Neuroendocrine tumours (NETs) of the lung are a rare type of lung cancer that arise from the cells called Kulchitzky cells of the bronchial mucosa . A few lung NETs can make high levels of hormone-like substances. If these substances are released in high amounts in the blood, the tumour is called a “functional” NET and it will cause a group of symptoms called Carcinoid Syndrome. These tumours can be benign or malignant and can cause a wide range of symptoms, depending on the location and size of the tumour, as well as the hormones that it produces.
Classification
NETs of the lung are classified into the following types:
- Typical Carcinoid
- Atypical Carcinoid
- Large cell neuroendocrine carcinoma (LCNEC)
- Small cell lung cancer (SCLC)
Clinical profile of NETs of Lung
The clinical spectrum of neuroendocrine tumors (NETs) of the lung is diverse and can range from asymptomatic, indolent tumors to rapidly growing malignancies.
Symptoms of NETs of the lung can include:
- Breathlessness
- Chest pain
- Cough
- Wheezing
- Haemoptysis
- Weight loss
- Fatigue
- Hormonal symptoms (such as flushing, diarrhea, and heart palpitations if the tumour is producing excess amounts of Serotonin)
Diagnosis
Most of the time lung NETs are found unexpectedly when people have annual health check-ups or imaging tests or a medical procedure done for reasons unrelated to the tumor. If a doctor suspects this disease, they will elicit a complete medical and family history and perform a complete physical examination.
Tests required to diagnose a lung NET:
- Chest X-ray
- CT scan
- Biopsy
- Bronchoscopy
- EBUS
- DOTA-NOC PET scan
- Blood or Urine tests e. 5-HIAA
Pathologic findings of NETs of the lung
These lesions are characterized by the presence of neuroendocrine cells (small cells with round nuclei and moderate amount of cytoplasm) arranged in a trabecular, organoid, or solid pattern. The cells may be arranged in nests, cords, or trabeculae. The degree of differentiation is an important prognostic factor for NETs, the well-differentiated tumors have better prognosis than poorly differentiated ones.
Immunohistochemistry is important to establish a diagnosis of NETs of the lung, The most commonly used markers are chromogranin, synaptophysin and CD56. The Ki-67 index, which measures the proliferation rate of the tumour cells, is also used to evaluate the aggressiveness of the tumour.
NETs of the lung are graded based on the degree of differentiation, the Ki-67 index, and the mitotic count. The grading system is important for prognosticating the disease and for planning treatment.
Radiological features
Chest radiographs: NETs appear as solitary, round or oval-shaped nodules that can be well-circumscribed or spiculated. They can also appear as multiple nodules or as a mass that can be associated with atelectasis, pleural effusion or lymphadenopathy.
Computed tomography (CT) scans: NETs of the lung can have a variety of appearances, including solid, ground-glass, or cystic. They may show central or peripheral enhancement after administration of IV contrast.
Carcinoid tumours appear as a spherical or ovoid nodule or mass with a well-defined and slightly lobulated border. When nonspherical, the tumour is elongated with its long axis parallel to adjacent bronchi. Calcification or ossification is seen in up to 30% of cases.
Positron Emission Tomography (PET) scans: A special form of PET scan is used to evaluate NETs of Lungs. They are called DOTA-NOC PET scan that uses a radioactive tracer called Ga-68 dotatate to bind to a tumour’s somatostatin receptors. Ga-68 dotatate is injected intravenously and then patients undergo the scan. NETs of the lung tend to have a high uptake of this radiotracer, indicating increased metabolic activity.
Treatment
Treatment options for neuroendocrine tumours (NETs) of the lung vary depending on the stage and grade of the tumour, as well as the patient’s overall health.
Surgery: Surgery is the primary treatment option for localized NETs of the lung. The goal of surgery is to remove the tumour and surrounding tissue with a healthy non diseased margin. Most localized (early stage I to II and some stage III) lung NETs require only surgery.
Depending on the size and location of the tumour, different surgical procedures may be used, such as lobectomy, segmentectomy, pneumonectomy or wedge resection. The surgeon will also remove the surrounding lymph nodes.
In case of a Bronchial Carcinoid a lung parenchyma preserving surgery like Sleeve Lobectomy may also be done. Endoscopic management of intraluminal Carcinoids like rigid bronchoscopic resection has also been described in literature but surgery remains the gold standard.
Radiation therapy: The most common type of radiation treatment for a lung NET is called external-beam radiation therapy (EBRT). Its role is mainly palliative to relieve symptoms, such as pain, caused by cancer that has spread to other areas of the body.
Chemotherapy: is most often used when the tumour has spread to other organs, is growing quickly, or is causing severe symptoms. The response to chemotherapy is not that great.
Most common agents that are used are:
- Carboplatin or cisplatin, plus etoposide
- Temozolomide, with or without capecitabine
- FOLFOX (Fluorouracil [5-FU] + leucovorin (folinic acid) and oxaliplatin)
- CAPEOX (Capecitabine + Oxaliplatin)
Targeted therapy: Targeted therapy is a newer type of treatment that targets specific molecules involved in the growth and spread of cancer cells. Everolimus is the only targeted therapy approved by the FDA currently for the treatment of lung NETs.
Peptide receptor radionuclide therapy (PRRT): This treatment uses a small amount of radioactive material that is attracted to the receptors on the tumour cells. This treatment is used for advanced or metastatic NETs. Its use in lung NETs is limited to clinical trials and the FDA has not yet approved it.
Embolization- Hepatic artery embolization: This is a procedure that blocks the blood supply to the tumour, which can shrink it or slow its growth.
Conclusion
It’s important to note that treatment plans for NETs of the lung are usually tailored to the specific needs of each patient and may involve a combination of these treatments. It is important to consult with a specialized team of doctors to determine the best treatment option for an individual patient.
