Understanding Your Diagnosis

Having a clear understanding of your diagnosis is your starting point. (As you move through the diagnostic process -- from detection of your cancer to, perhaps, surgery -- you'll learn the details of your unique situation.) Here are the essential components of a complete cancer diagnosis:

• The name of your cancer, which usually includes its type.
• The cancer grade, which conveys how your cancer cells are likely to behave.

If you're missing any of these pieces of information, ask your doctor about it. Your doctor should take the time to discuss each diagnostic finding and explain its impact on your treatment and prognosis.

Questions to Ask Your Doctor

The basic questions to ask about your diagnosis are:

• What is the medical name of my cancer?
• What is the type and subtype, if any?
• What stage is my cancer?
• What grade is my cancer?
• Are there any other prognostic indicators present?
• Are there any characteristics which may influence the course of the disease or affect treatment options?

It's useful to have a good dictionary, such as The Cancer Dictionary (Checkmark Books, 1999) or at least a general cancer book with a good glossary, such as Everyone's Guide To Cancer Therapy (Summerville House, 1998). On the Internet, the National Cancer Institute (cancernet.nci.nih.gov) and the American Cancer Society (www.cancer.org) have extensive glossaries.

Don't be shy to ask the doctor your questions. It will alleviate confusion down the road.

What's in a Name
It's often said that cancer is actually 400 different diseases, so it's no surprise that the names of each type and subtype can become complicated. It may help to think of the name as a puzzle that you're going to take apart. You're going to learn what each piece means and how, when it's put together with the others, a unique picture of your cancer is created. For instance, take a four-part name like "ductal breast carcinoma in situ."

Breast is the easy part. The name of the primary site, the organ in which the cancer originates, is typically part of its name. (However, there are exceptions. Paget's Disease is a type of breast cancer that involves the nipple. Wilm's Tumor is a kind of kidney cancer.)

Carcinoma is a malignancy that arises from the lining of an organ. It's one of several very broad categories of cancer. Another type of cancer is sarcoma, which is a malignancy in connective tissue, bone, or muscle. Others general types are leukemia, cancer of the organs that make blood; lymphoma, cancer in the lymphatic system; and myeloma, in the plasma cells in the bone marrow.

Ductal means the abnormal cells arise in a duct, or milk passage, draining a lobule. (In contrast, lobular breast carcinoma in situ, means the cancer started in the lobule, or milk gland, itself.) Although the name may not include what kind of subtype the cancer is, in some cases like ductal breast carcinoma, it's useful to know what the subtype is because it may affect the prognosis and, therefore, the treatment choices. For example, a "comedo" form of breast cancer is an aggressive subtype.

In situ means the cancer is confined to the area from which it started. It is not yet invasive, which would mean the cancer has broken through the wall of the duct or lobule where it began and entered the surrounding tissue, from where it could spread. When malignant cells do spread beyond the initial site, say from the breast, to another organ such as the lungs, it is said to be metastatic. However, keep in mind that regardless of where a metastatic lesion is found, the cancer retains the name of its primary site, which is where it began. So a metastatic lesion in the lung from a breast cancer is called metastatic breast cancer, not lung cancer, even when the lung is where the cancer is first detected.

Cancer Stages
There are several different systems used to describe how far a cancer has progressed at the time it is detected. The classification system used for most solid tumors was devised by the American Joint Committee on Cancer (AJCC) and is based on the concept that cancers in the same site have similar patterns of growth and spread. To determine the stage, the physician includes information about the cancer's clinical and pathological stages. The clinical stage is based on non-surgical diagnostic techniques, such as the doctor's physical examination of you and imaging and blood tests. The pathological stage uses information from excision of the tumor and examination of the surrounding region and lymph nodes.

The AJCC classifies cancer according to the TNM system: "T" represents the size of the tumor. "N" designates the presence and extent of the cancer spread to lymph nodes in the region. "M" indicates the presence of a spread beyond the region -- that is, a regional metastasis. A subscript number and sometimes a letter give more specific information. The TNM designation is then categorized into one of five stages, from the smallest non-invasive cancer, Stage 0, to the most advanced, Stage 4.

Certain cancers, such as cancer of the colon and gynecologic cancers are staged according to other systems in addition to the TNM system. Colon cancer is sometimes staged according to the Duke's staging system, devised by the British pathologist Cuthbert Dukes. A new staging system for ductal breast carcinoma in situ that includes whether necrosis (an area of dead cells) is present and the grade of the cells has been proposed, but its usefulness has not been proven. And some staging systems are quite simple and depend on whether the tumor can be removed surgically or not. For example, while pancreatic cancer is staged according to the TNM system, surgeons prefer to classify it as resectable, meaning the tumor can be removed, locally advanced or unresectable, and metastatic.

Cancers such as leukemia, that don't form solid tumors, use another staging system based on factors pertinent to that disease, such as the extent of bone marrow involvement.

There are several ways to learn more about cancer stages. The Manual for Staging Of Cancer (J.B. Lippincott), available at any medical library, provides very precise staging descriptions of solid tumors. Most good cancer compendiums, such as Informed Decisions (The American Cancer Society, 2001), include a a discussion of staging, but cancer-specific books, such Women and Cancer (American Cancer Society, 1999) or Prostate Cancer (American Cancer Society, 1999), give greater detail. Descriptions of cancer stages are also provided in the discussion of individual cancers on the American Cancer Society Web site (www.cancer.org), the University of Pennsylvania Web site (www.oncolink.com), and in the specific PDQ patient statements on the National Cancer Institute Web site (www.nci.nih.gov).

Grade One of the most important elements of your diagnosis is the cancer grade because it conveys how aggressive the cancer is. The grade is determined by a pathologist, based on a microscopic examination of tissue from the tumor. Anna Graham, president-elect of the American Society of Clinical Pathologists, explains that a pathologist evaluates three major components. "The first is how the individual cells look. Are they very different from normal? The second is the tissue pattern. How well does the pattern of cells resemble the normal architecture of breast tissue? The third is the cells' mitotic rate. What proportion of the cells are actively dividing? When you put these three together you know how deviant the cells are and whether they are responding to normal signals to form the structures they are supposed to."

After evaluating each of these factors, the pathologist classifies the cancer in order of severity as Grade 1, 2, 3 or 4. Grade 1 is sometimes referred to as "low grade," the least aggressive, and Grade 4 as "high grade," the most aggressive. GX means the grade cannot be determined.

You may also hear the word differentiated used to describe your cancer cells, as in well differentiated, moderately differentiated or poorly differentiated. This describes how mature the cancer cells are, how similar they are to healthy cells from the same tissue. Sometimes the term is used interchangeably with the cancer grade. For instance, a Grade 1 tumor is usually well differentiated, slower growing, and less likely to spread than a Grade 4, undifferentiated tumor.

Grading is so important in making treatment decisions that you may want to consider a second pathology opinion. At some medical centers all tissue samples that prove to be malignant are examined by more than one pathologist as part of a quality assurance program. Confirm with your doctor that this was done.. If it wasn't, or if you want another opinion from another institution, your physician can help you arrange this.

Although some sources recommend that you keep a slide of your tissue and/or the block of the paraffin in which the tissue is embedded, Dr. Graham believes it's much safer for the specimen to remain stored in the laboratory. If you want a second opinion, the original laboratory will package it properly and send it directly to the other lab, she says.

Other Prognostic Indicators
In recent years other molecular and genetic indicators, sometimes called prognostic factors, have been identified. Hormone receptors are one of the indicators routinely used in diagnosing breast cancer. If the cancer is said the be ER-positive, it means that the surface of the breast cancer cells is studded with molecules that attach to estrogen. These estrogen receptors (ER) stimulate cancer cell growth. Similarly, it may have progesterone receptors (PR), which make it PR-positive. Today ER and PR assays are routinely done on all breast cancer tumor tissue.

Although not yet a routine test, it is possible to identify a protein that is sometimes overproduced by a gene in breast cancer cells called HER-2/neu. Women with higher levels of the HER-2/neu protein may have a poor prognosis because it stimulates cancer cell growth. They may respond to a drug called Herceptin, which disrupts the growth of cells that have too much of this protein.

The aggressiveness of a cancer can also be evaluated with tests that look at the DNA of the cells. A technique called flow cytometry measures how much DNA is in a cell. It can also measure how many cells are dividing. These tests are expensive and require special equipment and may not be available at the hospital where you are treated. If not, you could ask your doctor whether this information would be useful to your diagnosis or if it will make a difference in your treatment options. If so, a sample of your tumor tissue can be sent to a laboratory that does the test.

When Is a Diagnosis Complete?
Newer tests to fine-tune a diagnosis are being developed. And as treatments evolve which will zero in on specific molecular behavior within the cancer cells, knowing these prognostic factors will become more important. But for now, with a few exceptions -- like estrogen and progesterone receptors in breast cancer --pathologist Dr. Graham says, "The gold standards for predicting prognosis and the best therapeutic approach to take are still the same as they were 20 or 30 years ago. The criteria depend on the size of the tumor, what kind of tumor it is, what grade it is, and the status of the lymph nodes. "