferation by 14% in cells cultured in 0% FBS (both, p<0.05). CONCLUSIONS: siRNA-mediated suppression of p75 inhibited apoptosis and increased proliferation of notochordal cells under conditions of serum deprivation, suggesting that RNAi might serve as a novel therapeutic approach for disc degeneration caused by insufficient viability of disc cells through the suppression of the expression of harmful genes.
Animals ; Apoptosis ; Cell Culture Techniques ; Cell Proliferation ; Densitometry ; Gene Silencing ; In Vitro Techniques ; Intervertebral Disc Degeneration ; Notochord* ; Rats* ; RNA Interference ; RNA* ; RNA, Double-Stranded ; RNA, Messenger ; RNA, Small Interfering ; Transfection

STUDY DESIGN: In vitro cell culture. PURPOSE: The purpose of the study was to investigate the effect of high glucose on premature stress-induced senescence of rat notochordal cells. OVERVIEW OF LITERATURE: Glucose-mediated increase of oxidative stress is a major causative factor for the development of diseases associated with diabetes mellitus such as senescence. However, no information is available for the effect of high glucose on premature stress-induced senescence of rat notochordal cells. METHODS: Notochordal cells were isolated from 4-week-old rats, cultured and placed in either 10% fetal bovine serum (FBS, normal control) or 10% FBS plus two high glucose concentrations (0.1 M and 0.2 M, experimental conditions) for 1 and 3 days. We identified and quantified the mitochondrial damage (mitochondrial transmembrane potential), reactive oxygen species (ROS) and antioxidants, such as manganese superoxide dismutase (MnSOD) and catalase, for each condition. We also identified and quantified senescence and telomerase activity. Finally, we determined the expression of proteins related to replicative senescence (p53-p21-pRB) and stress-induced senescence (p16-pRB) pathways. RESULTS: Two high glucose concentrations enhanced the disruption of mitochondrial transmembrane potential and excessive generation of ROS in notochordal cells for 1 and 3 days, respectively. The expressions of MnSOD and catalase were increased in notochordal cells treated with both high glucose concentrations at 1 and 3 days. The telomerase activity declined at 1 and 3 days. Two high glucose concentrations increased the occurrence of stress-induced senescence of notochordal cells by p16-pRB pathways at 1 and 3 days. CONCLUSIONS: Despite compensatory expression of antioxidants, high glucose-induced oxidative stress accelerates stress-induced senescence in rat notochordal cells. This may result in dysfunction of notochordal cells, leading to accelerated premature disc degeneration. The prevention of excessive generation of oxidative stress by strict blood glucose control is important to prevent or to delay premature disc degeneration in young patients with diabetes mellitus.
Aging* ; Animals ; Antioxidants ; Blood Glucose ; Catalase ; Cell Aging ; Cell Culture Techniques ; Diabetes Mellitus ; Glucose* ; Humans ; Intervertebral Disc Degeneration ; Membrane Potentials ; Notochord* ; Oxidative Stress ; Rats* ; Reactive Oxygen Species ; Superoxide Dismutase ; Telomerase

OBJECTIVETo report 2 rare cases of benign notochordal cell tumor (BNCT), according to WHO classification of tumors of soft tissue and bone (4th edition). Their radiologic and clincopathologic features and differential diagnosis were investigated.

METHODSTwo cases of BNCT were studied by retrospective review of the clinical, radiologic, pathologic and immunophenotypical findings. Related literatures were reviewed at the same time.

RESULTSCase 1 was a 53-year-old man, and case 2 was a 61-year-old woman. Radiographically, both patients presented with abnormal imaging findings in the fifth cervical vertebral body with the lesions located within the bone but without extra osseous mass. Histopathologically, the lesions lacked lobular architecture and extracellular myxoid matrix. The tumor cells were vacuolated and had centrally or peripherally placed round or oval nuclei with small nucleoli, mimicking mature adipocytes. No cytological atypia or mitotic figures were seen. The affected bone trabeculae were sclerotic and islands of bone marrow were often entrapped within the tumor.

CONCLUSIONSAlthough sharing similar anatomic distribution and immunophenotype to those of chordoma, BNCT has distinct radiologic and pathologic features and different treatment and prognosis. The differential diagnosis between BNCT and chordoma requires detailed clinical, radiologic and histopathologic evaluations.

Cervical Vertebrae ; diagnostic imaging ; pathology ; Chordoma ; pathology ; Diagnosis, Differential ; Diagnostic Imaging ; Female ; Humans ; Male ; Middle Aged ; Notochord ; diagnostic imaging ; pathology ; Radiography ; Retrospective Studies ; Spinal Neoplasms ; diagnostic imaging ; pathology

OBJECTIVE: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. METHODS: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. RESULTS: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-1beta stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. CONCLUSION: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.
Adult ; Coculture Techniques ; Culture Media, Conditioned ; Gene Expression ; Humans ; Inflammation* ; Insulin-Like Growth Factor I ; Interleukin-1beta ; Intervertebral Disc Degeneration* ; Macrophages ; Matrix Metalloproteinases ; Myristic Acid ; Notochord ; Polymerase Chain Reaction ; Rabbits ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

Thoracic chordomas are very rare malignant tumours originating from notochordal remnants. These tumours develop within a vertebral body and enlarge involving the mediastinal compartment. Because of their slow-growing attitude, they become symptomatic only when they invade or compress the spinal cord and/or mediastinal organs. We present a rare case of a thoracic spine chordoma presenting with increasing paraparesis with a huge mediastinal component which was surgically debulked to decompress the spinal cord and medistinal organs.
Bone Neoplasms ; Chordoma* ; Mediastinum ; Notochord ; Paraparesis ; Spinal Cord ; Spine*

The microRNAs (miRNAs) are small, non-coding RNAs that modulate protein expression by interfering with target mRNA translation or stability. miRNAs play crucial roles in various functions such as cellular, developmental, and physiological processes. The spatial expression patterns of miRNAs are very essential for identifying their functions. The expressions of miR-302 and miR-367 are critical in maintaining stemness of pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) but their functions in early development are not fully elucidated. So, we used Locked Nucleic Acid (LNA) probes to perform in situ hybridization and confirmed the temporal and spatial distribution patterns during early chick development. As a result, we found that miR-302 and miR-367 were expressed in various tissues such as primitive steak, neural ectoderm, neural plate, neural fold, neural tube, notochord, and oral cavity. Specially, we confirmed that miR-302 and miR-367 were strongly expressed in neural folds in HH8 to HH10. miR-302 was expressed on dorsal part of the neural tube but miR-367 was expressed on lateral and ventral parts of the neural tube. And also we performed quantitative stem-loop real-time PCR to analyze global expression level of miR-302 and miR-367. miR-302 and miR-367 expression was sustained before Hamburger and Hamilton stage (HH) 14. Thus, the temporal and spatial expression patterns of miR-302 and miR-367 may provide us information of the role of these miRNAs on tissue formation during early chick development.
Ectoderm ; Embryonic Stem Cells ; In Situ Hybridization ; Induced Pluripotent Stem Cells ; MicroRNAs ; Mouth ; Neural Crest ; Neural Plate ; Neural Tube ; Notochord ; Physiological Processes ; Pluripotent Stem Cells ; Protein Biosynthesis ; Real-Time Polymerase Chain Reaction ; RNA, Untranslated

PURPOSE: A sacral chordoma is a rare, slow-growing, primary bone tumor, arising from embryonic notochordal remnants. Radical surgery is the only hope for cure. The aim of our present study is to analyse our experience with the challenging treatment of this rare tumor, to review current treatment modalities and to assess the outcome based on R status. METHODS: Eight patients were treated in our institution between 2001 and 2011. All patients were discussed by a multidisciplinary tumor board, and an en bloc surgical resection by posterior perineal access only or by combined anterior/posterior accesses was planned based on tumor extension. RESULTS: Seven patients underwent radical surgery, and one was treated by using local cryotherapy alone due to low performance status. Three misdiagnosed patients had primary surgery at another hospital with R1 margins. Reresection margins in our institution were R1 in two and R0 in one, and all three recurred. Four patients were primarily operated on at our institution and had en bloc surgery with R0 resection margins. One had local recurrence after 18 months. The overall morbidity rate was 86% (6/7 patients) and was mostly related to the perineal wound. Overall, 3 out of 7 resected patients were disease-free at a median follow-up of 2.9 years (range, 1.6-8.0 years). CONCLUSION: Our experience confirms the importance of early correct diagnosis and of an R0 resection for a sacral chordoma invading pelvic structures. It is a rare disease that requires a challenging multidisciplinary treatment, which should ideally be performed in a tertiary referral center.
Chordoma* ; Cryotherapy ; Diagnosis ; Diagnostic Errors* ; Follow-Up Studies ; Hope ; Humans ; Notochord ; Perineum ; Rare Diseases ; Recurrence ; Sacrum ; Tertiary Care Centers ; Wounds and Injuries