How Pathologists Influence Treatment for Cancer

Assessing the type and spread of cancer is essential for proper treatment.

Putting their heads together

Yale Medicine pathologists review a scan of a skin lesion: (left to right) Paul Cohen, MD; Rita Abi-Raad, MD; Margeurite Pinto, MD; and Vinita Parkash, MD.

Credit: Robert A. Lisak

Important factors in cancer diagnosis
  • A pathologist's diagnosis often suggests the best treatment.
  • Cancer staging is a way to classify the progress of the disease, though stages vary with each type of cancer.
  • In addition to stage, cancers receive a grade, which may also factor into the recommended treatment plan.
  • Smaller tumors are less likely to become deadly than larger ones.

When someone learns that he or she has cancer, the initial reaction is often shock. Then come the questions: What kind of cancer is it? How bad is it? What sort of treatment will be needed?

At Yale Medicine, a multidisciplinary team of doctors convenes to answer those questions most accurately for each patient. One of those doctors, the pathologist, will never meet the patient but will make a definitive final diagnosis by examining the patient’s tissue samples.

The pathologists gathers information about the disease, gives a name to the cancer, defines how far it has spread, and orders additional tests to determine the most appropriate therapies. The goal is to characterize the cancer so that a patient can receive the best individualized treatment plan–and the best hope for a cure.

How cancers grow

Cancers are believed to start with one errant cell, which divides to produce many like itself. At a certain point, and with each successive division, the cells acquire mutations and become increasingly effective at replicating themselves. They eventually escape the body’s normal control mechanisms and become cancers, growing out of control.

“Generally speaking, cancers first grow bigger where they are, and then spread tentacles into surrounding areas, sometimes choking vital structures,” says Vinita Parkash, MBBS, associate professor of pathology at Yale Medicine. “At later stages, they can enter the blood or lymphatic stream and travel to distant parts of the body, such as the lung and the liver, and grow into a new tumor at this secondary site.” Secondary growth at this new site interferes with the ability of that organ to function normally, says Dr. Parkash. “The more extensively the tumor spreads, the worse it is."

A cancer growing in an organ after spreading from where it originated is called metastatic. This is usually very serious, although the patient may still respond to treatments. In rare instances, such as some testicular cancers, metastatic cancer can be cured.

Cancer staging, analysis performed by a pathologist, is a way to classify a person’s disease in terms of its progress from cancers that are just getting started all the way to those that have spread throughout the body. In general, earlier-stage cancer—Stage I or Stage II—is less serious than a later-stage cancer, typically designated with as Stage III or Stage IV.

Cancer cells can arise in almost any organ, but the staging system is slightly different for each one. For each type of cancer, Dr. Parkash says, “We use a systematic method for staging, so management and understanding of the disease is the same across the world.”

Assessing cancers

Radiologists, surgeons or other doctors may suspect cancer, but the final diagnosis can only be made by a pathologist. Once a cancer is diagnosed, a physician or surgeon can estimate a cancer's stage based on clinical signs and symptoms, and test results such as computerized tomography (CT) or positron emission tomography (PET) scans, or blood tests, in the case of blood cancers. This is called clinical staging. But the most accurate determiniation of stage usually requires the expertise of a pathologist, who examines tissue removed during a biopsy or surgery. 

The pathologist receives the tumor, which has been sampled or completely removed, along with nearby lymph nodes or other tissues, and examines those tissues. Using a microscope, she or he determines whether cancer cells are present and how far they have extended. Sometimes, this assessment is done during surgery.

The pathologist also measures the size of the tumor. It might be smaller or larger than it appeared on imaging studies. “You can have a breast tumor sitting next to a benign fibrotic area in the breast,” Dr. Parkash says. On an ultrasound, they might look like a single lesion, and the size could be overestimated. A pathologic evaluation is necessary to set the two apart and define the size of the tumor. Smaller tumors are less likely to become deadly than larger ones.

The pathologist also determines whether the cancer has been removed completely through surgery or whether it has grown beyond where it started. For instance, says Dr. Parkash, the question may be: “Has a colon tumor gone outside the wall of the colon into the surrounding fatty tissues? Tumors choking nerves or entering blood vessels can only be seen by tissue examination under the microscope, and that’s what we assess.”

Some cancers, such as ovarian cancer, tend to create colonies nearby, so the surgeon may sample areas in the belly to see whether cancer cells are growing there.

The pathologist also often looks for the presence and number of cancer cells in lymph nodes, both of which can also help doctors assess the stage.

Cancer ‘personalities’

Pathologists also examine individual cancer cells and assign them a grade. “This is about the personality of this tumor—how nasty it is,” Dr. Parkash says. Cells might be well, moderately or poorly differentiated. More colloquially, the cancer may be called low, middle or high grade. Well-differentiated, or low-grade, cancers, are less worrisome than poorly differentiated, or high-grade, cancers.

Dr. Parkash explains that a normal cell is very well differentiated because it is specialized for its work, whether it is a liver cell, a lung cell or some other specialized cell. “When cells turn bad, they look different from normal cells,” Dr. Parkash says. 

For example, the nucleus might be three times the expected size, or abnormally shaped. “Normal nuclei are typically rounded or oval in shape,” Dr. Parkash says. “Malignant nuclei will develop angles and elbows and become funny shaped.” The nucleolus, situated inside the nucleus, is typically small in normal cells. “In a malignant cell, it can become really prominent,” she says. “All those things help us define malignant cells.”

Grade doesn’t always play into cancer staging, but the multidisciplinary team considers it when establishing a treatment plan.

Why stage matters

The purpose of staging is to communicate prognosis. This, in turn, directs treatment. Factors a doctor will weigh when offering treatment options include the cancer’s grade, its biology, and the patient’s age and other health conditions.

Cancer treatments such as chemotherapy and radiation can have serious side effects, so doctors use them only when necessary. “We don’t want to give 100 people treatment when only one person might have a recurrence,” Dr. Parkash says. Instead, doctors might closely watch the 100 and treat only the person who has a recurrence. 

Staging is also used in studies to assess treatments of cancers among groups of patients. Survival at the five-year mark can serve as a barometer for how well treatments work.

That said, the overall statistics related to a cancer’s stage say little about individual patients. A patient may be the one in 100 patients diagnosed with a very early stage cancer who eventually succumbs to the disease. Or the patient may be the one in 100 diagnosed with very late-stage cancer who beats the odds. Still, assessment and staging by pathologists are vital to doctors' and patients' understanding of the nature of the disease they face.