Initial investigations will be guided by thorough history taking and vigilant clinical examination. In most patients who are relatively asymptomatic, baseline biochemical tests performed should include assessment of renal function, calcium, glucose, and serum chromogranin- A levels. Chromogranin- A is raised in up to 75% of lung carcinoids and 60% of SCLC. Neuron- specific enolase (NSE) may be raised in high- grade NETs. Specific tests such as serum/ urinary 5- hydroxyindoleacetic acid (5- HIAA), serum/ urinary cortisol, serum ACTH, and serum GHRH or IGF- 1 should only be requested if there is clinical suspicion of paraneoplastic syndromes. Serum calcium and parathyroid hormone (PTH) levels can be simple screening tests for MEN- 1, and further investigations should be undertaken by specialist ser vices with appropriate genetic counselling. Currently, there is no validated molecular tests used and therefore is not routinely re commended outside clinical trials.
Plain imaging with chest X- ray may be useful as a screening tool (up 40% of incidental cases) although smaller lesions are likely to be missed. All patients suspected to have NETs should have a contrast- enhanced full staging computed tomography (CT) scan of the thorax, abdomen, and pelvis as the standard of care. Note that DIPNECH are best diagnosed using high resolution CT (HRCT) scan with an additional expiration study. The current gold standard investigation in the diagnosis of lung carcinoids (both TC and AC) is 68 Gallium (68Ga)- DOTA (DOTATOC or DOTATATE)- PET CT scan (not indicated in DIPNECH), and is recommended as a baseline imaging for all patients including those who had curative resection for their disease and also in advanced lung carcinoids.
The main indication for performing an 18F- fluorodeoxyglucose (FDG)- PET CT scan is in high- grade (grade 3) tumours, although a proportion of patients might have already had this as part of their lung cancer preoperative work- up. This is generally only helpful in tumours with Ki- 67 of more than 10% [47]. Other nu clear medicine imaging modalities such as somatostatin receptor scintigraphy (SRS) with 111Indium pentetreotide and OctreoScan can be useful alternatives in instances when 68Ga- DOTA- PET CT scan is not available or funded. In other specific situations, MRI scan with contrast is often useful in characterizing indeterminate liver lesions when metastatic disease is suspected. Another simple alternative to MRI when contraindicated is a triple- phase contrast- enhanced ultrasound scan of the liver. In cases where bone metastases are suspected, a whole- body nuclear medicine bone scan is standard practice. MRI scan can also be useful to guide surgical or radiotherapy interventions in circumstances when patients are symptomatic of their specific areas of bone metastases.
As tissue biopsy is the gold standard for definitive diagnosis, both rigid and flexible bronchoscopy can be helpful to obtain tissue sample in centrally located tumours. This must be performed with caution in view of risks of bleeding. Most patients with peripheral tumours commonly have a CT- guided biopsy instead. In addition, it is also good practice to perform a baseline echocardiogram to ensure no evidence of carcinoid heart disease, particularly in symptomatic patients. Where patients are frail or elderly, there may be safety concerns in pursuing a biopsy to obtain a tissue diagnosis. In this situation, it is reasonable to assume the diagnosis if the lung lesion is negative on FDG- PET but avid on a 68Ga- DOTA- PET CT scan or OctreoScan.
