Continuing Education Activity

Mucoepidermoid carcinomas are rare salivary gland-type tumors that comprise mucin-secreting cells, squamous cells, and intermediate-type cells. They make up a distinct group of lung malignancies accounting for less than 1% of all lung cancers. Based on the current World Health Organization classification of pulmonary tumors, mucoepidermoid carcinomas are sub-classified into low-grade and high-grade tumors. This activity reviews the cause, pathophysiology, presentation, and diagnosis of mucoepidermoid tumors of the lung, and highlights the role of the interprofessional team in the management of these patients.

Objectives:

• Describe the classification of lung mucoepidermoid tumors.
• Outline the workup of a patient with a lung mass.
• Summarize the treatment options for lung mucoepidermoid lesion.
• Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by mucoepidermoid lung mass.

Introduction

Mucoepidermoid carcinomas are rare salivary gland-type tumors that comprise mucin-secreting cells, squamous cells, and intermediate-type cells. They make up a distinct group of lung malignancies, accounting for less than 1% of all lung cancers.[1] Based on the current World Health Organization classification of pulmonary tumors, mucoepidermoid carcinomas are sub-classified into low-grade and high-grade tumors. Most commonly occurs in the central bronchial region. The majority are low-grade mucoepidermoid carcinomas which have an excellent prognosis in contrast to high-grade tumors which behave as other non–small cell carcinomas of the lung.[2] The diagnosis of pulmonary mucoepidermoid carcinoma relies on histopathological examination of the biopsy and surgical specimen since the clinical and radiological manifestations are not specific.[3]

Etiology

Tobacco smoking does not seem to be a risk factor for pulmonary mucoepidermoid carcinoma.

Epidemiology

Mucoepidermoid carcinomas represent 0.1 to 0.2% of primary lung tumors. They affect all ages, although approximately 50% of cases present before 30 years of age and 20% before 20 years. Mucoepidermoid carcinomas affect males and females equally.[4] They are usually endobronchial and typically arise in the central airways (trachea, main or lobar bronchi, or segmental bronchi). Mucoepidermoid carcinomas are occasionally present in the lung periphery.[5]

Pathophysiology

Because of its rarity and the small number of studies published, the precise nature and the histogenesis of mucoepidermoid carcinoma are still not well-known. Mucoepidermoid carcinomas originate from submucosal minor salivary-type glands in large airways. A fusion gene CRTC1-MAML2 occurs in both low-grade and high-grade mucoepidermoid carcinoma,[6] more frequently in low-grade tumors.[7] This fusion gene has potential as a diagnostic marker. Reports exist of EGFR mutations in some cases, but their significance is unclear.[8]

Histopathology

Macroscopic examination:

Mucoepidermoid carcinomas are well-demarcated oval or round tumors usually soft in consistency sometimes hard or elastic, measuring 3 cm on average. They show a gray-white to pink-tan, sometimes mucinous and varyingly cystic cut surface. High-grade tumors are more infiltrative.[9]

Histologic examination:

The World Health Organization has proposed subclassification of mucoepidermoid carcinoma into low-grade and high-grade.

Low-grade mucoepidermoid carcinoma is distinguishable from high-grade mucoepidermoid carcinoma based on the following characteristics:

• Cytological atypia
• Mitotic activity
• Cellular necrosis

Low-grade tumors are composed of three cell types: mucin-secreting, squamous, and intermediate cells, and often show cystic patterns with solid areas. Tumor islands contain both cystic and solid patterns. Cystic components consist of cytologically bland columnar cells with mucin and rare mitoses. Solid components, consisting of squamoid and/or intermediate cells, typically surround the cystic areas. Intermediate cells are oval or polygonal with round nuclei, eosinophilic or clear cytoplasm, and rare necrosis. Stromal calcification and ossification, often with a granulomatous reaction are present around areas of mucous extravasation.

High-grade mucoepidermoid carcinoma is mainly composed of atypical squamoid and intermediate cells, with frequent mitosis and necrosis, accompanied by variable numbers of mucin-secreting cells. High-grade tumors are rare, and the diagnosis should be determined after careful exclusion of adenosquamous carcinoma. Criteria more typical of high-grade mucoepidermoid carcinoma include:

• Exophytic endobronchial growth 
• Surface epithelium lacking the changes of carcinoma in situ
• Absence of individual cell keratinization and squamous pearl formation
• Transitional areas to low-grade mucoepidermoid carcinoma 

Immunohistochemistry:

Immunohistochemically, the tumor cells show positive immunostaining for p63, p40, pan-cytokeratin, CK7, CK5/6 and Muc5Ac whereas TTF-1, CK20, SOX 10, androgen receptor, calponin, SMA, and smooth muscle myosin heavy chain and napsin A are not expressed.[10] S100, CEA, and EMA show variable staining.[11]

History and Physical

The diagnosis of pulmonary mucoepidermoid carcinoma often gets delayed for more than a year because of slow growth, non-specific signs and symptoms, and subtle findings on thoracic imaging.[12]

The most common presenting symptoms of mucoepidermoid carcinoma are symptoms of large airway irritation or obstruction.[5][13] They include:

• Hemoptysis
• Cough
• Chest pain
• Wheezing
• Obstructive pneumonia

Evaluation

Chest X-ray:

On chest x-ray, mucoepidermoid carcinomas are well-circumscribed, oval, round, or lobulated masses. Frequently, there are signs of bronchial stenosis or obstruction such as mucoid impaction, post-obstructive pneumonia, distal bronchial dilatation, atelectasis, air trapping, and peripheral lucency.  

Computed tomography scan:

The value of CT study in pulmonary mucoepidermoid carcinomas diagnosis is limited since the CT image findings are non-specific.

On CT, low-grade tumors are intraluminal homogeneous nodules or masses with or without obstructive change; some large lobular heterogeneous masses containing multilobular cystic structures filled with low-attenuation fluid and in some cases multiple punctate or coarse calcifications are noted.[14]

In high-grade tumors, mucus secretion decreases because of weak differentiation, cystic lesions are less common, and necrosis occurs more frequently than in low-grade tumors. On CT, certain high-grade tumors also present signs of common lung cancer, such as spiculation, pleural infiltration, lymphadenopathy, or even distant metastasis.[14]

PET imaging:

By PET imaging, pulmonary mucoepidermoid carcinoma is usually FDG-avid.[15] The size varies from 0.6 to 6 cm.

Bronchoscopy:

At bronchoscopy, pulmonary mucoepidermoid carcinomas appear as polypoid pink masses that can be confused with carcinoid tumor.[16]

Histopathology:

The diagnosis of pulmonary mucoepidermoid carcinoma relies on histopathological examination of the biopsy and surgical specimen since the clinical and radiological manifestations are not specific.[3]

Treatment / Management

Complete surgical resection is the treatment of choice of pulmonary mucoepidermoid carcinoma and can result in better long-term survival.[17] For advanced disease, especially in the case of high-grade mucoepidermoid carcinoma, adjuvant therapy should be administered when complete resection is impossible. However, the usefulness of chemotherapy and radiotherapy remains controversial.[17][18] Some patients with unresectable disease have responded favorably to EGFR-targeted therapy.[18] However, such results need confirmation and further studies.

Differential Diagnosis

Differential diagnosis of low-grade mucoepidermoid carcinoma:

• Mucous gland adenoma
• Carcinoid
• Squamous cell carcinoma
• Adenocarcinoma

Differential diagnosis of high-grade mucoepidermoid carcinoma:

• Adenosquamous carcinoma
• Necrotizing sialometaplasia
• Squamous cell carcinoma
• Adenocarcinoma

Staging

It is recommended to use the TNM system (eighth edition) of lung tumors for the staging of pulmonary mucoepidermoid carcinomas.

Prognosis

Low-grade mucoepidermoid carcinoma:

Despite occasional nodal involvement and metastases, the prognosis of low-grade mucoepidermoid carcinoma is excellent with a five-year survival rate approaching 95%.[13] The prognosis in children is slightly better than in adults.[19]

High-grade mucoepidermoid carcinoma:

Reports on the prognosis for high-grade tumors vary, but about 25% of patients with these tumors develop metastases, typically in lymph nodes, bone or skin.[12]

Poor prognostic factors include:

• Positive resection margins
• Lymph node metastasis

Enhancing Healthcare Team Outcomes

Mucoepidermoid carcinomas are ideally managed by an interprofessional team that consists of a pulmonologist, radiologist, thoracic surgeon, oncologist, and pathologist. Early diagnosis and prompt treatment improve the prognosis for most patients. Oncology nurse practitioners are involved in the care of patients, providing patient care, monitoring response to therapy, and providing feedback to the team.