Snapshot A 62-year-old woman presents to her primary care physician with complaint of malaise and weakness for the past two months. She describes that she has difficulty getting out of a chair as well as climbing the few steps up to her front door. The patient has a 36-pack-year smoking history. Physical examination is notable for weakness in the proximal upper and lower extremities bilaterally. Laboratory studies reveal autoantibodies against voltage-gated calcium channels. A chest radiograph is obtained and shown in the image. Introduction Overview paraneoplastic syndromes occur separately from the tumor itself, but result from substances produced by the tumor symptoms may affect various body systems (i.e., endocrine, hematologic, and neuromuscular) Endocrine Syndrome or Clinical Manifestation Associated Tumors Potential Tumor Products Hypercalcemia Squamous cell carcinomas of the lung, head, and heck Renal carcinomas Bladder carcinomas Breast carcinomas Ovarian carcinomas PTHrP↑ 1,25-(OH)2 vitamin D3 (calcitriol) Cushing syndrome Small cell lung cancer ↑ ACTH Hyponatremia (SIADH) Small cell lung cancer ↑ ADH Hematologic Syndrome or Clinical Manifestation Associated Tumors Potential Tumor Products Polycythemia Renal cell carcinoma Pheochromocytoma Hemangioblastoma Leiomyoma Hepatocellular carcinoma ↑ EPO Neuromuscular Syndrome or Clinical Manifestation Associated Tumors Potential Tumor Products Lambert-Eaton myasthenic syndrome Small cell lung cancer Antibodies against presynaptic Ca2+ channels at the neuromuscular junction Paraneoplastic encephalomyelitis Small cell lung cancer Antibodies against Hu antigens in neurons Myasthenia gravis Thymoma Antibodies against postsynaptic ACh receptors at the neuromuscular junction