The Art of Pathology 

Dr. Ronald Rapini discusses several helpful tips and insights when diagnosing skin disease for both the dermpath and the dermatologist.

Ronald Rapini, MD, Professor of Pathology, University of Texas Health Science Center & MD Anderson Cancer Center

“I think that dermpath is a specialty where there are home run hitters and base hitters. So the home run hitters…make a real specific diagnosis and they’re either really, really right or they’re really, really wrong,” said Ronald Rapini, MD, who presented “30 Dermpath Tips” at the 2022 Hawaii Dermpath Conference.

“I know some of the home run hitters will read out a biopsy that was done in the hospital and they’ll say it’s an arthropod bite, and it’s really a drug reaction.” 

Base hitters will provide a list of things it could be without being specific, which makes those people less than helpful, said Dr. Rapini. 

“I think the art of pathology is to try to give people as much information as you can without leading them down the primrose path and being too dogmatic about things.” 

Hedging terms like “consistent with” or “suggestive of” aren’t helpful either, said Dr. Rapini.

“It’s sort of like being the weatherman. You can say there’s 50% chance this is lupus and 50% chance it’s not, and you can just give a list of things that could be.”

Beware the Biopsy

Biopsies can’t be used to prove things, like drug reactions and bug bites, said Dr. Rapini.

“Biopsy will never prove that something is from a drug, and it won’t tell you what drug it is because drug reactions can do anything…. You know, usually we look for eosinophils… but that’s not specific for anything, and also some drug reactions don’t have eosinophils.”

Eye on Eosinophils

While eosinophils can provide diagnostic clues for some things, they generally are not present in lupus erythematosus and certain other related autoimmune diseases, said Dr. Rapini. 

“So if you see eosinophils, you can be pretty sure it’s not lupus erythematosus but that’s not 100%.” 

However, eosinophils can be helpful in diagnosing alopecia areata, he said. 

“There are some papers published saying that you can sometimes see eosinophils… and sometimes that could be a clue that you have alopecia areata.”

Eosinophils also can be found in some examples of vasculitis. 

“Some forms of vasculitis will have eosinophils, but that doesn’t prove that it’s from a drug, you know. Sometimes you can still have autoimmune disease or other forms of vasculitis and still have eosinophils, so you have to take that with a grain of salt.” 

The Neutrophil

The neutrophil is another cell seen on skin biopsies, but a collection of neutrophils around blood vessels does not mean vasculitis, said Dr. Rapini. 

“Vasculitis means that there’s inflammation around the blood vessels and that’s a reaction to things. And when neutrophils get real active in the skin, they fall apart like kamikazes and you get what’s called nuclear dust—fragments of their nuclei. But nuclear dust is not specific for vasculitis.” 

According to Dr. Rapini, neutrophils are also present in abscesses and Sweet syndrome. 


“Some people get the idea that nuclear dust is specific for vasculitis, but it’s not.” 

Deeper Cuts

Many pathologists are fixated on doing immunostains, said Dr. Rapini. 

“But the very best special stain is to cut deeper sections…. It’s actually better than than doing some of the immunostains in many cases.”

If It Quacks… 

If it quacks like a duck, it probably is a duck, said Dr. Rapini.

“I had a dermpath report from a lab recently where they tried to say the patient had papular elastolysis, which is incredibly rare. And it turned out, I think, the patient just had scars on their skin and the scars looked like papular elastolysis. But they were trying to make some weird diagnosis on the case.”

While it’s important to be aware of rare skin diseases, most people have common ones, said Dr. Rapini.

Clinical Correlation and Requisition Forms

Ultimately, both the dermpath and dermatologist have a responsibility to work together to make an accurate diagnosis, said Dr. Rapini.

“Some dermpath people are better than others at doing the clinical correlation. Some of them will do it for you in the report if you tell them what it looks like clinically, and they’ll read the biopsy, [and] they’ll do the correlation for you.”

However, others may report that clinical correlation is simply “indicated” and leave it to the dermatologist to do the correlation, said Dr. Rapini.

“It’s important [for the dermatologist] to give a good history when you do the biopsy on the requisition form… put down a good history and tell them what you’re seeing in the clinic so that they can correlate the clinical with the pathology better.”

That includes details, from describing rash lesions to the “why” behind ruling out a melanoma, said Dr. Rapini. 

“Some of the clinicians I get biopsies from are real busy and they just put down some very short curt thing on the requisition report. And they’ll say, ‘rule out melanoma,’ for example. Well, did you really think it was a melanoma? Or …I think it’s a nevus but I just want to rule out a melanoma. You know, it helps if I really know what they really think.” 

Description of rash lesions are particularly important to detail, said Dr. Rapini.

“Some people are good about putting the differential diagnosis for the different kinds of rashes they are thinking about, but they don’t put down a description of what the lesions look like. So that can help the pathologist try to figure it out.”