Biopsy: What the Diagnosis Means

The pathologist has just looked under the microscope at 12 tissue samples from your prostate. What’s in there? First, there are normal cells. Pathologists can tell that they’re normal, because they are round and uniform, with well-defined edges As cancer progresses, the cells he cancer gets more aggressive,clumps of algae

But wait – there’s more! A sample of prostate cells might also include “atypical” cells, which are a big question mark. They’re not normal, but the pathologist can’t definitely report that they’re cancerous, either. They’re just suspicious.

Note: This is one reason why you may want to get a second opinion on your biopsy slides from a pathologist who is an expert in prostate cancer. Having your slides sent to another pathologist is a lot cheaper than having a repeat biopsy just to get more conclusive information.

Your biopsy might also show cells called “high-grade PIN(PIN stands for “prostatic intraepithelial neoplasia”). These are abnormal cells. They’re not benign, and they’re not cancerous themselves; however, Nobody really knows what to do with ome evidence suggests that high-grade PIN might actually be cancer. However, other studies have shown that some PIN might be reversible with diet. Currently, if a man’s biopsy shows the presence of high-grade PIN, his urologist will probably want to do a repeat biopsy

The Gleason Score: The cells within the prostate are so chaotic that it wasn’t until the 1960swhen a pathologist named Donald Gleason, using the low-powered microscope of the day, came up with a brilliant solution – that someone figured out a way to the cancer. Basically, Gleason said, you can’t make sense of every single cancerous cell, but there seem to be some identifiable patterns here. He labeled each cancer pattern 1 through 5. Which pattern was the most common? Which pattern was second most common? Gleason figured out that if he added those two types together, this score, now known worldwide as the Gleason score, would be a pretty accurate way to determine how aggressive the cancer cells are.

Gleason’s original system had more than 25 different possible combinations. That has just been simplified into a new system, called “grade groups,” by Jonathan Epstein at Johns Hopkins. The World Health Organization has accepted Epstein’s new system, and your hospital may already be using it. Here’s what you need to know:

Grade Group I: Gleason score 3 + 3 = 6. Gleason 6, according to renowned Johns Hopkins urologist Patrick Walsh, M.D., “is as good as it gets.” Epstein describes cancer in Grade 1 as having “an indolent nature, and no metastatic potential.” Many men in this category can safely choose active surveillance.

Grade Group 2: Gleason score 3 + 4 = 7. Some men in this category may also be candidates for active surveillance, or for radiation therapy instead of surgery, depending on their age, extent of cancer, and general health.

Grade Group 3: Gleason score 4 + 3 = 7. The score is the same, but there is a difference – more pattern 4 than 3 – and this cancer needs to be treated with surgery or radiation.

Grade Group 4: Gleason score 8.

Grade Group 5: Gleason scores 9-10.

These are high-grade tumors. In the past, Gleason scores 8-10 were combined, but Epstein separated them because they have significantly different prognoses.

Now, what does all this mean? In an ideal world – one where men start getting screened for prostate cancer in their forties – prostate cancer is caught early. Let’s say a 58-year-old man, who otherwise is in very good health, is diagnosed with Gleason 6 disease. “If he has surgery, and we look at his prostate and there’s nothing but Gleason 6 cancer, that man is effectively cured,” says Johns Hopkins urologic pathologist Angelo De Marzo, M.D., Ph.D. One recent Johns Hopkins study showed that out of 14,000 men who had surgery and were found to have Gleason 6 cancer confined to the prostate, “zero of those 14,000 men had lymph node metastases.o one at Hopkins has ever died of prostate cancer if he had Gleason 3 + 3 cancer.”

In fact, some doctors have been questioning whether Gleason 3 + 3 disease should even be called cancer. Not so fast, says De Marzo, for one very important reason: “The malignant potential seems like it’s not there, but there are lots of reasons to keep calling it cancer, and the biggest one is that if men have Gleason 6 on their biopsy, and you take out their prostate, between 20 and 40 percent of them will actually turn out to have a higher-grade tumor. The biopsy missed it.”

Another important reason is uncertainty: Does the cancer change over time? Say a man has Gleason 6 cancer on a biopsy, and a year later, Gleason 7 is found. You might think, “Well, that Gleason 7 was there all the time, and it was just missed.” But are you sure? Nobody knows the answer to this question for certain. “There are some suggestions that cancer grade can progress,” says De Marzo. “Theoretically, it can happen. We just don’t know what fraction of the high-grade cancers started out as low-grade.”

It’s like those drawings you may have seen of the “Evolution of Man,” where there’s an ape, then a Neanderthal-type knuckle-dragger, then a basic human. Does high-grade cancer spring forth as a Gleason 9? Or did it start out as something that’s easier to treat?

In the future, De Marzo believes, we will be able to make much betterinformed decisions. Some blood tests using molecular tools can help determine whether cancer shows aggressive potential; De Marzo anticipates that urine tests will prove even more helpful. “The prostate is directly connected to the urinary system. I think urine will eventually beat blood as a test, in a few years.” One such test is called PCA3he basic PSA test is prostate-specific, but not cancer-specific. PCA3 is cancer-specific. Although it is not meant to replace the PSA test, it can be used as another test to help determine if a repeat biopsy is needed. If the PCA3 score is low, the odds of a positive biopsy are lower.

Molecular-based tests won’t replace the Gleason grading system, De Marzo notes. But they will add to it, reducing unnecessary biopsies, making biopsies smarter by targeting where to stick the needle, highlighting aggressive cancer that needs to be treated, and helping give peace of mind to men who truly have indolent cancer that may not ever need to be treated.

The Gleason score, based on what the cells actually look like, is like a mug shot of cancer. So think of a bunch of mug shots, hanging on the wall of shame at the Post Office. The biggest problem here is that not all pathologists are equal in their ability to look at thousands of mug shots and say, “that one’s a criminal,” or “that one’s not reallysuch a bad guy.” Nationally, there’s a big variability in the expertise of the pathologist reading prostate biopsies,” says De Marzo. “It can be very difficult. But it’s not good to have a situation where not all patients get their biopsy read by a true expert.” Molecular tests will help make sure that “everyone gets the same answer. You can’t argue with the future of molecular testing. It will help level the playing field.

But the biggest key to understanding what’s actually in the prostate, says De Marzo, is going to be better imaging.

Terms to know from this article:

Pathologist

A doctor who identifies diseases by studying cells and tissues under a microscope.

Biopsy

The removal of cells or tissues for examination under a microscope. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fine-needle aspiration.

Grade

The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer.

Prostatic

Of or pertaining to the prostate gland.

Intraepithelial

Within the layer of cells that form the surface or lining of an organ.

Neoplasia

Abnormal and uncontrolled cell growth.

Benign

Not cancerous. Benign tumors do not spread to tissues around them or to other parts of the body.

urologist

A doctor who has special training in diagnosing and treating diseases of the urinary organs in females and the urinary and reproductive organs in males.

Gleason

Gleason Score (GS) - Gleason Grade: A system of grading prostate cancer cells based on how they look under a microscope. Gleason scores range from 2 to 10 and indicate how likely it is that a tumor will spread. A low Gleason score means the cancer cells are similar to normal prostate cells and are less likely to spread; a high Gleason score means the cancer cells are very different from normal and are more likely to spread.

Active Surveillance

Active surveillance is an option offered to patients with very low-risk prostate cancer (low grade, low stage, localized disease). Patients are monitored carefully over time for signs of disease progression. A PSA blood test and digital rectal exam (DRE) and prostate biopsy are performed at physician-specified intervals. Signs of disease progression will trigger immediate active treatment.

Malignant

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

Grading

A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions.

Lymph

The clear fluid that travels through the lymphatic system and carries cells that help fight infections and other diseases. Also called lymphatic fluid.

Tumor

A mass of excess tissue that results from abnormal cell division. Tumors perform no useful body function. They may be benign (not cancerous) or malignant (cancerous).

PSA

prostate-specific antigen (PSA): A substance produced by the prostate that may be found in an increased amount in the blood of men who have prostate cancer, benign prostatic hyperplasia, or infection or inflammation of the prostate.

Janet Farrar Worthington is an award-winning science writer and has written and edited numerous health publications and contributed to several other medical books.

In addition to writing on medicine, Janet also writes about her family, her former life on a farm in Virginia, her desire to own more chickens, and whichever dog is eyeing the dinner dish.