expectoration call attention to localized, resectable disease. By the time other symptoms, such as hoarseness, chest pain, superior vena cava syndrome, pericardial or pleural effusion, or persistent segmental atelectasis or pneumonitis make their appearance, the prognosis is poor. Too often, the tumor presents with symptoms caused by metastatic spread to sites such as the brain (mental or neurologic changes), liver (hepatomegaly), or bones (pain). Although the adrenal glands may be nearly obliterated by metastatic disease, adrenal insufficiency (Addison disease) is uncommon, because islands of cortical cells sufficient to maintain adrenal function usually persist.
Overall, squamous cell carcinoma and adenocarcinoma carry a more favorable prognosis than SCLC. When squamous cell carcinomas or adenocarcinomas are detected before metastasis or local spread (as in high-risk patients undergoing surveillance imaging), cure is possible by lobectomy or pneumonectomy. Unresectable adenocarcinomas associated with targetable mutations in tyrosine kinases such as EGFR may show remarkable responses to specific inhibitors. A few of these patients have long-term remissions on the order of years, but relapse within months to a year or so is typical. Inevitably, resistant tumors are found to have new mutations that either alter the drug target themselves (e.g., an additional mutation in EGFR that prevents drug binding) or circumvent tumor dependence on the drug target. Much effort is currently being devoted to understanding the mechanisms of targeted drug resistance in order to develop strategies that prevent it from occurring. Immune checkpoint inhibitors produce responses in a subset of tumors, particularly those that are smoking related (perhaps because of a high burden of tumor
Table 13.7 Comparison of Small Cell Lung Carcinoma and Non–Small Cell Lung Carcinoma (Adenocarcinoma and Squamous Cell Carcinoma)
Forexample,densecoregranulesonelectronPresentAbsentmicroscopy;expressionofchromogranin,synaptophysin,andCD56
Epithelialmembraneantigen,carcinoembryonicantigen,PresentPresentandcytokeratinintermediatefilaments
EGFR mutationsAbsent~20%(adenocarcinomas,nonsmokers,women)
ALK rearrangementsAbsent4%–6%adenocarcinomas,nonsmokers,oftenhavesignetringmorphology http://ebooksmedicine.net neoantigens), and represent a hopeful new avenue for therapy.
By contrast, the picture for SCLC unfortunately has changed little. SCLCs have invariably spread by the time they are detected, even if the primary tumor appears to be small and localized; thus, surgical resection is not a viable option. SCLCs are very sensitive to chemotherapy but invariably recur, and as of yet targeted therapies are unavailable. The median survival even with treatment remains only 1 year, and only 5% are alive at 10 years. Because these tumors have a very high mutation burden, they are likely to be immunogenic. Accordingly, immune checkpoint therapies have produced encouraging responses in patients with advanced SCLC.