Based on the histological features and the immunohistochemical staining profiles described above, the present lung tumor was diagnosed as a low-grade mucoepidermoid carcinoma of the lung. Mucoepidermoid carcinomas are malignant tumors, but they usually have an indolent behavior. Low-grade mucoepidermoid carcinomas have a much better prognosis than high-grade carcinomas. Mucoepidermoid carcinomas of the lung are often treated by lobectomy, sleeve resection, local resection, segmental resection, or even endoscopic removal
[1, 2, 5, 6, 8]. Although some studies indicated the lymph node metastasis
[6, 8], the metastasis of low-grade mucoepidermoid carcinomas of lung are rare
The present tumor was composed of typical three cell types. The mucin-secreting cells were located in the cysts and nests regions, had light blue-gray mucinous cytoplasm, and were positive for cytokeratins staining. The majority of intermediate cells formed nests and solid regions, and were positive for cytokeratins and p63 staining. The intermediate cells also could be found at the periphery of the glandular structures. The squamoid cells formed small nests among intermediate cells, and were positive for cytokeratins and p63 staining. The tumor cells were relatively uniform, and had bland nuclei. The nuclear mitoses were very few. No individual cell keratinization or squamous pearl was observed. So, the diagnosis of adenosquamous carcinoma could easily be excluded. The negative expression of synaptophysin indicated this tumor had not neuroendocrine differentiation. All these evidences supported the diagnosis of a mucoepidermoid carcinoma of the lung.
Interestingly, the appearance of inner lining cells of the glandular structures was different to the typical three cell types. The inner lining cells were cuboidal and hobnail-like, had oval and bland nuclei. We hypothesized that the inner lining cells might be alveolar-epithelial-like cells and examined the expressions of TTF-1 and SP-B. Alveolar epithelial cells express TTF-1 and surfactant proteins, including SP-A, SP-B, SP-C, and SP-D, which are considered as the markers of pulmonary epithelial differentiation and are useful parts of immunohistochemical panel in pulmonary pathology
[9, 10]. TTF-1, a homeodomain nuclear transcription protein, is considered a specific marker of epithelial cells of the thyroid and lung. SP-B is synthesized and secreted primarily by alveolar type II epithelial cells and essential for normal lung surfactant function. The immunohistochemical staining revealed that the inner lining cells were positive for cytokeratins, TTF-1, and SP-B, but negative for p63. We considered that the inner lining cells might represent focal tumor cells differentiating toward alveolar epithelial cells or entrapped alveolar epithelial cells. But, this primary tumor of bronchus is 4.5 cm in diameter. The alveolar-epithelial-like inner lining cells could be found in more than 1/3 area of the tumor, including the glandular region and the center of some nests or solid regions. Furthermore, the inner lining cells were not only located at the edge of the tumor, but also could be found in the center region of the tumor. Taken together, we considered that these inner lining cells were tumor cells differentiating toward alveolar epithelial cells.
To the best of our knowledge, the alveolar epithelial differentiation was not reported previously in mucoepidermoid carcinomas of the lung. But, it was documented in other salivary gland tumors of the lung, such as salivary gland-type mixed tumors and epithelial-myoepithelial tumors
[11–13]. The TTF-1 positive tumor cells were also located at the inner layers of glandular components in these tumors, and were considered as alveolar epithelial differentiation
[11–13]. It is indicated that the alveolar epithelial differentiation of glandular epithelia might be a special character in the salivary gland tumors of the lung and should be noted.
Previous studies examined the expression of TTF-1 in a small numbers of mucoepidermoid carcinomas of the lung. They showed that all mucoepidermoid carcinomas of the bronchus in their series were negative for TTF-1
[2, 14]. So, it was considered that TTF-1 was useful in differentiating mucoepidermoid carcinoma of the bronchus from primary lung adenosquamous carcinoma
. Here, we reported a special and rare case of mucoepidermoid carcinoma with TTF-1 and SP-B positive glandular epithelial cells, which required attention in differential diagnosis. It was reported that the expression of TTF-1 was negative in the mucoepidermoid carcinomas of sinonasal tract (19 cases)
, But was positive in the mucoepidermoid carcinomas of thyroid gland (2 of 4 cases)
. So, we considered that only detecting the expression of TTF-1 was not enough for differential diagnosis. TTF-1 together with SP-B might be useful in distinguishing between primary mucoepidermoid carcinomas of the lung and metastatic tumors from other regions. More cases need to be examined to confirm this hypothesis.