Endoscopic resection of tracheal and bronchial granular cell tumours: A national multicentre retrospective study (2023)

Granular cell tumours (GCTs) are rare neoplasms accounting for 0.5% of all soft tissue tumours,1 usually presenting with a benign course. GCTs are currently believed to be neurogenic, deriving from Schwann cells. While more than 50% of GCTs are reported to occur in the head and neck regions, GCTs rarely affect the lungs, accounting for only 6%–10% of all cases.2 Few studies have investigated the endoscopic treatment of GCTs.3, 4 The objective of this retrospective and multicentre study was to provide data on the demographics, clinical, immunohistochemical and endoscopic features as well as on treatment modalities of tracheobronchial GCTs. The present work collected all cases reported by the members of the French-Speaking Group on Thoracic Endoscopy (GETIF) of the French Language Respiratory Society (Société de Pneumologie de Langue Française, SPLF), with histologically confirmed tracheal or bronchial GCTs. The 237 GETIF members were contacted by email and asked to declare GCT cases diagnosed and treated in their centre until June 2021. Participants filled a case report form, including histology, treatments, and follow-up data, and asked to provide iconography if available. The study protocol was approved by the Institutional Review Board for non-interventional research of our centre (protocol agreement # E2020-81). From 30 French centres, 12 declared one or more GCTs, including 3 centres reporting 6 cases; 1 centre reported 5 cases, and 8 centres reported one case each. Thirty-six tracheobronchial GCTs were diagnosed in thirty-one patients, which represents one of the largest series reported to date. As reported in other series,2 the male sex ratio was 1.4, with mean age 48.8 years, 64% were active smokers and only one patient was younger than 18 (13 years old). A history of head and neck, digestive or pulmonary cancer was found in four patients (12%). These cancers were histologically diverse, and in the literature the association appeared to be coincidental.5 Synchronous bronchopulmonary carcinoma was observed in three active smoking patients, including two patients with stage IV lung cancer at GTC diagnosis. No extrathoracic GCTs were identified in this series. Granular cell tumours were mainly discovered incidentally (23%), because of recurrent pneumonia (16%) or haemoptysis (10%). Four patients (12%) with tracheal lesions presented with respiratory symptoms including stridor, cough or dyspnoea. Among the 36 GCTs, 10 tumours were tracheal, with the same proportion in cervical or intrathoracic trachea, and 26 were bronchial, with no preference for a particular lobe or lung. The mean diameter of tracheal tumours was 20.4 mm (5–40 mm), and 9.5 mm (2–25 mm) for bronchial tumours. In accordance with the available literature,6 the lesions appeared polypoid in 69% of the cases or more rarely as mucosal thickening (22%), or flat lesions (8%). Hypervascularization was observed in 19% of our cases. The multifocal nature of GCTs involving the tracheobronchial tree is increasingly recognized, with multiple foci reported in 3%–18% of cases,2 and in up to 25% and 100% in the series described by Deavers et al.7 and Redjaee et al.,8 respectively. Our series included three patients with multifocal disease (10% of cases) mostly affecting the bronchi. All diagnosed GCTs were benign, according to Fanburg–Smith classification criteria9 with a Ki-67 proliferation index below 2%. Ten lesions (28%) presented with pseudo-carcinomatous hyperplasia of the overlaying epithelium. Staining for Protein S-100 was strongly and diffusely positive in all cases. These findings are consistent with benign GCTs.10 Seven patients (22%) did not receive any specific treatment: four of them because of the small size and the flat aspect of the lesion. Surgical resection was performed in only four patients (13%) including two patients with associated bronchial carcinoma, one patient with tracheal stenosis and one with undocumented surgical indication. Complete surgical resection with free margins was obtained in all four cases. Thirteen out of thirty-one patients (42%) underwent interventional bronchoscopy procedures, including scheduled resection (50%), emergency airway debulking (25% of cases) or haemoptysis treatment (17%). Patients underwent electrocautery (39%), mechanical resection (23%), cryotherapy (23%) and neodymium-doped yttrium aluminium garnet (Nd:YAG) laser (15%). Complete endoscopic resection was successful in 10 patients with complete restoration of the tracheal or bronchial airway, and absence of residual tumour cells on follow-up biopsies. Endoscopic resection was incomplete in three patients. No adverse event was reported after endoscopic treatment. Median duration of endoscopic follow-up, available for 24 patients, was 19.1 months. For the untreated patients, the tumour growth rate was low (3.5 mm per year). In addition, in patients with incomplete resection or simple observation, no malignant transformation was reported. Two patients died from concomitant advanced non-small cell lung cancer, while one patient died very soon after the diagnosis and three from unrelated causes during the follow-up period. These findings are consistent with previous reports of successful endoscopic ablation of small GCTs, without recurrence.4 Whereas the main reported treatment for tracheobronchial GCTs in previous studies is surgical resection,2 only four out of thirty-one patients of our series (13%) were suitable for complete surgical resection. Conversely, 13 patients (42%) underwent endoscopic resection, with complete endoscopic resection and no residual tumour cells on follow-up biopsies in 10 of these patients. To date, benign or malignant GCTs are known to be resistant to chemotherapy and radiation therapy. To the best of our knowledge, immunotherapy or targeted therapy have not been tested. Therefore, the treatment of choice for these tumours remains complete surgical resection, if possible.6 In non-operated patients, in the absence of symptoms and of clinical or histological sign of malignancy, a watchful waiting approach may also be an option.8 In symptomatic patients, conservative approaches, such as with laser therapy and endoscopic or sleeve resection, are proposed, which chances of cure dependent on the depth of the parietal infiltration. In the published series, a few cases2, 6, 7 (Table 1) of endocopic resection have been reported with, in the largest series2 (registered 31 GCT cases), four cases were without recurrence after 6–12 months. It has been suggested that full-thickness infiltration of the bronchial wall is more frequent in tumours >10 mm, resulting in higher recurrence rates after local treatment. Infiltration of the surrounding tissue is a common finding in benign GCTs, reported in 40%–48% of cases overall,7 and 36% of cases in our study. Daniel et al.3 reported that lesions with a diameter of at least 8 mm were more likely to invade the full thickness of the bronchial wall, with infiltration of the peribronchial tissue. Therefore, it seems reasonable to propose a ‘curative’ endoscopic treatment of GCT based on the following criteria: no histological malignancy, a lesion of less than 10 mm in diameter without local infiltration and absence of an indication for surgery.2-4, 6 Our series indicates that endoscopic treatment and follow-up is feasible in the majority of non-operable patients, with no recurrence at 19 months follow-up, and no complications of the procedure. However, a longer period of follow-up might be appropriate to confirm the absence of recurrence following endoscopic treatment. To conclude, this study has shown that complete endoscopic resection of tracheal and bronchial GCTs is feasible, with advantages in terms of complication rates and costs. This approach appears appropriate as first-line treatment for GCT management in patients with a high risk or who are unfit for surgery. Samy Lachkar: Conceptualization (lead); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). Maxime Roger: Conceptualization (equal); data curation (lead); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). Jean-Michel Vergnon: Data curation (equal); visualization (equal); writing – review and editing (equal). Adrian Crutu: Data curation (equal); visualization (equal); writing – review and editing (equal). Michel Febvre: Data curation (equal); visualization (equal); writing – review and editing (equal). Anas Mehdaoui: Data curation (equal); visualization (equal); writing – review and editing (equal). Radj Gervais: Data curation (equal); visualization (equal); writing – review and editing (equal). Laurence Geriniere: Data curation (equal); visualization (equal); writing – review and editing (equal). Francois Arbib: Data curation (equal); validation (equal); writing – review and editing (equal). Charles Dayen: Data curation (equal); validation (equal); writing – review and editing (equal). Valery Trosini-Desert: Data curation (equal); validation (equal); writing – review and editing (equal). Julie Perrin: Resources (equal); writing – review and editing (equal). David Mispelaere: Resources (equal); writing – review and editing (equal). Florian Guisier: Conceptualization (equal); data curation (equal); validation (equal); writing – review and editing (equal). Luc Thiberville: Conceptualization (equal); data curation (equal); methodology (equal); validation (equal); writing – review and editing (equal). Mathieu Salaun: Conceptualization (equal); formal analysis (equal); investigation (equal); methodology; validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). The authors are grateful to Nikki Sabourin-Gibbs, CHU Rouen, for her help in editing the manuscript. None declared. This study was performed in accordance with the Declaration of Helsinki and approved by the Institutional Review Board for non-interventional research of our centre (protocol agreement # E2020-81)—approval: E2020-81. All adult participants provided written informed consent to participate in this study. The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from Samy Lachkar on request. Visual Abstract Endoscopic resection of tracheal and bronchial granular cell tumours: A national multicenter retrospective study Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.