Diagnosis of cancer cells by shape and behavior

Cancer cells are usually somewhat abnormal in shape and structure, as seen under the microscope in histological sections.

The well known Pap test depends on this fact, although it uses tissue scrapings rather than sections. It is not unusual for cancer operations to begin with the surgeons cutting out a small chunk of the tumor, then sending it down the hall to the histology lab for quick fixation, sectioning, staining and examination by a skilled pathologist.

Just by looking at the shapes of the cells and particularly the shapes of the nuclei, the pathologist is supposed to be able to tell whether the tissue is malignant or not.

Often there are 3 options: (1) stitch up the incision, because the tissue is benign; (2) continue with the operation and try to remove as much as possible of the tumor, because it is malignant, or; (3) stitch up the incision, because the cells are so extremely malignant that experience has proven that there is no hope from surgery.

The patient, lying there waiting, and the family members waiting down the hall, might wonder what cellular differences the pathologist is looking for.

Books have been written summarizing the criteria used for this purpose. The quotation below is from "The Cytological Diagnosis of Cancer" by Ruth M. Graham, 3rd. edition Saunders, Philadelphia. (Health Sciences Library QZ 241 G 741 1972) page 379:

"Whether a cell is malignant or benign is determined by its nucleus; what type of malignant or benign cell it is determined by the cytoplasm."

"In examining a cell, the microscopist should first look at the nucleus and decide whether it is benign or malignant."

"The first feature to look for is the orderly arrangement of the chromatin. Are the chromatin particles of equal size? Are they distributed evenly throughout the entire nucleus? Is the nuclear border smooth and even in thickness? Does each part of the nucleus resemble every other part? If, in the mind's eye, the nucleus were bisected, would the two halves be mirror images of one another? If the answers to these questions are "yes", then one can be sure the nucleus is benign.

On the other hand, if the answers to these questions are "no"; if the chromatin particles differ in size; if they are distributed unequally at the nuclear border, and in the bisected nucleus no part is a mirror image of any other part, then one can be sure that the nucleus is malignant. "

Note that these criteria are entirely empirical (arrived at purely by experience, not based on any theory or other reason for expecting them). Cells with one set of properties always turned out to be malignant in their future behavior (if not removed), while cells with the other sets of properties always turned out to be benign. Mistakes are sometimes made, even mistakes in the direction of diagnosing malignant cells as benign; but given the amounts of money involved in malpractice lawsuits, it seems noteworthy to me that the quotes above could be so general and sweeping. It is almost as if the weather could be accurately predicted from the shapes of clouds, but no one had bothered to find out the physical causation relating the shapes of today's clouds to the occurrence of tomorrow's storms! There has been little or no research into the question of how cell and nuclear shape is related to oncogene function.

The histological organization of cancer cells is also abnormal; the cells' arrangements as "sloppy": they are irregular in shape, sizes and relative positions, as well as slightly out of alignment. What does this imply about the mechanisms that control cell shape, size, relative position, alignment, etc.? Would you prefer to say that the cancerous state interferes with these mechanisms? Or would you say that malignancy results from the disruption or failure of these mechanisms? Your new ideas might really help treatment.



Two videos of cancer cells compared with normal ones: cancer cell (upper right) is thicker and more active than normal cell (lower left)

a cancer cell (left) encounters normal cell (right)
Note the "ruffling" of the cell membrane.