Definition
• Uncommon benign tumors of the lung and airway
Clinical features
Epidemiology
• Most common in adults; no gender predilection
• Mucinous cystadenoma is more frequently diagnosed in tobacco smokers
Presentation
• Asymptomatic
• If endobronchial, may have obstructive symptoms, cough, recurrent pneumonia, hemoptysis
Prognosis and treatment
• Complete excision is curative
• Recurrences may occur with incomplete excision
Pathology
Histology, immunopathology, and differential diagnosis
• Pleomorphic adenoma
• Morphological features are similar to those of tumors originating in the salivary glands
• Circumscribed, unencapsulated biphasic tumor with epithelial and myoepithelial cells in a chondromyxoid stroma
• Histological spectrum:
– Cellular variant with sheets, nests, or trabeculae of round monomorphic epithelioid cells and/or myoepithelial cells with clear cytoplasm in a scant myxoid stroma
– Myoepithelial variant with spindled and clear tumor cells in a chondromyxoid or hyalinized stroma and only rare identifiable epithelial cells
– Tubular or ductal structures composed of epithelial cells with an outer layer of myoepithelial cells and PAS-positive luminal secretion may or may not be present
• Rarely may find squamous metaplasia, mature cartilaginous elements, or cribriform architecture
• Generally lack hemorrhage, necrosis, or mitoses
• Rare tumors may be large with infiltrative borders, nuclear pleomorphism, high mitotic activity, and angiolymphatic invasion and should be regarded as carcinoma ex pleomorphic adenoma
• Cytokeratin, glial fibrillary acidic protein, S100, vimentin, smooth muscle actin (SMA) are positive by immunohistochemical analysis
• Main differential diagnoses
– Metastatic pleomorphic adenoma from head and neck or from breast
– Cellular variant may be mistaken for other basaloid tumors
– Chondroma or chondromatous hamartoma
– Adenoid cystic carcinoma
– Squamous cell carcinoma
– Sarcomatoid carcinoma
– Pulmonary blastoma
• Alveolar adenoma
• Peripheral parenchymal or subpleural circumscribed tumor composed of multiple cystic spaces (larger centrally) filled with granular eosinophilic material and lined by low cuboidal or hobnail cells
• The interstitium contains bland TTF-1 negative spindle cells in a myxoid stroma
• Main differential diagnoses
– Lymphangioma: lining cells are CD31-positive and cytokeratin-negative
– Adenocarcinoma: infiltrative borders and cytological atypia
– Pneumocytoma (sclerosing hemangioma): positive for TTF-1
– Spindle cell sarcoma: negative for cytokeratins
• Mucinous cystadenoma
• Peripheral unilocular cystic lesion surrounded by a thin fibrous capsule
• The cyst is filled with mucus and lined by discontinuous cuboidal to columnar epithelial cells with abundant cytoplasmic mucin and basal nuclei
• Extravasated mucin with foreign-body giant cell reaction and chronic inflammation may be seen in the fibrous capsule associated with areas devoid of epithelial lining
• Epithelial cells are positive for CK7 and broad spectrum cytokeratins, and negative for CK20, TTF-1
• Ki-67 is positive in <5% of lesional epithelial cells
• Main differential diagnoses
– Mucinous cystadenocarcinoma and mucinous (colloid) adenocarcinoma: cytological atypia, mucous extravasation with floating tumor cells
– Metastatic mucinous adenocarcinoma, such as from colon: CK7 is negative
– Intrapulmonary bronchogenic cyst: partial ciliated columnar epithelial lining; cartilage and glands in fibrous capsule
• Mucous gland adenoma
• Well-circumscribed central exophytic proliferation of tracheobronchial mucous glands forming cysts filled with acid and neutral mucins; glands, tubules, microacini, and papillae may also be seen
• Lining cells are bland cuboidal, columnar, or mucous type and may have clear cell or oncocytic changes or focal cilia
• The intervening stroma has numerous spindled myoepithelial cells and may be focally hyalinized or have prominent lymphoplasmacytic infiltrate
• Overlying respiratory epithelium is intact and may undergo squamous metaplasia
• Epithelial cells: positive for cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen
• Stromal cells (myoepithelial origin): positive for SMA and S100
• Main differential diagnoses
– Mucoepidermoid carcinoma: three cell types
– Mucinous cystadenoma: peripheral unilocular cyst lined by bland mucous cells
– Adenocarcinoma: look for pleomorphism, invasion, and mitoses
• Glandular papilloma
• Mucosal-based papillary tufts with noninflamed fibrovascular cores lined by glandular epithelium; may be ciliated with interspersed mucinous cells
• Main differential diagnoses
– Papillary adenocarcinoma: usually peripheral, with features of malignancy and invasion
– Inflammatory polyp: no fibrovascular cores
– Papillary adenoma: not attached to airway; arises in lung parenchyma