Pleomorphic adenoma of the trachea: A case report and review of the literature

Qian-Nuan Liao, Ze-Kui Fang, Shu-Bing Chen, Hui-Zhen Fan, Li-Chang Chen, Xi-Ping Wu, Xi He, Hua-Peng Yu

Qian-Nuan Liao, Ze-Kui Fang, Shu-Bing Chen, Hui-Zhen Fan, Li-Chang Chen, Xi-Ping Wu, Xi He,Hua-Peng Yu, Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital,Southern Medical University, Guangzhou 510280, Guangdong Province, China

Abstract BACKGROUND Pleomorphic adenoma (PA) is the most common benign tumor that occurs in the salivary glands; however, tracheobronchial PA is rarely observed. To the best of our knowledge, fewer than 50 cases have been reported in the literature. We report a 49-year-old woman who had been treated for asthma for 2 years before being diagnosed with PA of the trachea.CASE SUMMARY A 49-year-old woman was referred to our hospital due to dyspnea upon exertion and chronic cough with wheezing for 2 years. Laboratory tests showed an elevated white blood cell count, absolute neutrophil count, and percentage of neutrophils. A chest computerized tomography scan showed a well-defined, softtissue density lesion measuring 2.4 cm × 2.1 cm in the lower trachea. Flexible bronchoscopy revealed that nearly 90% of the tracheal lumen was obstructed. The histopathological and immunohistochemistry features suggested PA of the trachea. Furthermore, we review the characteristics of 29 patients with tracheobronchial PA over the last 30 years.CONCLUSION Tracheobronchial PA occurs without gender predominance, mostly in the lower or upper trachea, and has a low recurrence rate. The median age at diagnosis is 48 years. The most common symptoms are cough, stridor, dyspnea, and wheezing.

Key Words: Pleomorphic adenoma; Trachea; Bronchoscopy; Review; Diagnosis; Case report

INTRODUCTION

Pleomorphic adenoma (PA) is an unusual type of salivary-gland neoplasm that occurs in the trachea[1]. The tumor is composed of recognizable epithelial tissue mixed with mucoid, myxoid, and chondroid tissues, which can also be observed in the soft palate,hard palate, upper lip, nasal septum, nasopharynx, orbital area, lower eyelid, buccal mucosa, cheek, and external auditory canal[2]. To the best of our knowledge, fewer than 50 cases have been reported[3-6]. Due to the lack of early specific symptoms, PA of the trachea is usually misdiagnosed as asthma[6-9]. In addition, cases of PA can progress to malignant tumors[10]. We present a case of PA of the trachea that was successfully treated by bronchoscopic interventions.

CASE PRESENTATION

Chief complaints

Dyspnea upon exertion and chronic cough with wheezing for 2 years.

History of present illness

A 49-year-old woman was referred to our hospital for dyspnea upon exertion and chronic cough with wheezing for 2 years. The above symptoms worsened with white mucus sputum for the past one week with no complaints of fever, chest tightness,chest pain, or hemoptysis.

History of past illness

The patient was previously diagnosed with asthma and treated with inhaled glucocorticoids for 2 mo.

Personal and family history

There was no history of tobacco use, and the patient denied having a personal or family history of other diseases.

Physical examination

In the physical examination, lip cyanosis, three depression signs (suprasternal fossa,supraclavicular fossa, and intercostal space), and expiratory and inspiratory wheezing were observed, and the sound of her lungs was decreased with crackles, but she did not have lymphadenopathy or weight loss. Furthermore, we could hear stridor in the trachea and neck.

Laboratory examinations

Routine blood tests showed an elevated white blood cell count (14.70 × 109cells/L;range, 3.5-9.5 × 109cells/L), absolute neutrophil count (11.36 × 109cells/L; range, 1.8-6.3 × 109cells/L), and neutrophil percentage (77.3%; range, 40%-75%); the serum potassium level was found to be decreased in the blood biochemistry results(2.78 mmol/L; range, 3.5-5.5 mmol/L). The tumor markers were normal. The arterial blood gas test suggested respiratory acidosis combined with metabolic alkalosis.

Imaging examinations

Pneumonia was detected from the chest X-ray, with no other abnormalities.A computed tomographic (CT) scan of the chest showed a sign of pulmonary infection,and computed tomographic virtual bronchoscopy (CTVB) showed a well-defined, softtissue density lesion measuring 2.4 cm × 2.1 cm in the lower trachea, located 2 cm above the carina (Figure 1). Fiberoptic bronchoscopy revealed that the surface of the mass was smooth and vasodilatory, and nearly 90% of the tracheal lumen was obstructed, so the bronchoscope failed to pass through (Figure 2).

Pathological examination

Histopathological analysis revealed that the tumor was composed of epithelial and myxoid mesenchymal elements and was characterized by the presence of ductal structures that appeared to contain double-layered cells in a mucoid or hyaline stroma.Notably, there was no sign of necrosis or mitosis (Figure 3). Immunohistochemically,the tumor cells did not express thyroid transcription factor-1 and cytokeratin 7 (CK 7),but were positive for CK, CK 5/6, p63, and the S-100 protein, with low expression of Ki-67 (10%). Moreover, the basement membrane was immunoreactive for AB/ paraaminosailcylic acid. After immunohistochemical staining, the definite diagnosis was determined to be PA of the trachea.

FINAL DIAGNOSIS

The patient was finally diagnosed with PA of the trachea.

TREATMENT

Considering that the patient's vital signs were stable, intratracheal tumor resection was performed by electron bronchoscopy under conscious sedation induced using intravenous midazolam. Finally, tumor tissues were excised with an electrosurgical snare and cryotherapy. Then, the edges and base of the mucosal defect were treated with argon plasma coagulation (APC) to enhance tumor clearance. There was no significant bleeding or perforation from the wound (Figure 2). After resection,the tracheal lumen was completely unobstructed, and there were no new organisms.

OUTCOME AND FOLLOW-UP

The patient's wheezing symptoms were remarkably relieved after the operation, but cough and expectoration remained. Regarding the sign of pulmonary infection from the chest CT, the patient was discharged 9 d after anti-infection treatment and remained asymptomatic at the 3-mo follow-up.

DISCUSSION

PA originating from the trachea is rare. According to Fitchettet al[11], it accounts for 1%of lung carcinomas and between 2% to 9% of all cases of PA. This type of PA consists of myoepithelial cells mixed with neoplastic ducts and stroma. The demographics and presenting characteristics of the 29 cases are shown in Table 1.Likewise, the major clinical features of the patients are listed in Table 2. According to the review, no gender predominance was found. The age of the patients ranged from 8 to 83 years, with a median age of 48 years, and there were four minors.More than half of these tumors were located in the lower or upper trachea;however, two cases originated from the airway and grew outward into the thyroid or mediastinum. Although a few patients presented with hemoptysis, the most common symptoms were cough, stridor, dyspnea, and wheezing, depending on the site and degree of airway obstruction. The patient in this case had a 2-year history of dyspnea upon exertion and chronic cough with wheezing before being properly diagnosed with PA of the trachea. The median clinical course was 5.5 mo, and the longest coursewas 10 years, which may reflect the benign nature of the tumor. In addition, it results in low recurrence rates at follow-ups.

Table 1 Summary of presenting characteristics of tracheobronchial pleomorphic adenoma reported in the English medical literature

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CK: Cytokeratin; EMA: Epithelial membrane antigen; GFAP: Glial fibrillary acidic protein; SMA: Smooth muscle actin; NSE: Neuron-specific enolase; APC: Argon plasma coagulation; TTF-1: Thyroid transcription factor-1; M: Male; F:Female; CK 7: Cytokeratin 7.

Tracheal tumors are difficult to identify in chest radiographs. Moreover, patients initially present with non-alarming symptoms mimicking asthma[11]. The patient in this case was previously misdiagnosed with asthma and treated with inhaled glucocorticoids for 2 mo. Therefore, chest CT and bronchoscopy play a critical role in making early and proper diagnoses. CTVB involves the three-dimensional reconstruction of high-resolution helical CT images of the tracheobronchial tree, which can facilitate the analysis of bronchial lesions beyond the limits of bronchoscopy and the assessment of airway patency distal to high-grade obstructions[12]. However, CTVB cannot be used to identify the nature of a lesion, while bronchoscopy can be used to complete this by biopsy.

Histologically, PA is also known as a “mixed tumor”, which describes its pleomorphic appearance rather than its dual origin from epithelial and mesenchymal components. The stroma may be mucoid, myxoid, cartilaginous, or hyaline.Approximately 6% of tumors have the potential to transform into carcinoma ex pleomorphic adenoma[10]. When it presents with atypical cells, an abnormal chromatin pattern, and necrosis, the diagnosis of carcinoma ex pleomorphic adenoma is made.Regarding immunohistochemistry findings, the tumor shows positive staining for creatine kinase, p63, S-100 protein, epithelial membrane antigen, and glial fibrillary acidic protein. S-100 protein and glial fibrillary acidic protein may be helpful markers in differentiating PA and adenoid cystic carcinoma[13]. In addition, the patient in ourstudy had a Ki-67 index of 10%. This marker is widely known as a proliferative marker, and numerous studies have shown a positive correlation between Ki-67 expression and the proliferative cell fraction in tumors[14].

Table 2 Outline of major features characterizing presentation of 29 cases of tracheobronchial pleomorphic adenoma

Given the rarity of tracheal PA, no standards for management have been established, but it is clear that the main goal is to remove the lesion and restore airway patency. Surgical resection and airway anastomosis have traditionally been applied in many studies[4,15,16]. Compared with surgery, endoscopic resection is less traumatic and allows a faster recovery after the operation. Endobronchial intervention using a rigid and flexible bronchoscope is widely performed in cases of airway stenosis. In our case,we successfully applied bronchoscopic interventional therapy to remove the tumor,such as electrosurgical snare, cryotherapy and argon plasma coagulation. Due to its rarity, its biological behavior and clinical course have not been well

described. One case of tracheal PA was reported to be recurrent in 2020 after surgical resection and end-to-end anastomosis were performed 10 years previously[17].Therefore, long-term follow-ups are essential for patients. According to the medical literature, there is no clearly recommended follow-up period or interval, of which the longest follow-up period is 5 years without recurrence[8]. We will follow this patient by periodic chest CT and flexible bronchoscopy at least 10 years after the tumor resection.

Figure 1 Computed tomographic presentation of the patient. A: Mediastinal computed tomographic scan of the chest showed a 2.4 cm × 2.1 cm homogenous well-defined, dense soft tissue lesion in the left lateral inner wall of the trachea (orange arrows); B: Computed tomographic scan with multiplanar reconstruction showed a round lesion in the lower trachea (black arrow); C: A tumor in the inner trachea observed by computed tomographic virtual bronchoscopy(blue arrow).

Figure 2 Bronchoscopic findings. A: A polypoid and vasodilatory mass originated from the right side of the lower trachea; B: After endoscopic resection, the tumor was removed almost completely, and the airway patency was restored.

Figure 3 Pathological presentation of the patient. The tumor was composed of epithelial and myxoid mesenchymal elements and characterized by the presence of ductal structures that appeared to contain double-layered cells in a mucoid or hyaline stroma. No signs of necrosis or mitosis were observed(hematoxylin-eosin staining, × 100).

CONCLUSION

Overall, we summarize the clinical presentation, clinical course, treatment, and prognosis of tracheobronchial PA according to the literature over the last 30 years[18-33].PA of the trachea is extremely rare, and patients initially present with nonspecific symptoms mimicking asthma. Chest CT and bronchoscopy play a critical role in making an early diagnosis, whereas a definite diagnosis is made on the basis of histopathological and immunohistochemistry features. Although surgical resection is traditionally performed, this article supports the notion that bronchoscopic interventions for PA of the trachea are viable treatment options.