[4] Over 50 different histological variants are explicitly recognized within the 2004 revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme.
[1] Currently, the only exception to this recommendation occurs in cases where anaplastic large cell lung carcinoma (LCLC) is the second histological component.
It is currently thought that most cases of lung cancer probably occur after damage to genomic DNA causes malignant transformation of a single multipotent cell.
[11] Other analyses suggest that, in at least in some cases, more highly differentiated variants of NSCLC (i.e. adenocarcinoma) can "progress" to give rise to areas within the primary (original) tumor (or its metastases) that develop histological and molecular characteristics of SCLC.
[12] Other molecular studies, however, suggest that — in at least a minority of cases — independent development of the components in c-SCLC occurs via mutation and transformation in two different cells in close spatial proximity to each other, due to field cancerization.
In these cases, repeated division and mutational progression in both cancer stem cells generate a biclonal "collision tumor".
[26] LD is roughly defined as a locoregional tumor burden confined to one hemithorax that can be encompassed within a single, tolerable radiation field, and without detectable distant metastases beyond the chest or supraclavicular lymph nodes.
A patient is assigned an ED stage when the tumor burden is greater than that defined under LD criteria — either far advanced locoregional disease, malignant effusions from the pleura or pericardium, or distant metastases.
TRT serves to increase the probability of total eradication of residual locoregional disease, while PCI aims to eliminate any micrometastases to the brain.
[31] Surgery is not often considered as a treatment option in SCLC (including c-SCLC) due to the high probability of distant metastases at the time of diagnosis.
[32] This paradigm was driven by early studies showing that the administration of systemic therapies resulted in improved survival as compared to patients undergoing surgical resection.
[36] Other experts recommend resection for residual masses of NSCLC components after complete local tumor response to chemotherapy and/or radiotherapy in c-SCLC.
Some studies suggest it may, when combined with other agents, improve some measures of survival in SCLC patients[69][70] and in some non-squamous cell variants of NSCLC.
[7][71] C-SCLC appear to express female hormone (i.e. estrogen and/or progesterone) receptors in a high (50–67%) proportion of cases, similar to breast carcinomas.
[31][35] Given proper multimodality treatment, SCLC patients with limited disease have median survival rates of between 16 and 24 months, and about 20% will be cured.
Tatematsu et al. reported 15 cases of c-SCLC (12%) in their series of 122 consecutive SCLC patients, but only 20 resection specimens were examined.
Therefore, given the significant incidence and mortality attributable to this malignancy,[83] (see Prognosis and survival) it is arguably critical to better understand these aggressive lesions so specific strategies for their management can be rationally designed.