Paraneoplastic Syndrome

Clinical syndromes Major underlying cancers Causal mechanism
Cushing syndrome Lung caner (small cell, bronchial
carcinoid, adeno, squamous)Thymoma
Medullary thyroid cancer
Pancreatic carcinoma Neural tumors
Pancreatic cancer, lung cancer,prostate cancer, carcinoid Corticotropin-releasing hormone(CRH)
SIADH Small cell carcinoma of Lung ADH or atrial natriuretic hormone
Intracranial neoplasms
Hypercalcemia (most common paraneoplastic syndrome) Squamous cell cancer (Head a neck, lung, skin)
Breast carcinoma
Gastrointestinal a Genitourinary tumors
Parathyroid hormone-related peptide (PTHRP) TGF-a, TNF, IL-1
Adult T cell leukemia/Lymphoma 1,25 dihydroxyvitamin D
Renal carcinoma, lung carcinoma (rare) Prostaglandin E2
Lung cancer, Ovarian cancer Parathormone
Hypoglycemia Ovarian carcinoma Sarcomas,Mesenchymal tumors Insulin or insulin like substance
Polycythemia Renal carcinoma
Cerebellar hemangioma
Hepatocellular carcinoma
Myasthenia Bronchogenic carcinoma Immunologic
Acanthosis nigricans Gastric carcinoma
Lung carcinoma
Uterine carcinoma
Immunologic, Epidermal growth factor
Dermatomyositis Bronchogenic carcinoma
Breast carcinoma
Hypertrophicosteoarthropathy andclubbing of fingers Bronchogenic carcinomaThymic neoplasms Unknown
Venous thrombosis(Trousseau phenomenon) Pancreatic carcinoma
Bronchogenic carcinoma
Tumor products (mucins that activate clotting)
DIC Acute promyelocytic leukemia
Prostatic carcinoma
Tumor products that activate clotting
Oncogenic osteomalacia Hemangiopericytomas, steoblastomas, fibromas, sarcomas, giant cell tumors Phosphatonin (fibroblast growth factor 23-FGF23)
Paraneoplastic syndromes associated with HCC
  • Hypoglycemia
  • Erythrocytosis
  • Hypercalcemia
  • Hypercholesterolemia
  • Dysfibrinogenemia
  • Carcinoid syndrome
  • Increased thyroxin-binding globulin
  • Changes in secondary sex characteristics (gynecomastia, testicular atrophy, and precocisous puberty)
  • ↑ levels of serum α-fetoprotein(AFP) (> 100 IU) seen in 50-75% cases but fails to detect small lesions
  • AFP is a clinically useful marker for follow-up
  • Des-y-carboxy prothrombin (DCP), a protein induced by vitamin K absence (PIVKA-2)is ↑ in 80% of HCC patients but may also be elevated in vitamin K deficiency; always elevated after Coumadin use
  • Recently staining for Glypican-3 has been used to distinguish early HCC from dysplastic nodules
  • Screening – USG
  • To determine tumor size and extent of portal vein invasion – Helical/Triphasic CT abdomen
  • TNM system – not routinely followed
  • Okuda system – older, simple
  • Cancer of the Liver Italian Program (CLIP) – most well-validated
  • Small tumors < 2cm can be removed surgically with 1-2cm margin of unaffected liver tissue
  • Extensive resections in patients with advanced cirrhosis carries high mortality due to post-op liver failure
  • Extensive resections for HCC in a non-cirrhotic liver are associated with low risk of liver failure (removal of 80% of liver is compatible with life)
  • Non-surgical therapy: transarterial embolization (TAE) transarterial chemoembolization (TACE) percutaneous ethanol ablation (PEA) or radiofrequency ablation (RFA) Regional chemotherapy or TACE: doxorubicin and cisplatin are used along with an embolizing agent ethiodol
  • Kinase inhibitor sorafenib can prolong life in advanced stage HCC
  • Bevacizumab plus Erlotinib is also effective in prolonging survival
  • Radiotherapy with pure beta emitting 90Yttrium microspheres has shown encouraging results
Exam Question
  • Paraneoplastic Syndrome seen in RCC are Acanthosis nigricans,Hypertension,Hypercalcemia,Amyloidosis and Polycythemia
  • Two important causes for paraneoplastic syndrome among the cancers are Small cell carcinoma lung and carcinoid
  • Cushing syndrome as paraneoplastic syndrome is seen with Bronchial carcinoid, Thymus, Medullary carcinoma thyroid
  • Paraneoplastic syndrome is associated with Renal Ca & Breast Ca
  • Parathyroid related peptide causes lung carcinoma, with paraneoplastic syndrome and increased PTH
  • ACTH ,ADH and Carcinoid syndrome are the paraneoplastic syndrome seen with small cell ca lung
  • The paraneoplastic syndrome associated with Hodgkin's disease is Cerebellar degenerative disease
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