Using " Endotracheal inflammatory myofibroblastic tumor, plasma cell granuloma, inflammatory pseudotumor, inflammatory fibrosarcoma and chlid" as key words, Chinese and English databases (PubMed, CNKI, WanFang database) were searched from the database construction to 03 November 2022. A total of 102 articles were retrieved. Eighty-seven papers were excluded because of duplicates and cases with an incomplete medical history.
The clinical data of 17 children were summarized and analysed, excluding repeated reports and incomplete histories (Table 1). There were nine boys and eight girls, ranging in age from two to sixteen. The main clinical manifestations of the patients were respiratory symptoms (17/17, 100%), such as cough, wheezing, stridor, dyspnea and respiratory distress. A few of the patients also had fever, chest pain and hemoptysis. The immunohistochemistry of 17 patients were different, including ALK (+), Vimentin (+), SMA (+), Desmin (+), muscle specific actin (MSA) (+), Ki-67 (+) and Calponin (+), among which mainly ALK (+), Vimentin (+) and SMA (+) (Table 1).
Table 1
Clinical features of intratracheal inflammatory myofibroblastic tumors
# | Age | Sex | Symptoms | Examinations | Location | Immunohistochemistry | First treatment | Recurrence after treatment | Treatment after recurrence | References |
1 | 2 years | Male | Cough, stridor, wheeze, severe respiratory distress | Chest CT: endotracheal mass | In the left anterolateral aspect of tracheal lumen in upper thoracic region | MSA (+), ALK (+) | Excision of the mass by bronchoscopy | (+) | Excision of the mass by rigid bronchoscopy, surgical excision of tracheal | (6) |
2 | 9 years | Female | Cough, cyanosis, wheeze, severe respiratory distress | Chest X-ray: collapse of the right lung | In the trachea near the carina extending up to the right main bronchus | SMA (+), vimentin (+) | Excision of the mass by fiber-optic bronchoscopy with forceps | (-) | / | (7) |
3 | 7 years | Male | Cough, stridor, respiratory distress | Chest CT: endotracheal polypoidal mass | In the left anterolateral wall of the trachea | (-) | Laser excision of the mass by endoscopic | (-) | / | (8) |
4 | 7 years | Male | Cough, wheeze, dyspnea | Chest CT: endotracheal calcified mass | In the anterior wall of lower trachea | Vimentin (+), ALK (+), Desmin (+) | Diode laser excision of the mass by ventilating bronchoscopy | (-) | / | (9) |
5 | 16 years | Female | Cough, stridor, dyspnea, severe respiratory distress | Chest CT: endotracheal mass | In the lumen of trachea below the cord vocals | Vimentin (+), SMA (+), Ki-67 (+) | Electrocautery snare of the mass by rigid bronchoscopy, APC, cryotherapy | (-) | / | (10) |
6 | 9 years | Female | Cough, fever, wheeze, severe respiratory distress | Chest CT: endotracheal mass | In the carina and left main stem bronchus | ALK (+) | Excision of the mass by thoracotomy, bronchotomy | (-) | / | (11) |
7 | 15 years | Female | Cough, wheeze, dyspnea | Chest CT: endotracheal mass | In the posterior wall of the trachea below the vocal cords | SMA (+), ALK (+) | Excision of the mass by rigid bronchoscopy with forceps | (-) | / | (12) |
8 | 6 years | Male | Cough, stridor, wheeze, severe respiratory distress | MRI: ovoid mass lesion | About 1cm below the vocal cords on the right lateral wall of trachea | SMA (+), ALK (+) | Surgical excision of a mass | (-) | / | (13) |
9 | 9 years | Female | Cough, sever respiratory distress | Chest CT: endotracheal mass | In the left main bronchus | SMA (+), Vimentin (+), Desmin (+) | Excision of the mass by bronchoscopy | (+) | Left upper lobe lobectomy | (14) |
10 | 14 years | Male | Cough, mild dyspnea | Chest CT: endotracheal mass | In the left tracheobronchial angle | (-) | Excision of left tracheobronchial angle with the tumor | (-) | / | (15) |
11 | 15 years | Female | Cough, chest pain, dyspnea | Chest CT: endotracheal mass | In the left main stem bronchus | ALK (+) | Surgical excision of the left main stem bronchus | (-) | / | (16) |
12 | 11 years | Female | Stridor | Chest CT: endotracheal mass | In the midtracheal | (-) | Excision of the mass by bronchoscopy | (+) | Double laser excision of the mass by bronchoscopy | (16) |
13 | 12 years | Male | Cough, blood-streaked sputum | Chest CT: endotracheal mass | In the anterior segmental bronchus | ALK (+) | Surgical excision of the right upper lobe | (-) | / | (17) |
14 | 9 years | Male | Cough, abdominal pain, fever, chest pain, dyspnea | Chest CT: endotracheal mass | In the right main bronchus | SMA (+), Vimentin (+), ALK (+) | Excision of the mass by rigid bronchoscopy | (+) | Surgical excision of the tumor and membranous portion of the bronchus | (18) |
15 | 12 years | Male | Cough, wheeze, dyspnea | Chest CT: tracheal lumen mass | In the left antero-lateral tracheal wall | SMA (+) | Forceps and diode laser excision of the mass by rigid bronchoscopy | (+) | Surgical excision of the tracheal | (19) |
16 | 10 years | Female | Cough, Wheeze, dyspnea | Chest CT: tracheal lumen mass | In the distal trachea | Unknow | Potassium titanyl phosphate laser excision of the mass by bronchoscopy | (-) | / | (20) |
17 | 5 years | Male | Cough, wheeze, hemoptysis, severe respiratory distress | Chest CT: tracheal lumen mass | Posterior wall of lower trachea | SMA (+), Vimentin (+), Calponin (+), Ki-67 (+), ALK (+) | Cryotherapy | (-) | / | This report |
MSA, muscle specific actin, SMA, smooth muscle actin, ALK, anaplastic lymphoma kinase, APC, argon plasma coagulation
IMT was first reported by Brunn et al in 1939(21). In 2020, IMT was defined by the WHO as inflammatory infiltration of myofibroblastic and fibroblastic spindle cells accompanied with a large number of plasma cells, lymphocytes, and/or eosinophils (1, 22). The etiology of IMT remains unclear. Some cases occur after surgery, trauma or inflammation, suggesting that IMT may be an abnormal or overreaction of the human body to injury (1, 23). It has also been reported that the occurrence of IMT may be related to malignant tumors or autoimmune reactions (23). Some people believe that respiratory tract infection may be the trigger factor of airway IMT (21). The presence of mycoplasma pneumoniae infection in this case suggests that mycoplasma pneumoniae infection may be the predisposition or trigger of trachea IMT in this case.
This disease can occur at any age, but is most common in children and adolescents (7). It can occur throughout the body, most commonly in the lungs. Although IMT accounts for only 0.7-1% of respiratory tumors, it is the most common lung tumor in children under 16 years of age (12).IMT occurring in respiratory tract is usually divided into two types: IMT in lung parenchyma and IMT in airway (10), and IMT occurring in trachea alone is extremely rare(8).Clinical symptoms of endotracheal IMT mainly include dyspnea, wheezing, cough, hemoptysis, etc.(24), and some patients may be misdiagnosed as asthma, pneumonia or airway foreign body(6, 12).This study collected 17 children endotracheal IMT (including this case), in which cough, wheezing, stridor, dyspnea and respiratory distress were the main clinical manifestations, and nearly half of the children were initially misdiagnosed as asthma (Table 1).
Imaging studies can identify the location of the tumor in the airway, but not the nature and involvement of the tumor. Bronchoscopy and transbronchoscopic biopsy are necessary for the evaluation, diagnosis and treatment of airway obstructive injury (25–26). Studies have found that the diagnosis of IMT is mainly determined by histopathology and immunohistochemical examination through biopsy (13–21). The pathological manifestations of IMT are as follows: [1] A large number of proliferating spindle cells are arranged in bundles;[2] The nuclei may be slightly heteromorphic, with mitotic images occasionally seen;[3] Lack of pathological mitosis and coagulation necrosis;[4] A mixture of spindle cells, lymphocytes, plasma cells and eosinophils existed (2, 27). Immunohistochemical examination of tissue biopsy showed that positive of vimentin, SMA, MSA and Desmin in the cytoplasm of spindle cell were characteristic manifestations of myofibroblasts (11, 27). ALK expression was detected in nearly half of IMT patients (26), which was consistent with the cases collected in this study (Table 1).The histopathological and immunohistochemical results of this case were consistent with the above IMT pathological and immunohistochemical changes.
There is no universal treatment for IMT occurring in the central airway tract. Although most people believe that IMT is a benign tumor, it has the risk of local invasion, recurrence, distant metastasis, and malignancy (25), so surgical resection is the preferred treatment (23). In addition to surgery, there have been reports of endoscopic laser, electrocautery and argon plasma coagulation (APC) treatment (26). Aditya et al. (12) made a systematic review of the treatment of endotracheal and main bronchial IMT in children. Among the 52 cases endotracheal IMTs, 29 cases were treated with surgery, 15 cases were treated with bronchoscopy, 5 cases were treated with surgery after bronchoscopy therapy, and 3 cases were treated with other methods. As a result, 36 cases were cured, 9 cases recurred (2 case with surgery, 7 cases under bronchoscopy), and 7 cases had unknown therapeutic effect. Of the 17 children collected, 5 cases were treated with surgery and 12 cases were treated with bronchoscopy (Table 1). Among the 17 patients, only this patient received endoscopic cryotherapy alone. Patient#5underwent APC and cryotherapy after endoscopic resection of the mass. As a result, 12 cases were cured, 5 cases recurred, including 0 cases of surgery recurrence and 5 cases of bronchoscopy recurrence (Table 1). For ALK (+) IMT patients with recurrence or metastasis after surgery or endoscopic intervention, it is suggested to be supplemented with ALK inhibitor therapy, chemotherapy and radiotherapy (28).
So far, there have been few reports on the treatment of pediatric airway IMT by cryotherapy alone through literature review. Only a few cases of pediatric airway IMT were treated with APC and cryotherapy. Patient #5 underwent bronchoscopic resection of the tumor, and APC and cryotherapy was performed on the surrounding tissue of the tumor. No recurrence was observed during follow-up. Wang Hongwu et al. (4) performed APC and cryotherapy on 4 children with IMT in airway through rigid bronchoscopy, and no recurrence was observed during the follow-up of 10 months, suggesting that APC and cryotherapy is one of the optional treatment methods for children with IMT alone (29).
Cryotherapy is a method that uses extremely low temperatures to destroy tissue. The cryogenic agents used by bronchoscopy are liquid carbon dioxide, liquid nitrogen and nitrous oxide. According to Joule-Thomson principle, liquid carbon dioxide (or N2O) will produce ice crystals after being released from the high-pressure gas storage cylinder, which can make the tip of the freezing probe reach − 80℃, which can make the water in the cell crystallize into ice, the cell stops dividing and dissolving, the blood flow stops, and micro-thrombosis is formed. Ischemic injury can cause cell necrosis or apoptosis, interrupt the growth of tumor tissue, granulation and scar tissue, and make them necrotic and shed. The sensitivity to freezing depends on different tissue characteristics. Tissues with high water content and rich blood vessels (such as skin, mucosa, granulation tissue, scar tissue, etc.) are sensitive to freezing, while tissues with low water content (such as fat, bone, fibrous connective tissue, etc.) have a good tolerance to freezing. The trachea and bronchial wall are composed of mucosa, submucosa, cartilage ring and connective tissue. Due to this histological feature of the trachea, it is highly tolerated and safe for cryotherapy, and few complications such as cicatricial stenosis, softening or perforation of the airway occur. Therefore, bronchoscopic cryotherapy is suitable for the treatment of children airway space occupying lesions such as benign and malignant tumors, granulation tissue hyperplasia and scar tissue hyperplasia (30).
In this case, because the tumor was located in the proximal carbotomy of the lower tracheal segment, surgical resection was difficult, and the tumor tissue was suitable for cryotherapy. With the consent of the patient's parents, we adopted flexible bronchoscopic cryotherapy. A total of 14 times of cryotherapy was performed, and good results were achieved without complications. This case shows that endotracheal cryotherapy is a new alternative method for the treatment of some tracheal tumors, especially in the growing airway of a child.
In conclusion, IMT in the airway is rare in children and should be distinguished from asthma and other airway obstructive diseases when clinically encountered. The preferred treatment method is surgery. Children with simple IMT who are not suitable for surgery can choose bronchoscopic interventional therapy, which not only has high safety, but also reduces the risk and complications of surgery, and also reduces the financial burden of patients' families.