Effects of tumor on host (cancer cachexia, paraneoplastic syndromes)

1. Concept

Tumors affect the host both locally (mass effects) and systemically (cachexia, paraneoplastic syndromes). Malignant tumors are more threatening, but all tumors cause morbidity/mortality.

2. Local effects

• Ulceration → bleeding (haemorrhagia per arrosionem) or infection/sepsis.
• Infarcts from vessel compression.
• Intussusception, obstruction or infarction of bowel (one segment slides into the adjacent one).

3. Cancer cachexia (wasting syndrome)

• Features: progressive weight loss (fat + muscle), fatigue, weakness, muscle atrophy, anorexia, anemia.
• Mechanism: soluble factors from tumor + host inflammatory cells:
  • TNF-α (central) — ↓food uptake, ↑energy mobilization, catabolic on skeletal muscle; IFN-γ, ILs synergize.
  • Lipid-mobilizing factor and proteolysis-inducing factor → muscle/fat breakdown.
  • High calorie expenditure + ↑BMR despite reduced intake.
  • Leptin/hypothalamic dysregulation → ↓appetite despite high demand.

4. Paraneoplastic syndromes

Symptoms not explained by tumor spread or by the tumor’s normal hormone product. Important because they may be the first sign, may be lethal, or may mimic metastasis.

Class	Syndrome	Typical tumor	Mechanism
Endocrine	Cushing	Small cell lung CA	Ectopic ACTH
SIADH	Small cell lung CA	Ectopic ADH
Hypercalcemia	Squamous cell lung CA, breast, renal	PTHrP, osteolysis
Neurologic	Lambert-Eaton, cerebellar degeneration, limbic encephalitis	Small cell lung CA	Autoimmune/immunologic
Mucocutaneous	Acanthosis nigricans, Leser-Trélat	Gastric/GI adenocarcinoma	—
Hematologic	Polycythemia (EPO), Trousseau sign (migratory thrombophlebitis), NBTE	Renal/HCC; pancreatic, lung	Erythropoietin; hypercoagulability/mucins

💡 High-yield: Cachexia is driven mainly by TNF-α (+ IFN-γ, proteolysis/lipid-mobilizing factors) → ↑BMR despite anorexia. Classic paraneoplastics: small cell lung CA → Cushing (ACTH), SIADH (ADH), Lambert-Eaton; squamous cell lung CA → hypercalcemia (PTHrP); renal/HCC → polycythemia (EPO); pancreatic → Trousseau (migratory thrombophlebitis). May be the first clue to an occult tumor.