Residency Program - Case of the Month

Answer:

Atypical mucous gland adenoma (MGA) of the bronchus, "Atypical bronchial gland adenoma"

Histologic description:

The tumor is composed of tightly packed tubular structures of varying sizes filled with pink mucous/serous material with secondary cholesterol-cleft formation in some areas. In other areas there are large cystic formations (figure 1), a cardinal feature of this lesion. The tumor mass was well-circumscribed (figure 2) and did not invade the overlying bronchial wall another cardinal feature of this lesion. The cells lining these tubular structures varied in cytologic appearance with some areas having atypical cytologic appearance which made this case so interesting. In some areas the cells were tall columnar to flat cuboidal cells with basally oriented bland nuclei and abundant mucous at the apical aspect (figure 3). In other areas there were some pseudo papillary enfolding and papillary formations of the cells lining the tubular structures and cystic structures respectively (figures 1&4). However, in some areas the cells had a more bizarre appearance with vesicular nuclei of varying size, shape, and polarity and containing prominent nucleoli. The cytoplasm of these atypical cells appeared devoid of mucous but were instead homogenously eosinophilic or oncocytic in appearance. In some instances areas of bland appearing bronchial gland mucous cells were adjacent to these areas of oncocytic change (figure 5). In some of the areas of atypical cells the tubular structures gave way to a more solid growth pattern with obliteration of the tubular lumens (figure 6). There were also areas where the tumor showed a smooth transition to myoepithelial or spindle cell morphology (figures 6&7). No significant amount of mitotic figures was identified and the tumor cells did not show any definitive evidence of stromal or bronchial wall invasion which was highlighted by smooth muscle actin positivity around the tubular structures. In addition there was no definitive squamous component present, and there was no abundant chondromyxoid component present.

Discussion:

Mucous gland adenoma (MGA) of the bronchus is listed by the WHO to be part of the spectrum of adenoms of salivary gland-type. Many pathologists use the term bronchial gland adenoma to describe these tumors, but this term is vague and outdated and should be avoided as it was initially used in the early 1950's to describe many tumors of bronchial origin without malignant potential as well as those with malignant potential such as carcinoids and salivary gland-type carcinoma. Therefore the more correct term for these tumors is mucous gland adenoma (MGA) of the bronchus.
Mucous gland adenomas of the bronchus are very rare lung tumors with no sex predilection and can occur in young and old individuals with a mean age of 52 years [1]. Grossly they are well-circumscribed lesions centered on the bronchus with an exophytic growth into the bronchial lumen. On cut surfaces they tend to be cystic and gelatinous or mucoid in appearance with alternating solid areas. They range in size with a mean size of 2.3 cm [1].
These lesions become clinically apparent either incidentally by X-ray or CT-scan which shows a well-circumscribed endobronchial mass with an air-meniscus sign [2] or when obstruction occurs within the bronchus causing post-obstructive pneumonia or asthma-like symptoms [3].
Microscopically the lesion is well-circumscribed and centered beneath the bronchial wall and epithelium but above the cartilage plates. There is no invasion of the bronchial wall and the cartilage plates may show focal involvement (pushing borders). The tumor is composed of variably sized tubules and cysts that are filled with mucin. The cells lining the cysts are bland columnar, cuboidal, and flattened shaped cells containing a variable amount of cytoplasmic mucin. There can be clear cell or oncocytic change but squamous metaplasia should not be present and if at all present it is restricted to the overlying bronchial epithelium. Cellular atypia is rare and the presence of infiltrative growth pattern and necrosis should not be present and mitotic figures should not be significantly increased. The background stroma may have dense lymphocytic infiltrate or can be hyalinized or can contain numerous spindled shaped cells.   
Immunohistochemistry pattern is positive for EMA, CEA, and pankeratin stains. The stroma may contain a variable amount of keratin, smooth muscle actin, and S-100 positive cells indicating a possible myoepithelial component of this tumor further supported by electron microscopy studies which have identified a myoepithelial component in these tumors [4]. This interesting finding has lead some to believe that mucous gland adenomas of the bronchus may be a monomorphic variant of pleomorphic adenoma [4].
The differential diagnosis of these tumors would include other salivary gland-type tumors such as low-grade mucoepidermoid carcinoma and pleomorphic adenomas. The presence of a squamous component, intermediate cells, and invasion of the bronchial wall would favor a mucoepidermoid carcinoma. The presence of a biphasic tumor with abundant myxoid or chondrodmyxoid stroma should prompt the diagnosis of a pleomorphic adenoma. In the most problematic cases of pleomorphic adenomas GFAP immunostain may be of assistance as a significant number of pleomorphic adenomas show reactivity for GFAP. Another entity to think about when discussing this tumor is mucinous cystadenomas. Mucinous cystadenomas unlike MGA's are peripherally located and tend to be predominantly cystic. Other things on the differential list would include adenocarcinoma, specifically mucinous or "colloid" type, and low grade neuroendocrine carcinoma. Adenocarcinomas will have an invasive growth pattern, mitotic figures, and possibly areas of necrosis while low-grade neuroendocrine carcinomas will show positivity for synaptophysin and/or chromgranin A.
The treatment and prognosis of mucous gland adenomas is good and often conservative resection is curative. There has been one report of adenocarcinoma arising in a MGA [5] but for the most part these are benign tumors.
The areas of cytologic atypia present in our tumor most likely represent the spectrum of oncocytic change.

References:

1. Travis W.D., Brambilla E., Muller-Hemerlink H.K., Harris C.C. (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. IARC Press: Lyon 2004.
2. Im, J G, Seo, J W, Seo, J B, et al. (1999). Mucous gland adenoma of the bronchus: CT findings in two patients. Journal of computer assisted tomography, 23(5), 758-60.
3. Stević, R, Mandarić, D, Stojsić, J, et al. (2007). Mucous gland adenoma simulating bronchial asthma: case report and literature review. The Journal of asthma, 44(9), 789-93.
4. Wick, M., & Mills, S. (2005) Benign and borderline tumors of the lung and pleura. In Leslie, K, & Wick, M., (Ed.). Practical Pulmonary Pathology A Diagnostic Approach. (pp. 677-678). New York: Churchill Livingstone
5. Okabe K, Aloe M, Nakata M. al. A case of bronchial mucous gland adenoma with cancer in adenoma. Kikanshigaku J (J Jpn Soc Bronchol) 1991;13:82