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lung adenocarcinoma with fetal lung–like morphology

Friday 17 May 2013

Low-grade lung adenocarcinoma of fetal lung type, which is well characterized by its unique clinicopathologic and molecular features, is recognized as a distinct variant of lung cancer.

High-grade lung adenocarcinoma with fetal lung–like morphology (HG-LAFM) is caracterized by at least a focal component resembling a developing epithelium in the pseudoglandular phase of the fetal lung.

These rare (ca. 0.4%) carcinomas occurred predominantly in elderly men with a heavy smoking history, who showed elevated serum α-fetoprotein in 80% of cases tested.

Histologic examination reveales a fetal lung–like component as a focal finding accounting for 5% to 60% of the total tumor volume. It is invariably admixed with tissues having a morphology not resembling that of a fetal lung.

A coexisting non–fetal lung–like element was quite heterogenous in appearance, showing various growth patterns. However, clear-cell (88%), hepatoid (29%), and large cell neuroendocrine carcinoma (24%) histology seemed overrepresented.

HG-LAFM was characterized immunohistochemically by frequent expression of α-fetoprotein (41%), glypican-3 (88%), SALL-4 (59%), neuroendocrine markers (82%), CDX-2 (35%), and p53 (65%). HG-LAFM was molecularly heterogenous in that EGFR or KRAS mutation was observed in 22% of cases tested for both.

HG-LAFMs might form a coherent subgroup of lung adenocarcinomas. However, the uniformly focal nature of the fetal lung–like element, widely diverse coexisting non–fetal lung–like histology, and inhomogenous molecular profiles lead us to believe that HG-LAFM is best regarded as a morphologic pattern showing characteristic association with several clinicopathologic parameters rather than a specific tumor entity.


- High-grade Lung Adenocarcinoma With Fetal Lung–like Morphology: Clinicopathologic, Immunohistochemical, and Molecular Analyses of 17 Cases. American Journal of Surgical Pathology: June 2013 - Volume 37 - Issue 6 - p 924–932 doi : 10.1097/PAS 0b013e31827e1e83