Comprehensive histologic analysis of ALK-rearranged lung carcinomas

Area of Science:

• Oncology
• Pathology
• Molecular Diagnostics

Background:

• A small subset of non-small-cell lung carcinomas (NSCLC) harbor the EML4-ALK fusion gene.
• Previous studies on the histomorphology of ALK-rearranged lung cancer show inconsistent data.
• The specific histologic parameters predicting ALK abnormality remain uncertain.

Purpose of the Study:

• To comprehensively analyze the histomorphology of ALK-rearranged lung carcinomas.
• To identify specific histologic parameters that characterize ALK-positive lung cancers.
• To evaluate the predictive accuracy of these parameters for ALK rearrangement.

Main Methods:

• Histologic analysis of 54 surgically resected ALK-rearranged lung carcinomas.
• Comparison with 100 consecutive resections of ALK-wild-type lung cancers.
• Multivariate analysis to identify powerful histologic indicators.

Main Results:

• ALK-positive cancers frequently showed solid or acinar growth, cribriform structures, mucous cells, and abundant extracellular mucus.
• Two distinct patterns, solid signet-ring cell and mucinous cribriform, were found in 78% of ALK-positive tumors but rarely in ALK-negative tumors.
• A combination of these two patterns was the strongest histologic predictor of ALK rearrangement.

Conclusions:

• Characteristic histologies are present in ALK-rearranged lung cancers, aiding in the identification of cases for ALK testing.
• Histologic findings can suggest ALK rearrangement but are not fully sensitive or specific.
• Histomorphology should complement, not replace, molecular or immunohistochemical testing for ALK status.