Based on the WHO Classification of lung tumors (2015), primary salivary gland-type tumors(pSGTs) can be divided into the following four types: mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), epithelial-myoepithelial carcinoma (EMC), and pleomorphic adenocarcinoma (PA) . Pulmonary mucoepidermoid carcinoma is the most common type of pSGTs, followed by PACC . In clinic, the age range of PACC had been reported to be 21-80. PMEC had a broad spectrum in age from 3 to 78 years old and often occurred in 40s [5,10]. According to the study conducted by Kumar, PACC was mostly localized to the trachea and main bronchus, while PMEC was more commonly diagnosed in the lung. Patients with PMEC had a better prognosis than PACC. The age span of our series is from 18 to 67 year-old and the average age is 45. Interestingly, in accordance with recent reports, we also found that PMECs were commonly found in men . 80% patients had clinical presentations and the positive rate of tumor markers was 78%, although no specific markers were found. Chest CT had an important value in the diagnosis of PMEC despite rare tumors exhibited an endobronchial pattern. If these patients were accompanied with persistent respiratory symptoms or elevated tumor markers, bronchoscopy examination and biopsy should be conducted to avoid misdiagnosis. TTF-1 was negative in all PMECs, conforming that it was of great value in distinguishing PMEC from lung adenocarcinoma, adenosquamous carcinoma and PMEC-like tumors . Surgery is the main procedure of PMEC. Most patients were alive without evidence of disease after completely resection . Our study showed that 3-year survival rate of PMEC is 72%, and 80 percent of those patients achieved disease-free alive. Histological grade was widely recognized as a prognostic factor. Our series also demonstrated that high-grade PMEC patients tend to harbor older age, larger tumor volume and higher index of ki-67. Due to the small size of samples, we did not find significant difference in TNM stage and metastasis between low and high grade of PMEC. However, some large series had revealed the worse outcomes of patients who accompanied with advanced TNM staging and earlier metastasis [14-16].
Accumulated evidences demonstrated that earlier diagnosis and complete surgical resection would benefit prognosis of PMEC. Histological examination is the most reliable way to distinguish it from other PMEC-like tumors and confirm its differentiation grade. It is worth mentioning that in small biopsies the distinction between PMEC and mucous gland adenoma can be very difficult. Mucous gland adenoma is a benign tumor composed of acini lined by mucus-containing cuboidal cells, while PMEC is a malignant tumor contain three cell types：mucin-secreting, squamoid, and intermediate cells. The absence of squamous and intermediate cell, immunohistochemically negativity for cytokeratin 5/6，P63 and P40, lack of malignancy features such as cellular atypia, mitotic activity and invasive growth pattern suggests mucous gland adenoma. Poorly differentiated mucoepidermoid carcinoma is sometimes difficult to distinguish from squamous carcinoma in the form of HE under the microscope. The differential diagnosis of high grade PMEC from squamous carcinoma may depend on: (1) surface epithelium lacking the changes of carcinoma in situ; (2) absence of individual cell keratinization and squamous pearl formation; (3) the presence of transitional areas to low-grade mucoepidermoid carcinoma or scattered mucin-secreting cells.
At present, there were few studies focused on driven genes of PMEC. Evidences indicated that the most frequent gene mutation in PMEC is MAML2, which belongs to MasterMind-like gene family on chromosome 11q21. In salivary gland tumors, MAML2 rearrangement has been identified in 40–75% of mucoepidermoid carcinoma [17-18]. However, the association between MAML2 rearrangement and prognosis is still in suspense. The current view suggests that MALML2 is more prone to occur in lower-grade PMEC and has no value for prognosis [19-21]. PMEC has a low preoperative diagnosis rate through bronchoscopy and CT-guide percutaneous lung puncture biopsy. Most of our cases had been treated as non small cell lung cancer (NSCLC) before and during surgery. It suggested that the application of molecular techniques to detect the MAML2 rearrangement and TTF-1 expression may be helpful in improving the preoperative diagnosis. Targeted therapy has brought survival benefit to NSCLC patients. So far there is no effective treatment for PMEC patients who cannot undergo surgery. Few studies had paid attention to driven genes such as EGFR and ALK. It was noted that the mutational frequency of EGFR in PMEC was 40% and mutations were all L858R mutation. A case of ALK-rearranged PMEC was reported by Wong et.al in 2009 [22-24]. In our retrospective cases, we identified ALK rearrangement in a non-smoking woman with high grade PMEC. However, due to the small scale of such report, no predictive markers have been found. More attention should be paid to investigate mutational profile of PMEC to provide alternative therapy for advanced patients, especillay MAML2 rearrangement.