Primary epithelial-myoepithelial carcinoma (EMC) is rare subset of salivary gland-type tumor in tracheobronchial tree, and only about 50 cases have been reported in English literature^1,2. In salivary glands, most EMC are considered as low grade malignancy, although local recurrence is occurred. In spite of its rarity, typical two-cell component of EMC-inner epithelial and outer myoepithelial cells-is diagnostic histologic feature. However, other than biphasic pattern, histological spectrum and prognosis are not well established in EMC of tracheobronchial tree. To date, only five patients have been reported to have recurrence or metastasis^1,2,3,4,5, and only one patient has been reported to have lymph node metastasis at presentation⁴. Herein, we present an EMC of tracheobronchial tree with unusual solid lobular growth pattern and lymph node metastases in a 53-year-old woman.

A 53-year-old woman presented with blood tinged sputum. She was a never-smoker and had a history of diabetes on medication. Chest computed tomography scan revealed endobronchial obstructive lesion in right bronchus intermedius (Figure 1A). Bronchoscopic examination showed lobulated mass in endobronchial lesion (Figure 1B), and bronchoscopic biopsy for mass was performed. Preoperative positron emission tomography-computed tomography revealed multiple fluorodeoxyglucose uptake in right bronchus intermedius and lymph nodes in right paratracheal area (Figure 1C). On biopsy specimen, subepithelial infiltrating nests of atypical cells were identified, and differential diagnoses were neuroendocrine carcinoma such as carcinoid and poorly differentiated nonsmall cell carcinoma (Figure 2A). Subsequent biolobectomy of right middle lobe and right lower lobe with mediastinal lymph node dissection was performed.

On cut section, a 2.2-cm-sized endobronchial polypoid mass was identified (Figure 2B). The yellow-tan, solid mass was relatively well-defined, but focal interruption of bronchial cartilage was found. Microscopically, central area of the mass was composed of variable sized solid lobules of tumor cells. Tumor cells were evenly distributed in solid lobules, and central necrosis was found in the lobules. Nuclei of tumor cells showed moderate atypia and cytoplasm was eosinophilic and partly granular (Figure 2C). At the periphery, transition from small infiltrating duct-like structures to solid lobules were identified (Figure 2D). These duct-like structures resembled bronchial submucosal glands but showed nuclear atypia and infiltrative growth into peribronchial soft tissue, which were typical features of EMC. Due to the solid lobular area, differential diagnoses included collision tumor with EMC component such as metastatic lobular breast cancer, carcinoid, lymphoma, and pulmonary adenocarcinoma with solid pattern. To make final diagnosis, immunohistochemical stainings for thyroid transcription factor 1 (TTF-1; 1:100, 8G7G3/1, Dako, Carpinteria, CA, USA), p63 (1:200, 4A4, Biocare Medical, Concord, CA, USA), cytokeratin (CK; 1:500, AE1/AE3, Dako), chromogranin A (1:400, DAK-A3, Dako), CD56 (1:200, CD564, Novocastra, Newcastle upon Tyne, UK), smooth muscle actin (SMA; 1:1,000, 1A4, Dako), and Ki-67 (1:300, MIB1, Dako) were performed. Tumor cells were positive for CK (AE1/AE3) and SMA, whereas negative for remaining TTF-1, p63, chromogranin A, and CD56. In solid area, CK (AE1/AE3) was positive in inner center of the lobules and SMA was positive in the outer layer of the lobules. Peripheral duct-like structures also showed CK (AE1/AE3) positive cells in inner layer, and SMA positive cells in outer layer (Figure 2E, F). S-100 protein highlighted myoepithelial component of the peripheral duct-like structure, whereas only focal area of positivity was found in the solid lobules (Figure 2G). Ki-67 revealed high proliferative index in outer area of solid lobules, up to 40%. However, the center of solid lobules and adjacent duct-like structure showed less than 1% of proliferative index (Figure 2H). Finally, diagnosis of poorly differentiated EMC was rendered. Since there were metastases in right hilar and subcarinal lymph nodes, patient underwent adjuvant chemotherapy.

Clinically, endobronchial mass may cause hemoptysis and pulmonary parenchymal obstruction. Primary endobronchial lesions are benign in most cases. However, malignancy is more common when endobronchial lesion presents as mass lesion⁶. Benign endobronchial mass lesions include infection, foreign bodies, vascular marformation and broncholith etc. Malignant endobronchial mass lesions include squamous carcinoma, primary lung adenocarcinoma, small cell carcinoma, bronchial carcinoid and salivary gland type tumors such as mucoepidermoid carcinoma, adenoid cystic carcinoma and EMC.

EMC is a rare malignant tumor in the salivary glands, accounts for about 1% of salivary gland tumors, and EMC of pulmonary system is much rarer, and only handful of case reports are exist^1,2. Most of EMC have been considered to have low malignant potential, but precise prognosis of EMC patients is not established due to its rarity. So far, only five patients with EMC have been reported to demonstrate recurrence or metastasis^1,2,3,4,5, which is summarized in Table 1. Among five patients, lymph node metastasis was found in only one patient who received pneumonectomy due to EMC at left main bronchus⁴. Although six patients, including present case, had metastasis or recurrence, no patients have died of disease, which supports the low malignant potential of EMC and importance of complete resection of tumor.

Interestingly, proliferation of epithelial and myoepithelial component in present case made the solid architecture, mimicked other neoplasms rather than typical EMC and caused diagnostic difficulty. Furthermore, myoepithelial component of solid lobules showed relatively higher proliferative index and central necrosis, which would be responsible for the aggressive behavior in our patients, such as lymph node metastasis. In previous study, myoepithelial component has been considered to play an important role in the malignant potential of EMC¹. Song et al.¹ and Pelosi et al.⁷ suggested the malignant and proliferative role of myoepithelial cells, as p27/Kip-1 protein was aberrantly expressed in myoepithelial cells of dysplasia and well differentiated carcinoma. p27/Kip-1 protein is a cyclin-dependent kinase inhibitor, and thought to play a role in unrestricted proliferation of the myoepithelial component⁷. Although proportion of myoepithelial component has not been clearly described in previous studies with recurrence or metastasis of EMC, predominant myoepithelial component would be expected in patients with recurrence or metastasis of EMC.

In summary, we described a rare case of EMC in tracheobronchial tree that demonstrated unusual solid lobular pattern with predominant myoepithelial component and lymph node metastasis. Although implication of the solid lobular pattern in pulmonary EMC needs to be further elucidated, the possibility of aggressive EMC should be included in differential diagnoses when patient presents with endobronchial mass and unusual solid lobular area is encountered in pathologic examination.