The Clinical Relevance of Recent Developments in Pathology and Biology of Small Cell Lung Cancer

In: Lung Cancer

13 Nov 2014

The Clinical Relevance of Recent Developments in Pathology and Biology of Small Cell Lung CancerSmall cell lung cancer (SCLC) has emerged over the last 10-15 years as a distinct pathologic and clinical entity, characterized by early and wide dissemination and with a great sensitivity to both chemotherapy and radiotherapy. Despite the objective response to chemotherapy in more than 85%, most of the patients sooner or later develop clinical relapse, and fewer than 10% become long-term survivors. The need is thus urgent for more biologic knowledge about this disease, and great efforts have been put into this field of research by scientists all over the world. Through detailed studies, especially on more than 100 established cell lines from SCLC, much biologic information has been accumulated including the relationship of SCLC to both other histologic types of lung cancers and to endocrine tumors. The present short overview deals with the clinical significance of recent scientific developments in the histopathologic and biologic studies of SCLC. Link

Histopathologic Classification of SCLC
The World Health Organization (WHO) published the first international classification of malignant lung tumors in 1967, with a subsequent revision in 1981. In the last revision SCLC was subdivided into 3 morphologic subtypes: “oat-cell type,” “intermediate,” and “combined oat-cell;” the last includes SCLC in combination with squamous cell and adenocarcinomas. The criteria for the histopathologic classification have been discussed in detail previously. The recognition of some SCLC tumors having features of large cell carcinoma was made by the WHO panel of pathologists, and these tumors were included in the “intermediate” category.
Since the last WHO revision much attention has been given in clinical-pathologic studies to the search for a prognostic significance of the WHO classification of SCLC. Two large independent studies from the National Cancer Institute, USA, and the Finsen Institute, Denmark, failed to demonstrate any difference in response and survival to chemotherapy comparing patients with “oat-cell” and “intermediate” subtypes.

However, patients having SCLC with some large cell features showed a significantly lower response rate and shorter survival than those with pure SCLC. These studies subsequently led to a modification of the subclassification by the International Association for the Study of Lung Cancer (IASLC), in which all pure SCLC tumors were put into the same category, while SCLC with large cell features was separated as a special subgroup. More recently, a preliminary report was published by the Eastern Cooperative Group in USA, in which the IASLC classification was applied and no clinical difference between the pure SCLC and SCLC/large cell tumors was found for SCLC patients with “extensive disease.” The differences in results between the studies might reflect interobserver variability problems in the morphologic classification, which ought to be solved prospectively in future studies.
Comparing pretreatment and posttreatment histopathologic material, a considerable change in morphology has been observed.* The clinical relevance of the morphologic variations was studied by 2 investigators. In both studies patients with mixed histology after treatment had a significantly shorter survival than those with pure SCLC morphology. Whether these morphologic variations were preexisting or due to the treatment with cytostatic drugs is still uncertain.


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