Testing Biopsy and Cytology Specimens for Cancer

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What do doctors look for under the microscope?

General principles

Over 100 years ago, scientists realized that various tissues and organs look different from each other under a microscope. This is because they are formed by different cell types and because the cells are arranged differently. Even more importantly, it was discovered that the usual appearance of each type of tissue or organ is changed by diseases like cancer. During the past century, this science, known as pathology, has advanced greatly.

Most tissue and cell samples are looked at by pathologists – doctors with special training in diagnosing diseases by lab tests. Sometimes, other doctors will also examine specimens or tissues of organs related to their area of expertise. For example, hematologists often look at blood and bone marrow samples from their patients and some dermatologists will look at their patients’ skin biopsy specimens.

Some features that doctors look for under a microscope are important only when found in 1 or 2 types of tissue, while others are more important if found in almost all tissues.

Here are a few general concepts explained in less technical terms to help you to better understand how doctors decide whether cancer is present.

Size and shape of the cells

The overall size and shape of cancer cells are often abnormal. They may be either smaller or larger than normal cells. Normal cells often have certain shapes that help them do their jobs. Cancer cells usually do not function in a useful way and their shapes are often distorted. Unlike normal cells that tend to have the same size and shape, cancer cells often are very different in their sizes and shapes.

Size and shape of the cell’s nucleus

The size and shape of the nucleus of a cancer cell is often abnormal. The nucleus is the center of the cell that contains the cell’s DNA. The nucleus is surrounded by cytoplasm. Imagine looking at a fried egg, in which the central yolk is the nucleus and the surrounding white is the cytoplasm (this is only a way of picturing cells, and does not truly reflect what cells are made of).

Cancer cells typically have a nucleus larger than that of a normal cell. And, like the overall cell size and shape, the size and shape of the cell nucleus is usually much the same among normal cells of each tissue, but can vary greatly among cancer cells. Another feature of the nucleus of a cancer cell is that after being stained with certain dyes, it looks darker when seen under a microscope. The nucleus from a cancer cell is larger and darker because it often contains too much DNA.

Arrangement of the cells

The arrangement of normal cells reflects the function of each tissue. For instance, cells can form glands that produce substances that are taken to other parts of the tissue. Gland tissue in the breast, which produces milk during breastfeeding, is organized into lobules and ducts that carry milk from the lobules to the nipple. Cells of the stomach also form glands, to produce enzymes, acid, and mucus that digest the food and protect the stomach lining.

When cancers develop in the breast, stomach, and many other tissues, the cancer cells do not form glands as they should. Sometimes the cancer cells form abnormal or distorted glands. Sometimes they form cell clumps that do not look like glands at all.

Cancer cells grow into (invade) other tissues. Normal cells stay where they belong within a tissue. The ability of cancer cells to invade reflects the fact that their growth and movement is not coordinated with their neighboring cells. This ability to invade is how cancer spreads to and damages nearby tissues. And, unlike normal cells, cancer cells can metastasize (spread through blood vessels or lymph vessels) to distant parts of the body, too. Knowing this helps doctors recognize cancers under a microscope, because finding cells where they don’t belong is a useful clue that they might be cancer.

The type of cancer

There are several basic kinds of cancers, which doctors can further classify into hundreds or even thousands of types, based on how they look under a microscope. Cancers are named according to which type of normal cells and tissues they look like most. For example, cancers that look like glandular tissues are called adenocarcinomas. Other cancers that resemble certain immune system cells are called lymphomas, and those that look like bone or fat tissue are osteosarcomas and liposarcomas, respectively.

Grading the cancer

While identifying the cell type or tissue a cancer looks like, doctors also decide how closely they look like the normal cells or tissues. This is the grade of the cancer. Cancers that look more like normal tissues are called low grade, and those that do not look much like normal tissues are high grade. A high-grade cancer tends to grow and spread faster than a low-grade cancer. Patients with high-grade cancers tend to have a poorer prognosis (outlook).


Last Medical Review: 01/29/2013
Last Revised: 03/07/2013