Most arise in and around the tracheobronchial tree, with rare tumors arising in the peripheral lung.
The tumor is biphasic, with both ductal epithelial and myoepithelial cells. Immunoperoxidase stains for CD117 (c-KIT), keratin, EMA, actin, and S-100 are often positive.
The tumor tends to show 3 histologic patterns:
(1) cribriform (cylindromatous), with hyaline material that is Alcian blue positive
(2) tubular
(3) solid (which may be misdiagnosed as small cell undifferentiated carcinoma or other type of carcinoma)
Tumors often are slow-growing and indolent, but some may be aggressive. Aggressive growth is associated with:
(1) high proportion of the tumor showing the solid growth pattern
(2) high-grade transformation (which may be associated with overexpression of p53).
Tumors often show perineural spread and may run along nerves.
The diagnosis requires exclusion of a salivary ACC metastatic to the lung. This is particularly important in tumors arising in the peripheral lung. An ACC primary to the lung should be positive for TTF-1 while metastases are not.
Surgical excision may be effective, but the tumor is often infiltrative, especially when it runs along nerves. The tumor is often either resistant to chemotherapy or becomes resistant. The tumors are usually radiosensitive but it may be difficult to localize the tumor. It is hoped that sorafenib or other tyrosine kinase inhibitor will be effective therapeutic agents.
