Non-small cell carcinoma


Non-small cell carcinoma is a general term doctors use to describe a large group of cancers composed of large, abnormal-looking cells. Most of the time, this term refers to cancers that originate in the lungs, although it can also be used to describe cancers that begin in other parts of the body.

About 85% of all lung cancers fall into this group. Compared to another type of lung cancer called small cell carcinoma, non-small cell carcinoma usually grows and spreads more slowly. This distinction is very important because treatment options and outlook (prognosis) are different depending on whether the cancer is small cell or non-small cell.

What are the types of non-small cell carcinoma?

Doctors and pathologists categorize non-small cell carcinoma into several main types based on the type of cell where the cancer originated and its appearance under the microscope.

Adenocarcinoma

Adenocarcinoma is the most common type of lung cancer. It starts in gland-forming cells, usually found in the alveoli, which are the tiny air sacs in the lungs where oxygen enters the blood and carbon dioxide is removed. Adenocarcinoma is especially common in people who have never smoked.

Squamous cell carcinoma

Squamous cell carcinoma starts in squamous cells, which are thin, flat cells that line the inside of the airways in the lungs. This type of lung cancer is strongly linked to smoking and is often found in the central areas of the lungs near the larger airways.

Large cell carcinoma

Large cell carcinoma is the name given to lung cancers that do not fit neatly into the other categories. Under the microscope, the cells look unusually big and abnormal. Large cell carcinoma tends to grow and spread more quickly than adenocarcinoma or squamous cell carcinoma, which can make it harder to treat.

When is this diagnosis made?

In most cases, the first diagnosis of non-small cell carcinoma is made after a biopsy. The sample may be taken during a bronchoscopy (a thin tube with a camera that looks inside the airways), with a fine needle through the chest wall, or during surgery.

A pathologist examines the tissue under the microscope to determine if the tumor is a type of non-small cell carcinoma and, if possible, to identify the subtype. Because the amount of tissue in a biopsy is limited, the pathologist may only be able to say that the tumor is non-small cell carcinoma without confirming the exact subtype.

For this reason, doctors often recommend collecting more tissue later, either through a larger biopsy or during surgery. A bigger sample allows the pathologist to confirm the subtype, perform molecular tests, and provide more complete information that guides treatment.

Other tests that may be performed to confirm the diagnosis

Immunohistochemistry (IHC)

Pathologists often use immunohistochemistry (IHC) to help determine the type of non-small cell carcinoma. IHC is a special test that uses antibodies to look for specific proteins inside the cancer cells. The pattern of proteins can help distinguish between different subtypes of cancer.

For example:

  • TTF-1 and Napsin A are commonly positive in adenocarcinoma.

  • p40 and p63 are markers that support a diagnosis of squamous cell carcinoma.

  • Cytokeratins (CK7 and CK20) can also help show the origin of the tumor.

IHC is especially useful when the biopsy sample is very small or when the cancer cells look unusual under the microscope.

Molecular tests

Molecular tests look for changes in the DNA or proteins of the cancer cells. The most advanced method is called next-generation sequencing (NGS). This test can examine many genes at the same time to look for mutations or rearrangements that may guide treatment.

Commonly tested genes and results include:

  • EGFR mutations, which may respond to drugs called tyrosine kinase inhibitors.

  • ALK or ROS1 rearrangements, which can also be treated with specific targeted drugs.

  • KRAS mutations, including KRAS G12C, which may guide the use of new targeted therapies.

  • BRAF mutations, which can respond to targeted treatments.

  • PD-L1 expression, which helps predict whether immunotherapy will be effective.

These results are very important because they help doctors choose the treatment most likely to work for each patient’s cancer.

Questions to ask your doctor

  • What type of non-small cell carcinoma do I have (adenocarcinoma, squamous cell carcinoma, or large cell carcinoma)?

  • Do I need another biopsy or surgery to get more tissue for testing?

  • What stage is my cancer, and what does that mean for treatment?

  • Were any molecular tests performed on my tumor? If so, what were the results?

  • What treatment options are available for my specific type and stage of cancer?

A+ A A-