From our limited data, we found that men and adolescents were more frequently affected by mediastinal tumors, especially lymphoma or leukemia tumors, than women and young children. Meanwhile, neuroblastomas should be most highly suspected among children younger than 5 years old. Nevertheless, the age of onset and sexual distribution of mediastinal tumors may vary, however, among different studies. Liu et al from China showed a bimodal age distribution for mediastinal tumors, with increased incidences in patients aged <10 years old and between 60 and 70 years old. That study also showed a higher incidence of respiratory discomfort in pediatric patients as compared with adult patients, probably owning to smaller intrathoracic volumes for tumor compression in children than in adults. Gun et al from Turkey showed that among 120 cases of mediastinal tumors, the patients were predominantly women (59%) and had a median age of around 5.8 years old, which was much younger than the median age of the patients in our study. Moreover, 28% of the mediastinal tumors in the Gun et al study were benign in nature with neurogenic origin. The difference in disease spectrum between that study and the present study could have resulted from the different age distribution of the patients in both studies. In the Gun et al study, the patients had a younger average age and were more likely to have had posterior mediastinal involvement. On the other hand, in our study, the mean disease onset age was higher and the tumors were more likely to be lethal. The effect of ethnicity on disease distribution, particularly among Asians, could be investigated further in the future.
Among the patients in this study, lymphoma tumors were the most common type of mediastinal tumors. However, despite their high incidence rate, the prognosis for lymphoma tumors was better than those for other types of tumors, a finding which could have resulted from the advanced nature of current lymphoma therapy.[7,8] The 7-year event-free survival rate of non-Hodgkin lymphoma reported for the Taiwan Pediatric Oncology Group (TPOG) 2000 protocol exceeded 60%. Meanwhile, a study from Japan by Osumi et al reported that the 5-year survival rate of mediastinal B-cell lymphoma in children and adolescents could even reach up to 80%, which is much better than the 5-year survival rates for many types of pediatric malignancies. Since lymphoma could occasionally be diagnosed from laboratory results such as elevated lactic dehydrogenase (LDH) levels or the presence of blast cells in hemograms, early induction therapy or cytoreduction therapy with corticosteroids could alleviate its symptoms and improve long-term outcomes. Nevertheless, tumor lysis syndrome should be monitored carefully during lymphoma treatment in case of nephrotoxicity and electrolyte imbalance.
It is noteworthy that neuroendocrinal tumors tend to arise from the paravertebral area in the posterior mediastinum, though most of the tumors in our study arose from the anterior mediastinum. Originating from neural crest cells of the adrenal glands and sympathetic chains, neuroblastomas constitute the most common solid malignancy in young children. In the present study, 4 cases of neuroblastoma were identified in children under 5 years of age. This result was quite similar to that of a study from Spain conducted in 2007, which showed a predominance of neuroblastomas (47%), ganglioneuroblastomas (30%), and ganglioneuromas (23%) among 56 patients. Thoracic neuroblastomas have many unique clinical features compared with abdominal neuroblastomas, including Horner syndrome, opsoclonus, empyema, and even Guillain Barre-like syndrome.[13–15] In addition, thoracic neuroblastomas can also occasionally be discovered in adolescence or adulthood.[16,17] Thoracic neuroblastomas have relatively better outcomes than neuroblastomas originating from other areas. Evidence has shown that early surgical intervention to treat localized mediastinal neuroblastomas improves the associated overall survival rate. Since patients with thoracic neuroblastomas tend to be younger than those with other mediastinal tumors, careful clinical evaluations, assessments, and treatments should be performed for these patients.
The location, initial presentation, age of disease onset, and pathological types of tumors may also highly affect patients’ clinical outcomes. Commonly, patients with mediastinal tumors present with obvious respiratory or circulatory symptoms and signs such as cough, shortness of breath, hemoptysis, and chest pain. Thus, the early detection of such tumors and the prevention of possible life-threatening events constitute a key challenge for clinical practitioners. Such tumors can even be lethal if they overly compress large airways or blood vessels (such as the superior vena cava or internal jugular artery), leading to ventilation/perfusion mismatch and resulting in decompensated cardiopulmonary circulations. Pericardial or pleural effusion may further impair patients’ respiratory capacity. Moreover, sedation can be dangerous in patients with impending respiratory or circulatory failure, which requires advanced life-support. Therefore, for patients with severe airway compromise, securing airway integrity should be the priority of management. Symptomatic mediastinal tumors are often detectable through a chest x-ray or chest CT scan. Echocardiography and pulmonary ultrasounds can further be used for the evaluation of cardiac and pleural involvement.[1,21]
In our study, the patients with mediastinal lymphomas were notably more likely to have SVC syndrome, which may be easily discovered by healthcare providers upon physical examination, such as facial and neck edema, neck vein engorgement, and even blurred visions. The blood flow of the SVC is reduced in patients with SVC syndrome due to external compression of the vein by the tumor mass, enlarged lymph nodes, or intravascular thromboembolism. The central venous pressure may be elevated and accompanied by the development of collateral venous circulations (varices). Swelling of the affected side of the face, upper extremities, and respiratory tract mucosa may become prominent if the condition progresses. The treatment of SVC syndrome is focused on reducing the severity of venous obstruction. Glucocorticoids may be useful in the cytoreduction of lymphomas and thymomas, while radiotherapy may be used for solid tumors. An intravascular stent and surgical bypass are occasionally used for refractory cases. In our study, most of the lymphoma patients with SVC syndrome received systemic corticosteroids for cytoreduction to release their venous compression.
Since most pediatric mediastinal tumors are malignant in nature, and since their long-term outcomes are not predictable based on their initial presentations, establishing a definitive diagnosis of mediastinal tumors is crucial for the planning of their future treatment. In most cancers, diagnosis and staging should be made based on the histopathological results. Nonetheless, the risk and benefit of obtaining the necessary tissue via a procedure with general anesthesia require careful measurement. Airway problems are prevalent in the majority of such patients, and these problems can sometimes be lethal. A chest CT scan with contrast is a highly sensitive tool for identifying the locations of mediastinal lesions and their thoracic involvements, especially the degree of large airway and great vessel compression, and should be performed prior to any invasive procedure.[21,24] A CT-guided fine-needle biopsy performed by an interventional radiologist is commonly used to obtain tumor tissue. The success rate of this procedure has been reported to be approximately 30%. MRI is another excellent tool for assessment of mediastinal lesions owning to its clear soft tissue image resolution and direct multiplanar imaging.
Sedation may be dangerous due to the risk of cardiopulmonary compromise caused by the compression of both large airways and the pulmonary vessels by the tumor mass, resulting in a V/Q mismatch of pulmonary blood flows. Moreover, during deep sedation, the respiratory rate and tidal volume may be decreased due to reduced respiratory muscle tone, while the airflow of the bronchi may be obstructed thanks to increased airway compressibility. Furthermore, bleeding and pneumothorax are other potential complications of lung biopsy, while pleural effusion, pericardial effusion, and tumor embolism may further hinder cardiopulmonary function. A high level of tracheal or bronchial stenosis caused by the tumor mass is associated with poor outcomes. Among the patients enrolled in our study, there was one who experienced sudden hypotension and desaturation during a CT-guided biopsy. Immediate cardiopulmonary resuscitation was performed but in vain, requiring extracorporeal membrane oxygenation (ECMO) for stabilization. Unfortunately, the patient did not survive. A study from Japan showed that for 12 patients with mediastinal tumors, the median time of symptom onset to diagnosis was 8.5 days, yet warning signs leading to admission were noted on average only 2 days prior to admission, and 5 of the patients underwent cardiopulmonary resuscitation. The author concluded by noting the importance of the early awareness and recognition of airway symptoms by medical providers in patients with mediastinal tumors.
Many methods have been proposed for maintaining airway patency and cardiopulmonary function in patients with mediastinal tumors undergoing sedation and invasive procedures. The initiation of preventive VA-ECMO before de-bulking surgery or open lung biopsy should also be considered in critical cases even without intubation.[25,30] For patients proven by imaging study to have a severe degree of airway obstruction, Shamberg et al have suggested using a pulmonary function test to provide an additional preoperative evaluation of flow restriction. Peak expiratory flow rate (PEFR) may be limited in patients with airway obstruction. A multidisciplinary approach by surgeons, anesthesiologists, and intensivists should be planned initially to reduce the risk of emergency resuscitation, and the medical team should have clear communications and informed consent with the patient's family prior to the invasive intervention to avoid legal issues afterwards.
The greatest drawback to our study was the limited number of cases from a single hospital. Due to the low incidence of mediastinal tumors in general populations, there were only 40 cases of mediastinal tumors at the hospital over a period of 15 years. Nevertheless, to the best of our knowledge, this study is still the largest case series review of pediatric mediastinal tumors in Taiwan. We found that the survival rate of lymphoma tumors was higher than those for other types of mediastinal tumors, possibly due to the more effective chemotherapy protocol used to treat lymphoma. Meanwhile, it is important to assess and manage the airway during invasive procedures or sedation in these patients. Further multicenter large-scale studies should be performed to investigate the epidemiology of pediatric mediastinal tumors in Asians and possible prevention methods for the long-term complications of mediastinal tumors.
Lymphoma has better prognoses than other types of malignant tumors; however, patients with lymphoma are more likely to have SVC syndrome and neck mass. Neuroblastoma should be most highly suspected among children younger than 5 years old. Deep sedation in patients with mediastinal tumors may be life-threatening due to high risk of acute airway obstruction, so its use should be assessed and managed carefully through cooperative teamwork.
Conceptualization: Chieh-Ho Chen, Chien-Heng Lin.
Formal analysis: De-Fu Weng.
Investigation: Kang-Hsi Wu, Yu-Hua Chao.
Methodology: Kang-Hsi Wu, Yu-Hua Chao.
Writing – original draft: Chieh-Ho Chen, Chien-Heng Lin.
Writing – review & editing: Chieh-Ho Chen, Kang-Hsi Wu, Jeng-Sheng Chang.
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Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
airway obstruction; lymphoma; neuroblastoma; pediatrics