What is the management of paraneoplastic syndromes?

Management of Paraneoplastic Syndromes

The management of paraneoplastic syndromes primarily involves treating the underlying malignancy while simultaneously providing targeted therapy for the specific syndrome to improve morbidity, mortality, and quality of life. 1

Classification and General Approach

Paraneoplastic syndromes can be broadly categorized into two main mechanisms:

• Hormonally-based syndromes: Caused by ectopic hormone production by tumor cells 1
• Immunologically-based syndromes: Caused by autoimmune mechanisms targeting normal tissues 1

Management of Specific Paraneoplastic Syndromes

Endocrine Paraneoplastic Syndromes

Ectopic Cushing Syndrome

• Commonly associated with small cell lung cancer (SCLC) and bronchial carcinoid 1
• Diagnostic approach:
  • Exclude iatrogenic causes of Cushing syndrome before biochemical testing 1
  • Initial testing with 24-hour urinary free cortisol, late-night salivary cortisol, or dexamethasone suppression test 1
• Management:
  • Primary treatment is surgical resection of the tumor when possible 1
  • Medical therapy with steroidogenesis inhibitors (ketoconazole, metyrapone) for symptom control 1

Carcinoid Syndrome

• Associated with neuroendocrine tumors, particularly bronchial carcinoids 1
• Diagnostic approach:
  • Measure 24-hour urinary 5-HIAA (specificity ~90%) 1
  • Serum chromogranin A (highest reliability among NET biomarkers) 1
• Management:
  • Surgical resection when feasible 1
  • For metastatic disease: somatostatin analogs (octreotide) 1
  • Additional therapies: serotonin receptor blockers, interferon, antidiarrheal medications 1
  • Prevention of carcinoid crisis during procedures with IV octreotide acetate 1

Neurological Paraneoplastic Syndromes

Anti-Hu Syndrome

• Most common PNS in lung cancer, particularly SCLC (>90% of cases) 1
• Clinical manifestations: limbic encephalitis, cerebellar degeneration, sensory neuropathy 1
• Management:
  • Treatment of the underlying malignancy is the primary approach 1
  • Immunosuppressive therapy with IVIg, methylprednisolone, and cyclophosphamide may provide transient stabilization but rarely long-term improvement 1

Lambert-Eaton Myasthenic Syndrome (LEMS)

• Associated with SCLC in 1-1.6% of cases 1
• Characterized by proximal muscle weakness, predominantly affecting hip girdle 1
• Management:
  • Treat underlying malignancy 1
  • Intravenous immunoglobulin (IVIg) per established guidelines 1
  • 3,4-diaminopyridine to improve neuromuscular transmission 2

Anti-Yo Syndrome (Paraneoplastic Cerebellar Degeneration)

• More commonly associated with ovarian and breast cancers than SCLC 1
• Clinical features: brainstem abnormalities and cerebellar degeneration 1
• Management:
  • IVIg within 1 month of onset may stabilize neurological symptoms 1
  • Consider plasmapheresis or plasma exchange 1
  • High-dose IV glucocorticoids (benefit unclear when added to IVIg) 1

Dermatologic Paraneoplastic Syndromes

Dermatomyositis

• Associated with lung cancer and often diagnosed within 1 year of cancer diagnosis 1
• Diagnostic criteria: progressive symmetrical proximal muscle weakness, elevated muscle enzymes, characteristic skin findings 1
• Management:
  • Corticosteroids as first-line therapy 1
  • Additional immunosuppressive agents: methotrexate, cyclophosphamide, azathioprine, mycophenolate 1
  • Rituximab and IVIg for refractory cases 1

General Management Principles

1. Early recognition and diagnosis are critical to improve outcomes 1, 3

   • Prompt identification can lead to detection of occult malignancies at treatable stages 3

2. Treat the underlying malignancy as the primary approach 1, 3

   • Successful cancer treatment often improves paraneoplastic symptoms 1

3. Syndrome-specific therapy based on mechanism:

   • For immunologic PNS: immunosuppression with IVIg, corticosteroids, cyclophosphamide 1
   • For hormonal PNS: targeted therapies to block hormone effects 1

4. Balance treatment timing:

   • Consider parallel workup of paraneoplastic syndromes alongside cancer diagnosis to minimize delays 1
   • In some cases, controlling the paraneoplastic syndrome before cancer treatment may be necessary 1

Important Considerations

• Paraneoplastic syndromes can cause significant morbidity that may limit effective cancer treatment if undiagnosed 1
• Early intervention can limit associated morbidity and mortality, facilitating more effective cancer therapy 1
• Response to immunotherapy for neurological PNS is often limited, especially for syndromes targeting intracellular antigens 2
• Better outcomes are generally seen with cell-surface antibody-mediated syndromes compared to those mediated by intracellular antibodies 2