A watch, wait, and rescan approach for incidental benign-appearing notochordal lesions of the skull base.

OBJECTIVE: The aim of this study was to describe the natural history of incidental benign-appearing notochordal lesions of the skull base with specific attention to features that can make differentiation from low-grade chordoma more difficult, namely contrast uptake and bone erosion. METHODS: In this retrospective case series, the authors describe the clinical outcomes of 58 patients with incidental benign-appearing notochordal lesions of the clivus, including those with minor radiological features of bone erosion or contrast uptake. RESULTS: All lesions remained stable during a median follow-up of almost 3 years. Thirty-seven (64%) patients underwent contrast-enhanced MRI; lesions in 14 (38%) of these patients exhibited minimal contrast enhancement. Twenty-seven (47%) patients underwent CT; lesions in 6 (22%) of these patients exhibited minimal bone erosion. CONCLUSIONS: These data make the case for monitoring selected cases of benign-appearing notochordal lesions of the clivus in the first instance even when there is minor contrast uptake or minimal bone erosion.

Ecchordosis physaliphora: a cautionary tale.

BACKGROUND: Ecchordosis physaliphora is a congenital, benign lesion originating from notochordal remnants along the craniospinal axis, most frequently located at the level of the clivus and sacrum. Sometimes ecchordosis physaliphora is difficult to recognise and treat, with a total of twenty-six cases described in the literature. METHODS: This study reports on three cases of previously undiagnosed ecchordosis physaliphora presenting with cerebrospinal fluid rhinorrhoea and meningitis. CONCLUSION: Endoscopic transclival or transsphenoid surgery including three-layer (fat, fascia and nasoseptal flap) reconstruction was used in all cases with complete resolution of the symptoms.

Systematic Review of Clinical, Radiologic, and Histologic Features of Benign Notochordal Cell Tumors: Implications for Patient Management.

BACKGROUND: There are no absolute defining criteria for benign notochordal cell tumors; the diagnosis is usually based on small size and the absence of aggressive features. Therefore, by definition, the diagnosis is subjective and usually determined by multidisciplinary consensus. A benign notochordal cell tumor should not grow during surveillance, and this may be used to confirm the diagnosis, but is a tautologic definition. Diagnostic ambiguity leads to uncertainty in management. If a tumor is a small chordoma then early surgery is likely to provide a better outcome. However, unnecessary treatment of a benign tumor may incur unjustified risk. OBJECTIVE: To propose clearer guidelines for the definition and management of benign notochordal tumors. METHODS: We performed a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) review of the reported definitions for benign notochordal tumors and their management. RESULTS: The accepted features of benign notochordal tumors vary considerably: a typical tumor may be diagnosed in the absence of neurology, radiologically well-corticated bony margins, size <35 mm, no enhancement with contrast, no soft tissue extension, no dural penetration, no progression on scans, histologic absence of extracellular myxoid matrix, and low Ki67 index. If these criteria are fulfilled, it is reasonable to use radiologic surveillance in the first instance. Biopsy may be offered depending on the relative risks of performing the biopsy, or if there are atypical features. CONCLUSIONS: We suggest a clearer definition for a benign notochordal tumor and a management algorithm that incorporates a level of diagnostic uncertainty.

Tumor benigno de células notocordales / Benign notochordal cell tumors

Los tumores benignos de células notocordales (TBCN) son lesiones con diferenciación notocordal que afectan al esqueleto axial. Se caracterizan por cursar asintomáticos o con sintomatología inespecífica, y por pasar desapercibidos radiológicamente por su pequeño tamaño, o bien por ser confundidos con otras lesiones óseas benignas, como hemangiomas vertebrales. Cuando son grandes o sintomáticos pueden plantear el diagnóstico diferencial con metástasis, tumores óseos primarios y cordomas. Presentamos el caso de un TBCN de difícil diagnóstico, en una mujer de 50 años de edad, con una lesión sacra vista en la resonancia magnética (RM). Se programó una biopsia guiada por tomografía computarizada (TC) para filiar la lesión, pero la tumoración no era claramente identificable en la TC, por lo que se utilizaron las referencias anatómicas de la RM para seleccionar el plano adecuado. Tanto la planificación del abordaje como la correlación radiopatológica fueron determinantes para llegar al diagnóstico definitivo

Benign notochordal cell tumors (TBCN) are lesions with notochordal differentiation which affect the axial skeleton. They are characterized by asymptomatic or non-specific symptomatology and are radiologically unnoticed because of their small size, or because they are mistaken with other benign bone lesions, such as vertebral hemangiomas. When they are large, or symptomatic, can be differential diagnosis with metastases, primary bone tumors and chordomas. We present a case of a TBCN in a 50-year-old woman, with a sacral lesion seen in MRI. A CT-guided biopsy was scheduled to analyze the lesion, finding that the tumor was not clearly recognizable on CT, so the anatomical references of MRI were used to select the appropriate plane. The planning of the approach and the radio-pathological correlation were determinant to reach the definitive diagnosis

Postnatal Development of the Murine Notochord Remnants Quantified by High-resolution Contrast-enhanced MicroCT.

The notochord gives rise to spinal segments during development, and it becomes embedded within the nucleus pulposus of the intervertebral disc (IVD) during maturation. The disruption of the notochord band has been observed with IVD degeneration. Since the mechanical competence of the IVD relies on its structural constituents, defining the structure of the notochord during aging is critical for investigations relating to IVD function and homeostasis. The assessment and imaging of the notochord has classically relied on histological techniques, which introduces sectioning artifacts during preparation and spatial biases. Magnetic resonance imaging (MRI) does not offer sufficient resolution to discriminate the notochord from the surrounding the nucleus pulposus, especially in murine models. Current X-ray based computed tomography systems provide imaging resolutions down to the single- and sub- micron scales, and when coupled with contrast-enhancing agents, enable the high-resolution three-dimensional imaging of relatively small features. Utilizing phosphomolybdic acid to preferentially bind to collagen cationic domains, we describe the structure of the notochord remnants with aging in the lumbar IVDs of BALB/c mice. These results provide a highly quantitative and sensitive approach to monitoring the IVD during postnatal development.

SMD Kozlowski type caused by p.Arg594His substitution in TRPV4 reveals abnormal ossification and notochordal remnants in discs and vertebrae.

Spondylometaphyseal dysplasia Kozlowski type (SMDK) is a monogenic disorder within the TRPV4 dysplasia spectrum and has characteristic spinal and metaphyseal changes. We report skeletal MR imaging in a two-year-old patient who manifested typical clinical and radiographic features of SMDK. The diagnosis was confirmed by molecular analysis which revealed a mutation NM_021625.4:c.1781G > A - p.(Arg594His) in exon 11 of the TRPV4 gene. We have documented abnormalities in endochondral formation of the long and short tubular bones as well as round bones of the wrists and feet. The vertebral bodies had increased thickness of hyaline cartilage which enveloped ossification centers. The vertebrae and discs also had abnormalities in size, shape and structure. These anomalies were most likely the consequence of notochordal remnants presence within the intervertebral discs and in the vertebral bodies. The advantages of MR imaging in bone dysplasias caused by TRPV4 mutations are emphasized in this article.

Identification of a new mineralized tissue in the notochord of reared Siberian sturgeon (Acipenser baerii).

In a study aiming to improve knowledge on the mineralization of the axial skeleton in reared Siberian sturgeon (Acipenser baerii Brandt, 1869), we discovered a new mineralized tissue within the notochord. To our knowledge, such a structure has never been reported in any vertebrate species with the exception of the pathological mineralization of the notochord remains in degenerative intervertebral disks of mammals. Here, we describe this enigmatic tissue using X-ray microtomography, histological analyses and solid state NMR-spectroscopy. We also performed a 1-year monitoring of the mineral content (MC) of the notochord in relation with seasonal variations of temperature. In all specimens studied from 2-year-old juveniles onwards, this mineralized structure was found within a particular region of the notochord called funiculus. This feature first appears in the abdominal region then extends posteriorly with ageing, while the notochord MC also increases. The mineral phase is mainly composed of amorphous calcium phosphate, a small amount of which changes into hydroxyapatite with ageing. The putative role of this structure is discussed as either a store of minerals available for the phosphocalcic metabolism, or a mechanical support in a species with a poorly mineralized axial skeleton. A pathological feature putatively related to rearing conditions is also discussed.

A Case of Ecchordosis Physaliphora in the Prepontine Cistern: A Rare Entity in the Differential Diagnosis of an Epidermoid Cyst.

BACKGROUND: Ecchordosis physaliphora (EP) is a benign notochordal remnant that is usually asymptomatic. We report a case of a symptomatic large EP mimicking an epidermoid cyst. CASE DESCRIPTION: A 44-year-old woman presented with right facial dysesthesia. Brain magnetic resonance imaging showed a mass with a diameter of 3.2 cm that was hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging, isointense to hyperintense on diffusion-weighted imaging, and hyperintense on apparent diffusion coefficient map (1.2-1.6 × 10-3 mm2/second). There was no apparent contrast enhancement. Differential diagnoses included epidermoid cyst, dermoid cyst, EP, chordoma, chondrosarcoma, neurenteric cyst, and arachnoid cyst. Clinicopathologic examination revealed that the mass was an EP. CONCLUSIONS: EP in the prepontine cistern should be considered in the differential diagnosis of epidermoid cyst.

Ecchordosis Physaliphora: Evaluation with Precontrast and Contrast-Enhanced Fast Imaging Employing Steady-State Acquisition MR Imaging Based on Proposed New Classification.

PURPOSE: Ecchordosis physaliphora (EP) is a notochordal remnant typically located at the dorsal surface of the clivus, which has to be distinguished from the other retroclival lesions. Our aim is to investigate the imaging features of intracranial EP using precontrast and contrast-enhanced fast imaging employing steady-state acquisition (FIESTA). METHODS: We retrospectively evaluated the precontrast and contrast-enhanced FIESTA images of 399 patients with temporal magnetic resonance imaging to detect "classical EP" and "possible EP." The classical EP was classified into type A (hyperintense excrescence (cyst-like component) on the dorsal surface of the clivus) and type B (hyperintense excrescence plus a hyperintense lesion within the clivus). Possible EP was subdivided as incomplete EP (T2-hypointense protrusion of the clivus) and EP variant (hyperintense lesion within the clivus alone). RESULTS: We found 31 (31 of 399, 7.7 %) EPs of which 11 were defined as classical EP (2.7 %) and 20 were defined as possible EP (5.0 %). Of the 11 classical EPs, 7 (63.6 %) were diagnosed as type A and 4 (% 36.4) were diagnosed as type B. Of the 20 possible EPs, 19 were classified as incomplete EP (95.0 %) and one was classified as EP variant (5.0 %). CONCLUSIONS: Contrast-enhanced FIESTA images are helpful in the assessment of EP, although we do not define a role in the current classification proposed by Chihara et al. (Eur Radiol 23:2854-2860, 2013).

Incidental findings of skull-base abnormalities in cone-beam computed tomography scans with consultation by maxillofacial radiologists.

INTRODUCTION: Cone-beam computed tomography (CBCT) gives orthodontists and other dental clinicians 3-dimensional information for planning treatment in the craniofacial region. Often overlooked are incidental findings outside the treatment region of interest. METHODS: Two patients with incidental findings of skull-base abnormalities are presented. The orthodontic patient was tentatively diagnosed with a notochordal remnant in the clivus; the implant patient exhibited an empty sella turcica. RESULTS: For the clivus lesion in the orthodontic patient, an artifact was ruled out after a second CBCT image and further distinguished from a fat-containing tumor after magnetic resonance imaging. The impression after magnetic resonance imaging was a notochordal remnant, although chordoma was also included in the differential, warranting a 6-month follow-up magnetic resonance image to confirm the diagnosis. The CBCT study for the implant patient demonstrated an enlarged sella turcica. The impression after the magnetic resonance imaging was an enlarged and partially empty sella with no evidence of a pituitary mass. CONCLUSIONS: Orthodontists and implant surgeons may come across incidental findings outside their area of expertise on CBCT scans, highlighting the importance of appropriate consultation with maxillofacial radiologists. Notochordal remnants may present as nonexpansile intraosseous low-density areas. The challenge in distinguishing these lesions radiographically with chordomas warrants follow-up to confirm a diagnosis. An empty sella is a noteworthy finding because of its potential for endocrine and neuro-ophthalmological disorders despite an asymptomatic presentation.

Cytomorphologic findings of intraosseous notochordal rest on touch preparation: a case report.

Intraosseous notochordal rest is a rare intravertebral lesion of notochord origin which is presumably benign. It is usually an incidental finding in microscopic examination of vertebrectomy due to unrelated lesions or autopsy cases. Chordoma is a malignant neoplasm originating from notochord with a different clinicoradiographic presentation, prognosis, and treatment. However, the histology of intraosseous notochordal rest and chordoma is almost identical. Herein, we report cytomorphologic findings of a case of intraossous notochordal rest on touch preparation.

X-ray micro-diffraction studies on biological samples at the BioCAT Beamline 18-ID at the Advanced Photon Source.

The small source sizes of third-generation synchrotron sources are ideal for the production of microbeams for diffraction studies of crystalline and non-crystalline materials. While several such facilities have been available around the world for some time now, few have been optimized for the handling of delicate soft-tissue specimens under cryogenic conditions. Here the development of a new X-ray micro-diffraction instrument at the Biophysics Collaborative Access Team beamline 18-ID at the Advanced Photon Source, and its use with newly developed cryo-diffraction techniques for soft-tissue studies, are described. The combination of the small beam sizes delivered by this instrument, the high delivered flux and successful cryo-freezing of rat-tail tendon has enabled us to record data to better than 4 Šresolution. The ability to quickly raster scan samples in the beam allows selection of ordered regions in fibrous samples for markedly improved data quality. Examples of results of experiments obtainable using this instrument are presented.

[Benign notochordal cell tumor of cervical vertebrae: a clinicopathologic analysis].

OBJECTIVE: To 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. METHODS: Two cases of BNCT were studied by retrospective review of the clinical, radiologic, pathologic and immunophenotypical findings. Related literatures were reviewed at the same time. RESULTS: Case 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. CONCLUSIONS: Although 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.

Mutations in the T (brachyury) gene cause a novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal.

BACKGROUND: The T gene (brachyury gene) is the founding member of the T-box family of transcription factors and is vital for the formation and differentiation of the mesoderm and the axial development of all vertebrates. RESULTS: We report here on four patients from three consanguineous families exhibiting sacral agenesis, a persistent notochordal canal and abnormal ossification of the vertebral bodies, and the identification and characterisation of their underlying genetic defect. Given the consanguineous nature and the similarity of the phenotypes between the three families, we performed homozygosity mapping and identified a common 4.1 Mb homozygous region on chromosome 6q27, containing T, brachyury homologue (mouse) or T. Sequencing of T in the affected individuals led to the identification of a homozygous missense mutation, p.H171R, in the highly conserved T-box. The homozygous mutation results in diminished DNA binding, increased cell growth, and interferes with the normal expression of genes involved in ossification, notochord maintenance and axial mesoderm development. CONCLUSIONS: We have identified a shared homozygous mutation in three families in T and linked it to a novel syndrome consisting of sacral agenesis, a persistent notochordal canal and abnormal ossification of the vertebral bodies. We suggest that screening for the ossification of the vertebrae is warranted in patients with sacral agenesis to evaluate the possible causal involvement of T.

Benign notochordal lesions of the posterior clivus: retrospective review of prevalence and imaging characteristics.

BACKGROUND AND PURPOSE: Distinguishing BNCT from chordoma with imaging is critical because of the profound differences in prognosis and management. Yet few reports define the variable imaging characteristics of BNCT. This study aims to evaluate the prevalence and characteristics of BNCT. METHODS: A total of 916 patients with 64-section CT and 1.5T MR imaging through the posterior fossa between 2004 and 2009 were evaluated to catalogue the prevalence, clinical presentation, morphology, and imaging properties associated with BNCT. RESULTS: BNCTs were identified in 7 patients (imaging prevalence of 0.76%). All were midline, T1 hypointense, and T2 hyperintense. When present, the bony stalk often associated with EP measured between 1.65 and 3.72 mm. Five cases demonstrated atypical features such as absence of bony stalk (one case), arterial enhancement (one case), clival erosion (four cases), clinical symptoms (one case), and mass effect (one case). CONCLUSION: Many notochordal lesions do not fit neatly into the diagnostic criteria for either EP or chordoma. It may be useful to consider these atypical cases along a spectrum of notochord remnant lesions. Close inspection of imaging reveals BNCTs at a similar frequency to its pathologic prevalence. BNCTs such as EP vary in size and may be easily overlooked.

Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath.

We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord.

Not the typical Tornwaldt's cyst this time? A nasopharyngeal cyst associated with canalis basilaris medianus.

We report a patient with a cystic structure in the nasopharynx mimicking a Tornwaldt's cyst, which was felt to represent a different entity owing to the lack of the distinct features of a typical Tornwaldt's cyst. It was associated with a bony cleft in the basiocciput that was considered to be a canalis basilaris medianus (CBM), thought to represent an embryological vestige of the cephalic end of the notochord along its course within the basiocciput.

Giant vertebral notochordal rest: magnetic resonance and diffusion weighted imaging findings.

A giant vertebral notochordal rest is a newly described, benign entity that is easily confused with a vertebral chordoma. As microscopic notochordal rests are rarely found in adult autopsies, the finding of a macroscopic vertebral lesion is a new entity with only seven previously presented cases. We report here radiological findings, including diffusion weighted images, of a patient with a giant notochordal remnant confined to the L5 vertebra, with an emphasis on its distinction from a chordoma.