Learning Objective

By the end of this section, learners should be able to recognize key paraneoplastic syndromes, understand their clinical manifestations and underlying mechanisms, and identify the tumors most commonly associated with each syndrome.

1. Musculoskeletal and Cutaneous Syndromes

Syndrome	Clinical Features	Mechanism / Description	Commonly Associated Tumors
Dermatomyositis	Progressive proximal muscle weakness, Gottron papules, heliotrope rash	Autoimmune muscle and skin inflammation	Adenocarcinomas, especially ovarian
Acanthosis nigricans	Hyperpigmented, velvety plaques in axilla/neck	Tumor-secreted growth factors stimulate skin proliferation	Gastric adenocarcinoma, other visceral malignancies
Sign of Leser-Trélat	Sudden onset of multiple seborrheic keratoses	Tumor growth factor–mediated skin proliferation	GI adenocarcinomas, other visceral malignancies
Hypertrophic osteoarthropathy	Clubbing, arthralgia, joint effusions, periostosis of tubular bones	Abnormal proliferation of skin and bone at the distal extremities	Adenocarcinoma of the lung

2. Endocrine Syndromes

Syndrome	Clinical Features	Mechanism / Description	Commonly Associated Tumors
Hypercalcemia	High serum calcium	PTHrP secretion or ↑ 1,25-(OH)2 vitamin D3	Squamous cell lung, head/neck, renal, bladder, breast, ovarian carcinomas; lymphoma
Cushing syndrome	Hypercortisolism	Ectopic ACTH production	Small-cell lung cancer
Hyponatremia (SIADH)	Low sodium	Ectopic ADH secretion	Small-cell lung cancer

Activty

3. Hematologic Syndromes

Syndrome	Clinical Features	Mechanism / Description	Commonly Associated Tumors
Polycythemia	High hematocrit	Erythropoietin secretion	Pheochromocytoma, renal cell carcinoma, HCC, hemangioblastoma, leiomyoma
Pure red cell aplasia	Anemia with low reticulocytes	Autoimmune marrow suppression	Thymoma
Good syndrome	Hypogammaglobulinemia	Immunodeficiency due to a thymic tumor	Thymoma
Trousseau syndrome	Migratory superficial thrombophlebitis	Hypercoagulability	Adenocarcinomas, especially pancreatic
Nonbacterial thrombotic endocarditis	Sterile platelet thrombi on valves	Hypercoagulability	Adenocarcinomas

4. Neuromuscular / Neurologic Syndromes

Syndrome	Clinical Features	Mechanism / Description	Commonly Associated Tumors
Anti-NMDA receptor encephalitis	Psychiatric disturbances, memory deficits, seizures, dyskinesias, and autonomic instability	Autoantibodies against NMDA receptors	Ovarian teratoma
Opsoclonus-myoclonus-ataxia syndrome	“Dancing eyes, dancing feet”	Autoimmune	Neuroblastoma (children), small cell lung cancer (adults)
Paraneoplastic cerebellar degeneration	Ataxia	Antibodies against Purkinje cells	Small cell lung (anti-Hu), gynecologic/breast (anti-Yo), Hodgkin lymphoma (anti-Tr)
Paraneoplastic encephalomyelitis	Multifocal neurologic deficits	Antibodies against neuronal Hu antigens	Small-cell lung cancer
Lambert-Eaton myasthenic syndrome	Weakness improves with activity	Antibodies against presynaptic P/Q-type Ca2+ channels at NMJ	Small-cell lung cancer
Myasthenia gravis	Fatigable muscle weakness	Antibodies against postsynaptic ACh receptors	Thymoma

Activty

High-Yield Step 1 Points

Dermatomyositis in adults → screen for ovarian cancer.
Hypercalcemia due to PTHrP → most commonly SCC of the lung.
SIADH & Cushing syndrome → classic paraneoplastic syndromes of small cell lung cancer.
Lambert-Eaton → improves with activity, often SCLC; myasthenia gravis → worsens with activity, often thymoma.
Trousseau syndrome → migratory thrombophlebitis in pancreatic cancer.
Neurologic syndromes → often antibody-mediated, can precede tumor detection.