Paraneoplastic syndromes: an overview

Hypercalcemia is an elevated serum calcium concentration, most often caused by primary hyperparathyroidism in ambulatory patients or malignancy in hospitalized patients. Mild disease requires only treatment of the underlying cause, while severe or symptomatic hypercalcemia is treated with aggressive IV isotonic fluids, followed by an IV bisphosphonate or denosumab for sustained control and subcutaneous calcitonin as a rapid but short-lived bridge.

SIADH is euvolemic hypotonic hyponatremia caused by antidiuretic hormone secretion or action that is inappropriate for the patient's osmotic and volume status. First-line treatment is fluid restriction to about 800-1,000 mL/day, with vasopressin receptor antagonists (vaptans) or hypertonic saline reserved for severe or symptomatic hyponatremia resistant to fluid restriction.

Cushing syndrome is the clinical state of chronic glucocorticoid excess from any cause, most often exogenous glucocorticoid use, diagnosed by demonstrating loss of normal cortisol suppression or diurnal rhythm with at least two of three screening tests. Treatment targets the underlying source: withdrawal or tapering of exogenous steroid, transsphenoidal surgery for a pituitary cause, or adrenalectomy for an adrenal or ectopic tumor, with steroidogenesis inhibitors reserved for persistent or unresectable disease.

Dermatomyositis is a complement-mediated inflammatory myopathy causing symmetric proximal weakness with pathognomonic skin findings, heliotrope rash and Gottron papules, that separate it from polymyositis. It carries a 3- to 12-fold increased malignancy risk and a distinct interstitial lung disease burden that drive workup and therapy. First-line treatment is high-dose prednisone with an early steroid-sparing agent.

Acanthosis nigricans is a symmetric, velvety, hyperpigmented thickening of intertriginous skin that is most often a cutaneous marker of insulin resistance, and occasionally a paraneoplastic sign of visceral adenocarcinoma. Management is directed at the underlying driver, primarily glycemic control and weight loss, rather than the plaques themselves.

Myasthenia gravis is an autoimmune disorder of the postsynaptic neuromuscular junction, most often caused by acetylcholine receptor antibodies, producing fluctuating, fatigable weakness of ocular, bulbar, and limb muscles. Diagnosis rests on antibody testing and electrodiagnostics; first-line treatment is pyridostigmine, with glucocorticoids and steroid-sparing immunosuppression for generalized disease and thymectomy for eligible patients.

Autoimmune encephalitis is antibody-mediated brain inflammation, most often N-methyl-D-aspartate (NMDA) receptor antibody disease, that classically opens with a psychiatric prodrome and psychosis in a young patient before progressing to seizures, abnormal movements, and autonomic instability. Diagnosis requires antibody testing of blood and cerebrospinal fluid plus a tumor search; treatment is tumor removal plus immunotherapy, intravenous methylprednisolone and immune globulin first, escalating to rituximab or cyclophosphamide.

Deep vein thrombosis or pulmonary embolism occurring in a patient with active malignancy, driven by tumor-derived procoagulant activity plus stasis and vascular injury. Diagnosis is confirmed by compression ultrasonography or CT pulmonary angiography, and first-line treatment is apixaban, rivaroxaban, or low molecular weight heparin continued while cancer is active.

Renal cell carcinoma is the most common kidney cancer, arising from renal tubular epithelium (most often clear cell), and is now diagnosed incidentally on imaging in most patients rather than through the classic triad of flank pain, hematuria, and mass. Contrast CT or MRI showing an enhancing solid renal mass is usually sufficient to diagnose and stage disease, and treatment is surgical for localized tumors versus tyrosine kinase inhibitors and immune checkpoint inhibitors for metastatic, chemo- and radio-resistant disease.

Lung cancer is the leading cause of cancer death worldwide, split into non-small cell lung cancer (NSCLC, 80% of cases: adenocarcinoma, squamous cell, large cell) and small cell lung cancer (SCLC, 10-15%), both driven overwhelmingly by cigarette smoking. Diagnosis requires tissue histopathology, staging drives treatment (TNM staging for NSCLC, limited versus extensive stage for SCLC), and management ranges from lobectomy in early-stage disease through concurrent chemoradiation and consolidation immunotherapy in locally advanced disease to targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, or platinum-based chemotherapy in metastatic disease.