Neuroendocrine Lung Neoplasms and Paraneoplastic Syndromes

Neuroendocrine Lung Neoplasms

There are four types of neuroendocrine lung neoplasms.

• Bronchial Carcinoid
• Atypical Carcinoid
• Small Cell Lung Cancer
• Large Cell Neuroendocrine Carcinoma

These lung cancers share morphologic and biochemical features with cells of the neuroendocrine system. The lung normally contains neuroendocrine cells, so these diseases are malignancies of normal lung cells. All the neuroendocrine lung neoplasms have histological similarities but different survival outcomes (so pay attention!). Neuropeptides are produced, such as bombesin, calcitonin, gastrin, somatostatin, and serotonin. 

Small cell lung cancer and large cell carcinoma were already discussed, so only bronchial carcinoid and atypical carcinoid will be included now.
 

Bronchial Carcinoid

Its old name was Bronchial Adenoma. 

It comprises 1-5% of all lung cancers. It usually occurs in young people and is not correlated to smoking. There is low mortality rate – almost a 100% curative rate if surgically resected. 

Electron microscopy shows tumor cells containing dense core neurosecretory granules. These cells are small and uniform. 

Tumors grow intraluminally, obstructing bronchi. Patients present with cough, wheezing, and recurring pneumonia.
 

Atypical Carcinoid

This is an intermediate neuroendocrine cancer, meaning that it has features that are similar to both carcinoid and small cell carcinoma. However, there are more characteristics that resemble small cell carcinoma.           

In this cancer, the organoid architecture is retained and the bronchiolar epithelium present with lots of cellular and nuclear pleomorphism (larger and more irregular cells), mitosis, and necrosis. Atypical carcinoid is considered an aggressive cancer because there is deep parenchymal infiltration, a high probability of recurrence, and metastatic potential. The survival prognosis is from 3-4 years.
 

Histologic Classification of Neuroendocrine Lung Tumors

 Well-differentiated (Grade I) – Bronchial Carcinoid

Moderately (Grade II) – Atypical Carcinoid

Poorly differentiated (Grade III) – Small Cell Lung Cancer

Paraneoplastic Syndromes

Paraneoplastic syndromes, biological and biochemical disturbances associated with malignant neoplasms, are usually the first signs of lung cancer.
 

Small Cell Lung Cancer can cause the following 3 paraneoplastic syndromes.

• SIADH
  • An inappropriate amount of ADH is secreted, resulting in hyponatremia.
• Cushing’s Syndrome
  • Excess ACTH is secreted by an ectopic neoplastic tumor, such as lung cancer.
• Lambert-Eaton Myasthenic Syndrome
  • This is an auto-immune neurologic disease clinically manifested by proximal muscle weakness.
  • Auto-antibodies are directed against neuronal calcium channels to prevent ACh release from the motor end terminal. Therefore, ACh never reaches the post-synaptic muscle membrane to exert its effect.
     

Non-Small Cell Lung Cancer

• Hypertrophic Ostearthropathy
  • Clinically, this condition presents as clubbing in the fingers (“frog fingers”) and toes.
• Hypercalcemia
   

Now, the lung cancers will be discussed according to their therapeutic categories. 

Lung cancers are divided into two categories in terms of treatment options.

• Small Cell Lung Cancer
  • Chemotherapy/Radiation
• Non-Small Cell Lung Cancer
  • These cancers include squamous cell carcinoma, adenocarcinoma, and large cell carcinoma.
  • Surgery & Chemotherapy
     

The majority of people diagnosed with lung cancer die within that first year of diagnosis. Most lung cancer patients are excluded from surgery. 75% of patients clinically evaluated for surgical resection end up to be non-operable cases, due to different reasons (e.g. heart disease/emphysema patients are not medically capable of surviving surgery). Patients who do not get surgery have a prognosis of 6-15 months of survival. 

The 5-year survival rate is highest for bronchoalveolar carcinoma and lowest for small cell carcinoma. The histologic subtypes of cancer are different for smokers and non-smokers. In non-smoking patients, adenocarcinoma is the 2nd highest cancer diagnosed. These patients are emotionally devastated because they feel as if they’ve been branded as smokers. Interestingly, non-smokers with adenocarcinoma do not have better survival prognoses as smokers with adenocarcinoma.

Benign Lung Neoplasm

Pulmonary Hamartomas are benign tumor-like malformations composed of tissues normally found in the lung (fat, cartilage, and bronchial epithelium) but

in disarray. They can be visualized on chest x-ray.  

Patients are usually in their 30s, and hamartomas usually occur more frequently in men than in women. It composes about 8% of all solitary lung nodules. Removal doesn’t make the condition worse. 
 

Smoking is a time bomb. If it doesn’t cause lung cancer then it will most surely cause emphysema or heart disease!

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