Epidemiology

• History: first described in 1937 (distinguished from bronchial adenomas)
• Median Age mid 40’s (rare in children)
• Sex: M=F
• Race: bronchial carcinoids may be slightly more common in African-American males
• Incidence
  • <2000 per year in USA annually: account for only 0.5-1.0% of all primary lung tumors
  • Bronchial carcinoids account for about 25% of all carcinoids
• Risk Factors
  • Risk is unrelated to smoking or other environmental factors
• Associated with:
  • Multiple Endocrine Neoplasia Syndromes (rarely)

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Physiology

• Malignant lung neoplasm (originate submucosally) derived from neural crest cells (Kulchitsky cells)
• Interestingly, neuroendocrine cells are present in higher numbers in the lungs of smokers
• Similar origin to carcinoids found in GI tract, gallbladder, and pancreas
• Bronchial carcinoids have similar neuroendocrine properties to APUDomas, pheochromocytomas, medularry carcinomas of thyroid, etc.
• Metastasis: usually local and well-defined, but they may metastasize via lymphatic (to hilar/mediastinal nodes) or hematogenous spread (to liver/bones/brain/adrenals)
  • Size and degree of differentitation may be related to risk of metastasis
  • Local nodal mets occur in 10% of cases, while distant mets occur in 3% of cases
• Serotonin-Producing Carcinoids: these are unusual in the lungs (and only 50% of those with elevated serotonin metabolites have the carcinoid syndrome)

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Pathology

• Small uniform cells with acidophilic cytoplasm and finely stippled chromatin
• EM: neurosecretory granules
• Immunohistochemical stains: positive for neuron-specific enolase, chromogranin-A, synaptophysin, serotonin, and other neurosecretory cell markers
• Neuroendocrine Carcinomas (also known as Atypical Bronchial Carcinoids): variant with larger cell size and at least some neurosecretory neoplastic features
  • These have higher incidence of local nodal and distant mets than normal carcinoids

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Diagnosis

• LFT’s: may be useful in staging
• Serum Serotonin/Urinary 5-HIAA: elevated in <25% of cases at time of diagnosis
  • Note: only 50% of patients with elevated urinary serotonin metabolites have the carcinoid syndrome

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Clinical

• Asymptomatic: 25-60% of cases
• Endobronchial Nodule/Mass (see Obstructive Lung Disease)
  • Epidemiology: 75-80% of cases present endobronchially
  • Diagnosis
    • CXR/Chest CT
      • Atelectasis (see Atelectasis)
      • Post-Obstructive Pneumonia (see Pneumonia)
      • Bronchiectasis (see Bronchiectasis)
      • Lung Abscess (see Lung Abscess)
      • Normal CXR: some cases
      • Hilar/Mediastinal Lymphadenopathy (metastatic)
      • Local nodal mets are only seen in 10% of cases
      • Distant mets are only seen in 3% of cases
    • FOB
      • BAL and Brush: usually not diagnostic
      • EBB/TBB may be diagnostic: bleeding risk is low, despite vascularity
  • Clinical
    • Cough (most common presenting symptom)
    • Post-Obstructive Pneumonia
    • Stridor
    • Wheezing: may be exercise-associated
    • Bronchiectasis (see Bronchiectasis, [[Bronchiectasis]])
    • Lung Abscess (see Lung Abscess, [[Lung Abscess]])
• Lung Nodule (see Lung Nodule or Mass, [[Lung Nodule or Mass]])
  • Epidemiology: 20-25% of cases present as lung nodule
  • Diagnosis
    • CXR/Chest CT
      • Lung Nodule
      • Round or oval, sharply-defined, slightly lobulated nodule
      • Location: predilection for RUL, RML, and lingula (80% are central in location)
      • Calcification: rare (<10% of cases have visible calcification on CXR, but it may be detectable on CT scan)
      • Cavitation: rare
      • Vascularity may be noted
      • Hilar/Mediastinal Lymphadenopathy (metastatic)
      • Local nodal mets are only seen in 10% of cases
      • Distant mets are only seen in 3% of cases
    • FNA: may be necessary
• Broncholithiasis (see Broncholithiasis): in cases with ossifying carcinoid
• Hemoptysis (18-35%) (see Hemoptysis): due to vascular nature of carcinoid
• Carcinoid Syndrome: uncommon in bronchial carcinoid
• Systemic Symptoms/Symptoms of Metastasis (bone pain, etc.): uncommon
  • Metastatic work-up of <2 cm resectable, typical bronchial carcinoids is usually not necessary
• Paraneoplastic Syndrome
  • Cushing Syndrome (see Cushing Syndrome)
  • SIADH (see Syndrome of Inappropriate Antidiuretic Hormone Secretion)
• Fever (see Fever): has been reported

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Treatment

• Thoracotomy with Resection: curative treatment of choice
  • Hilar mediastinal node sampling: indicated for tumor >2 cm or poor differentiation
  • Persistent elevation of 5-HIAA post-op merits metastatic work-up
• Tracheal Carcinoid: amenable to tracheal sleeve-resection
• FOB: laser/fulguration have high recurrence rate
  • Procedure of choice for poor surgical candidates
• XRT (45-50 Gy): palliative (80% have partial/complete response but cure is not expected)
  • Spinal and bone mets may be treated well with XRT
  • Liver and lung mets are not well-treated with XRT
• Chemo (5-FU/Streptozotocin/Cytoxan/Doxorubicin): <40% response rates, with no survival benefit
  • Hepatic arterial therapy: useful for isolated liver mets
• Octreotide: useful for symptoms of Carcinoid syndrome in metastatic disease (does not decrease tumor burden or prevent long-term effects of serotonin on heart)
  • Tachyphylaxis: may occur
• Interferon-alpha: may induce tumor regression (SE limit use, but responders may be identified in advance)

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Prognosis

• Median Survival: >10 years (some cases survive <1 year)
• 10 year survival: >95%
  • In patients with small, typical carcinoid, completely resected
• 10 year survival: <55%
  • In patients with systemic symptoms, unresectable tumors (including positive hilar nodes)
• Male Patients: poorer outcome
• Atypical Bronchial Carcinoid (Neuroendocrine Carcinoma): <50% long-term survival (even with small tumor)

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References

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