Bronchial Carcinoid

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)

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)

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

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

Clinical

  • Asymptomatic: 25-60% of cases
  • Endobronchial Nodule/Mass (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Epidemiology: 75-80% of cases present endobronchially
    • Diagnosis
      • CXR/Chest CT
        • Atelectasis (see Atelectasis, [[Atelectasis]])
        • Post-Obstructive Pneumonia (see Pneumonia, [[Pneumonia]])
        • Bronchiectasis (see Bronchiectasis, [[Bronchiectasis]])
        • Lung Abscess (see Lung Abscess, [[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, [[Broncholithiasis]]): in cases with ossifying carcinoid
  • Hemoptysis (18-35%) (see Hemoptysis, [[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
  • Fever (see Fever, [[Fever]]): has been reported

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)

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)

References

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