The clinical significance of variant-morphology small-cell carcinoma of the lung

Past attempts to subclassrfy small-cell lung cancer (SCCL) histology (oat cell, fusiform, polygonal, intermediate, etc) have not been useful because of interrater variability and a lack of clinical significance. A review of outcome in a previous series suggested that a different histologie subtype, small-cell/large-cell (SC/LC) conferred an inferior response and survival analogous to the relative chemotherapy and radiation resistance seen in the variant-morphology (SC/LC) cultured cell lines. To evaluate the clinical impact of SC/LC we applied the proposed International Association for the Study of Lung Cancer (IASLC) histology subclassification that incorporates the SC/LC category for patients with extensive-disease SCCL entering Eastern Cooperative Oncology Group (ECOG) protocol 1582. All cases were reviewed for eligibility by one pathologist, and all possible SC/LC (variant) plus 10% of all cases were reviewed together with a second pathologist; 577 of the 628 patients who entered were eligible, of whom 550 had histologie material submitted for review and are considered for this analysis. Initial review disclosed 24 cases with SC/LC (4.4%) and 526 with "classic" histology. The second review showed 100% agreement for classic form, but only 11 SC/LC cases with concordance between the reviewing pathologists. Eight of 74 (33%) cases from first review and three of 11 (27%) with concordance on second review achieved complete response (CR) compared with 101 of 526 (19%) for "classic" SCCL (P = .11 and .45, respectively, for the first and second review groups). There were also eight partial responses (PRs) on first and four PRs on second review groups (P = NS for PR plus CR comparisons). Thus regardless of which review is considered, extensive-disease SC/LC is highly unlikely to be less responsive than classic SCCL. There were no detectable differences in median survivals between classic (44.6 weeks), and first review SC/LC (53.1 weeks) or classic and concordant SC/LC (52.7 weeks). These data suggest that the SC/LC subtype in extensive disease is rare, and does not signify a worse prognosis.