Bronchial Carcinoid

Description

Uncommon, slow-growing, low-grade malignant neuroendocrine neoplasms with metastatic potential, arising from enterochromaffin Kulchitsky cells on the surface of bronchial epithelium. Carcinoid tumours can be histopathologically subclassified into typical and atypical carcinoids.

Formerly known as bronchial adenomas.

Pathophysiology

Carcinoids are neuroendocrine tumours that arise from neoplastic proliferation of enterochromaffin or Kulchitsky cells.

Bronchial carcinoids synthesise and secrete neuroendocrine peptides into the central circulation such as serotonin, ACTH, somatostatin and bradykinin. Its ability to synthesise serotonin from dietary tryptophan is thought to be pathognomonic of carcinoids.

Atypical bronchial carcinoid tumours have mutations or abnormalities of p53, BCL2 or BAX genes, while typical tumour do not. 

Epidemiology, Risk Factors and Associations

• Mean age of diagnosis approximately 45 years of age. No sex or racial predilection.
• Not associated with any known carcinogen or environmental factors
• Approximately 20 – 40% are non-smokers.
• Sporadically occurring however uncommonly associated with multiple endocrine neoplasia type 1 (MEN-1 syndrome).
• 10-year survival:
  • Typical: 80 – 90% (low grade)
  • Atypical: 40 – 60% (more aggressive)

Clinical Features

• Asymptomatic (25%) – particularly if peripheral
• Haemoptysis (25 – 50%) – due to central origin and hypervascularity
• Localised wheeze – due to endobronchial obstruction
• Non-resolving recurrent obstructive pneumonitis
• Persistent productive/non-productive cough (35%), chest pain (40%) and fever
• Carcinoid Syndrome – systemic release of vasoactive substances such as serotonin, intermittent episodes of diarrhoea, cutaenous flushing and bronchospasm/cyanosis. Associated with 10% of bronchial carcinoids and almost always seen in concurrence with hepatic metastases.
• Cushing’s Syndrome – ectopic production of ACTH. Uncommon (2% of bronchial carcinoid tumours), mostly seen with atypical carcinoid.

Complications

• 15% of cases metastasise to liver, bone, adrenal glands or brain.

Pathological Features

Macroscopic

• Grow as finger-like or spherical polypoid masses that common project into the lumen of the bronchus, rarely exceeding 3 to 4 cm in diameter
• Collar-button lesion – lesion penetrates the bronchial wall to fan out in the peribronchial tissue.

Histopathology

• Organoid, trabecular, palisading, ribbon or rosette-like arrangements of cells separated by stroma.
• Typical carcinoids – fewer mitoses (<2) and lack necrosis
• Atypical carcinoids – more mitoses (2- 10) and/or foci of necrosis. Additionally demonstrates increased pleomorphism and is likely to grow in a disorganised fashion, invading lymphatics.

Immunohistochemistry

• Atypical: positive staining for chromogranin, CD56 and synaptophysin 

Biochemical

• Urinary 5-hydroxyindoleacetic acid (5-HIAA) and serum chromogranin A 
• Platelet serotonin and chromogranin A are useful biomarkers for detection and follow-up

Radiological Features

Recommendation

• Contrast-enhanced CT due to hypervascularity
• CT and somatostatin receptor scintigraphy are the most sensitive diagnostic modalities

General 

• Most commonly endobronchial, however approximately 20% are peripheral pulmonary nodules
• Pulmonary nodules/masses are well-marginated, lobulated and maybe solitary ± lymphadenopathy
  • Central and perihilar location are more common than peripheral – 75% arise from the lobar bronchi, 10% arise from mainstem bronchi, 15% arise from periphery
  • Peripheral location more common with atypical carcinoid tumours
  • Central carcinoids seen as endobronchial iceberg lesion, hilar or perihilar masses ± lymphadenopathy postobstructive atelectasis, pneumonia or mucous plugging
• Calcifications uncommon (<5%)
• Plain radiography is able to detect 75% of cases
• Rarely found in mediastinal structures
• Lymphadenopathy may represent metastasis.
• Reactive lymphoid hyperplasia from recurrent/chronic obstructive pnuemonia
• Hepatic metastases occur in 25-90% of patients with neuroendocrine tumours

Plain Radiography

• Central lesion on chest x-ray
• Homogenous increased opacities with volume loss

CT

• Central location, typically 2-5 cm.
• Intensely homogenously enhancing endobronchial lesion
• Associated post-obstructive atelectasis, air-trapping, pneumonitis and mucoid impaction.

MR

• T2/STIR: High signal intensity

Differential Diagnoses

• Lung Cancer
  • Non-small cell lung-cancer: Comprise 95% of malignant endobronchial tumours. Squamous cell most common for endobronchial tumours. Post-obstuctive lobar/segmental atelectasis. Bronchial or vascular compression may be present.
  • Small cell lung-cancers: Usually peribronchial and can invade into bronchial submucosa, extending intraluminally. Extensive metastative lymphadenopathy common.
  • History of cigarette smoking common to both, but more strongly associated with small cell lung cancer.
• Pulmonary Metastasis: Multifocal lung nodules endobronchial calcified nodule. History of known primary malignancy. Breast, rectal, and renal carcinomas and melanoma most common.
• Mucoepidermoid Carcinoma: Rare salivary gland tumour, located in lobar or segmental bronchi. Ovoid polypoid or lobular lesion and well-defined margins. Calcification in 50%.
• Adenoid Cystic Carcinoma: Salivary gland tumour. 90% arise in trachea or mainstem bronchi (more proximal airway distribution than carcinoid). Locally aggressive, requires careful evaluation for extraluminal or mediastinal growth
• Aspiration: Foreign body. Most common in children (peak 1 – 2 years). Pneumonia and post-obstructive atelectasis common. Bronchiectasis may developed from prolonged retention of FB.
• Broncholithiasis/Broncholith: Small endobronchial calcified nodule. Tends to be entirely calcified, while carcinoid are usually only partially calcified. History of tuberuclosis and histoplasmosis is common. Haemoptis is common. Lithoptysis is uncommon though virtually diagnostic. Temporal migration may be seen.
• Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): Uncommon syndrome characterised by multiple foci of neuroendocrine hyperplasia or carcinoid tumours and bronchiolitis obliterans. Multiple pulmonary nodules with mosaic attenuation of the lungs secondary to air trapping
• Hamartoma: Typically a lung nodule with macroscopic intralesional fat and popcorn calcification however can be endobronchial in 5% of cases and represents the most common benign endobronchial tumour. Less enhancement than carcinoid.
• Laryngeal Papillomatosis: Human papilloma virus mediated papillomatosis of upper aerodigestive tract

Management

• Complete surgical resection confers a good prognosis, particularly in typical carcinoids
• Hemihepatectomy or segmental resection is feasible when metastases are solitary
• Liver transplantation is considered for multiple, diffuse, unresectable hepatic metastases, hepatomegaly and medically uncontrollable symptoms.
• Hepatic arterial embolisation and local ablative therapy also considered.