Review Question - QID 220326

This patient who presents with cough, hemoptysis, unintentional weight loss, a central lung mass, and a daily smoking history most likely has lung cancer. Given the concurrent findings of hypertension, central obesity, and skin striae, the most likely diagnosis is small cell lung cancer with paraneoplastic Cushing syndrome.

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that is located centrally and originates in the bronchi with early metastases. This disease predominately occurs in patients who smoke tobacco. Symptoms of SCLC overlap with other lung cancers and may include cough, hemoptysis, dyspnea, unintentional weight loss, muscle wasting, and chest pain. SCLC is a neuroendocrine tumor that is associated with multiple paraneoplastic syndromes, including Cushing syndrome, syndrome of inappropriate antidiuretic hormone secretion, and Lambert-Eaton myasthenic syndrome. Cushing syndrome associated with SCLC presents with obesity, hypertension, skin striae, muscle wasting, moon facies, easy bruising, and poor wound healing. Metabolic derangements in Cushing syndrome include hyperglycemia, hypokalemia, and metabolic alkalosis due to mineralocorticoid activity of the excess corticosteroids produced. SCLC is typically treated with chemotherapy and radiation.

Nagy-Mignotte et al. reviewed the diagnosis and prognosis of patients with paraneoplastic Cushing syndrome in SCLC. They found that patients who had this syndrome had lower median survival compared to patients who had other paraneoplastic syndromes. They recommended that palliative care be considered early in the course of treatment, especially in cases of relapse.

Figure/Illustration A is a chest radiograph demonstrating a central perihilar mass (red circle). This location of a lung mass is classically seen in patients with small-cell lung cancer.

Incorrect Answers:
Answer 1: Adenocarcinoma of the lung is the most common lung cancer and the most common type of lung cancer in patients who do not smoke. Adenocarcinoma is associated with hypertrophic osteoarthropathy (clubbing) on physical exam and does not have any strong association with paraneoplastic syndromes.

Answer 2: Bronchial carcinoid tumors are tumors of neuroendocrine origin that may present with carcinoid syndrome, which is caused by excess production of 5-hydroxyindoleacetic acid (5-HIAA), a compound related to serotonin. Carcinoid syndrome presents with flushing, diarrhea, and wheezing among other symptoms.

Answer 3: Large cell carcinoma of the lung is a highly undifferentiated tumor with a strong association with tobacco exposure. The tumor may produce human chorionic gonadotropin (hCG), which can lead to gynecomastia. Large cell carcinoma of the lung has a poor prognosis.

Answer 5: Squamous cell carcinoma of the lung is associated with hypercalcemia, due to the production of parathyroid hormone-related peptide (PTHrP). Although hypercalcemia can be asymptomatic, it can present with nephrolithiasis, altered mental status, and constipation.

Bullet Summary:
Small cell lung cancer is associated with Cushing syndrome as a result of ectopic production of adrenocorticotropic hormone.