the inner surface of the bone, may be needed. This involves basically the same type of procedure but with a slightly different needle. In any event, you can think of these bone marrow tests as, basically, biopsies of the blood-making site.
WHAT A TISSUE DIAGNOSIS MEANS
In the great majority of cases—there are a very small number of exceptions—the whole plan of treatment and the discussions about your condition and your plans, is based on the pathologist’s examination of the biopsy under the microscope. That is what is meant by the phrase tissue diagnosis, having the actual cancer cells under the microscope. Broadly speaking, there are four main clinical settings possible with the biopsy.
First, a biopsy has been taken and the result is clear. This is the most common situation. You have had a lump in the breast. Or a bronchoscopy was done to investigate a shadow on your chest x-ray and an abnormality was found. The pathologist will examine a piece of the abnormal area. In most situations this process takes a few days. Remember, now, what I’ve said before about the way cancers behave and the rate at which they change. Although a few days may feel like a very long time, it is of enormous importance that the tissue sample be carefully examined, and it is genuinely worthwhile taking the necessary amount of time to ensure the result is trustworthy. As one of my patients said about the expertise of the pathologist, ‘You need a really good map-reader in order to trust the “You Are Here” sticker.’
In the majority of situations, the result of the biopsy is conclusive. The pathologist’s report analyses literally dozens of different features of the cells and can state with certainty whether or not there are cancer cells present and, if there are, the way they are arranged. The pathologist analyses many features about the cells’ appearance, important features that have been shown partly to predict how the cancer is going to behave.
The most important of those features are usually:
The type of the cancer, meaning which tissue it started in. This is important because, for example, cancer of the breast that has spread to the lung still behaves like cancer of the breast and is sensitive to the kind of treatment used for cancer of the breast. If cancer of the lung has spread to the bone or the liver, for example, it will still behave like cancer of the lung.
The type of tumour is also significant, and there are many subtypes of tumour. Examples include whether the cancer is forming glands, makes mucus, whether the cells are small (very important in lung cancers and lymphomas), or flat like skin cells (squamous). Sometimes (but not always) the subtype of the cancer influences the way it behaves and this may help decide how the cancer should be treated (its response to chemotherapy, for example).
The size of the cancer, and—for some kinds of cancer, for example, the bowel and the uterus—how deep into the surrounding normal tissue it invades. The pathologist may be able to determine the depth of invasion, which may make a huge difference to the whole treatment approach (in uterine cancer, vulva cancer and melanomas, for example). She or he may also look at whether the cancer has spread into lymph vessels or capillaries or into nearby lymph nodes. If a specimen has been removed surgically, the pathologist can check the margins and if cancer is still present at the borders, more surgery may be needed.
The grade of the cancer, meaning how aggressive it looks under the microscope. The way a cancer is graded varies from site to site. Pathologists all over the world look at certain standard features of the cancer cells and can correlate these with the way the cancer behaves, as a result of large numbers of research studies looking at those features and the outcomes. For example, they look at how many features of the original normal cells are still there in the cancer cells. If most of them are there, the tumour is well differentiated or low grade. If very few original features remain, the cancer is poorly differentiated or high grade. Low-grade tumours usually grow more slowly and have a lesser tendency to spread. High-grade tumours are usually more aggressive and have a greater tendency to spread to other parts of the body and may be under the microscope invading through normal barriers (basement membranes) or into blood vessels of lymph vessels.
Some features are common to most cancers—for example, very big nuclei occupying most of the cell, and many cells being seen in the process of reproducing—and the pathologist will measure the size or rate of these features. But some features are specific to a particular type of cancer cell. So the grading system for cancer of the breast, say, is similar to, but not the same as for brain tumours.
Usually, the pathologist can also determine much more than that. She or he can take slides of the tumour and stain them with different antibodies that bind to different kinds of molecular patterns on the cancer cells. For example, special stains can be used on breast cancer to see if there are oestrogen or progesterone receptors on the cells; if these are present, hormone therapies have a high chance of being effective. Stains can also reveal other molecular groups. For example, again in breast cancer, if an antigen (molecule) called her2/neu is present, the pathologist knows that the cancer may grow more quickly, but also that the cancer cells are susceptible to the drug Herceptin (trastuzumab). Some of the many other stains used by pathologists are to detect: mucin, which may indicate certain types of bowel, stomach and ovarian cancers; cytokeratin-7 and cytokeratin-20, often found on colon and ovarian cancer cells; CEA, found in many colon cancer and breast cancer cells; calretinin, found on the rare cancer, mesothelioma; and melan-A, found only on melanoma cancers.
With most biopsies, the pathologist can determine clearly what type of cancer is present and how aggressive, or what grade, it is. Sometimes, however, the result isn’t clear, and this can be very upsetting to you and your family. So let’s take some time to discuss what ‘We don’t have the full answer yet’ actually means. This brings us to the second clinical setting after a biopsy.
Second, a biopsy has been taken but the result is not clear. ‘You’ve got the piece of abnormal tissue right there under the microscope. Why can’t you tell what it is?’ When you first think about it, it might seem that a biopsy should always yield a definite and certain answer. But there are several situations in which a definitive answer isn’t clear. Think of analysing handwriting. If the sample of the writing includes a variety of letters and flourishes, the analyst may well be able to identify the writer. But if the sample is only a fragment, it becomes increasingly difficult.
It’s worth considering a couple of examples, because this result, naturally enough, causes so much distress.
There are some cancers that under the microscope appear to be so dormant and slow growing that it is actually difficult to determine whether they are truly cancers or not. One example is borderline tumour of the ovary.
In other cases, the cancer cells may have lost so many of the features of the cells from which they originated that it is not possible to say with certainty where the tumour started. In fact between 5 and 10 per cent of all cancers fit into this category and some are known as cancers of unknown primary—it can be seen that the cancer cells form little gland-like formations or have other features, but have lost all of the identifying features of the tissue that they started from (e.g., lung, bowel or breast). It’s important that you know about that, because many people, when they hear the diagnosis of unknown primary, think that this simply means the pathologist is not very good.
In an increasing number of cases these days, much more information can be gained by using special stains. If the cells have oestrogen receptors, for example, it is quite likely that the cancer originated from the breast.
Third, a biopsy has not yet been taken and the diagnosis is based on the results of a test. If one of the tests that you had suggests a cancer diagnosis but a biopsy has not yet been done, then this period of waiting is naturally going to be filled with anxiety. It can hardly be otherwise. As one patient put it, ‘It’s the feeling of not having anything to go on that knots you up. You almost long for news, whether it’s good or bad, because it’s better to know than not know.’
Almost everybody can understand those types of feelings. If you don’t know whether there is something serious going on or not, then you don’t know how to prepare yourself, or even what to prepare yourself for. You are genuinely