What is small cell neuroendocrine carcinoma?

Small cell neuroendocrine carcinoma is an aggressive type of cancer that arises from neuroendocrine cells, specialized cells found in many organs throughout the body. These cells help regulate important body functions by releasing hormones in response to signals from the nervous system.

Under the microscope, the tumour is composed of very small, round or oval cancer cells that divide rapidly. Because the tumour grows and spreads rapidly, early diagnosis and treatment are important.

Small cell neuroendocrine carcinoma can arise in many different organs. When it develops in the lung, it is called small-cell lung carcinoma, the most common form. When it develops outside the lung, it is called extrapulmonary small cell carcinoma.

Where in the body can small cell neuroendocrine carcinoma arise?

Because neuroendocrine cells are found in many tissues, small cell neuroendocrine carcinoma can develop in many parts of the body. Common locations include the lung, digestive tract, urinary tract, gynecologic organs, and head and neck region. Regardless of where the tumour originates, small cell neuroendocrine carcinoma tends to behave similarly and requires prompt medical attention.

What do small cell neuroendocrine carcinoma cells look like under the microscope?

Under the microscope, small cell neuroendocrine carcinoma has very characteristic features.

The cancer cells in small cell neuroendocrine carcinoma:

• Are much smaller than most normal cells.

• Have scant cytoplasm, meaning very little visible cell body.

• Show fine, grainy chromatin in the nucleus, often described as “salt and pepper.”

• Show many mitotic figures, which indicate that the cells are dividing quickly.

• Often grow in sheets, nests, or diffuse patterns without forming normal structures.

• Frequently show crush artifact, which means the cells appear distorted or smudged. This happens because the tumour is very fragile and can be damaged easily during tissue handling.

Pathologists often use immunohistochemistry to confirm the diagnosis. These special stains highlight proteins typically found in neuroendocrine cells.

What causes small cell neuroendocrine carcinoma?

The exact cause depends on the tumour’s location, but several factors may increase the risk.

For small-cell lung carcinoma, the strongest known risk factor is cigarette smoking. Most cases occur in people with a history of tobacco use. Exposure to secondhand smoke, radon, or certain chemicals can also increase risk.

For tumours arising outside the lung, the causes are less clear. Possible contributing factors include chronic inflammation in the affected organ, certain viral infections such as HPV or EBV, and genetic changes that allow cells to grow uncontrollably. In many cases, no clear cause is identified.

How do pathologists confirm the diagnosis?

Pathologists diagnose small cell neuroendocrine carcinoma by examining a biopsy under the microscope and performing additional tests when needed. These may include immunohistochemistry to detect neuroendocrine proteins, proliferation markers such as Ki-67 to assess tumour growth rate, and molecular tests to look for genetic changes. Because this tumour can resemble other cancers, these tests are important for making an accurate diagnosis.

How does small cell neuroendocrine carcinoma behave?

Small cell neuroendocrine carcinoma is considered a high-grade cancer, meaning it grows and spreads quickly. It can invade nearby tissues and may spread to lymph nodes or distant organs such as the liver, bone, brain, or lungs. Because early spread is common, treatment usually includes systemic therapy, which can treat cancer cells throughout the body. Depending on the tumour’s location, treatment may also include radiation therapy or surgery. Close follow-up is important because the tumour can progress rapidly if not treated promptly.

Why is identifying this tumour important?

A diagnosis of small-cell neuroendocrine carcinoma helps guide urgent and appropriate treatment. This cancer almost always requires systemic therapy, and accurate classification helps doctors choose the most effective approach. Knowing the exact tumour type also helps predict how the tumour is likely to behave and what follow-up may be required.

Questions to ask your doctor

• Where in my body did the tumour start?

• Did the biopsy confirm small cell neuroendocrine carcinoma?

• Has the cancer spread to lymph nodes or other organs?

• What treatment options are recommended for my situation?

• Will I need chemotherapy, radiation therapy, surgery, or a combination?

• How aggressive is this type of cancer in my case?

• What follow-up care or monitoring will I need?