Why give light to a man of grief?
Why give life to those bitter of heart,
who long for a death that never comes.
Believe me, God neither spurns a stainless man,
nor lends his aid to the evil.
Once again your cheeks will fill with laughter,
from your lips will break a cry of joy.
From a drop of water, a logician could infer the possibility of an Atlantic or a Niagara without having seen or heard of one or the other. So all life is a great chain, the nature of which is known whenever we are shown a single link of it. Like all other arts, the Science of Deduction and Analysis is one which can only be acquired by long and patient study, nor is life long enough to allow any mortal to attain the highest possible perfection in it.
Sherlock Holmes, in A. Conan Doyle's A Study in Scarlet
A portion of the tumor that the surgeon has taken out sits in a jar of formaldehyde in the pathologist's laboratory. The tumor is now about as malignant as a dill pickle. A portion of this pickled tumor will be processed and sliced tissue paper thin. It will be stained and then looked at through a microscope. Depending upon the appearance of this little piece of tissue, a number of inferences will be drawn in true Sherlock Holmes style. From the appearance of the tumor under the microscope, the pathologist will give it a name. The name will infer what its properties would have been had this tumor remained in the individual. It will also infer what will probably happen to the individual if some of this tumor is still left in his body. Biologists also look at living tissues, and can learn a good deal from them. What we really want to know is how the living cells behave, not how dead cells look. It is possible to infer from the appearance of the dead tissue what occurred when it was alive. Since this is technically much
simpler than the use of living tissues, the use of stained dead tissue is the tool of choice of the pathologist.
The process of deducing what the tumor on the microscope slide is goes somewhat this way: The pathologist knows, to begin with, that it is a lump of a specific size in a specific area. The fact that it is a lump and that it doesn't belong there tells him immediately that it is abnormal. The next question is, What caused the lump? There are many things that can cause the appearance of a lump, such as an infection, a foreign body (a splinter or a piece of glass), or a tumor. Infection and the reaction to a foreign body result in the appearance of certain specific types of cells, and a specific pattern of distribution of the cells. After he has ruled out infection or foreign body reaction, generally the only thing left is a tumor. He then asks how much does this tissue deviate from what would normally be in this area. If the deviation is small (the cells look relatively normal in size and shape, and the pattern in which they are distributed is also normal), the tumor is usually of the benign variety. Malignant tumors often tend to have cells that look bizarre, and the ways in which they are distributed do not conform to the normal pattern for the particular tissue. For example, a malignant tumor of the breast will have mammary gland cells penetrating into muscle or connective tissues where they are not generally found; they will be in large masses, and the cells often look bizarre. They may have large misshapen nuclei, and the cells are large and have a lot of RNA in their cytoplasm. For every rule, however, there are lists of exceptions. With the more common tumors, pathologists have seen so many of them that they no longer have to go through the long deductive process, but can recognize them as you would recognize an old friend or enemy. Nevertheless, someone once upon a time went through the entire deductive process, drew his conclusions, and then watched the patient to see if those conclusions were correct.
Pathologists being similar to other men, the accuracy of their predictions will depend upon their experience and general judgment. There are a lot of ifs in the prognosis for an individual with cancer. If one considers the massive number of variables, the accuracy with which many of these predictions are made is almost uncanny. Yet, there are errors made by the best and wisest of these men. They are made because many of the variables are simply not known.
Let us go back to the pickled tumor. If it was a small cancer of the skin, and if it was discovered early, the individual who had it removed can go about his business with very little concern about his immediate future. If, on the other hand, it should turn out to be one of the rapidly spreading tumors of the pigment cells of the body (a melanoma; which Alexander Solzhenitsyn calls "the queen of malignant tumors"), then he had best consider the distinct possibility that his future life span might shortly be abbreviated.
The pickled piece of tumor may be one which goes by the name of Hogkin's disease. If the tumor is of this type, then the probability of its having been removed by surgery is very slim because cells of this tumor tend to migrate out of the original tumor mass very readily. Yet, the growth characteristics of this tumor are such that it is difficult to predict if the individual having it will survive less than one year, or up to thirty years. The treatments for Hodgkin's disease are very effective, and 20 percent of treated cases (this was before the new improved x-ray treatments) will survive beyond ten years. Furthermore, there are long periods during which the patient is free of any symptoms of the disease and functions as a normal healthy individual. Yet, all of the aforementioned tumors, regardless of their relative lethality, go by the common name "malignant."
There are some tumors of the brain which cannot be entirely removed; the patient generally succumbing within a short period of time. These deadly tumors (craniopharyngiomas) are referred to as benign because they lack many of the characteristics of the so-called malignant tumors.
Fundamentally, a pathologist makes his judgments on the same basis on which all judgments are made --experience. Both his own and the accumulated and recorded experience of many other pathologists. With common tumors he can draw on his own experience: "I saw 100 tumors that looked like this and most patients did or did not recover." With rare tumors he has to rely on others; the authority who may have seen a large number of rare cases drawn from many other laboratories. If the pathologist cannot draw on either his own or someone else's experience, there is little basis for a rational judgment. Sometimes a reasonable guess can be made on the basis of some of the generalities that have been derived about tumors. Judgments made on this basis are highly unreliable.
The surgeon makes similar judgments based on his experience, and the appearance of the tumor at the operating table. The probability of a correct judgment increases when the surgeon and pathologist pool their experience. It goes without saying that the more extensive the experience of the surgeon and the pathologist, the more reliable their judgment will be.
What is the rationale which leads people to divide tumors into malignant or benign? For the physician, there might possibly be a reason for this oversimplification. He is sometimes faced with the decision as to how to proceed in treatment; for example, whether to amputate a limb or simply to remove a tumor. To the patient, however, it may mean completely unreasonable terror.
This simple dichotomy of malignant versus benign has misled many a scientist who thinks that there is a sharp dividing line, and that the pathologist can always make the distinction.
The limit of pathology is that, at best, it can only tell you what may happen, and what the odds are. It cannot tell you what will happen. To find that out, you have to wait and see. No one has yet devised a way of looking into the future. Two people may have identical-appearing cancers of identical size and distribution. They are treated surgically by the same operation performed by the same surgeon. One dies two years later because of the cancer, and the other dies thirty years later of a heart attack. There is no way of telling what will occur before it happens; only odds can be given about what might happen. Sometimes even the longshots pay off.
The reader would do well to remember that the tumor which is removed and placed in a bottle of formaldehyde is as harmless as a dead tiger.
The word leukemia means "white blood." It is called this because, being a tumor of circulating white blood cells, the cells, following their normal predilection, circulate, resulting in large numbers of these cells in the blood. Sometimes the cells do not circulate, but remain in the organs of origin, such as the bone marrow (the tissue inside of the bones which produces most of the blood cells), or the lymph nodes, or the spleen. When it behaves in this manner, it is referred to as aleukemic leukemia (without white blood-white blood). Leukemia is the special bailiwick of the hematologist, with hematology being considered a branch of internal medicine rather than pathology. He does the same thing that the pathologist does with his piece of pickled tissue. Hematologists, however, do it with a drop of blood and a drop of bone marrow. The hematologist infers from this drop of fluid what is occurring or will occur in the entire individual.
Again, as with other types of cancer, there is a wide spectrum of ways in which these blood cell tumors behave. In the case of acute leukemia, death occurs relatively soon. In the case of the chronic forms, a person may live for many years. Leukemia is an especially tragic form of cancer because, in contrast to other cancers, it has a relatively high incidence in children.
To many research biologists leukemia is also an exciting form of cancer because a number of viruses have been identified which cause this condition in mice. This has raised some interesting speculation, that if it is a manifestation of a virus infection, then perhaps a person might be immunized against a leukemia virus in much the same way as he is immunized against smallpox.
To produce leukemia with a virus, it has to be introduced into the mouse at birth. It does not produce its effect until the animal becomes an adult. If the virus is given to the animal as an adult, it produces typical immunity, but no tumors. The implication of this is that when the virus is introduced into an infant, rather than causing an infection as we know it, it enters the cell and becomes a part of the genetic material. (Because of this, some scientists have questioned the wisdom of immunizing babies with live virus vaccines.) This, in some way, results in impaired control of cell division. While a number of viruses have been isolated from cases of human leukemia, none have been shown to cause it. Obviously, no one will attempt an experiment in which a potential leukemia virus is deliberately given to a newborn child. It is a very reasonable inference that if some forms of leukemia in mice are caused by viruses, then humans also have viruses which similarly cause leukemia. It is a reasonable inference, but is by no means proved. Could a single virus be isolated from all cases, it might be more indicative. Since many viruses cause leukemia in animals, it is probable that many viruses are also involved in human leukemia. (See chapter "Yes, Virginia, Viruses Do Cause Cancer.")