What do doctors look for in biopsy and cytology specimens?

General characteristics

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, diseases like cancer change the usual appearance of each type of tissue or organ.

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 (doctors who specialize in blood disorders) often look at blood and bone marrow samples from their patients, and some dermatologists (doctors specializing in skin diseases) will look at their patients’ skin biopsy specimens.

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

Here are a few general concepts explained in less technical terms to help you better understand how doctors decide if 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 vary in their sizes and shapes.

Size and shape of the cell’s nucleus

The nucleus is the center of the cell that contains the cell’s DNA. The size and shape of the nucleus of a cancer cell is often abnormal. Typically, the nucleus of a cancer cell is larger and darker than that of a normal cell and its size can vary greatly. 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 make substances that are taken to other parts of the tissue. Gland tissue in the breast, which produces milk during breastfeeding, is organized into lobules where the milk is made, and ducts that carry the milk from the lobules to the nipple. Cells of the stomach also form glands, to make enzymes and acid that digest the food, as well as mucus that helps 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 don’t 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 don’t 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).