Pathologists Decode Diagnoses in Body’s Tiniest Structures



The pathology frozen room on the second floor of University of Cincinnati Medical Center is much smaller than its neighboring operating rooms.

There is enough space for one or two people to stand at a counter as they slice through specimens, dip slides in dye or receive fresh tissue at the window from a nurse in the middle of a surgery.

But the role of pathology on this floor is far from small—what pathologists see under their microscopes can make the difference in what happens next for patients.

“In the public, most people don’t know what we in pathology do,” said Jiang Wang, MD, PhD, chief of anatomic pathology and director of surgical pathology for the UC College of Medicine. “But we really play a very key role, especially for cancer patients.”

Pathologists are trained to identify and diagnose diseases from the body’s tissues and organs, often at microscopic levels. What may look like scattered purple and pink dots to others looks like a high-grade malignant tumor to a pathologist.

These physicians, whose work happens backstage from clinic rooms and hospital beds, confirm suspected diagnoses and then some. They deliver key details that can mean all the difference to a patient’s care.

While pathologists still must interpret what they see, the truth is right in from of them. The cells don’t lie.

On a particular day, Dr. Wang receives a plastic bucket containing a bright red lump the size of a forearm—a portion of a stomach, pancreas and duodenum (the first part of the small intestine) from one of the most medically complex modern surgeries—a Whipple procedure.

The patient’s surgeon, Syed Ahmad, MD, has expertly removed these organs to treat either cancer or inflammation of the pancreas, depending on what is found.

It’s up to Dr. Wang to determine if Dr. Ahmad, director of the UC Health Pancreatic Disease Center and associate director of UC Cancer Institute, has removed enough cancerous tissue, or whether a tumor is hiding in the inflamed organ—in which case Dr. Ahmad would need to surgically remove more.

If Dr. Wang can see the margins, or the line between the good tissue and the diseased tissue, then the surgeon has been successful.

“Usually from when we receive the specimen to the reporting, it’s been only 15 minutes,” Dr. Wang says. “So, it’s pretty fast.”

Dr. Wang removes this shining mass of organs from the bucket and gently places it on a sterile surface. To his left lay more than two dozen metal instruments. Tweezers, scalpels, knives and clamps.

He chooses a large pair of tweezers and a scalpel, delicately holding the organs in place as he slices through the middle. With a long cotton swab dipped in black ink, he traces the edge of the organs to mark their margins and cuts off a pea-sized sample.

Dr. Wang and his resident, Ramya Velagapudi, MD, flash-freeze this sample in a negative-20-degree machine that allows a blade to cut paper-thin sheets that are imprinted onto slides.

As Dr. Wang is creating a frozen sample, Ady Kendler, MD, PhD, director of neuropathology, comes into the room carrying a small cup with a brain tumor. He suspects it’s something called a pituitary adenoma, a benign growth that presses along a gland in the brain that is responsible for making hormones. But he needs to be sure it’s not a cancer.

“A pathologist wrote a book about surgical pathology called ‘Guiding the Surgeon’s Hand,’” Dr. Kendler says. “I’m not sure that’s how the surgeons see it, but from our point of view, we help them figure out what the next step is.”

Dr. Kendler opts for a quicker way to look at his tissue sample—a touch prep, where the tissue is lightly pressed onto a glass slide, followed by staining of the cells. He dips his sample into cartridges with different chemicals. The blue liquid lights up the cell’s nuclei, or centers. The orange-pink shows the cytoplasm, the jelly-like substance that fills the rest of the cell.

He places his slide under a microscope and peers through the lens.

“Looks like pituitary adenoma,” Dr. Kendler says.

Not much later, Dr. Wang looks at his tissue sample: pancreatitis, confirmed. No tumor. That means Dr. Ahmad has successfully removed the tissue needed.

For this tissue sample, its journey in physicians’ and researchers’ care has only just begun.

Most organs, once diagnoses are confirmed, are stored in a lab for up to a month in case more samples need to be examined later. Then, the rest is incinerated.

But some receive much more rigorous scrutiny—the kind of scientific research that can only happen at academic health systems like UC Health.

This pancreatic tissue sample goes down to the lab of Yana Zavros, PhD, professor of physiology at the UC College of Medicine, to be grown into an organoid.

Organoids are microscopic versions of human organs, grown from the major cells that make the organ from which they are grown.

Though they don’t look like their mother organs—rather, like tiny circles floating in a petri dish—they have enough basic structures to give answers about what treatments will be most effective for people with pancreatic cancer.

“It’s personalized medicine,” said Loryn Holokai, a molecular genetics PhD student. “Our goal is to use these organoids to tell the physician what we found and what we think is the best treatment.”

That level of precision is exactly what pathology is all about: finding answers in the human body’s tiniest structures and using these answers to deliver the best possible care for the people who trust physicians and researchers with their lives.