What Does Cancer Look Like?

Biopsy is a scary word because of how closely it’s associated with a cancer diagnosis. If your healthcare provider orders a biopsy, you might be wondering what they’re doing with your tissue and what the pathologists studying your sample are looking for. 

Most types of cancer are diagnosed with the help of a biopsy—a sample of potentially diseased tissue. It can be obtained via needle aspiration, excision, or surgery. The sample goes to a pathology lab, where a specialist doctor (pathologist) looks at the tumor under a microscope to see what its cells look like.

They analyze the cytology and histology of the specimen to identify the type of cancer, its characteristics, and its grade, and they write a pathology report. Your oncologist uses this report, along with your other symptoms and test results, to make a cancer diagnosis, guide treatment, and predict the outcome (prognosis).

If you’re getting a biopsy or want to understand your pathology report better, you might be interested to hear more about cancer cell histology and what cancer looks like. This article dives into the specifics of this process and what the pathologist looks at in the biopsy.

Biopsy and Gross Examination

A biopsy is a sample of potentially diseased or cancerous tissue. Your surgeon might take a biopsy before or during tumor removal surgery.

Healthcare providers take biopsies in several different ways based on the type of tumor they’re sampling:

• The simplest biopsy is a needle guided either by touch or an imaging test to find the tumor. The needle can be thin, as in a fine-needle aspiration biopsy, or a little thicker, as in a core biopsy. 
• Skin can be biopsied directly by cutting away pieces of skin that may be diseased.
• An endoscopic biopsy is when the healthcare provider uses a flexible tube through your mouth or rectum to see and sample the various parts of the respiratory tract and digestive tract. 
• Getting more invasive—your healthcare provider might need to do a laparoscopic biopsy, in which a surgeon passes a small tube into the abdomen through a small cut in the skin.

Samples for analysis may also be obtained during surgery aimed at locating and removing the tumor, such as a laparotomy or lobectomy. Nearby lymph nodes may also be removed to see if cancer has spread or metastasized locally.

The most interesting thing about a biopsy is what happens after it’s taken—the analysis. The sample, which may include the tumor and the surrounding normal tissues, is sent to a histology and pathology lab for evaluation by a pathologist.

The first step in analyzing the tumor sample is gross examination. In medicine, gross means the feature or characteristic can be seen without a microscope.

The gross examination is when the pathologist uses their own senses to examine the tumor and compare it to a healthy organ. The pathologist looks at the sample’s size, color, shape, and consistency, noting anything that looks abnormal.

This information is useful in staging cancer, which is one way that healthcare providers classify how advanced a cancer is. For some types of cancer, the number of tumors, tumor location, and tumor size are all important in deciding what stage the cancer is in.

The pathologist—one of the many unseen members of your healthcare team—takes this information, determines what type of cancer the tumor might be, and analyzes its general characteristics. They also prepare samples for the next step—looking at them under the microscope.

Histology and Cytology

You might hear that your biopsy sample is in the histology and cytology lab. Histology is the study of tissues (groupings of cells that perform a specific function), and cytology is the study of individual cells.

When talking about these in the context of a pathology lab, histopathology is the analysis of abnormal tissues and cytopathology is an analysis of abnormal cells. 

To prepare biopsy samples for microscopic analysis, the pathologist embeds the sample in a wax cube, then slices it into thin pieces to see the individual layers of cells. The samples are then dyed with chemicals that stick to cells with specific characteristics, making it easier to see different cells and structures within the cells. 

At this point, the sample is ready for analysis under a microscope. When the healthcare provider looks at the tissues, they take note of:

• The size and shape of the cells
• The size and shape of the cell’s nucleus, the brain of the cell that holds most of its genetic material
• The arrangement of cells: Do they look as they should in healthy tissue?
• The areas around the edges of the tumor are called the surgical margins. Are they diseased or is there normal tissue at the edge?
• How fast the suspected cancerous cells divide
• How much the tumor has grown into the tissues surrounding it

The pathologist uses these characteristics to determine a cancer’s type, grade, and prognosis.

Cancer Type

Identifying the cancer type is one of the primary aims of histopathology. The cancer type can tell your healthcare provider what types of treatments might work best and what to expect as the cancer progresses. 

A cancer’s type is the kind of tissue that it originated from. Most tissues and organs in the body are made up of many different types of cells that fall into six major categories. When cancers arise from these categories, they’re classified as that type:

• Carcinomas are cancers that come from the epithelial tissue, which is most associated with lining the organs. It’s common in the skin and the lining of the gut.
• Lymphomas are solid tumors arising from cells in the lymph nodes or organs of the lymphatic system, which are found all over the body.
• Myelomas are cancerous growths of plasma cells, a type of white blood cells found in the bone marrow that produce antibodies.
• Leukemia is a cancer of the bone marrow cells that make blood cells, leading to defective white blood cells, red blood cells, or platelets.
• Sarcomas develop from the connective tissue—muscles, bones, fat, cartilage, and tendons. 
• Mixed type tumors have components of more than one cancer type.

To determine which category a certain cancer fits into, the pathologist will do several types of tests on the sample.

Immunochemical (IHC) stains use antibodies that have chemicals attached to them that change color when exposed to a specific solution. The antibodies are created to find, attach to, and color a very specific protein in a cell or tissue sample.

Flow cytometry is a technique used to analyze cells in a liquid sample, like bone marrow, lymph node, or blood samples. Antibodies (like those used in IHC) are used to tag specific types of cells in the sample. The sample containing these tagged cells is passed in front of an energy beam, making the antibodies glow.

The flow cytometry instrument detects the light they’re giving off, telling how much of the sample is made up of those cells the antibody targeted. Sometimes the antibodies will be used to detect cells with proteins called tumor markers, indicating they’re cancerous.

Hematoxylin and eosin (H&E) is a classic stain used in pathology for more than a century. Hematoxylin turns the cell’s genetic material a deep purple color, and eosin turns proteins pink. This combination gives incredible detail in tissue sections, and studies have identified clear staining patterns for different types of cells.

Tumor Grade

When grading a given tissue sample, the pathologist looks at how closely the sample’s cells mirror normal cells. From this information, the cancer cells get graded. If a tumor is low grade, its cells look pretty normal, and the cancer is typically slower growing.

A high-grade tumor is likely to be more aggressive, look less like a normal cell, and spread quickly. Healthcare providers call these undifferentiated or poorly differentiated tumor cells because they lack the features and structures of normal cells and tissues. 

The tumor grades are: 

• GX: The pathologist wasn’t able to determine the tumor’s grade from the sample.
• G1: The cells in the sample are well differentiated, look relatively normal, and the sample is considered low grade.
• G2: The sample shows signs of moderate differentiation and is classified as intermediate grade.
• G3: The cells in the sample are poorly differentiated; the sample is determined to be of a high grade.
• G4: Only a few cancers have a G4 (such as kidney cancer). The sample is undifferentiated, the cells look highly abnormal, and the cancer is classified as high grade.

Several cancers have their own grading systems based on characteristics specific to that type of cancer:

• Breast cancer samples use the Nottingham grading system. This system looks at the appearance of the glandular and duct structure in the tissue and the size and shape of the cell’s nucleus. It also uses the mitotic rate, which is how fast they’re dividing. The system goes from a low grade of 3 to a high grade of 9.
• Prostate cancers use the Gleason scoring scale, which is based on tissue patterns within the biopsy. The scale ranges from 2 (low grade) to 10 (high grade), with X for undetermined. 

The sample’s grade factors into the cancer’s diagnosis, treatment, and staging. 

Molecular and Cytogenetic Studies

The pathology lab might do several additional tests to learn more about your cancer. These cytogenetic studies don’t look at cancer cells per se; they utilize tissue culture and other diagnostic techniques.

These additional molecular and cytogenetic studies can tell your healthcare provider about genetic changes the cells have undergone when they become cancerous, predicting cancer’s behavior as it evolves and deciding which treatments have the best chance of being effective.

For example, changes in the 23 pairs of mega-molecules that hold our genetic material, called chromosomes, can be a major factor in the development of some cancers.

The Philadelphia chromosome is one such change. It happens when chromosomes 22 and 9 swap sections. This change is found in chronic myelogenous leukemia and sometimes in acute lymphocytic leukemia.

Some cancers develop changes in the HER2 gene, which produces an important protein in controlling cellular growth in normal cells. If the cells start making larger than normal amounts of this protein, they can grow more quickly and are more likely to spread. This can guide treatment decisions in breast cancer and stomach cancer.

Some of the tools used in molecular and cytogenetic analyses include:

• FISH: A technique that uses fluorescent tags to determine the positions of genes within a cell’s genome and identify genetic abnormalities in the sample
• Polymerase chain reaction (PCR), including RT-PCR and quantitative PCR—molecular techniques: Gives your healthcare provider more information about the amount of genetic material in the cancer cells
• Southern blot: A way to detect specific DNA sequences that might give insight into abnormalities in the cancerous cells
• Western blot: A way to detect specific proteins or protein segments that might help diagnose a specific type of cancer

Pathology Report

All of the information from these various tests will be compiled into a pathology report. It may take up to 10 days for the tests to be done and analyzed. 

If you’ve been diagnosed with cancer, you can take an active role in your treatment by asking your healthcare provider to walk you through the pathology report, with the aim of better understanding what the histology findings from your biopsy mean. This can help you make more informed choices about your health and actively participate in your treatment decisions.