High‐grade fetal adenocarcinoma of the lung is a tumour with a fetal phenotype that shows diverse differentiation, including high‐grade neuroendocrine carcinoma: a clinicopathological, immunohistochemical and mutational study of 20 cases. Issue 6 (5th June 2015)

• Record Type: Journal Article
• Authors: Suzuki, Masaki; Yazawa, Takuya; Ota, Satoshi; Morimoto, Junichi; Yoshino, Ichiro; Yamanaka, Shoji; Inayama, Yoshiaki; Kawabata, Yoshinori; Shimizu, Yoshihiko; Komatsu, Masayo; Notohara, Kenji; Koda, Kenji; Nakatani, Yukio
• Is Part Of: Histopathology. Volume 67:Issue 6(2015)
• Page Start: 806
• Page End: 816
• Publication Date: 2015-06-05
• Subjects: fetal adenocarcinoma -- genetic analysis -- neuroendocrine carcinoma -- α‐fetoprotein -- β‐catenin; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12711
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : Aims: High‐grade fetal adenocarcinoma (H‐FLAC) is a rare variant of pulmonary adenocarcinoma; this study aims to elucidate its clinicopathological features and genetic abnormalities. Methods and results: Clinicopathological, immunohistochemical and mutational analyses were performed on 20 surgically resected lung cancers that showed H‐FLAC histology in various proportions. These tumours predominantly occurred in elderly males and in 10 patients who were heavy smokers. Four cases were pure H‐FLAC, and 16 cases were mixed H‐FLAC, which were found to be combined with conventional‐type adenocarcinoma (15 cases), large‐cell neuroendocrine carcinoma (three cases), small‐cell carcinoma (one case), enteric adenocarcinoma (two cases), choriocarcinoma (two cases), and a solid–clear cell pattern (seven cases). The fetal phenotype and diverse differentiation were supported by the immunoexpression of α‐fetoprotein (95%), thyroid transcription factor‐1 (TTF‐1) (50%), neuroendocrine markers (30–45%), proneural markers (50–69%), and CDX2 (40%). Except for TTF‐1 expression (pure H‐FLACs, 0%; mixed H‐FLACs, 63%), there were no significant differences in histological or immunohistochemical findings between pure and mixed H‐FLACs. EGFR, KRAS, BRAF and PIK3CA mutations were identified in 20%, 0%, 0% and 7% of the tumours, respectively. Conclusions: Lung adenocarcinomas with H‐FLAC features possess the potential for multidirectional differentiation, and are not strongly associated with known major driver gene mutations.