IgA multiple myeloma-associated mediastinal spinal plasmacytoma presenting as spinal cord compression.

Multiple myeloma associated with extramedullary plasmacytoma at initial presentation is rare. We describe a case of a man in his 30s who initially presented with symptoms of spinal cord compression. Further imaging revealed a mediastinal tumour, with a biopsy confirming plasmacytoma. Immunofixation revealed IgA lambda paraprotein. Bone marrow biopsy demonstrated atypical T-cell cytotoxic proliferation and trilineage hypoplasia. The patient was diagnosed with extramedullary plasmacytoma with active IgA multiple myeloma. The patient received mediastinal radiation to the tumour, followed by anti-myeloma therapy. This diagnosis is critical as managing a solitary plasmacytoma drastically differs from an extramedullary plasmacytoma with active multiple myeloma.

Cervicomedullary Compression in Achondroplasia: A Feared Complication and an Unforeseen Risk Factor of Posterior Circulation Stroke.

Achondroplasia is an autosomal dominant disorder with defect in the ossification of the cartilage of long bones. Many bony abnormalities constitute its clinical features, with craniovertebral junction (CVJ) anomalies being one of most common issues which need to be addressed at the earliest. CVJ anomalies in individuals may cause neurovascular compression, which may warrant an early surgery to prevent catastrophic complications. Posterior circulation strokes secondary to CVJ anomalies are well known. We hereby present an unusual case of posterior circulation stroke in an achondroplastic dwarf who presented to our tertiary care centre. Prospective case study. The present case adds to the existing literature about one of the preventable causes of fatal posterior circulation strokes in the young. A high index of suspicion for neurovascular compression at the foramen magnum and early initiation of treatment in achondroplastic young individuals may have gratifying results.

[Analysis of imaging characteristics and effectiveness of cervical spondylotic myelopathy with cervical kyphosis].

Objective: To investigate the imaging characteristics of cervical kyphosis and spinal cord compression in cervical spondylotic myelopathy (CSM) with cervical kyphosis and the influence on effectiveness. Methods: The clinical data of 36 patients with single-segment CSM with cervical kyphosis who were admitted between January 2020 and December 2022 and met the selection criteria were retrospectively analyzed. The patients were divided into 3 groups according to the positional relationship between the kyphosis focal on cervical spine X-ray film and the spinal cord compression point on MRI: the same group (group A, 20 cases, both points were in the same position), the adjacent group (group B, 10 cases, both points were located adjacent to each other), and the separated group (group C, 6 cases, both points were located >1 vertebra away from each other). There was no significant difference between groups ( P>0.05) in baseline data such as gender, age, body mass index, lesion segment, disease duration, and preoperative C 2-7 angle, C 2-7 sagittal vertical axis (C 2-7 SVA), C 7 slope (C 7S), kyphotic Cobb angle, fusion segment height, and Japanese Orthopedic Association (JOA) score. The patients underwent single-segment anterior cervical discectomy with fusion (ACDF). The occurrence of postoperative complications was recorded; preoperatively and at last follow-up, the patients' neurological function was evaluated using the JOA score, and the sagittal parameters (C 2-7 angle, C 2-7 SVA, C 7S, kyphotic Cobb angle, and height of the fused segments) were measured on cervical spine X-ray films and MRI and the correction rate of the cervical kyphosis was calculated; the correlation between changes in cervical sagittal parameters before and after operation and the JOA score improvement rate was analyzed using Pearson correlation analysis. Results: In 36 patients, only 1 case of dysphagia occurred in group A, and the dysphagia symptoms disappeared at 3 days after operation, and the remaining patients had no surgery-related complications during the hospitalization. All patients were followed up 12-42 months, with a mean of 20.1 months; the difference in follow-up time between the groups was not significant ( P>0.05). At last follow-up, all the imaging indicators and JOA scores of patients in the 3 groups were significantly improved when compared with preoperative ones ( P<0.05). The correction rate of cervical kyphosis in group A was significantly better than that in group C, and the improvement rate of JOA score was significantly better than that in groups B and C, all showing significant differences ( P<0.05), and there was no significant difference between the other groups ( P>0.05). The correlation analysis showed that the improvement rate of JOA score was negatively correlated with C 2-7 angle and kyphotic Cobb angle at last follow-up ( r=-0.424, P=0.010; r=-0.573, P<0.001), and positively correlated with the C 7S and correction rate of cervical kyphosis at last follow-up ( r=0.336, P=0.045; r=0.587, P<0.001), and no correlation with the remaining indicators ( P>0.05). Conclusion: There are three main positional relationships between the cervical kyphosis focal and the spinal cord compression point on imaging, and they have different impacts on the effectiveness and sagittal parameters after ACDF, and those with the same position cervical kyphosis focal and spinal cord compression point have the best improvement in effectiveness and sagittal parameters.

Unusual case of spinal cord compression revealed a double primary Hodgkin's lymphoma of the spinal cord.

Hodgkin's lymphoma revealed by a medullary compression with a double primary vertebral localisation is extremely rare. We report the case of a boy in middle childhood who was presented with slow progression of medullary compression syndrome over 9 months, ultimately leading to paraplegia with loss of sphincter tone. The spinal MRI showed two tumour processes at T9 and L1 with epidural extension. An anatomical-pathological examination of the biopsy of the tumour mass, along with immunohistochemical analysis, confirmed the diagnosis of a lymphocyte-rich classic Hodgkin's lymphoma, stage IV according to the Ann Arbor classification. The therapeutic strategy was based on chemotherapy. This study aims to report a unique clinical presentation of Hodgkin's lymphoma in a paediatric patient and underscores the diagnostic challenges encountered in such an uncommon scenario.

Non-traumatic complete cervical spine dislocation with severe fixed kyphosis: successful multidisciplinary approach to a challenging case.

BACKGROUND: To our knowledge, there is no previous report in the literature of non-traumatic neglected complete cervical spine dislocation characterized by anterior spondyloptosis of C4, extreme head drop, and irreducible cervicothoracic kyphosis. CASE PRESENTATION: We report the case of a 33-year-old Caucasian man with a 17-year history of severe immune polymyositis and regular physiotherapy who presented with severe non-reducible kyphosis of the cervicothoracic junction and progressive tetraparesia for several weeks after a physiotherapy session. Radiographs, computed tomography, and magnetic resonance imaging revealed a complete dislocation at the C4-C5 level, with C4 spondyloptosis, kyphotic angulation, spinal cord compression, and severe myelopathy. Due to recent worsening of neurological symptoms, an invasive treatment strategy was indicated. The patient's neurological status and spinal deformity greatly complicated the anesthetic and surgical management, which was planned after extensive multidisciplinary discussion and relied on close collaboration between the orthopedic surgeon and the anesthetist. Regarding anesthesia, difficult airway access was expected due to severe cervical angulation, limited mouth opening, and thyromental distance, with high risk of difficult ventilation and intubation. Patient management was further complicated by a theoretical risk of neurogenic shock, motor and sensory deterioration, instability due to position changes during surgery, and postoperative respiratory failure. Regarding surgery, a multistage approach was carefully planned. After a failed attempt at closed reduction, a three-stage surgical procedure was performed to reduce displacement and stabilize the spine, resulting in correct spinal realignment and fixation. Progressive complete neurological recovery was observed. CONCLUSION: This case illustrates the successful management of a critical situation based on a multidisciplinary collaboration involving radiologists, anesthesiologists, and spine surgeons.

Imaging Assessment of Nontraumatic Pathologic Conditions at the Craniovertebral Junction: A Comprehensive Review.

Nontraumatic pathologic conditions of the craniovertebral junction encompass a range of conditions affecting the complex anatomy of this region without direct physical injury. These conditions include congenital syndromes that predispose individuals to ligamentous laxity, potentially leading to instability. Additionally, rare but noteworthy cases such as Grisel syndrome, a cause of pediatric torticollis, may arise without a traumatic trigger. Inflammatory diseases, including rheumatoid arthritis, ankylosing spondylitis, and crystal deposition, can lead to cervical instability and spinal cord compression. Infections at the upper cervical spine are dominated by tuberculosis, typically transmitted through hematologic or lymphatic routes with characteristic imaging findings. On the other hand, purulent bacterial infections in this area are rare. Furthermore, although tumors involving the structures of the craniovertebral junction are infrequent, they can lead to significant complications, albeit less frequently through cord compression and more commonly via pathologic fractures or subluxation. The craniocervical junction is a complex anatomic region comprising ligaments, bones, joints, and muscles that support the head's weight and enable its wide range of motion. Accurate recognition and understanding of the complex anatomy and the various nontraumatic pathologic conditions at the craniovertebral junction are pivotal for initiating timely and appropriate treatment strategies. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

A Novel Technique for Basilar Invagination Treatment in a Patient with Klippel-Feil Syndrome: A Clinical Example and Brief Literature Review.

Objectives and Background: To present a novel technique of treatment for a patient with basilar invagination. Basilar invagination (BI) is a congenital condition that can compress the cervicomedullary junction, leading to neurological deficits. Severe cases require surgical intervention, but there is debate over the choice of approach. The anterior approach allows direct decompression but carries high complication rates, while the posterior approach provides indirect decompression and offers good stability with fewer complications. Materials and Methods: A 15-year-old boy with severe myelopathy presented to our hospital with neck pain, bilateral upper limb muscle weakness, and hand numbness persisting for 4 years. Additionally, he experienced increased numbness and gait disturbance three months before his visit. On examination, he exhibited hyperreflexia in both upper and lower limbs, muscle weakness in the bilateral upper limbs (MMT 4), bilateral hypoesthesia below the elbow and in both legs, mild urinary and bowel incontinence, and a spastic gait. Radiographs revealed severe basilar invagination (BI). Preoperative images showed severe BI and that the spinal cord was severely compressed with odontoid process. Results: The patient underwent posterior surgery with the C-arm free technique. All screws including occipital screws were inserted into the adequate position under navigation guidance. Reduction was achieved with skull rotation and distraction. A follow-up at one year showed the following results: Manual muscle testing results and sensory function tests showed almost full recovery, with bilateral arm recovery (MMT 5) and smooth walking. The cervical Japanese Orthopedic Association score of the patient improved from 9/17 to 16/17. Postoperative images showed excellent spinal cord decompression, and no major or severe complications had occurred. Conclusions: Basilar invagination alongside Klippel-Feil syndrome represents a relatively uncommon condition. Utilizing a posterior approach for treating reducible BI with a C-arm-free technique proved to be a safe method in addressing severe myelopathy. This novel navigation technique yields excellent outcomes for patients with BI.

Systematic Review and Meta-Analysis on Optimal Timing of Surgery for Acute Symptomatic Metastatic Spinal Cord Compression.

Introduction: Symptomatic acute metastatic spinal epidural cord compression (MSCC) is an emergency that requires multimodal attention. However, there is no clear consensus on the appropriate timing for surgery. Therefore, to address this issue, we conducted a systematic review and meta-analysis of the literature to evaluate the outcomes of different surgery timings. Methods: We searched multiple databases for studies involving adult patients suffering from symptomatic MSCC who underwent decompression with or without fixation. We analyzed the data by stratifying them based on timing as emergent (≤24 h vs. >24 h) and urgent (≤48 h vs. >48 h). The analysis also considered adverse postoperative medical and surgical events. The rates of improved outcomes and adverse events were pooled through a random-effects meta-analysis. Results: We analyzed seven studies involving 538 patients and discovered that 83.0% (95% CI 59.0-98.2%) of those who underwent urgent decompression showed an improvement of ≥1 point in strength scores. Adverse events were reported in 21% (95% CI 1.8-51.4%) of cases. Patients who underwent emergent surgery had a 41.3% (95% CI 20.4-63.3%) improvement rate but a complication rate of 25.5% (95% CI 15.9-36.3%). Patients who underwent surgery after 48 h showed 36.8% (95% CI 12.2-65.4%) and 28.6% (95% CI 19.5-38.8%) complication rates, respectively. Conclusion: Our study highlights that a 48 h window may be the safest and most beneficial for patients presenting with acute MSCC and a life expectancy of over three months.

Surgical Outcomes of Extensive Dome-Like Laminoplasty Using En Bloc Resection of C2 Inner Lamina for Patients With Severe Cord Compression Behind C2 Body.

STUDY DESIGN: A retrospective, single-center study. OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a newly developed extensive dome-like laminoplasty using en bloc resection of the C2 inner lamina in patients with severe cord compression behind the C2 body. SUMMARY OF BACKGROUND DATA: A surgery for severe cord compression behind C2 body is challenging for spinal surgeons. To date, there has been no established solution for severe cord compression behind the C2 body. MATERIALS AND METHODS: Patients with severe cord compression behind the C2 body who underwent posterior surgery consecutively were enrolled. Extensive dome-like laminoplasty that was newly developed was performed to remove en bloc removal of the C2 inner lamina were performed. Preoperative and postoperative canal diameters behind the C2 and mean removed area of the C2 inner lamina were measured using MRI and CT scan. Clinical and radiographic parameters were assessed preoperative and postoperative periods. In addition, perioperative complications were analyzed. RESULTS: A total of 36 patients underwent extensive dome-like laminoplasty and their diagnoses were ossification of the posterior longitudinal ligament (OPLL, 66.7%) and congenital stenosis with spondylosis (33.3%). The mean canal diameter behind the C2 increased from 9.85 (2.28) mm preoperatively to 19.91 (3.93) mm at the last follow-up ( P <0.001). Clinically, neck and arm visual analog scale, Japanese Orthopaedic Association score, and neck disability index significantly improved at postoperative 1 month ( P <0.05), and the scores were maintained until the last follow-up. No meaningful radiographic changes occurred after the surgeries. During the procedures, there were no particular complications, but one patient showed deteriorated myelopathic symptoms and underwent additional C1-C2 decompressive surgery. CONCLUSIONS: After extensive dome-like laminoplasty, surgical outcomes are satisfactory, and complications are rare. This technique may be a viable option for patients with severe cord compression behind the C2 body. LEVEL OF EVIDENCE: Level IV.

Evaluation of computed tomography artefacts of carbon-fiber and titanium implants in patients with spinal oligometastatic disease undergoing stereotactic ablative radiotherapy.

This study evaluated artefacts on computed tomography (CT) images using Hounsfield units (HU) in patients with spinal oligometastatic disease who received carbon-fiber (CF; n = 11) or titanium (n = 11) spine implants and underwent stereotactic ablative radiotherapy (SABR). Pre- and postoperative HU were measured at the vertebral body, pedicle, and spinal cord at three different levels: the lower instrumented vertebra, the level of metastatic spinal cord compression, and an uninvolved level. Areas measured at each level were delicately matched pre- and postoperatively. Significant differences in HU were observed at the vertebral body, the pedicle, and the spinal cord at the lowest instrumented vertebra level for both CF and titanium (average increase 1.54-fold and 5.11-fold respectively). At the metastatic spinal cord compression level, a trend towards a higher HU-increase was observed in titanium compared with CF treated patients (average increase 2.51-fold and 1.43-fold respectively). The relatively high postoperative HU-increase after insertion of titanium implants indicated CT artefacts, while the relatively low HU-increase of CF implants was not associated with artefacts. Less CT artefacts could facilitate an easier contouring phase in radiotherapy planning. In addition, we propose a CT artefact grading system based on postoperative HU-increase. This system could serve as a valuable tool in future research to assess if less CT artefacts lead to time savings during radiotherapy treatment planning and, potentially, to better tumoricidal effects and less adverse effects if particle therapy would be administered.

Post-operative complications affect survival in surgically treated metastatic spinal cord compression.

PURPOSE: The prevalence of metastatic epidural spinal cord compression (MESCC) is increasing globally due to advancements in cancer diagnosis and treatment. Whilst surgery can benefit specific patients, the complication rate can reach up to 34%, with limited reporting on their impact in the literature. This study aims to analyse the influence of major complications on the survival of surgically treated MESCC patients. METHODS: Consecutive MESCC patients undergoing surgery and meeting inclusion criteria were selected. Survival duration from decompressive surgery to death was recorded. Perioperative factors influencing survival were documented and analysed. Kaplan-Meier survival analysis at one year compared these factors. Univariate and multivariate Cox proportional hazard regression analyses were performed. Additionally, univariate analysis compared complicated and uncomplicated groups. RESULTS: Seventy-five patients were analysed. Median survival for this cohort was 229 days (95% CI 174-365). Surgical complications, low patient performance, and rapid primary tumour growth were significant perioperative variables for survival in multivariate analyses (p < 0.001, p = 0.003, and p = 0.02, respectively) with a hazard ratio of 3.2, 3.6, and 2.1, respectively. Univariate analysis showed no variables associated with complication occurrence. CONCLUSION: In this cohort, major surgical complications, patient performance, and primary tumour growth rate were found to be independent factors affecting one year survival. Thus, prioritizing complication prevention and appropriate patient selection is crucial for optimizing survival in this population.

Evaluation of the structural integrity of different spinal cord tracts with magnetization transfer ratio in degenerative cervical myelopathy.

PURPOSE: Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction. In this study, we explored the potential of magnetization transfer ratio (MTR) for evaluating the structural integrity of spinal cord tracts in patients with clinically significant DCM. METHODS: Fifty-three patients with DCM and 41 patients with cervical radiculopathy were evaluated using high-resolution cervical spinal cord magnetic resonance imaging (MRI), which included the magnetization transfer technique. MRI data were analyzed with the Spinal Cord Toolbox (v5.5); MTR values in each spinal tract were calculated and compared between groups after correction for patient age and sex. Correlations between MTR values and patients' clinical disability rate were also evaluated. RESULTS: A statistically significant reduction in the average MTR of the spinal cord white matter, as well as the MTR of the ventral columns and lateral funiculi, was revealed in the DCM group (adjusted p < 0.01 for all comparisons). Furthermore, reductions in MTR values in the fasciculus cuneatus, spinocerebellar, rubrospinal, and reticulospinal tracts were found in patients with DCM (adjusted p < 0.01 for all comparisons). Positive correlations between the JOA score and the MTR within the ventral columns of the spinal cord (R = 0.38, adjusted p < 0.05) and the ventral spinocerebellar tract (R = 0.41, adjusted p < 0.05) were revealed. CONCLUSION: The findings of our study indicate that demyelination in patients with DCM primarily affects the spinal tracts of the extrapyramidal system, and the extent of these changes is related to the severity of the condition.

Isolated Rosai-Dorfman disease of the spine: A systematic literature review.

INTRODUCTION: Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis involving the central nervous system in 5% of cases. Spinal location occurs in less than 1% of extranodal RDD and can be responsible for neurological manifestations. We present a systematic review of cases of isolated spinal RDD. We also report a new case of isolated spinal RDD revealed by spinal cord compression. MATERIALS AND METHODS: The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE and SCOPUS databases and included case reports and case series describing isolated RDD of the spine. RESULTS: There were 53 patients with isolated spinal RDD (including our case). The mean age was 35.85±16.48 years. Neurological deficit was the most frequent clinical presentation (89%). RDD lesions were mainly located in the thoracic spine (51%), then the cervical spine (32%). The lesion was reported to be extradural (57%), intradural extramedullary (26%), intramedullary (7%), and in the vertebral body (10%). Histological examination showed emperipolesis in 73%. Histocytes were positive for S-100 protein in 83%. Treatment was based on surgery 96%), radiotherapy, chemotherapy, and adjunctive steroid therapy were indicated in four, one, and eight cases. After a mean follow-up period of 14.84±13.00 months, recurrence of RDD was noted in 15%. CONCLUSION: Spinal RDD is a rare condition, requiring meticulous histological examination for accurate diagnosis. Complete surgical resection is the treatment of choice. Adjuvant chemotherapy and radiotherapy can also be indicated in patients demonstrating partial improvement following surgery.

Capillary Hemangioma of the Spinal Cord: Case Report and Systematic Review of Literature.

BACKGROUND: Capillary hemangiomas are rare vascular lesions that rarely affect the central nervous system. When they present within the spinal canal, they are typically confined intradurally, with intramedullary extension rare. We present a rare case of spinal intramedullary capillary hemangioma, with a systematic review of the literature. METHODS: Medical records and imaging data were retrospectively reviewed using the health record software EPIC (Verona, Wisconsin, USA) and the radiology management software system RIS/PACS (Radiology Information System/Picture Archiving and Communication System; QREADS). The report was written in accordance with the CARE (case reports) guidelines. We also performed a systematic review of the literature on all cases of intramedullary spinal capillary hemangiomas in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. RESULTS: We report a case of a 54-year-old man who presented with progressive paraplegia and sensory deficits in the lower extremities. Spinal magnetic resonance imaging showed an intramedullary enhancing lesion centered at T11 with associated spinal cord compression. He underwent thoracic laminectomy and gross total resection of the lesion without complications and subsequent improvement on his neurological examination. Histological examination showed findings consistent with a capillary hemangioma. The literature review also documented 21 studies with a combined total of 38 cases of intramedullary spinal capillary hemangioma. CONCLUSIONS: Purely intramedullary capillary hemangiomas are unusual spinal lesions with only a few cases reported in the literature. These should be considered in the differential diagnosis of intramedullary tumors. Surgical management remains the first line of treatment for symptomatic patients.

Aggressive B-Cell Lymphoma with Metastatic Spinal Cord Compression: Treat the Patient, Not the Disease.

INTRODUCTION: The management of metastatic spinal cord compression (mSCC) is a demanding task. The main challenges of mSCC include various manifestations and unpredictable outcomes with indiscriminate treatment recommendations. Because of attendant urgency with potentially devastating health consequences, the SCC is an emotionally disturbing experience whose management could take an impulsive rather than rational approach. The treatment strategy is particularly problematic when mSCC is caused by a malignant lymphoma with its protean attributes. CASE REPORT: A 68-year-old female presented with generalized body pain and weight loss. Imaging studies revealed a vast bulk of the disease involving lymph nodes, spleen, visceral organs, musculature, marrow, and bones including vertebrae with extension into the spinal canal. A biopsy of the chest wall mass showed high-grade diffuse large B-cell lymphoma. A magnetic resonance imaging (MRI) of the spine demonstrated diffuse marrow replacement by the tumor of the thoracic and lumbar spine with compression of the cord. The prompt treatment with corticosteroids and immunochemotherapy (ICT) was recommended, but the patient elected to seek a second opinion. After two doses of radiation therapy, the patient's general condition rapidly deteriorated and she was hospitalized for systemic ICT. Despite the treatment, her condition continued to deteriorate, and she died 3 weeks after the presentation. CONCLUSION: The presented case demonstrates some hitherto unaddressed challenges in evaluation and treatment of mSCC caused by aggressive non-Hodgkin lymphoma (LSSC). The case scrutinizes the role of MRI in uncommon clinical situations. The case has also exposed some ethical issues associated with the proper management of LSCC.

Incidence of skeletal-related events in patients with Ewing sarcoma: An observational retrospective study in Japan.

BACKGROUND: Skeletal-related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. METHODS: We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE-free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses. RESULTS: During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE-free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs. CONCLUSIONS: SREs are non-rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future.