Masaki Suzuki1,2, Takuya Yazawa1, Satoshi Ota2, Junichi Morimoto3, Ichiro Yoshino3, Shoji Yamanaka4, Yoshiaki Inayama5, Yoshinori Kawabata6, Yoshihiko Shimizu6, Masayo Komatsu7, Kenji Notohara8, Kenji Koda9, Yukio Nakatani1,2. 1. Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan. 2. Department of Pathology, Chiba University Hospital, Chiba, Japan. 3. Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. 4. Department of Pathology, Yokohama City University Hospital, Yokohama, Japan. 5. Department of Pathology, Yokohama City University Medical Centre, Yokohama, Japan. 6. Department of Pathology, Saitama Cardiovascular and Respiratory Centre, Kumagaya, Saitama, Japan. 7. Department of Pathology, Yamamoto Kumiai General Hospital, Noshiro, Japan. 8. Department of Pathology, Kurashiki General Hospital, Kurashiki, Japan. 9. Department of Pathology, Fujieda Municipal General Hospital, Fujieda, Japan.
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.
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.