Cytological markers for predicting ALK-positive pulmonary adenocarcinoma

BackgroundALK gene rearrangement is an important class of gene mutations in pulmonary adenocarcinoma. ALK-positive pulmonary adenocarcinoma exhibits characteristic histological features, such as signet ring cell carcinoma (SRCC) and a mucinous cribriform structure. However, when insufficient histological specimens are obtained, ALK-positivity must be predicted based on cytological features. The purpose of this study was to clarify the cytological characteristics of ALK-positive pulmonary adenocarcinoma. MethodsWe compared the cytological findings of 16 ALK-positive cases with 40 ALK-negative cases. We examined various cytoplasmic features of SRCC, including the presence of pink, yellow, or orange mucin; green, vacuolar, or vesicular cytoplasm; and green globular cytoplasmic secretions. We also examined whether the SRCC cells exhibited a pattern of individually scattered cells, the formation of cell clusters, and formation of a mucinous cribriform pattern. ResultsA univariate analysis showed that significantly frequent cytological findings included pink mucin, green cytoplasm, vacuolar cytoplasm, vesicular cytoplasm, green globular cytoplasmic secretions, an individually scattered pattern, cluster formation, and a mucinous cribriform structure (all, P<.05). A stepwise multivariate logistic regression analysis identified three significant contributing factors: pink mucin (P=.03), vesicular cytoplasm (P=.06), and an individually scattered pattern (P=.01) of SRCC. If the specimens showed two or three of these features, the sensitivity and specificity were both 88% for the prediction of ALK-positive cancers. ConclusionThree cytological features of SRCC (pink mucin, vesicular cytoplasm, and an individually scattered pattern) could be useful cytological markers for the prediction of ALK-positive pulmonary adenocarcinoma.