Large-cell carcinoma of the lung: a diagnostic category redefined by immunohistochemistry and genomics

The current classification system defines large-cell carcinoma (LCC) morphologically as an undifferentiated lung carcinoma lacking features of adenocarcinoma (ADC), squamous cell, or small-cell carcinoma. As a result, LCC has evolved into a clinicopathologically heterogeneous entity. In the current era of histology-driven predictive molecular testing and oncologic management, ambiguous diagnostic categories frustrate attempts to provide more personalized cancer care, thus the pathology community has engaged in a concerted effort to revise the criteria for LCC.

Most cases of LCC are immunophenotypically similar to ADC or squamous cell carcinoma. LCC lacking squamous and neuroendocrine features is clinically and genomically indistinguishable from solid ADC. Even cases of LCC lacking immunophenotypic differentiation may contain genomic alterations characteristic of other forms of lung carcinoma.

Applying ancillary techniques, most cases of LCC can be reclassified into more informative categories that may guide molecular testing for predictive biomarkers and enable selection of more appropriate therapies.