Bronchial carcinoids, the most common primary lung neoplasm of childhood, typically presents with persistent cough, haemoptysis, and recurrent pneumonia, and appear as a well-defined bronchial homogeneously enhancing, Dotatate-positive mass, often with post-obstructive pneumonia.
Description
Bronchial carcinoids are a type of low-grade neuroendocrine tumour that originates in the bronchial epithelium of the lungs. They are generally slow-growing and less aggressive than other types of lung cancers. However, they can metastasise, particularly if not treated promptly.
Pathogenesis
The exact cause of bronchial carcinoids is not fully understood. They are thought to arise from neuroendocrine Kulchitsky cells found in the bronchial epithelium.
Two types of bronchial carcinoids are recognised:
- Typical carcinoid – Less aggressive and constitute about 85-90% of cases. It is characterised by uniform cells in sheets, trabeculae or gland-like structures, separated by thin fibrovascular stroma.
- Atypical carcinoid – More aggressive and accounts for the remaining 10-15%. More likely to metastasise (to lung, lymph nodes, liver, bone, adrenal glands). It features tumour necrosis, loss of typical architecture with increased cellularity, and an increased nuclear:cytoplasmic ratio or nuclear pleomorphism.
Epidemiology, Risk Factors & Associations
- Bronchial carcinoids represent about 1-2% of all lung tumours.
- They tend to occur in younger individuals compared to other lung cancers, often presenting in the 40s or 50s.
- There is no clear association with smoking, unlike most other lung cancers.
- Bronchial carcinoids are the most common primary lung neoplasm of childhood.
- Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) – This is a rare condition characterised by the proliferation of neuroendocrine cells in the bronchiolar epithelium. It can present with multiple small nodules throughout the lungs, typically less than 5 mm in size. DIPNECH may be associated with obstructive lung disease due to small airways involvement and may present with mosaic attenuation on CT scan. It is considered a precursor lesion for carcinoid tumours.
Clinical Features
- Many patients with bronchial carcinoid are asymptomatic, particularly in the early stages.
- When symptoms do occur, they can include cough, haemoptysis, and recurrent pneumonia.
- Carcinoid syndrome – Caused by secretion of hormones (especially serotonin) characterised by flushing, diarrhoea, and wheezing, can occur but is rare unless the tumour has metastasised to the liver.
- Cushing syndrome – caused by prolonged exposure to cortisol. Characterised by rapid weight gain, particularly of the trunk and face (moon face), a buffalo hump (a lump of fat on the back of the neck), purple stretch marks, and thinning of the skin leading to easy bruising. Almost always presents with hepatic metastases from gastrointestinal carcinoid.
Pathological Features
Histopathological
- These tumours often appear as well-circumscribed, lobulated masses on gross examination.
- Microscopically, they are composed of uniform cells with ‘salt-and-pepper’ chromatin.
- Typical carcinoids lack necrosis and have fewer than 2 mitoses per 2 mm².
- Atypical carcinoids show focal necrosis and/or 2-10 mitoses per 2 mm².
Biochemical
- Bronchial carcinoids can produce hormones like serotonin, but this is more common in carcinoids located in the gastrointestinal tract.
Radiological Features
General Features
- Typical carcinoids are endobronchial lesions found in the central hilar or perihilar regions, usually distal to the carina
- Atypical carcinoids are pulmonary nodules found in the peripheral lung
When metastasis occurs, it most frequently involves the following areas:
- Liver Metastases: Liver metastases from carcinoids may appear as multiple well-defined, low-attenuation lesions on CT. On MRI, these lesions are typically T1-hypointense and T2-hyperintense. The lesions may show intense enhancement in the arterial phase due to the hypervascularity of carcinoid tumours.
- Bone Metastases: Bone metastases from carcinoids are typically sclerotic (increased density) rather than lytic. They may be identified as hot spots in bone scintigraphy.
- Lung and Pleura Metastases: Additional pulmonary nodules or masses may be identified on CT, typically demonstrating similar characteristics to the primary tumour. Pleural effusion or nodularity may suggest pleural involvement.
- Lymph Node Metastases: Lymph nodes may be enlarged and may demonstrate enhancement on CT. Carcinoid tumours often spread to regional lymph nodes first (hilar and mediastinal nodes in the case of bronchial carcinoids), but distant lymph node metastasis can also occur.
- Adrenal Gland Metastases: Although less common, adrenal metastases can occur and may present as well-defined, enhancing adrenal masses on CT or MRI.
CXR
- May show a well-defined, round or oval nodule or mass centrally (typical carcinoid) or peripherally (atypical carcinoid).
- Central lesions may cause bronchial obstruction leading to lobar collapse (post-obstructive collapse or atelectasis) or pneumonia.
CT
- Typical bronchial carcinoids present as a well-defined, round or oval mass which may enhance homogeneously after contrast administration.
- They may be endobronchial, partially or entirely endoluminal, or may abut the bronchus.
- Around 30% of central carcinoids exhibit variable calcification or ossification, and they show marked, homogeneous contrast enhancement.
- Effects of central airway obstruction such as atelectasis, post-obstructive pneumonia, bronchiectasis, lung abscess, and mucoid impaction may also be observed.
- Atypical carcinoids tend to be peripheral with lobulated or irregular contours and less uniform enhancement.
MRI
- Isointense or slightly hyperintense on T1-weighted images
- Hyperintense on T2-weighted images.
NM
- FDG PET: Typically demonstrates low uptake due to the relatively low metabolism of carcinoid tumours. However, an SUV > 5.0 may be indicative of more aggressive behaviour.
- Octreotide scan: Characteristically demonstrates high uptake in carcinoid tumours, aiding in both diagnosis and localisation.
- Gallium-68-DOTATATE: Superior to Octreoscan in detecting small tumours and identifying lymph node involvement, with carcinoids characteristically demonstrating intense uptake.
Differential Diagnosis
- Lung cancer – May have irregular or spiculated margins. Can also exhibit post-obstructive pneumonitis or atelectasis, as well as mediastinal lymphadenopathy. FDG-avid on PET.
- Metastatic lesions to lung – Multiple and randomly distributed throughout the lung. May vary in size and demonstrate cavitation. Typically don’t cause endobronchial obstruction.
- Harmatoma – Well-defined, solitary nodule with macroscopic fat and calcification, can be endobronchial in location although uncommon.
- Tuberculosis – Tree-in-bud opacities, cavitation, upper lobe predominance. Usually associated with lymphadenopathy. Lack intense contrast enhancement which is characteristic of carcinoid tumours.
Management
- Surgical resection is the treatment of choice for localised bronchial carcinoids.
- For patients with unresectable or metastatic disease, treatment options include somatostatin analogues, peptide receptor radionuclide therapy (PRRT), chemotherapy, and targeted therapies.
- Follow-up with regular imaging is necessary to monitor for recurrence or metastasis.