Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In ...particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the ...blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% 95% confidence interval (95% CI) = 57−88% of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88−100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P< 0.0001, Fisher’s exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.
Pediatric intramedullary spinal cord low-grade gliomas (pLGGs) are rare diagnoses among central nervous system (CNS) tumors in the pediatric population. The classic presentation of the patients ...includes some degree of neurologic deficit, although many times the symptoms are vague which leads to delayed diagnosis.PURPOSEPediatric intramedullary spinal cord low-grade gliomas (pLGGs) are rare diagnoses among central nervous system (CNS) tumors in the pediatric population. The classic presentation of the patients includes some degree of neurologic deficit, although many times the symptoms are vague which leads to delayed diagnosis.The first step in the diagnosis includes special parameters in spinal imaging, particularly magnetic resonance imaging (MRI), and surgical resection remains the cornerstone for both diagnosis and treatment. Yet, recent years advancement in molecular and genetic understanding of CNS tumors allows for better adjustment of the treatment and follow-up regimens. Based on postoperative status, adjuvant therapy may provide additional therapeutic advantage for some types of tumors.MATERIAL AND METHODSThe first step in the diagnosis includes special parameters in spinal imaging, particularly magnetic resonance imaging (MRI), and surgical resection remains the cornerstone for both diagnosis and treatment. Yet, recent years advancement in molecular and genetic understanding of CNS tumors allows for better adjustment of the treatment and follow-up regimens. Based on postoperative status, adjuvant therapy may provide additional therapeutic advantage for some types of tumors.Ultimately, patients have a very promising prognosis when treated appropriately in most of the cases of pediatric spinal cord LGG with continued advances arising. This manuscript summarizes the most contemporary evidence regarding clinical and treatment features of intramedullary pLGGs.CONCLUSIONUltimately, patients have a very promising prognosis when treated appropriately in most of the cases of pediatric spinal cord LGG with continued advances arising. This manuscript summarizes the most contemporary evidence regarding clinical and treatment features of intramedullary pLGGs.
Introduction
Spinal cord surgery has and always will be a challenging operation with satisfying results, but also with potentially devastating results. Over the last century, there has been an ...evolution in the way we perceive and conduct spinal cord surgery. The phenomenal evolution in technology from the very first x-ray pictures helps to localize the spinal pathology through the use of high-resolution MRI and ultrasonography that allows for high precision surgery with relatively minimal exposure.
Methods
The advancements in the surgical technique and the utilization of neuromonitoring allow for maximal safe resection of these delicate and intricate tumors. We also are beginning to understand the biology of spinal cord tumors and vascular lesions, as in the recent 2021 WHO classification which identifies specific entities such as spinal ependymomas,
MYCN
-amplified, as separate entity from the other subtypes of ependymomas. Surgeons have also accepted the importance of maximal safe resection for most of the spinal cord pathologies rather than just performing biopsy and adjuvant treatment.
Conclusion
There have been significant advances since the first resection of an intramedullary tumor including diagnosis, imaging, and surgical technique for children. These advances have improved the prognosis and outcome in these children.
Purpose
Intramedullary spinal cord tumors are an uncommon pathology in adults and children. Most descriptive studies of intramedullary spinal cord tumors have not focused on a possible association ...with future brain lesions. To the best of our knowledge, few reports describe this potential relationship. This is one of the most extensive case series of secondary brain lesions of intramedullary spinal cord tumors in the pediatric population.
Methods
Retrospective chart review was performed on pediatric patients (21 years old and younger) who underwent resection of an intramedullary spinal cord tumor at two tertiary care hospitals from 2001 to 2020. Patients previously treated or diagnosed with spinal cord tumor, and subsequent development of intracranial manifestation of the same or different tumor, were included. Data regarding epidemiology, surgical intervention, and clinical and follow-up course were gathered. Data analysis was performed according to a standardized clinical protocol with a literature review.
Result
More than 500 patients underwent intradural spinal tumor resection surgeries at participating hospitals from 2001 to 2020. After excluding adult patients (older than 21 years old) and those with extramedullary lesions, 103 pediatric patients were identified who underwent resection of an intramedullary spinal cord tumor. Four underwent resection of an intermedullary tumor and later in their follow-up course developed a secondary intracranial neoplasm. In every case, the secondary neoplasm had the same pathology as the intramedullary tumor. Three of the patients had tumors at the cervico-thoracic junction, and one patient had a high cervical tumor. These patients had a negative primary workup for any metastatic disease at the time of the presentation or diagnosis. Complete and near complete resection was performed in three patients and subtotal in one patient.
Conclusion
Secondary brain tumors disseminated after initial spinal cord tumor are extremely rare. This study aims to allow specialists to better understand these pathologies and treat these rare tumors with more certainty and better expectations of unusual associated lesions and conditions.
Malignant Spinal Tumors Noureldine, Mohammad Hassan A; Shimony, Nir; Jallo, George I
Advances in experimental medicine and biology,
2023, Letnik:
1405
Journal Article
Recenzirano
Malignant spinal tumors constitute around 22% of all primary spinal tumors. The most common location of metastases to the spinal region is the extradural compartment. The molecular and genetic ...characterization of these tumors was the basis for the updated WHO classification of CNS tumors in 2016, where many CNS tumors are now diagnosed according to their genetic profile rather than relying solely on the histopathological appearance. Magnetic resonance imaging (MRI) is the current gold standard for the initial evaluation and subsequent follow-up on intradural spinal cord tumors, and the imaging sequences must include T2-weighted images (WI), short time inversion recovery (STIR), and pre- and post-contrast T1-WI in the axial, sagittal, and coronal planes. The clinical presentation is highly variable and depends on the tumor size, growth rate, type, infiltrative, necrotic and hemorrhagic potential as well as the exact location within the spinal compartment. Surgical intervention remains the mainstay of management of symptomatic and radiographically enlarging spinal tumors, where the goal is to achieve maximal safe resection. Tumor recurrences are managed with repeat surgical resection (preferred whenever possible and safe), radiotherapy, chemotherapy, or any combination of these therapies.
Benign Spinal Tumors Noureldine, Mohammad Hassan A; Shimony, Nir; Jallo, George I
Advances in experimental medicine and biology,
2023, Letnik:
1405
Journal Article
Recenzirano
Benign spinal intradural tumors are relatively rare and include intramedullary tumors with a favorable histology such as low-grade astrocytomas and ependymomas, as well as intradural extramedullary ...tumors such as meningiomas and schwannomas. The effect on the neural tissue is usually a combination of mass effect and neuronal involvement in cases of infiltrative tumors. The new understanding of molecular profiling of different tumors allowed us to better define central nervous system tumors and tailor treatment accordingly. The mainstay of management of many intradural spinal tumors is maximal safe surgical resection. This goal is more achievable with intradural extramedullary tumors; yet, with a meticulous surgical approach, many of the intramedullary tumors are amenable for safe gross-total or near-total resection. The nature of these tumors is benign; hence, a different way to measure outcome success is pursued and usually depends on functional rather than oncological or survival outcomes.
Purpose
To date, the description of the natural course of concurrent tethered cord syndrome with a low-lying conus medullaris and split cord malformation is lacking in the literature. We report a ...cohort of adult and pediatric patients with concurrent malformations and long-term follow-up.
Methods
Patients with concurrent diagnoses of split cord malformation and tethered cord (radiographic evidence supporting clinical symptomatology) were identified between 2000 and 2020. Patients without sufficient documentation or at least 6-month follow-up were excluded.
Results
Nine patients were identified with an average of 8.9 years follow-up (range 2–31 years). The most common symptoms were radiating leg pain and lower extremity paresthesias, occurring in 44% of patients; and bladder/bowel dysfunction, worsening scoliosis, and acute motor deterioration were less common. Two patients were successfully treated conservatively for mild leg pain and paresthesias. For those who underwent surgery, all experienced symptomatic relief upon first follow-up. Two had late symptomatic recurrence; one 4 and 8 years after initial surgery; and the other, 11, 26, and 31 years after initial surgery.
Conclusion
The rarity of concurrent split cord and tethered cord syndrome with a low-lying conus makes management difficult to formulate. This series supplements our knowledge of the long-term outcomes and lessons learned from the management of these patients. Approximately 25% of patients were managed conservatively and had symptomatic improvement. For surgically managed patients, with intractable pain or worsening neurological function, symptoms can still recur over a decade after intervention. Reoperation, however, can still be beneficial, can provide years of relief, and should be considered.
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