Paraneoplastic Syndromes

Question 1

What is the definition of paraneoplastic syndrome?

Answer 1

• —A disease or symptom that is an in-direct effect of cancer in the body.
  
  • —Mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor.
• —Typical among middle aged to older patients, and they most commonly present with cancers of the lung, breast, ovaries or lymphoma.
  
  • —Symptoms of paraneoplastic syndromes can present before the diagnosis of a malignancy, during or after.
  • —NB: Can have non cancer associated paraneoplastic syndromes

Question 2

What are definite paraneoplastic syndromes?

Answer 2

• —A “classical” syndrome and cancer that develops within five years of diagnosis of the neurologic disorder
• —A nonclassical syndrome that resolves or significantly improves after cancer treatment without concomitant immunotherapy, provided that the syndrome is not susceptible to spontaneous remission
• —A nonclassical syndrome with paraneoplastic antibodies and cancer that develops within five years of the diagnosis of the neurologic disorder.
• —A neurologic syndrome (classical or not) with “well-characterized” paraneoplastic antibodies and no cancer. These well-characterized antibodies include anti-Hu, CV2, Ri, Yo, Tr, Ma2, and amphiphysin.

Question 3

What are possible paraneoplastic syndromes?

Answer 3

• —A classical syndrome as defined above, no paraneoplastic antibodies, no cancer, but at high risk to have an underlying tumor
• —A neurologic syndrome (classical or not) with partially characterized paraneoplastic antibodies (eg, not the well-characterized antibodies described above) and no cancer
• —A nonclassical syndrome, no paraneoplastic antibodies, and cancer present within two years of diagnosis

Question 4

What are the neurologic paraneoplastic syndromes?

Answer 4

• —CNS
  
  • —Brain
    
    • —Seizures
    • —Cerebral dysfunction
    • —Cerebellar dysfunction
    • —Brainstem dysfunction
  • —Eyes
  • —Spinal Cord
• —PNS
  
  • —Spinal roots/nerves
  • —Muscle

Question 5

What is the pathophysiology and clinical findings of paraneoplastic cerebellar degeneration?

Answer 5

• —Clinical Symptoms-Acute to sub-acute
  
  • —Dysarthria
  • —Truncal, limb and gait ataxia
  • —Vertigo
  • —Diplopia and nystagmus
• —Pathophysiology: Anti-pukinje cell anti-bodies
  
  • —Anti-Yo = Ovarian Cancer
  • —Anti-Hu = SCLC
  • —Others: Anti-Tr, -VGCC,-Zinc
• —MRI-Cerebellar atrophy
• —CSF: pleocytosis, increased protein

Question 6

What is the pathophysiology and clinical findings of paraneoplastic limb encephalitis?

Answer 6

• —Symptoms
  
  • —Psychiatric
  • —MS changes/Memory Loss
  • —Seizures
• —Pathophysiology:
  
  • —Onco-neural anti-bodies
    
    • —Anti-Hu = SCLC
    • —Anti-Ma = Testicular cancer
  • —Cell surface or synaptic protein Anti-bodies
    
    • —VGKC = SCLC/Thymoma
    • —AMPA receptor = SCLC, Breast and Thymus
    • —GABA-b receptor = SCLC
    • —NMDA = Ovarian Cancer/Teratoma

Question 7

What is the pathophysiology and clinical findings of LEMS?

Answer 7

• —Symptoms
  
  • —Muscle Weakness (mostly below the neck), LE > UE
  • —Dry mouth
• —Pathophysiology
  
  • —Reduced numbers of P/Q Ca++ channels on presynaptic terminals
  • —VGCC anti-body = SCLC, lymphoproliferative disorders, thymoma, NSCLC
• —EMG-Incremental response
  
  • The more you use the muscle, the more likely to fire
  • Patients get stronger with activity

Question 8

What is the pathophysiology and clinical findings of paraneoplastic sensory neuronopathies?

Answer 8

• —Symptoms:
  
  • —Painful paresthesias & dysesthesias
  • —Asymmetric; Distal or Proximal
  • —Sensory loss (95%)
    
    • —All modalities involved
    • —Ataxia: Sensory
    • —Pseudoathetosis
  • —Proximal & Distal
    
    • —Asymmetric or Symmetric
    • —Discomfort: Pain; Paresthesias
• —Pathophysiology: Anti-Hu = SCLC
• CSF: pleocytosis, increased protein

Question 9

What is paraneoplastic acanthosis nigricans?

Answer 9

• —Thickened brown to black, poorly defined, velvety hyperpigmentation of the skin
• —Found in body folds such as armpits, groin, navel, neck. Mucous membranes.
• —GI malignancies and GU
  
  • —Gastric and Adenocarcinoma
• —Older age approx 40
• —EGF/TGF-alpha, IGF-1 and FGF

Question 10

What is paraneoplastic dermatomyositis?

Answer 10

• —Connective tissue disease with inflammation of the muscles and skin
  
  • —Heliotrope and Gotton’s sign
  • —Malar erythema
  • —Piokiloderma
• —Lab: increased CPK and ESR
  
  • —EMG, muscle bx
• —Adenocarcinoma
  
  • —Breast, Lung, ovarian

Question 11

What are the findings of paraneoplastic Cushing syndrome?

Answer 11

• —Symptoms
  
  • —Muscle weakness, peripheral edema, HTN, increased weight, cushingoid features
• —Lab: hypokalemia, increased cortisol, nl to elevated ACTH
• —Ectopic ACTH or ACTH-like substance
  
  • —SCLC, Pancreatic, thymoma, Neuro-endocrine tumors—

Question 12

What are the findings of paraneoplastic SIADH?

Answer 12

• —Symptoms
  
  • —Unsteady gait/falls, HA, Nausea, fatigue/lethargy, confusion, seizures
• —Lab: low sodium, increase urine osmolality
• —SCLC, some others
• —Tumor produces ADH (increase free water resorption) and atrial natiuretic peptide (natiuretic and anti-diuretc properties)