title: High-grade lung adenocarcinoma with fetal lung-like morphology: clinicopathologic, immunohistochemical, and molecular analyses of 17 cases.
abstract: 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. In contrast, high-grade lung adenocarcinoma with fetal lung-like morphology (HG-LAFM) has not been studied widely. To characterize this subset better, we analyzed 17 high-grade adenocarcinomas with at least 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 4 of 5 cases tested. Histologic examination revealed a fetal lung-like component as a focal finding accounting for 5% to 60% of the total tumor volume. It was 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. Our data indicate that 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.
authors: Department of Pathology and Clinical Laboratories, Thoracic Surgery Division, National Cancer Center Hospital, Japan.
authors: Shigeki
authors: S
authors: Morita
authors: Akihiko
authors: A
authors: Yoshida
authors: Akiteru
authors: A
authors: Goto
authors: Satoshi
authors: S
authors: Ota
authors: Koji
authors: K
authors: Tsuta
authors: Karin
authors: K
authors: Yokozawa
authors: Hisao
authors: H
authors: Asamura
authors: Jun
authors: J
authors: Nakajima
authors: Daiya
authors: D
authors: Takai
authors: Masaya
authors: M
authors: Mori
authors: Teruaki
authors: T
authors: Oka
authors: Junichi
authors: J
authors: Tamaru
authors: Shinji
authors: S
authors: Itoyama
authors: Koh
authors: K
authors: Furuta
authors: Masashi
authors: M
authors: Fukayama
authors: Hitoshi
authors: H
authors: Tsuda
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D004252:DNA Mutational Analysis; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D000509:alpha-Fetoproteins / Q000032:analysis; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000509:alpha-Fetoproteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins