)
DIAGNOSIS
Pulmonary Mucoepidermoid Carcinoma
FISH for the MALM-2 translocation: positive (See Figure 6)
DISCUSSION
Pulmonary mucoepidermoid carcinoma (MEC) belongs to the category of salivary gland-type tumors of the lung (SGT) which comprise less than 1% of all lung cancers (1). It has been reported in patients from 3-78 years of age; however, it usually present in patients between 10 and 40 years of age (3, 7). SGT of the lung originate from the submucosal glands of the tracheobronchial tree. The most common histologic subtype of SGT of the lung is adenoid cystic carcinoma (ACC) followed by MEC, epithelioid-myoepithelial carcinoma and pleomorphic adenoma. However, theoretically, any tumor found in the salivary glands could arise in the bronchial wall; in fact, cases of clear cell carcinoma, acinic tumors, and carcinoma ex pleomorphic adenoma have been reported (2).
The majority of thoracic MEC arise in segmental bronchi, followed by main bronchi and trachea (2, 5). At the time of initial diagnosis, two-thirds of these tumors present with localized or regional disease, and only a small proportion present with distant organ involvement. Grossly, most tumors measure from 17 to 38 mm with a median diameter of 25 mm (2). Symptoms at the time of presentation are related to the site of primary involvement, with bronchial tumors presenting with dyspnea, cough, wheezing and hemoptysis, and peripheral tumors presenting with chest pain, cough and pneumonia (3). Imaging studies demonstrates a median SUV max of 4.50 (1.5-6.3) compared to a median of 8.6 (3.7 - 17.6) in ACC (5). The prognosis of MEC of the lung is significantly better than that of NSCLC, with cause-specific survival rates of 71% and 58.1 % at 5 and 10 years, respectively (2).
Histopathologically, pulmonary MEC is characterized by different degrees of cystic and solid growth patterns and a proliferation of mucin-secreting, squamoid, and intermediate cells. Tumors are classified into low and high-grade categories; features of low-grade tumors include well-circumscribed borders, a predominance of mucinous cells, and a cystic growth pattern. Features of high-grade tumors include frequent mitoses (usually > 4/10 HPF), atypical squamoid, and intermediate cells (nucleomegaly, hyperchromatism, irregular chromatin) and necrosis (1, 3, 10). Approximately 50% to 75 % of the tumors are low-grade, and 20% are high-grade at initial diagnosis (2, 4).
Preoperative diagnosis of PMEC can be challenging in small biopsies; notably, its distinction with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma can be particularly challenging. Features that suggest the diagnosis of MEC include the presence of exophytic endobronchial growth, a lack of squamous carcinoma in-situ in the contiguous bronchial epithelium, absence of individual cell keratinization and squamous pearls, and the presence of transitional areas to low-grade MEC (9).
A potentially difficult morphological distinction in small biopsies is with mucous gland adenoma and hyalinizing clear cell carcinoma (CCC) (3). Mucus gland adenoma is a bronchial, well-circumscribed, predominantly exophytic nodule arising above the cartilaginous plates of the bronchial wall, and formed by mucin-filled cysts lined by non-atypical mucus-secreting cells (1). The distinction with clear cell carcinoma could be more challenging because CCC might demonstrate areas of squamous and mucinous differentiation. However, CCC usually demonstrates clear cell differentiation, an infiltrative growth pattern with perineural invasion, and abundant sclerotic or hyalinized stroma (15). Additionally, CCC consistently demonstrates EWSR1-ATF1 gene fusion (16).
The distinction of primary pulmonary MEC from a metastatic head and neck MEC is vital. Monaco et al. demonstrated that during six years of study, only 2 of 22 cases of pulmonary salivary gland-type tumors were primary, with the remaining 20 cases being metastases from the parotid, submandibular glands, tongue, nasal cavity and soft palate (14).
Although the diagnosis of PMEC is primarily based on morphologic findings, immunohistochemical evaluation demonstrates the tumor cells to be positive for squamous cell markers such as p40, CK 5/6, and p63, with the mucin-producing cells positive for mucicarmine and PASD (Periodic acid-Schiff, diastase-resistant). Additionally, tumor cells are negative for TTF1 and napsin A (9).
The MAML2 rearrangement (t(11; 19)(q21;p13) is found in 77-100 % of PMEC and has been identified in low and high-grade tumors (8, 9). It involves the fusion of CRTC1, CREB-Regulated Transcription Coactivator1 (formerly MECT1), and mammalian mastermind-like 2 (MAML2) genes located at chromosomes 19p13 and 11q21 respectively (8).
Initial treatment of bronchial obstruction in patients with MEC or endobronchial extension of NSCLC requires the use of a variety of treatment modalities. Among these is photodynamic therapy (PDT). This method involves the intravenous administration of a photosensitizer, after which the tumor is exposed to a light source. PDT has been shown to be effective and safe in the management of hemoptysis or malignant airway obstruction (13).
Surgery is the preferred definitive treatment modality for PMEC; it might consist of endoscopic removal for tumors limited to the bronchial mucosa up to segmental resection, lobectomy, and even pneumonectomy for more centrally located tumors (11, 12). In conclusion, mucoepidermoid carcinomas of the tracheobronchial tree are very rare tumors with a relatively good prognosis. They tend to arise in the in submucosa of segmental airways and frequently demonstrate intraluminal exophytic growth. Their distinction from more common entities like adenosquamous carcinoma is supported by a lack of individual cell keratinization and the presence of intracytoplasmic mucin; features that can be highlighted with special stains like mucicarmine and PASD. The presence of MAML2 fusions assist in the distinction with more rare entities like mucous gland adenoma and hyalinizing clear cell tumor. Finally, radical surgery after management of possible symptomatic bronchial obstruction is the preferred treatment modality for localized disease.
REFERENCES
Contributed by Daniel Martinez MD, and Paul Ohori MD
  |
