Considerable attention has been devoted to the diagnosis of small cell lung carcinoma (SCLC) and its subtypes. In the literature contradictory opinions have been published concerning the clinical implications of subtyping, largely because of the different criteria used by different pathologists. This article is a consensus report by the Pathology Committee of the International Association for the Study of Lung Cancer. The following classification of SCLC is recommended: (1) Small cell carcinoma. This subtype includes most of the tumors previously included in the oat cell and intermediate subtypes. More than 90% of untreated SCLC fall into this category. (2) Mixed small cell/large cell carcinoma. This subtype, which may be associated with a poor prognosis and response to therapy, contains a spectrum of cell types ranging from typical SCLC to larger cells having prominent nucleoli and resembling large cell carcinoma. (3) Combined small cell carcinomas. Typical SCLC elements are intimately admixed with areas of differentiated squamous cell or adenocarcinoma. This simplified classification of SCLC will facilitate uniformity in the diagnosis and further our understanding of the clinical significance of the rarer SCLC with variant morphologies.
Although histologic heterogeneity of lung cancer is well recognized, little information is available related to possible effects of this heterogeneity on prognosis. We collected 100 consecutive lung cancer cases, including 35 autopsies and 65 surgical resections, which were extensively sampled (average, ten blocks per case) and analyzed for histologic heterogeneity. Slides were randomized and classified by five pathologists using the 1981 World Health Organization (WHO) classification scheme. Five-year follow-up data were obtained for the surgical cases, and detailed information on staging and survival from time of diagnosis was available in 91 cases. Survival time was analyzed with respect to the patient's age, sex, stage, predominant histologic pattern, and presence or absence of major heterogeneity. The latter is defined as the presence on at least one slide of a major histologic pattern different from that of the remaining slides for that case. The only statistically significant predictor of survival was tumor stage (P less than 0.0001). Heterogeneous tumors appeared to have a worse survival, but this did not reach statistical significance. There was no relationship between survival and predominant histologic pattern (cell type), sex, or age.
Six-hundred-twenty cases of small-cell carcinoma of the lung entered into the Veterans Administration Lung Group protocols 9-15 were retrospectively subdivided into histologic subtype, as proposed by the WHO (1977). Medium survival was greater for subtype No. 21 (lymphocyte-like) than for subtype No. 22 (intermediate) (17.2 vs. 12.6 weeks; P = .005). Patients with extensive disease survived longer with subtype No. 21 than subtype No. 22 (14.5 vs. 10.9 weeks; P = .026). However, no median survival difference was seen with limited disease. Survival for subtype 21 was greater than No. 22 (P = .016) for patients with poor initial performance status (IPS; Karnofsky 70 or less); for ambulatory patients (IPS 80-100) a survival advantage was seen for subtype No. 21 compared with No. 22, but did not quite reach statistical significance (P = .09). Survival in subtype No. 21 was better than in subtype No. 22 (24.3 vs. 14.7 weeks; P = .001) when no weight loss (less than 10 pounds over the six-month period prior to therapy) was documented. However, with weight loss (greater than 10 pounds) survival in each subtype was similar.
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