STEPTRACKERGENERAL PRINCIPLES | PATHOLOGY + EPIDEMIOLOGY | HIGH-YIELD REVIEW

Paraneoplastic Syndromes & Cancer Epidemiology

Effects caused by hormones or antibodies a tumor triggers — not by the mass or its metastases — plus who gets which cancer.

FOCUS ON
Small cell lung carcinoma causes the most paraneoplastic syndromes: ACTH, ADH, Lambert-Eaton, anti-Hu. Squamous cell carcinoma makes PTHrP. RCC makes EPO. These syndromes can appear before the cancer is found, so treat them as clues.
SYNDROME
MEDIATOR
TUMOR(S)
CLUE
Cushing syndrome
endocrine
Ectopic ACTH
Small cell lung carcinoma; carcinoid
Rapid onset, hypokalemia, hyperpigmentation, little cushingoid habitus
SIADH
endocrine
Ectopic ADH
Small cell lung carcinoma
Euvolemic hyponatremia, concentrated urine
Hypercalcemia
endocrine
PTHrP · 1,25-(OH)₂ vitamin D · local osteolysis
Squamous cell (lung, head & neck), renal, breast · Hodgkin/NHL · myeloma, bone mets
↓ PTH with ↑ Ca²⁺
Polycythemia
endocrine
Erythropoietin
RCC, HCC, hemangioblastoma, leiomyoma, pheochromocytoma
High hematocrit + flank mass
Hypoglycemia
endocrine
IGF-II
HCC, large mesenchymal tumors
Low insulin, low C-peptide
Lambert-Eaton syndrome
neuromuscular
Antibodies to presynaptic voltage-gated Ca²⁺ channels
Small cell lung carcinoma
Proximal weakness that improves with repeated use; dry mouth, ↓ reflexes
Myasthenia gravis · red cell aplasia
thymic
Anti-AChR · T-cell attack on red cell precursors
Thymoma
Anterior mediastinal mass
Cerebellar degeneration
neurologic
Anti-Yo (Purkinje cells), anti-Hu, anti-Tr
Ovarian, breast (Yo) · small cell (Hu) · Hodgkin (Tr)
Subacute ataxia, dysarthria
Encephalomyelitis · sensory neuronopathy
neurologic
Anti-Hu
Small cell lung carcinoma
Limbic encephalitis, sensory loss
Anti-NMDA receptor encephalitis
neurologic
Anti-NMDA receptor antibodies
Ovarian teratoma
Young woman: psychosis, seizures, orofacial dyskinesia, autonomic instability
Opsoclonus-myoclonus
neurologic
Anti-Hu (child), anti-Ri (adult)
Neuroblastoma · breast, small cell
"Dancing eyes, dancing feet"
Hypercoagulable states
hematologic
Mucin, tissue factor
Pancreatic, gastric, lung adenocarcinoma
Trousseau migratory thrombophlebitis; marantic (nonbacterial) endocarditis
Skin & bone signs
other
Growth factors, unknown
Gastric (acanthosis nigricans) · GI (Leser-Trélat) · lung adenocarcinoma (hypertrophic osteoarthropathy) · dermatomyositis (lung, ovary, GI)
Sudden many seborrheic keratoses; clubbing + periostitis

Mechanism — action at a distance

TumorMakes hormone or peptide
→
Endocrine effectACTH, ADH, PTHrP, EPO
Tumor antigenShared with neurons
→
Antibodies / T cellsOnconeural immunity
→
Neurologic syndromeOften before diagnosis

Cancer epidemiology (US adults)

RANK
INCIDENCE
DEATHS
Men
Prostate > lung > colorectal
Lung > prostate > colorectal
Women
Breast > lung > colorectal
Lung > breast > colorectal
Children
Leukemia (ALL) > CNS tumors > neuroblastoma
CNS tumors and leukemia lead

Cancer is the 2nd leading cause of death in US adults after heart disease. Cervical cancer is far more common where screening is limited.

How it's tested

COMMON CONFUSIONLambert-Eaton gets better with repeated effort. Myasthenia gravis gets worse with repeated effort.
THE TRAPA smoker with hypercalcemia and a central lung mass has squamous cell carcinoma (PTHrP). A smoker with hyponatremia or Cushing has small cell carcinoma — both are central tumors.
YOUR APPROACHName the hormone or antibody from the lab picture, then pick the tumor known to make it.

If you see… think…

Smoker, confusion, Na⁺ 118, concentrated urine → SIADH (small cell)
Smoker, Ca²⁺ 14, ↓ PTH, central mass → PTHrP (squamous cell)
Smoker, hypokalemic alkalosis, weight loss, hyperpigmentation → ectopic ACTH (small cell)
Weakness that eases after repeated effort, dry mouth → Lambert-Eaton
Young woman with psychosis, seizures, odd facial movements → anti-NMDA encephalitis (ovarian teratoma)
Woman with gynecologic cancer and new ataxia → anti-Yo cerebellar degeneration
Toddler with dancing eyes and jerks → neuroblastoma (opsoclonus-myoclonus)
Migrating superficial thrombophlebitis → Trousseau sign (pancreatic cancer)
High hematocrit + flank mass → EPO from RCC
Dozens of seborrheic keratoses appearing suddenly → Leser-Trélat (GI adenocarcinoma)