Path Image
Subpleural adenocarcinoma

Adenocarcinomas are most typically located in the lung periphery as seen in this image of a firm tan-gray bulging mass.

A cohesive cluster of cells obtained from a bronchial brushing demonstrates malignant features (marked hyperchromasia, prominent nucleoli, etc...)

Bronchial washing shows a cluster of large neoplastic cells with prominent nucleoli on the left, in comparison with ciliated bronchial epithelial cells on right

Again, neoplastic cells in the upper portion, compared to normal cells (left side of image).

The cell block material contains a two distinct populations, one of neoplastic cells - dark and irregularly enlarged -- admixed benign ciliated columnar cells.

A typical area shows acinar and tubular appearing structures lined by columnar hyperchromatic cells.

Not infrequently, the tumor edge shows a lipidic growth pattern of cells along the alveolar surfaces. This alone does not qualify the tumor as a bronchioalveolar carcinoma, and is not infrequently encountered in ordinary adenocarcinoma along the tumor edges.

Variable degrees of cytological atypia are not uncommon in adenocarcinomas.

This core biopsy shows extensive crush artifact of the tumor cells, which abut the bronchial cartilage. This is somewhat unusual in that most adenocarcinomas are peripherally situated.

Immunostaining is helpful because these cells are strongly TTF-1 positive consistent with the impression of adenocarcinoma.

Another growth pattern of pulmonary adenocarcinoma is shown here with these irregular jagged glands with some solid growth and intervening desmoplasia.

A different case shows a large central scar, demonstrated by light pink cytoplasm but punctated by pleomorphic malignant cells, presumably arising from the scar.

Here is another similar area of extensive scar with tumor arising within it. a more solid area along periphery of the scar.

Aspiration of adenocarcinoma yields a cell block of pulmonary adenocarcinoma showing a glandular structure in a background of smaller mesothelial cells and lymphocytes. This is a more well-differentiated example and gives rise to the diagnostic possibility of mesothelial hyperplasia.

The tumor cells stain for keratin 7 and MOC-31, and are negative for keratin 20. Positivity for MOC-31 is particularly helpful in excluding a mesothelial explanation for this cluster.

Occasionally clear cytoplasmic vacuoles are evident; an acinar growth pattern is seen here - acini lined by cuboidal cells that resembling bronchial epithelial cells

Bizarre multinucleated cells are often found in higher grade adenocarcinoma. The tumor still makes glands.

This solid and papillary adenocarcinoma is strongly TTF-1 positive and bears some resemblance to metastatic renal cell carcinoma -- clear voluminous cytoplasm, distinct cell borders, etc.

Yet another case of adenocarcinoma -- there is reverse polarity to nuclei!

Adenocarcinoma likes to metastasize to bone as seen in this gross image.


Lung adenocarcinomas are malignant glandular neoplasms can be well to poorly differentiated. In well differentiated tumors, glands are lined by columnar or mucinous epithelium with basally oriented nuclei containing prominent nucleoli. There frequent mitotic figures. In poorly differentiated adenocarcinomas, the only clue to their glandular nature may be the presence of intracytoplastic mucin, as they form solid sheets. Variants of adenocarcinoma, according to the WHO schema, include bronchioloalveolar, mucinous and papillary (Fletcher).

Approximately half of lung adenocarcinomas exhibit genetic lesions, with the most common being EGFR (10% to 20%) and K-ras mutations (20% to 30%). Epidermal growth factor receptor mutations are present in a subtype of lung adenocarcinomas, and tumors harboring this mutation are highly sensitive to gefitinib, a chemical inhibitor of the kinase activity of EGFR (Paez).

K-ras is a downstream mediator of EGFR-induced cell signaling, mutations confer constitutive activation of the signaling pathways without EGFR activation. Kras mutations (usually at codon 12) are strongly associated with smokers. Patients with EGFR mutations have a great (up to 80%) response rate to tyrosine-kinase inhibitors in contrast to those with KRAS mutations which exhibit no response to TKIs.

Lung adenocarcinomas harboring the translocation of the ALK gene to the EML4 gene, creating the EML4-ALK fusion gene, comprise a small percentage (~5%) of NSCLC, but are quite interesting. EML4-ALK NSCLC tumor genes are more likely to have intracytoplastic mucin and a signet-ring morphology. The patients tend to be younger and nonsmokers (Sasaki).

Lung adenocarcinomas may invade the pleura or grow along the pleural surface, and it may be necessary to distinguish this from epithelioid mesothelioma. The following four IHC markers will help you (Ordonez):


Symptoms depend on the location of the tumor and most lung adenocarcinomas are peripherally located (versus a more central location for squamous cell carcinomas).


Pleura : Fibrous Pleurisy

Pleura : Mesothelioma, Epithelioid Type


Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd Ed. Philadelphia, PA: Elsevier; 2007: 183-4.

Ordóñez NG. The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg Pathol. 2003 Aug;27(8):1031-51.

Paez, J. G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004. 304:1497–1500.

Sasaki T, et al. The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer. 2010 Jul;46(10):1773-80. Epub 2010 Apr 24.

Last updated: 2012-01-14
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