Large cell carcinoma of lung: On the verge of extinction?

Pulmonary large cell carcinoma is a tumor whose existence as a defined entity has been challenged in recent years in the wake of advances in techniques to subtype lung cancer. Large cell carcinoma has been defined in the past as a tumor that lacks morphologic evidence of either glandular or squamous differentiation. This rather vague definition and the inclusion of more specific entities such as large cell neuroendocrine carcinoma, basaloid carcinoma, lymphoepithelioma-like carcinoma, clear cell carcinoma, and large cell carcinoma with rhabdoid phenotype as subtypes of large cell carcinoma has not only diluted the homogeneity of this entity but has also contributed to its use as a "wastebin" category for tumors lacking a definitive morphologic pattern. Today, there is increasing evidence that a large proportion of these tumors can be subtyped further using modern immunohistochemical and molecular methods. This is of special value not only from a diagnostic point of view but becomes increasingly important in terms of treatment choice since the selection of therapeutic modalities is often based on specific tumor histology. When viewed in this light, large cell carcinoma of the lung--as defined today--appears to be an outdated entity that needs to be reevaluated taking into account not only light microscopic findings but also the results of adjunct techniques such as immunohistochemistry and molecular profiling so that patients can benefit from more targeted therapies. This review examines the entity of pulmonary large cell carcinoma from these aspects and tries to delineate a practical diagnostic approach until further redefinition of this tumor is in place.