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Back when he was a young student in medical school some 30 years ago, pathologist Neil Theise wasn't taught much about a common, widespread connective tissue in human bodies. Scientists assumed it was just a typical connective tissue, so they didn't look much further.

"You see what you’re prepared to see," Theise, now a pathologist at New York University's Langone Medical Center, said in an interview. Now, he knows differently.

"It looks like it's connective tissue -- but it's not."

Theise and his research team published their findings in the journal Scientific Reportson Tuesday, revealing that this thin tissue -- when alive -- is a lattice-like mesh of fluid-filled bubbles. They've named it the "interstitium." And if this widespread anatomical feature is more widely proven by other scientists, it wouldn't just be one of the larger organs in the human body.

According to Theise, it would be the largest.

How could the interstitium have escaped notice for so long?

These thin tissues surround our major organs, muscles, arteries, and veins. Even when alive and filled with fluid, they aren't easy to see. But new technology allowed Theise -- who spends most of his days closely inspecting dead tissue samples on slides -- to see this tissue in a new way.

"Any time there’s a new technology that allows you to look at tissue in a different way, you're gonna see things you didn’t see before," said Theise.

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An endoscope -- a thin snake-like medical device that allows doctors to view the inside of a body -- had been retooled to view tissues on a microscopic level. This enabled doctors to observe the tissues as they exist in actual flesh -- not a slide.

One day, while using the camera-probe, gastroenterologists inspecting a patient's bile duct for cancer stumbled upon a previously unknown feature: Mesh-like tissue filled with fluid.

They showed Theise the curious images, who then put the flesh samples on biopsy slides. But when he looked at the now-dead tissue, the mesh-like patterns had disappeared; instead, he saw cracks in the tissue. "I was taught that these were tears," said Theise, referring to his medical school days.

An illustration of the interstitium shown below a thin layer of skin.Credit: Illustration by Jill Gregory/Printed with permission from Mount Sinai Health System

Upon closer inspection, these weren't tears in hardened connective tissue. They were indeed cracks, reminiscent of where the fluid had been before the tissue dried out. When drained, the collapsed tissue now appeared as it had for decades before: As torn, flat, and common connective tissue. It's no wonder it had been overlooked. It couldn't be seen.

This discovery of a previously unknown organ, however, doesn't come as a shock to those who research organs.

"I’m not surprised," Khalil Bitar, the director of the Gastrointestinal Program at the Wake Forest Institute for Regenerative Medicine, said in an interview.

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Bitar noted that the omentum, a membrane over the gut, had been known about for ages. But last year it had been upgraded to organ status. (It's unclear who gives final word on such a promotion. Even some anatomists scratch their heads on that one, but it's clear that a large consensus of scientists now consider the omentum an organ.) Until then, anatomists didn't fully recognize the importance and complexity of an anatomical feature that might have been easy to overlook. Even after its promotion, Bitar still called it a "flab."

Is the interstitium really an organ?

"Yes and no," said Bitar.

No organ exists on its own, said Bitar. They're connected to each by channels and vessels, and Bitar thinks of the interstitium as one of these vital connections, similar to a major highway connecting important parts of a city. There's no doubt it serves an important purpose, he said, but is hesitant to endow full organ status upon the interstitium.

Theise, however, is more certain that it's an organ. "It's everywhere," he said. At minimum, it appears to be a hugely widespread feature of our anatomy, like the nerves of our nervous system or blood vessels of our cardiovascular system.

Microscopic images of the interstitium.Credit: nature Scientific Reports

Our skin, while not shaped like what we might consider a traditional, vegetable-shaped internal organ, is considered an organ.

And the interstitium certainly serves purposes -- both known and hypothesized.

"We already know that it functions as a shock absorber," said Theise, noting the fluid-filled tissue can absorb impacts.

Although more research needs to be done, Theise speculates the interstitium holds around 20 percentof the water in our bodies. It's well known that about two-thirds of our bodies' water lives in our cells. That leaves a third that is extracellular (outside of our cells). Of this extracellular fluid, about a fourth is in our blood and a tiny amount in our spinal fluid. That leaves a lot left over -- around 20 percent.

"No one knew how to account for it," said Theise.

And if all this water truly exists in this cavity-filled tissue, "It would make it the largest organ," said Theise.

Why is a pathologist, who studies diseases, interested in the interstitium?

These roomy tissues could be an easy place for cancerous tumors to invade, although there's still much research to be done on this potential disease process.

"It's a wide open space," said Theise. "They act like a railroad for cells, to allow cells to move easily."

Cancer often spreads, or becomes metastatic, by getting into the lymphatic system, where it can then travel around the body. "We could prove that this space flows into lymphatic channels," said Theise. If so, "we might get a therapeutic intervention," to stop the cancer before it can have a devastating effect.

Bitar agrees.

"If it provides access for cancer it provides access for potential treatments," Bitar said. "We can start tracking cancerous cells. We can develop some technologies for proactive treatment."

It could be a good thing, then, that a curious Theise took a closer look at this overlooked tissue.

"If you think you know everything, then there’s nothing to see," he said.

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