Benign Neoplasms of the Lungs

Gross Findings

Well-circumscribed and lobulated peripheral hamartomas are surrounded by compressed lung parenchyma. These bulging tumors can often be shelled out from surrounding lung parenchyma and usually are not connected to airways. Cut surfaces range from semifirm white and pearly in tumors with large amounts of cartilage to tan and gelatinous in cartilage-poor lesions ( Fig. 31.1A ). Gritty specks are also appreciated in those cases with calcification. Focal cystic change is often seen, whereas rare tumors may be largely cystic with interspersed solid areas. Endobronchial lesions are often fleshy, yellow, and glistening due to the large amount of adipose tissue in the tumor. These tumors are usually found in the large central airways and are broad-based polyps.

Microscopic Findings

Hamartomas are composed of varying proportions of benign mesenchyme, including cartilage, adipose tissue, smooth muscle, bone, and fibrovascular tissue ( Fig. 31.1A ). In most peripheral lesions, one sees lobulated masses of mature cartilage surrounded by strands or islands of fibromyxoid connective tissue, fat, bone, and smooth muscle ( Fig. 31.1B ). The edges of the lesion feature cleftlike spaces or invaginations of respiratory-type epithelium ( Fig. 31.1C ). Rare peripheral hamartomas without cartilage must demonstrate at least two mesenchymal elements such as adipose tissue, smooth muscle, or primitive fibromyxoid tissue in order to diagnose this entity. Up to 15% of tumors feature calcification.

Endobronchial lesions differ from parenchymal lesions in several aspects. These polypoid tumors often feature large amounts of mature adipose tissue surrounded by a compressed layer of myxoid tissue, whereas smooth muscle and seromucinous glands may be admixed. Cartilage is either absent or present in very small amounts. Rarely, the cartilage shows increased cellularity and/or nuclear pleomorphism but certainly not malignant features. Although attached to the bronchial wall, these central lesions are not continuous with bronchial cartilage plates. Epithelial invaginations, if present, are shallow, and surface epithelium is intact.

Cytogenetics

Hamartomas often have the t(3;12)(q27–28;q14–15) translocation, which results in gene fusion of the high-mobility group protein gene HMGA2 and the LPP gene. This fusion usually contains exons 1 to 3 of HMGA2 and exons 9 to 11 of LLP.

Fine-Needle Aspiration Biopsy

In theory, fine-needle aspiration biopsy (FNAB) diagnosis of pulmonary hamartoma is quite simple because one needs only to recognize nonorganized epithelial and mesenchymal tissues on smears and/or cell blocks ( Fig. 31.2 ). However, many pitfalls exist (evidenced by a false-positive rate of over 20%), and extreme caution in addition to radiographic correlation is recommended in each case. Whereas Diff-Quik–stained smears highlight the cartilaginous/fibromyxoid material, these elements may be subtle on Papanicolaou-stained smears. Also, the invaginated epithelium accompanying lesions can be plentiful and reactive and thus easily mistaken for adenocarcinoma or even carcinoid tumor. The absence of background necrosis, blood, and inflammation should aid in avoiding a diagnosis of malignancy, whereas a cell block should highlight the mesenchymal elements and nonneoplastic nature of the epithelium.

Gross Findings

The cases reported to date have a similar gross appearance. They are well-circumscribed, tan/white masses that bulge out from the surrounding lung. Some are solid and others have a more papillary gross appearance with a variegated surface. They may be single or multiple nodules and range in size from 0.8 to 2.6 cm.

Microscopic Findings

Histologically, the tumor has areas of intermixed bland glandular and spindle cell epithelium. The glandular epithelium surrounds lumens that have an abundance of eosinophilic, colloid-type material. The glandular epithelium is composed of a double layer of pneumocytic cells with mild cytologic atypia ( Fig. 31.4 ).

Gross Findings

Rare case reports have documented polypoid masses growing out of proximal airways. These masses are soft and usually lobulated polyps of 1 to 1.5 cm ( Fig. 31.5A ).

Microscopic Findings

Primary endobronchial or peripheral PAs are less likely to feature either a prominent glandular component or chondroid stroma than the salivary gland counterpart and rather resemble “cellular mixed tumor” with sheets or islands of epithelial and/or myoepithelial cells and a myxoid matrix ( Fig. 31.5B and C ).

Gross Findings

Tumors range in size from 0.7 to 7.5 cm with a mean diameter of 2.3 cm. The white-pink to tan, smooth, and shiny tumors have solid and cystic gelatinous cut surfaces.

Microscopic Findings

Mucous gland adenomas are well circumscribed and noninvasive exophytic masses located above the cartilage plates of the bronchial wall. Numerous neutral and acid mucin–filled cystic spaces protrude into bronchial lumens with an intact overlying respiratory epithelium ( Fig. 31.6A ). Tubulocystic and papillocystic appearances are also common. Cysts are lined by cytologically bland columnar, cuboidal, or flattened mucus-secreting cells ( Fig. 31.6B ). Oncocytic and clear cell changes are often observed. Intervening stroma is usually fibrous or hyalinized, and cyst contents may resemble colloid. Hyperchromasia, pleomorphism, and mitoses are not seen.

Immunohistochemistry

Epithelial cells stain for cytokeratin, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA) but not TTF-1, whereas stromal cells are focally positive for SMA and S-100 protein. This latter finding indicates a myoepithelial component.