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Lung Cancer Grading: How Cancer Cells Look and Behave Compared With Normal Cells

Posted on August 01, 2022
Medically reviewed by
Richard LoCicero, M.D.
Article written by
Aminah Wali, Ph.D.

As part of the diagnostic process for lung cancer, a doctor might discuss cancer cell grading. The grade of cancer refers to how abnormal the cancer cells are, in appearance and behavior, relative to normal cells. There are many tests used to help grade cancer cells, and the results can explain how advanced the cancer is and what treatment options are likely to be effective.

Grading Cancer Cells

To determine the cancer’s grade, a doctor performs a biopsy to surgically remove a tumor or part of a tumor. The tumor sample will then be analyzed under a microscope by another specialist called a pathologist. The pathologist will perform histology on the sample, using laboratory staining techniques to distinguish cancer cells from normal cells in the same tissue.

Based on the appearance and organization of the cancer cells, the pathologist will assign a grade using the following scale:

  • Grade X (undetermined) — The grade cannot be accurately determined.
  • Grade 1 (well differentiated) — Tumor cells look similar to normal cells, are in an organized pattern, and grow slowly.
  • Grade 2 (moderately differentiated) — Tumor cells are somewhat similar to normal cells but have some abnormal features.
  • Grade 3 (poorly differentiated) — Tumor cells are more abnormal and lack regular organization like normal cells.
  • Grade 4 (undifferentiated) —Tumor cells are dividing rapidly and look the most abnormal, no longer resembling normal tissue.

Apart from breast cancer, prostate cancer, and blood cancers, most types of cancer are graded by the same system used to grade lung cancer. A low-grade tumor (grades 1-2) correlates with early-stage disease or slow-growing cancer, whereas a high-grade tumor (grades 3-4) correlates with more aggressive or advanced-stage disease.

Appearance of Lung Cancer Cells

The left panel shows hematoxylin and eosin-stained tissues from normal lung tissue, and on the right is non-small cell lung cancer. Cancer cells are more crowded and are darker due to larger nuclei.
(Medical Images USA, left, Wikimedia Commons, right)


To analyze the appearance of cancer cells under a microscope and determine the cell grade, a pathologist will generally use hematoxylin and eosin (H and E) staining on cells taken from a tumor biopsy. H and E staining allows the pathologist to visualize the shape and organization of the cells, as well as overall tissue structure.

The left panel shows normal lung tissue with hematoxylin and eosin-staining, while the right shows crowded cells of small cell lung cancer. Cancer cells appear darker because of their larger nuclei.
(Medical Images USA, left and right)


After H and E staining, healthy lung cells appear mostly pink and are properly organized to form the normal structures of the lung. In contrast, lung cancer cells appear mostly dark purple due to having large nuclei (the portion of the cell that contains DNA). Cancer cells may also be observed in a crowded, clustered pattern as a result of their irregular growth.

In cancerous lung tissue, cells break through the tissue membrane. (Medical Images USA)


There are many types of cells in the lungs. A pathologist can determine the subtype of lung cancer based on what type of cell has become cancerous and other features that can be seen under the microscope.

Behavior of Lung Cancer Cells

Pathologists can also look at how lung cancer cells appear to be moving and spreading. Unlike normal cells, cancer cells divide rapidly and may migrate to other parts of the body. A pathologist might observe cancer cells moving beyond the normal structures of the lung. This is described as invasive or infiltrating cancer. Invasive lung cancer may spread to nearby lymph nodes or even to more distant organs in a process called metastasis. Invasive cancer is more often associated with tumor cells of a higher grade.

Cancer Grading vs. Staging

Although both are indicators of how the disease is progressing, cancer grading is distinct from cancer staging. Staging is a measure of how advanced the cancer is based on how far it has spread. There are different systems for cancer staging doctors may use, depending on the type of lung cancer.

TNM Staging

TNM stands for tumor, node, metastasis. The TNM staging system is generally used for non-small cell lung cancer (NSCLC), the most common form of cancer, but may also be used for small cell lung cancer (SCLC).

This system takes into account the size of the main tumor (T), if it has spread to a nearby lymph node (N), or if it is metastatic (M) and has spread to other parts of the body.

Limited and Extensive Staging

For SCLC, doctors commonly categorize cancer as either limited stage or extensive stage. In the limited stage of disease, the cancer is located only in a lung or nearby tissues. In the extended stage, the cancer is located throughout the lung and in distant lymph nodes or bones.

How Is Grading Used in Lung Cancer?

Doctors use cancer cell grading to better understand how lung cancer might grow and spread, so they can decide on the most effective treatment plan. A high-grade tumor calls for a more aggressive treatment strategy to keep disease from spreading.

Grading is also used to inform the prognosis (outlook) of lung cancer. Low-grade tumors are associated with a better prognosis, while high-grade tumors have worse overall survival. Determining the cancer grade and stage is an important part of the diagnostic process to ensure people with lung cancer have the best chance of survival.

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Richard LoCicero, M.D. has a private practice specializing in hematology and medical oncology at the Longstreet Clinic Cancer Center, in Gainesville, Georgia. Review provided by VeriMed Healthcare Network. Learn more about him here.
Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here.

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