Discussion

Small cell lung cancer accounts for roughly 15% to 20% of the 180,000 new cases of lung cancer in the United States annually. It is highly lethal, with only a small minority of those diagnosed alive at 5 years. It is related directly to smoking history, and usually presents with distant metastasis. The staging system does vary from the more commonly used tumor-node-metastasis system, with only 2 stages: limited stage (meaning all disease is confined to one hemithorax, which can be treated with one radiation field) and extensive disease (for those with metastasis). Treatment for patients with extensive stage disease is palliative, but response rates to various chemothera-peutics are significant, offering temporary shrinkage of the areas of involvement, and consequent improve-ment in malignancy-related symptoms. For the minority of patients who present with limited stage disease, the goal of treatment is cure, with the standard of care being concomitant chemotherapy and radiation. With this approach, 2-and 5-year survival rates of 44% and 23%, respectively, have been reported.

Unfortunately, the majority of patients with limited stage disease at presentation will eventually recur despite treatment. The site of first recurrence may vary, but the incidence of relapse in the brain has decreased due to the routine use of prophylactic brain irradiation in patients attaining a complete response in the lung. Survival after recurrence is generally measured in months, although the introduction of newer treatments has improved the outlook slightly. The most important class of drugs in this regard is the topoisomerase-1 inhibitors, specifically topotecan and irinotecan. Multiple phase II and III trials have docu-mented response rates in untreated patients of up to 80%. This patient showed a rapid anti-tumor response, with resolution of the lymphadenopathy and decline in the anti-Hu antibody level, even before starting consolidative radiation.

A fascinating aspect of small cell lung cancer is the potential for so-called paraneoplastic manifestations. While these processes are seen in other histologic cancers, they are most described in the neuroen-docrine malignancies, of which small cell lung cancer is the most common. Specific paraneoplastic syndromes include the syndrome of inappropriate anti-diuretic hormone (SIADH), Eaton-Lambert syndrome, and neuropathies associated with anti-Hu antibodies, as seen in this patient. This syndrome most commonly presents as a peripheral sensory neuropathy, although a mixed motor and sensory process is also commonly encountered. Other manifestations may include pain in up to 80% of patients. Work-up generally includes electrophysiologic testing, which is fairly sensitive, but definitive diag-nosis is made with serologies for the anti-Hu antibody. Management involves treating the under-lying malignancy with appropriate chemotherapy. Non-specific strategies to suppress the immune response, such as steroids, immunoglobulin, and plasma exchange, have been reported without much success.