New paths through hematologic neoplasms

Moreover, he says, “It has included the multidisciplinary input of experts throughout the process, at the authorship level as well as at the editorial level.” This means the classification “is closely aligned with current clinical and pathology practices while being rooted in a cancer genetics foundation.”

“This was a huge effort,” says Dr. Khoury. The upcoming volume (it may be a two-volume set, he says) will be one of the largest in the series. “It’s about a thousand pages.” Though the material “could be the subject of a three-day conference,” he continues, the Leukemia papers provide the official summaries of what the new WHO classification entails.

Dr. Khoury notes additionally that the WHO authors streamlined the terminology used to name certain tumor types, consolidating advances in the field. They also adopted the most recent genetic nomenclature principles, those of the Human Genome Organization Gene Nomenclature Committee, and embedded them into the names of the various types of tumors as appropriate.

Other changes included expanding the number of entities that are diagnosed based on specific molecular alterations, Dr. Khoury says. “We also introduced, for the first time, placeholders that would allow for the introduction of genetically detected entities that we envision will be increasingly recognized in the next five years.”

Given the global impact and reach of the WHO, Dr. Khoury says, those who developed the WHO classification were mindful of making it applicable worldwide. The goal was to make it useful in places that might not have abundant resources, yet without compromising the science. “There are places in our own country that don’t have as many resources, in fact,” he says.

With two classifications available, pathologists might feel like they’re being forced to choose between two radically different choices—the difference between, say, the brisk theatrical release of Once Upon a Time in America and Sergio Leone’s make-yourself-comfortable director’s cut.

How should pathologists navigate differences that might occur between the two classifications? Says Dr. Khoury: “I think that’s one of the biggest areas of confusion in the community: people asking, ‘Do we use the WHO classification, or do we use the ICC?’ Which I find very unfortunate.”

Nobody benefits from a confusing situation, he continues. “Not the patients, not the providers, not the scientists.” To avoid confusion, Dr. Khoury recommends what he calls a “simple solution”: following the WHO classification. “It’s the standard that has underpinned the field for over two decades,” he says. “People propose classifications all the time, but when it comes to a standard-setting framework, the WHO classification should be it for all cancers.”

It’s worth remembering, as pathologists consider the two classifications, that they overlap by more than 90 percent, Dr. Khoury says. “There are areas of different opinion, but that’s where the data is just still lacking. And because they don’t have enough scientific data, they end up relying on consensus—and consensus can look different when different groups look at the same data.”

With that in mind, the best approach is to keep it simple, advise both Dr. Khoury and Dr. Arber.

Says Dr. Arber: “If the diagnosis is different in the two classifications, I think for a while people are just going to need to report that.” It’s similar to what happened with changes that occurred with the fourth edition of the WHO, he suggests. “Any time you change a classification, you have to explain what is in the prior classification to kind of bring people along, particularly clinicians.”

He provides one example from the ICC classification, which changed the name of nodular lymphocyte-predominant Hodgkin lymphoma to nodular lymphocyte-predominant B-cell lymphoma. “When I make the diagnosis of that disease now, I call it nodular lymphocyte-predominant B-cell lymphoma, and I’ll say, ‘ICC 2022,’ and in parentheses I add, ‘previously termed nodular lymphocyte-predominant Hodgkin lymphoma in the revised WHO fourth edition.’

“That’s what we did in the past when we had more than one classification,” Dr. Arber continues, “or when there was a change. Even as the WHO changed, you had to do that when there were changes between the classifications.”

Every institution will have its own approach. When there are differences, Dr. Khoury says, some laboratories may choose to present explanations when alternative viewpoints have been expressed, doing so in the comment portion of the report, but not the formal diagnostic line.

At UChicago Medicine, Dr. Arber says, “we continue to use the revised fourth edition WHO terminology, because that’s what everyone is most familiar with. If there are differences, we tend to use the ICC. But when the fifth edition WHO is finalized, we’ll also list that if there is a different diagnosis.”

He and his laboratory colleagues are discussing the changes with their clinical colleagues. “They’re familiar with what’s going on with the WHO and ICC classifications,” he says.

Other institutions have decided to use the WHO fifth edition, he says. Some are considering a hybrid approach, “which I don’t think is a great idea because I think that will create confusion.”

Nevertheless, he says, when there are differences between the WHO and ICC classifications, “I think you’ve got to use both to convey the differences.”

It’s possible an entity might be called one disease in one classification and a different disease in the other because of differences in criteria. “I’m hoping that’s not going to be a very common thing,” says Dr. Arber. If it does occur, “We’d just have to state, That although we’re calling it disease X in the WHO, it would be disease Y in the ICC, and then explain why. Then the clinician can decide.” He doesn’t think the differences will be a source of major treatment conundrums. “If it’s explained well, clinicians will understand.”

One area where a difference is likely to remain is on the myeloid side, Dr. Arber says. For patients who have 10 to 20 percent blasts, and who don’t have one of the recurring genetic abnormalities, the ICC adopted terminology to refer to these entities as MDS/AML, versus MDS-EB2 (excess blasts 2). The reason for this, he says: “Many of the clinicians wanted more flexibility in how to treat those patients.” The WHO classification has not adopted that approach, he notes. “Clinicians understand the blast counts, and they understand that these are equivalent between the two classifications, but it could cause confusion,” he says.

For physicians who practice in the community setting, any differences might seem onerous, at least at first, given that they’re treating so many different diseases, sans specialists. “They have a really hard job trying to keep up with every disease group they treat,” Dr. Arber says. “So the pathologist will have to help them in those settings. But I don’t think the terminology is so off the wall that it will be a huge problem. But the first time they encounter a diagnosis of MDS/AML, it may result in a conversation with the pathologist if they’re using that terminology.”

Dr. Arber hopes the two classifications will be quite close in their final forms. “Even now, they’re very close,” he says. “I’d say if the WHO keeps what they’ve proposed, there will be at least 90 percent overlap, if not more.” Which shouldn’t necessarily come as a surprise. “It’s two groups of people looking at the same literature—90 percent of the time they’re going to come to the same conclusions.”

For his part, Dr. Khoury says “the only obligation is to use the WHO classification,” noting the WHO is the global standard-setting organization for cancer classification and the basis for tumor registries, cancer epidemiology and surveillance, and third-party payers, for example. The WHO classification will also continue to be the standard for the CAP cancer protocols, he says, “including those for reporting hematolymphoid cancers.”

Karen Titus is CAP TODAY contributing editor and co-managing editor.