Diagnosis and Treatment: Pathology

As the study of disease, pathology has long been associated with medical development and patient treatment and care. Throughout history pathologists have been trained to observe and recognize the abnormal in order to diagnose and treat the condition.
Today, many disorders including cancers are diagnosed and confirmed by pathologists. Sub-specialities such as cytopathology, or molecular pathology are making use of new diagnostic tools in the continuing "study of disease."
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Angelo De Marzo MD., Ph.D. is a pathologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. His current research focuses on the inflammatory response and its link to prostate cancer. The research may lead to new diagnostic tests for early detection.

Every laboratory test in the hospital is run in theory by pathologists, and so they actually are responsible for the output of every lab value, even blood, blood work, serum analysis and what not. The type of pathologist that I am that actually is fairly common that people would know about or maybe not know about or maybe they don’t know about is a surgical pathologist. So if you think about at Hopkins we have maybe 30 operating rooms, every single specimen from a little tiny piece of skin to a very large tumor mass ends up in the department of surgical pathology. The surgeons never make their own diagnosis anymore. In the early 1900’s they did, now what they do is they take out the specimen, it goes to pathology, surgical pathology, the pathologist or technician will basically slice up that specimen into a portion that will ultimately be looked at under a microscope. And then the surgical pathologist looks at it under the microscope and decides whether it is benign, malignant, or is cancer or is not. So every diagnosis of a piece of tissue is done by a surgical pathologist. There is another branch of pathology called cytopathology. Instead of looking at tissue we looked at individual cells. So a surgeon or clinician might stick a needle into a lesion and pull out individual cells and smear them on a slide and that way you have individual cells that a cytopathologist looks at and can determine whether it is benign or malignant for instance.

Most people don't realize all human tissue is actually transparent until we actually apply special dyes. So we typically use hemotoxilyn – a very beautiful dye – hemotoxilyn is actually from the bark of a tree. We've been using it for almost 100 years in this country. When we look at that under the microscope we look for a couple things. We usually use the architecture of the cells, how they are arranged together, and also the individual cells themselves. And so a cancer cell, the nucleus of the cell gets very big and it absorbs more dye. It's called hyperchromasia. The nucleus gets abnormal in shape and so in general, pathologists can tell the biological behavior and can guess it by changes in cell shape and structure.

If you think about the cells as a community of people, normal people would be a group of students in a lecture that are kind of sitting with there, shirt and ties nice and orderly. They’re not talking, they’re not throwing spitballs. They are behaving very nicely and listening to the teacher. A cancer cell would be a population of student who are running around throwing paper airplanes, they are not dressed properly, another one might be sitting on another one’s lap. The cells literally don’t behave in terms of their structure and they might invade their next door neighbor’s space. Some of them are too big and some of them are too small so you get what is called polymorphism. So normal, in this analogy, all the kids in the class are the same height and weight. In the cancer cell you have a 300 pounder, next to a one pounder, next to you know all different types of people. So that they really socially don’t behave properly as a cell and that’s really what we are looking for.

These are examples of cell preparations that pathologists examine in order to determine a diagnoisis.  See if you can identify the abnormal sample (right or left) and then click on the answer button to find out if you're correct.

Image reproduced with permission from CytoPathology, author G. McKee, Publisher Mosby (Elseviere),1997.

This shows a normal section of the cervix with two different types of cervical cells:  endocervical and ectocervical epithelium.

This shows an abnormal section of the cervix with cancerous cells, metaplastic squamous epithelium, mixed in with normal endocerivcal epithelium.

These are cells, centrocytes, collected from a normal lymph node.  Note the similar sizes and shapes of all the cells.

These are cells, centrocytes, collected from a lymphoma. Note the size and shape differences.

These are cells collected from a prostate gland with adenocarcinoma. Note how the cells are less distinct and have less cytoplasm.

These are cells collected from a normal prostate gland.