The Post Investigates The Pancreas.

The Emerging Role of Cytology: Part II of a Continuing Series

Cytopathology--the study of cellular changes in disease--is a relatively new field of medicine and one not yet fully utilized in this country. Imaging techniques such as CT and MRI scans are integral to a diagnosis, but the procedures are not able to differentiate microscopic variations on the cellular level. Subsequently, a cytopathologist can play a key role on the diagnostic team.

"Not all tumors are the same," explains Dr. Liang-Che Tao, researcher and author of a textbook on cytopathology who has studied cancer cells under the microscope for over 30 years. "Just like mangoes are not all the same. Some are sweet, some are fabulous, some are the same or different than others."

There is currently a difference of opinion among those studying a recently identified tumor of the pancreas called an intraductal papillary mucinous tumor, or IPMT (see August 2001 Medical Update). Even the best pancreatic cancer centers in the world do not always agree over whether or when these more indolent and less-dangerous lesions should be carefully watched or quickly removed.

In the May 2001 issue of the American Journal of Gastroenterology, French researchers concluded that preoperative indicators of malignancy in IPMTs are still lacking. The study, among others, highlights the critical need for cytopathology in differentiating between malignant and nonmalignant cells in these lesions and, in the process, helping physicians determine the most appropriate course of action.

But the party line has been to remove what are considered "precancerous" lesions, even if signs of malignancy may not be present. Many individuals then undergo the daunting Whipple procedure--the same surgery used for patients with pancreatic cancer. Typically, IPMTs appear late in life and, without confirmation that the slow-growing lesions are cancerous, the risky and complicated surgery may actually pose more problems than it solves.

Post medical editors recently spoke with Dr. Tao to learn more about how cytopathology can help monitor the biological behavior and progress of IPMTs.

Q: Does recurrence of an IPMT after fine-needle aspiration indicate a cancerous lesion?

A: The only diagnostic criterion, I believe, is the cell pathology. Some IPMTs never come back, and that clearly tells you it is a benign condition. Others recur because ducts are obstructed and the mucin has nowhere to go. They may still be benign. If a sample contains malignant cells, of course, it is a different story.

Q: If an IPMT recurs, would you recommend another fine-needle aspiration?

A: Yes. We would need to determine whether any abnormal, or dysplastic, cells were present. As is seen in cases of cervical cancer, epithelial cells continue to show dysplastic changes unless the lesion is removed. If we see mild dysplasia one year, moderate dysplasia the next year, and severe dysplasia the following year, that means the lesion is progressing. If mild dysplastic cells are seen year after year, the lesion is not progressing.

Q: Can you describe the cellular changes you might observe in benign versus malignant cells?

A: When normal or benign cells die, they go through karyorrhexis, a process in which you see fragmentation of nuclei. Cells with no nuclei are called ghost cells. When I see a karyorrhexic cell, I know that it is a benign cell undergoing necrosis.

On the other hand, if I see karyopyknotic cells, that is a bad sign. When malignant cells die, they undergo karyopyknosis--a degenerative condition marked by clumping of the chromosomes and shrinking of the nucleus--before becoming ghost cells. The presence of ghost cells does not help one differentiate between a malignant and benign lesion. However, if I see many karyopyknotic cells, I know the tumor cells are malignant.

Q: Do you take into account the person's age and overall health when considering treatment options?

A: In my view, one must first assess the individual's health and the seriousness of the lesion and then discuss possible treatments. The Whipple is not minor surgery. However, if the lesion is proven to be malignant, the choice is obvious. You have to take that risk.

Q: When we interviewed Dr. Craig Venter of Celera Genomics, he said that although we have talked so much about the impact that genetic discovery is going to have on our lives, we are really just at the doorstep of discovery. The missing link seems to be cytology.

A: We have yet to utilize the potential benefits that cytology has to offer. Cytology is not easy. Technicians don't like it; some specialists even consider it competition. Many years ago, I realized that cytology is very useful, and I have chosen to concentrate on it. It makes sense to start with a minimally invasive procedure before moving to a surgical intervention.