Digital Pathology Is Just Pathology, But Does It Matter Anymore?

By Dr. Keith J. Kaplan

Since the 1990s, many innovators to Fortune 500 and Fortune 50 companies have worked to make digital pathology a reality. While not mainstream and perhaps less than 10% of US based pathology groups have any serious implementations of digital pathology, the technology has caught up to our retinas and the legal, regulatory, and business practices have followed along nicely in terms of clinical business practices. Of course, in the United Kingdom and throughout Europe, there have been large scale implementations going back decades, first for frozen sections and within the past decade for whole slide imaging (WSI) for primary diagnosis.

Having done robotic telepathology beginning in the late 90s and more recently as of mid-last year, using WSI for primary diagnosis in my own practices over the years, I always assumed that the use of WSI for digital pathology, or just pathology, as many would argue, would be the holy grail for pathology. The comparable workflow to our colleagues in radiology, cardiology, neurology and so forth, all digital, all the time. No more films, videos and printouts of studies.

And arguably where it is has been implemented, it has. Up to 80% of my clinical workload I can and do manage digitally using WSI, paperless reporting and voice recognition for placing into the LIS and thus the EMR. While we thought we would use our eyes more and our hands less, I am not so sure about this right now and the topic for another article.

However, in the decades to adopt WSI, ensure safe use and timely effectiveness, mitigate risks and maintain reimbursement, something else has happened in the world of surgical pathology.

If you went to any oncology related meetings in the past decade you saw this coming and there was little, we could do to stop it. If you were at ASCO in 2015 or 2016 you saw dozens of presentations and hundreds of posters on PDL-1 in every tumor imaginable and response (or lack thereof) to PDL-1 therapies, so called immunotherapies. Enabling the hosts cells to respond to tumor cells while not destroying the host cells, as with conventional chemotherapies that disrupt cell cycle mechanisms in many cell types, including normal and abnormal cells. Hence, targeted therapies.

This was the tip of the iceberg. Since then, there is a plethora of next-generation sequencing (NGS) platforms and commercial laboratories offering testing for nearly every tumor type.

When the salesperson dropped off Oncotype DX mailing boxes in my office 15 years ago, this was a sign what we did and were going to do was changing.

20 years ago, when we called oncologists back about a lung biopsy, without having a chance to tell them first, they would ask “Small cell or non-small cell?” Each was worked up and managed differently, as they are today, systemic treatment vs. surgery with or without additional therapy.

10 years ago, when we called oncologists back about a lung biopsy, without having a chance to tell them first, they would ask “Is there enough tumor in the block to do ROS, ALK-1, EGFR and PDL-1?” The morphology was important but less so, particularly for the non-small cell category; surgical pathologists were tasked with selecting blocks and in many cases, checking boxes on a form from a larger laboratory for further evaluation.

Today, before the biopsy or fine needle aspiration is even performed, the oncologists are calling you to ask if there is enough tissue for NGS. Without knowing if it is malignant or what type of tumor, the necessity is ensuring there is enough tissue from smaller and smaller samples from smaller and smaller lesions for molecular testing. Again, if it is malignant, I pick a block and check some boxes and report fixation times and so forth. And off it goes. Separate report to follow for any actionable mutations with reported treatments and/or clinical trials.

I am not opposed to molecular testing of course, but it is changing the role of the surgical pathologist and our role on the healthcare team.

Last week I received a liver biopsy on a patient with a reportedly “large liver mass – HCC”. A quick review of the chart reported a 15 cm liver mass in patient without a reported history of any risk factors associated with hepatocellular carcinoma (HCC). I found this reassuring because the biopsy I reviewed contained a cholangiocarcinoma, presumably primary intrahepatic cholangiocarcinoma, although metastasis from other sites would have to be considered.

When I called the oncologist to let him know that it was not HCC, but an adenocarcinoma and I favored a primary intrahepatic cholangiocarcinoma, his response only confirmed my suspicions, “We only did the biopsy do see if we could get tissue for NGS for HCC.” He went on to say, “We only biopsy these patients for NGS, not for diagnosis.” What? Huh? Okay…

He went on to ask me why it wasn’t HCC, as it should be in his mind. I explained the morphologic features, the non-neoplastic liver findings (lack of cirrhosis or significant other pathology), the immunohistochemical findings that supported an adenocarcinoma rather than a HCC with a high degree of sensitivity and specificity, and the findings by his own history and physical examination for the lack of risk factors for liver disease, cirrhosis, clinical signs and symptoms of cirrhosis and physical examination findings consistent with that.

The oncologist simply replied, “Is there enough tissue for molecular?” to which I replied, “I already told the secretaries which block, send the order and we will send it out.”

We are on the path to molecular replacing morphology. It has been a slow march, but it is advancing.

Tumor boards are now more focused (no pun intended) on scores from assays, risk assessments, predictive genes, NGS and if there is enough tissue to do more testing than on histologic type, grade and stage.

Long gone are the days of standing at a flimsy cart with a microscope and stacks of slides trying to show a positive margin or lymph node in a dark room over a video projector thanks to digital imaging. Also long gone are the days where showing the area of a focus of poorly differentiated tumor or the result of an immunohistochemical stain as a surrogate towards differentiation or source of tumor is required. The presentations usually end with “the patient has a low recurrence score based on her testing” or “based on the NGS, there are potential targets” or “is there enough tumor cells to send for NGS?”

Giving the CAP/AJCC staging summary of “pT2N1” or pT3N2” is now largely checking other boxes in the templates for reporting purposes for registries and inspections of such documents.

I think surgical pathologists will increasingly use their gross pathology examination skills, in many cases, selecting blocks of tumor solely for “other testing” other than H&E and immunohistochemistry. These will be the “Tempus” or “Oncotype DX” or “Agendia” blocks.

Maybe they will have their own number wheel in the LIS and not be filed with the other blocks but will be in a special section called “Diagnostic Blocks”.

Assessing for tumor adequacy will soon be as common as the 88307 or 88309 for the actual reporting of the specimen.

Of course, this doesn’t cover ALL of surgical pathology, perhaps 20% of cases, unless you work at a cancer center exclusively, we will still have the basal cell carcinomas, nevi, appendixes, gall bladders, placentas, lipomas and hernia sacs.

And for those we will need pathology slides to be digitized to do the AI to diagnose.

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