on Friday, March 14, 2014
The correct identification and naming of a tumor’s type is increasingly important in the era of personalized medicine, and tumors that exhibit features of more than one type can complicate that process.
We start with a tumor. How it is found varies: The patient felt it, the physician felt it, a scan picked it up, or maybe it was found accidentally while looking for something else. At this point it has no name, it’s just a tumor, which is a term used for a mass of tissue that is not normal.
How does a tumor get a name? It first needs to make its way to a pathologist’s microscope. It can be a piece of the tumor from a biopsy or sometimes the whole thing, removed by a surgeon. The pathologist then begins the naming process. At first it’s a general description of size, color, and consistency, and then the examination becomes progressively more detailed and specific.
The cells and the pattern they make are carefully detailed. Sarcomas, for example, are often composed of cells that are long and thin, classically described as spindle shaped. Clustering together, these cells form sinuous whorls that appear as if they were created from the brush of Edvard Munch. A tumor at this stage of classification may graduate to be called cancer, based on numerous characteristics such as how abnormal the cells are or if they invade adjacent structures such as nerves, lymph channels, or blood vessels.
At this point, the tumor generally is given a name. Sarcoma, carcinoma, and lymphoma are among the most common, but there are numerous others with multiple subclassifications. To achieve a level of even greater certainty, the pathologist tries to determine the normal tissue from which this tumor originated. Sarcomas for instance can come from muscle, bone, nerve, and even fat. Breast carcinoma for the most part originates from the glands of the breast, and it can be further localized to either the ducts or the lobules that together make up the functional unit of a breast gland.
Improving the Accuracy of the Diagnosis
Apart from the gross, or general, description (the size, color, and consistency) and the microscopic appearance, an added level of accuracy is obtained by using special stains to determine what proteins the tumor cells are making. Why such detail? It has broad implications for prognosis and treatment. The detailed pathologic description of a tumor allows one to use databases to estimate, with ever-greater accuracy, the probability of recurrence, metastasis, and survival.
Work by investigators from Memorial Sloan Kettering and elsewhere has revealed genetic alterations that are specific to individual subtypes of cancer; many of these alterations can be targeted both experimentally and clinically. These findings are the basis of numerous promising clinical trials that are available only to patients whose tumor has been classified and given a specific name. The naming process is therefore critical for dictating patient care.Back to top
The Challenges of Metaplastic Tumors
As a breast surgeon at Memorial Sloan Kettering, I see patients with breast carcinoma and breast sarcoma, but upon occasion the line gets blurred. There is a category of breast tumors with characteristics of both sarcoma and carcinoma. These are described as metaplastic, meaning that one form is turning into another.
Some are more carcinoma like and others are more sarcoma like. For instance, they may have the characteristic waves of long spindly cells seen in sarcoma but a special stain will indicate that they originated from a breast duct, typical of a carcinoma.
How we treat a sarcoma is very different from how we treat a carcinoma. Sarcoma rarely makes its way to the lymph nodes but carcinoma frequently will, and so further surgery is performed to examine the lymph nodes in the armpit of patients with breast carcinoma.
The chemotherapeutic regimens are also very different. Entry into clinical trials for either sarcoma or carcinoma is not available to patients with these confused tumors. Patients and their doctors are left unsettled, as there is no answer for the most basic of questions: What is it?
Our lack of understanding is not without consequences, since these tumors recur with an unacceptable frequency after they are removed.Back to top
Assigning an Accurate Name
Giving an accurate name to these metaplastic tumors will involve defining their biology. To do this, a number of cutting-edge techniques can be used to systematically reveal the tumor’s exact genetic and metabolic abnormalities. Although figuring out which side of the fence these tumors sit on will have important implications for the people who have them, it also gives us an incredible opportunity to learn something about cancer.
As mentioned above, metaplasia implies a state of flux or plasticity. If these tumors are becoming sarcomas, then we have a window of opportunity to learn about that process. Are all sarcomas born sarcomas, or were they something else beforehand? Can we turn them back? Can understanding the process of this metamorphosis reveal weaknesses that can be targeted?
James Baldwin, writer, civil rights activist, and victim of cancer, said, “Know from whence you came. If you know whence you came, there are absolutely no limitations to where you can go.” While he certainly was not referring to metaplastic breast tumors, his words hopefully still apply. Understanding the dynamic processes of change within these tumors will undoubtedly yield more than just a name.Back to top