Bronchial Epithelial-Myoepithelial Carcinoma

While epithelial-myoepithelial tumor is relatively common in salivary glands,1 it is rarely found in the respiratory tract. To date, 20 cases have been reported in the lung, with various biological behavior.2,3 Fourteen of the reported cases were categorized as malignant. We describe an epithelial-myoepithelial carcinoma obstructing the airway in a 73-year-old man and present a brief review of the literature.

A 73-year-old man presented with progressive shortness of breath. His past medical history was remarkable for atrial fibrillation, mild chronic obstructive pulmonary disease, multiple episodes of bronchitis and pneumonia, glaucoma, and benign prostatic hypertrophy. He had a smoking history of 60 pack-years, but had stopped smoking 27 years earlier. The patient denied cough, bloody sputum, or weight loss. Chest radiography revealed an opaque shadow in the left lobe. Computed tomographic scan demonstrated a well-circumscribed tumor located medially in the left upper lobe of the lung, which partially compressed the left pulmonary arteries (Figure 1).

The lobectomy specimen showed a well-circumscribed tumor located in the posterior aspect of the left upper lobe, measuring 3.8 × 2.9 × 2.9 cm. The tumor was completely intrabronchial and caused mucus plugging of the distal airway (Figure 2). The cut surface of the tumor was firm and gray-white.

Microscopically, the tumor showed 2 histologic patterns. The predominant pattern consisted of glands lined by a dual population of epithelial and myoepithelial cells, along with a minor component of spindle cells in a fascicular pattern (Figure 3). The myoepithelial cells were diffusely positive for smooth muscle actin (Ventana, Tucson, Ariz) and S100 protein (Dako Corporation, Carpinteria, Calif), and focally positive for glial fibrillary acidic protein (Ventana) and calponin (Vector Laboratories, Burlingame, Calif). Ki-67 (MIB-1; Ventana) staining varied from less than 5% to more than 20% of the tumor cell population in different areas of the tumor (Figure 4, A). The tumor cells also stained extensively positive for p53 (Ventana) (Figure 4, B) and focally positive for c-Kit (CD117; Vector) (Figure 4, C). The stromal background had a myxoid and myxochondroid appearance. There was no evidence of perineural or vascular invasion, and resection margins appeared free of tumor. No metastasis was identified in the regional lymph nodes.

Epithelial-myoepithelial carcinoma was first described in salivary glands in 19724 and has been recently incorporated into the World Health Organization's classification system.5 Although the tumor has been described in the salivary glands, sweat glands, and breast, epithelial-myoepithelial carcinoma is extremely rare in the respiratory tract.

Epithelial-myoepithelial carcinoma exhibits glandular differentiation with a dual population of epithelial and myoepithelial cells. Although myoepithelial cells contain both actin and myosin, they are still classified as epithelial cells in that they are always located between the parenchyma and the basement membrane.6 The growth pattern and proportion of the 2 components of epithelial-myoepithelial carcinoma vary in individual cases.2,3,7–9 

In our case, the tumor cells had mixed architectural patterns. In the predominantly glandular areas, the glands were lined by the typical epithelial and myoepithelial components. The inner layer of glandular cells had characteristic features of epithelial cells, with extensively positive stains for cytokeratin and epithelial membrane antigen, whereas the outer layer of myoepithelial cells showed strong positivity for S100 and smooth muscle actin. A minor component of spindle cells was also present. All previously reported tumors had low mitotic counts. While the average count in this patient was equally low (<5% of tumor cells), a few areas within the tumor showed marked cytological atypia and increased mitotic activity (20% of tumor cells) (Figure 4, A). There are no reliable histopathologic features that are able to predict the prognosis in epithelial-myoepithelial carcinoma. Although it is believed that DNA ploidy is a valuable prognostic indicator in various cancers, no correlation has been shown between the ploidy and prognosis in epithelial-myoepithelial carcinoma.10 

As in other malignant lesions, tumorigenesis of epithelial-myoepithelial carcinoma involves a multiple-step process, including overexpression of oncogenes,11 inactivation of tumor suppressor genes,12–14 and deletion of certain chromosomal fragments.15 

A recent report adds to previous evidence implicating the p53 gene in the pathogenesis of epithelial-myoepithelial carcinoma.12 A point mutation of the p53 gene has been shown in an epithelial-myoepithelial carcinoma of the parotid gland by polymerase chain reaction–single-strand conformation polymorphism assay. In our case, p53 protein was extensively expressed in tumor cells, and to our knowledge, this is the only case of bronchial epithelial-myoepithelial carcinoma with p53 expression reported to date (Figure 4, B). Another tumor suppressor gene that may be involved is the APC (adenomatous polyposis coli) gene. Although inactivation of APC mostly occurs in familial adenomatous polyposis, extracolonic lesions have also been reported. Young et al13 presented a case recently in which a 14-year-old girl displayed a myoepithelial carcinoma of the right neck with inactivation of both copies of APC genes and a history of familial adenomatous polyposis. The APC protein has been implicated in many aspects of tumor development.14 It seems that the direct interaction between APC protein with the cytoskeleton involves the early stage of tumor formation, while transcriptional regulation of β-catenin concentration by APC may be important in later stages. However, the involvement of APC in epithelial-myoepithelial carcinoma has not been thoroughly examined, and more information will be needed to provide definitive correlation between the mutation of APC and epithelial-myoepithelial carcinoma development.

In addition to the inactivation of tumor suppressor genes, it has been demonstrated that overexpression of c-Kit is unique in epithelial-myoepithelial carcinoma compared with other types of salivary gland carcinomas.11 Although that observation suggests possible involvement of c-kit in the development of epithelial-myoepithelial carcinoma of the salivary gland, no gene mutation has been identified. Focal expression of c-Kit confined to the epithelial layer, as seen in our case, is also intriguing (Figure 4, C).

In summary, we report a case of bronchial epithelial-myoepithelial carcinoma with 2 architectural patterns: an epithelial-myoepithelial component in the glandular area and a spindle-shaped myoepithelial component in the solid area. The tumor showed focal atypia and increased mitotic activity without neural or vascular invasion or nodal metastasis. The patient has been followed up for 8 months and is alive with no evidence of recurrence.