Most ALK-Positive Lung Adenocarcinomas Exhibit Characteristic Histology.
Akihiko Yoshida, Koji Tsuta, Takashi Kohno, Masashi Fukayama, Tatsuhiro Shibata, Koh Furuta, Hitoshi Tsuda. National Cancer Center Hospital, Tokyo, Japan; National Cancer Center Research Institute, Tokyo, Japan; University of Tokyo, Japan
Background: EML4-ALK translocation occurs in 1—5% of all lung adenocarcinomas. Histological identification of ALK-rearranged tumors holds potential impact on the clinical management, because these tumors may respond to ALK inhibitor treatment. Although previous studies suggested that the histology of ALK-rearranged adenocarcinomas may be characteristic, there is no large-scale comprehensive morphological analysis with surgically resected materials. In this study, we examined the largest cohort of ALK-positive tumors to delineate the morphological aspect of this subgroup of lung cancer.
Design: We collected 50 cases of surgically resected lung adenocarcinoma that had shown strong reactivity in the highly sensitive ALK immunohistochemical test. RT-PCR and/or FISH analyses were performed for 32 selected cases, all of which were confirmed to harbor EML4-ALK translocation or ALK rearrangement. All the glass slides were reviewed, and histological findings were compared with those of 100 consecutive surgical cases of lung adenocarcinomas that were immunonegative for ALK. All the tumors had been extensively sampled. Student t-test and χ2 test were used for statistical analyses, and p < 0.01 was considered significant.
Results: The following histological features were significantly more frequent in ALK-positive tumors than ALK-negative tumors: predominant acinar pattern (42% vs 11%), at least focal solid pattern (60% vs 33%), cribriform formation(78% vs 16%), abundant extracellular mucus (66% vs 10%), signet-ring cells (64% vs 1%), and any mucous cells (including goblet cells and signet-ring cells) (82% vs 4%). In contrast, ALK-positive tumors showed significantly less frequent occurrence of predominant lepidic pattern (2% vs 31%), at least focal lepidic pattern (26% vs 83%), and nuclear pleomorphism (8% vs 45%). Two frequently observed constellations of findings in ALK-positive tumors were cribriform structure associated with abundant extracellular mucus (58%) and solid growth admixed with clusters of signet-ring cells (34%). Most (82%) ALK-positive tumors contained at least focal areas exhibiting either or a combination of these 2 constellations, while these patterns were rare (1%) in ALK-negative tumors.
Conclusions: ALK-immunopositive tumors are histologically distinguishable from ALK-negative tumors in most instances if adequately sampled. Characteristic histological features, which may be present only focally, should serve as clues to prompt immunohistochemistry and confirmatory genetic testing for ALK-rearrangement.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 261, Tuesday Afternoon