Clinical Features and Management of Endobronchial Hamartoma


 Background: Endobronchial hamartoma(EH) is a benign endobronchial tumor with low incidence. The objective of this study was to explore the clinical features and management of patients with endobronchial hamartoma, improve the diagnosis and treatment.Methods: Retrospective study on the clinical data of 13 cases of endobronchial hamartoma confirmed by pathology in The First Affiliated Hospital of Soochow University from July 2000 to October 2019.Results: The 13 patients, 11 males and 2 females, aged 48-74 years, mean(63±9)years, were diagnosed with EH. Three of the 13 patients with EH are asymptomatic, others had atypical symptoms. CT showed obstructive pneumonia in 10 of the 13 patients. Among the 13 patients, visible endobronchial tumor were present in 7 patients on CT, and only 3 cases were diagnosed with endobronchial tumor by radiologists. All cases received bronchoscopy. Seven patients were treated via flexible bronchoscopy, using electrocautery, argon plasma coagulation(APC) and cryotherapy. Six patients received pulmonary lobectomy via thoracotomy. Follow-up CT scan was performed in 7 of 13 patients(mean 47 months, range 17-69 months), which revealed no recurrence in all 7 patients.Conclusions: In clinical work, EH sometimes may be neglected in CT images. Bronchoscopy plays an important role in diagnosis. Pathological study is required to confirm the diagnosis. The management of endobronchial hamartoma should be individualized, bronchoscopic treatment is the first choice for EH. But in some instances, surgery should be considered.

Pulmonary hamartoma is the most common lung benign tumor, accounting for about 75 % of lung benign tumor [1]. Most pulmonary hamartomas are parenchymal hamartomas, and endobronchial hamartomas are very rare. In the largest review series published(N=215), only 1.4% of hamartomas were endobronchial, with the remainder located on the parenchyma [2]. EH sometimes may cause airway obstruction, different degrees of obstructive pneumonia and even irreversible lung damage. The treatment of EH involves surgical treatment and bronchoscopic intervention. Here we present a series of patients with EH to raise awareness of this disease.

Methods
Retrospective study on the clinical data of 13 cases of endobronchial hamartoma confirmed by pathology. Research of patients with EH in this study concluded the following contents: the patient's age, sex, clinical symptoms, accompanied diseases, image features include chest radiograph and CT, diagnosis given by radiologists, distributions of EH, bronchoscopic features, treatment involves bronchoscopic intervention and surgery, and follow-up.
Results 301 cases of pulmonary hamartoma confirmed by pathology in The First Affiliated Hospital of Soochow University from July 2000 to October 2019 were retrospectively reviewed, including 13(13/301, 4%) cases of endobronchial hamartoma. The patients included 11 males and 2 females, aged 48-74 years, with an average age of(63±9) years. All 13 cases of EH were single lesion.
Among the 13 patients, eight patients were found incidentally during health examination or examination for another reasons, including CT and bronchoscopy. Three of the 13 patients with EH are asymptomatic. For the remaining 10 patients had atypical symptoms: cough in 6 cases, chest tightness in 4 cases, chest pain in 1 case, fever in 2 cases and hemoptysis in 2 cases.
There were 3 patients having underlying respiratory diseases: one had chronic obstructive pulmonary disease(COPD), one had allergic alveoli, and one had interstitial lung disease and died of respiratory failure during hospitalization finally. Other basic diseases include hypertension in 5 cases, diabetes in 2 cases and renal carcinoma in 1 case. Six patients had a history of smoking and one had a history of exposing to dusts.

The location of EH
The location of these tumors are as follows: one was found in the right upper lobe bronchus, one in the right middle lobe bronchus, three in the right lower lobe bronchus, one in the right intermediate bronchus, three in the left upper lobe bronchus, two in the left lower lobe bronchus and two in the left main bronchus.

Image features
The following image features of 13 cases are obtained from image and image report records.
Chest radiograph findings were abnormal in 3 of the 11 patients(excepting the 2 patients with allergic alveolitis and Interstitial lung disease), main performance is obstructive pneumonia.
Chest CT showed obstructive pneumonia in 10 of the 13 patients. However, in our study, many cases may be poorly demonstrated or may not be seen at all on chest CT. After our careful review of CT, among 13 patients with EH, visible endobronchial tumor were present in 7 patients, retrospectively. Among these 7 cases, however, before the diagnosis of EH, only 3 cases were diagnosed with endobronchial tumor by radiologists. In addition, two case was misdiagnosed as lung cancer according to CT.
Among 7 visible endobronchial tumors on CT, areas of focal fat were observed in 4 lesions.
Calcification can be seen in 3 lesions of all 13 cases. Contrast-enhanced CT was performed in 3 cases, which showed no enhancement in 1 case, slight enhancement in 1 case, obvious heterogeneous enhancement in 1 case. (Figure 1)

Bronchoscopic features
All cases received bronchoscopy. We recorded 10 cases of bronchoscopy images, as follows.
Bronchoscopy showed mass with visible stalk during bronchoscopy in 5 of 10 cases.
But we believe that mass with stalk is much more than 5 cases, because some EH obstruct the airway severely, we may not be able to see the stalk of EH of the posterior airway Three patients received bronchoscopic treatments more than once: One case(N1) failed in the first interventional treatment with snare via flexible bronchoscope due to difficulty in exposing the stalk of the mass, and then switched to argon plasma coagulation(APC) therapy. Residual tumors was found in the second bronchoscopy, APC was performed the second time. Four months later, bronchoscopy showed that the EH was completely removed, but hyperemia of the mucosa. CT examination showed no recurrence 6 One case(N2)'s EH was removed partially with snare via flexible bronchoscopy the first time. So a second intervention, rigid bronchoscopy was performed initially, but we found it was difficult to insert rigid bronchoscopy due to patient's narrow oropharynx. Then we switched to flexible bronchoscopy via laryngeal mask airway(LMA). Using APC combined with cryotherapy, the mass was removed completely, taken out by wire basket.
One case(N3) received bronchoscopic intervention 4 times. The mass was cauterized with APC the first time, APC and cryotherapy were used at the second time due to recurrence, and cryotherapy was used the third time. Scar stenosis was found during the fourth bronchoscopy, then dilated by endoscopic biopsy forceps.
For the remaining 4 patients, both of them were treated with snare electrocautery via flexible bronchoscopy, and then mass root was treated with APC or cryotherapy, or combination of the two.
There were no major complications in these 7 cases, except a little bleeding in some patients and one patient who developed slight pneumomediastinum and pneumothorax, successfully recovered with simple oxygen therapy.

Surgical treatment
Six patients received pulmonary lobectomy via thoracotomy. All patients who underwent surgery received bronchoscope biopsy and brush biopsy in the initial bronchoscopy.
However, no definite diagnosis of EH was given.
One of them appeared intolerance and sharp increased blood pressure during bronchoscopy, though under adequate local anesthesia with lidocaine. In addition, bronchoscopy showed the mass with a lot of necrotic, which was highly suspected of malignancy. So we gave up the interventional treatment through bronchoscope, and switched to surgery.
For the remaining 5 patients, CT scan showed moderate or severe irreversible pulmonary damage which require pulmonary lobectomy or enlargement of hilar or mediastinal lymph node, which cannot rule out malignancy lymphatic metastasis. The enlargement of hilar and mediastinal lymph node finally confirmed as chronic inflammation by surgical pathology.
Chylothorax occurred in 1 case, and hydrothorax became clear and significantly reduced after 5 days of drainage. No other complications were observed.
The clinical characteristics of 13 cases of endobronchial hamartoma are summarized in Table 1.

Follow-up
Follow-up CT scan was performed in 7 of 13 patients(mean 47 months, range 17-69 months), which revealed no recurrence in all 7 patients. Unfortunately, follow-up bronchoscopy was not performed except two cases(N1, N3) mentioned above, which spanned a longer time period for bronchoscopy(4 months and 5 months in total ).

Discussion
Pulmonary hamartoma can be divided into parenchymal type and endobronchial type according to its location, the latter is rare. Parenchymal hamartoma usually has no symptoms, but endobronchial hamartoma often causes atypical symptoms, including cough, sputum, fever, hemoptysis, chest pain, chest tightness [3]. The clinical symptoms of endobronchial hamartoma usually relate to its location and the severity of the obstruction.
In this study, chest radiograph showed abnormalities only in patients with moderate or severe obstructive pneumonia caused by EH. CT can indicate EH by showing endobronchial lesion directly or obstructive pneumonia and atelectasis caused by EH indirectly. However, definite diagnoses of endobronchial mass given by radiologists in our study were not many. We think there are many reasons for missed diagnosis: There were 6 cases of EH in segmental and subsegmental bronchi in our study, which can be easier missed than lesion located in main and lobar bronchus. In addition, it is not easy to distinguish endobronchial lesion on CT when obstructive pneumonia and atelectasis mixing with EH.
Fat and calcification density are the characteristics of pulmonary hamartoma. It has been reported that EH contains more fat density [4]. In our study, calcification within the lesion were presented in only 3 cases, which was more likely to be missed. In imaging diagnosis, radiologists sometimes may neglect examination of airway, which also caused missed diagnosis.
Bronchoscopy is an important diagnostic method for EH, which can directly observe the tumor and evaluate the location, size, shape, base and surface mucosa of the tumor. At bronchoscopy, most EHs appeared as smooth surfaced round masses with stalk [5]. It is difficult to identify with malignant tumor when necrotic tissue exist on the surface of EH.
All surgical cases in this study had biopsy and brush biopsy in the initial bronchoscopy before surgery, but no definite diagnoses were made. Because biopsy tissue is too little to provide adequate pathological information, the positive rate of EH routine biopsy via bronchoscope is low, except complete or partial excision via bronchoscopic intervention [6]. However, it plays an important role in confirming endobronchial lesion and providing preliminary information about judgment of benign lesion and strategies for further treatment. In this study, bronchoscopy had important effects on diagnosis of EH, especially in those whose EH cannot be clearly showed on CT. So when endobronchial lesions are suspected on CT, then further bronchoscopy should be considered.
The traditional treatment of EH is surgical treatment.
With the development of bronchoscopic interventional techniques, bronchoscopic intervention provide an opportunity of non-operational treatment for EH, has the advantages of simple operation, high security, significant effect, less postoperative complications, fast recovery and low cost. The common interventional techniques of EH treatment include the use of electrocautery, APC, cryotherapy, laser, and balloon dilatation. The above methods have their own indications and advantages, but some limitations [5,6,7,8,9,10].
Electrocautery is an effective therapeutic option for endobronchial tumor.
Snare electrocautery is a good option for EH especially, because EH usually have pedicle attached to bronchial wall. For EH with stalk, it is critical to find the location of stem before snare electrocautery [6]. The snare is placed over the lesion and wrapped around the stem. The stalk is then cut while concurrently providing hemostasis [7,8,9,10]. Snare electrocautery can quickly remove the large tumor in the airway at one time, reducing the treatment time and avoiding multiple complications such as perforation of the airway wall, bleeding and airway burn caused by repeated electrocautery, compared with other electrocautery instruments like forceps, knives or rounded probes.
Endobronchial hamartoma has the possibility of recurrence [3]. The key to prevent recurrence is the treatment of residual root, which is usually done by APC or cryotherapy.
APC is complementary to other techniques usually. With its superficial effect on tissue, it is safer to remove the tumor in the airway and can also be used for superficial hemostasis, but it can't avoid the disadvantage of granulation tissue proliferation after treatment [7,8,9,10]. Cryotherapy is based on cytotoxic effects of low temperature on living tissue by repeated freeze thaw cycle, which is both immediate and delayed.
Because of low water content of cartilage, collagen and poorly vascularized tissue, cryotherapy has less effects on them. So the scarring is minimal and the damage of cartilage is few [8,9,10].
Each technique has its own characteristics. Therefore, in practical applications, various techniques should be combined according to intraoperative situation and experience of operators. However, in one case(N3), even with the combination of APC and cryotherapy, bronchial stenosis caused by scar hyperplasia occurred. We suspected that scar hyperplasia may be related with repeated treatment.
Despite the widespread use of flexible bronchoscope, rigid bronchoscope has many advantages in airway maintenance, controlling massive hemoptysis, shorter intervention time and getting out large tissue, compared with flexible bronchoscope. But rigid bronchoscope can only reach the main bronchi and intermediate bronchus, cannot reach peripheral bronchus, especially superior lobar bronchus. Nowadays, the combination of rigid and flexible bronchoscope intervention technology can compensate for this shortcoming. The difficulty of rigid bronchoscope implantation and anatomic contraindications limit its wide application. Rigid bronchoscopy should be performed under general anesthesia [8,9,11,12]. In this study, a patient failed in inserting rigid bronchoscope due to his narrow oropharynx after general anesthesia. Then we switched to flexible bronchoscopy via laryngeal mask airway(LMA). LMA is a new type of ventilation, with the advantage of simple operation, less airway irritation and less influence on hemodynamics. Flexible bronchoscopy can be performed easily via LMA, which can ensure patients' ventilation function during general anesthesia and improve the safety of bronchoscopic treatment [12,13,14].
Although bronchoscopic treatment is the first choice for EH. But in some instances, surgery is inevitable mainly because of irreversible lung damage, especially difficulty in differentiating benign and malignant lesions. Surgical treatments may include sleeve resection with bronchoplasty, lobectomy, and even pneumonectomy in complicated cases, while normal lung tissues should be reserved as much as possible [15,16,17]. In this study, many cases accompanied with irreversible lung damage, more importantly, some of them were highly suspicious of malignancy, therefore lobectomy take a high proportion of treatment in this study.

Acknowledgements
Not applicable.

Funding
This study was supported by the Gusu youth medical talent (3101030342000318), Science and education of public health project for young medical talents of Jiangsu Province (QNRC2016747), National Science and Technology Major Project (2017ZX10204401003).

Availability of data and materials
The data of this study are available from the corresponding author upon reasonable request.