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‘Split’ decisions in CNS tumor update

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Karen Titus

October 2017—Classifying central nervous system tumors has recently become both more complex and easier. Surgical pathologists now have guidance that helps them work through the whys, hows, and what-ifs of using molecular studies when making diagnoses. The 2016 WHO classification for CNS tumors, which has been described as a conceptual and practical advance over the previous incarnation, from 2007, should also help them move closer to precision medicine.

“At the heart of personalized medicine,” says Dr. Eyas Hattab,  “is our ability to diagnose each patient’s tumor and categorize it to the narrowest possible classification.” The 2016 WHO classification of CNS tumors is another step on that road.

“At the heart of personalized medicine,” says Dr. Eyas Hattab, “is our ability to diagnose each patient’s tumor and categorize it to the narrowest possible classification.” The 2016 WHO classification of CNS tumors is another step on that road.

But the journey will have its challenges, says Eyas Hattab, MD, MBA, the AJ Miller professor and chair of pathology and laboratory medicine, University of Louisville (Ky.) School of Medicine. “What we found is this has been very intimidating to general surgical pathologists, and even to many surgical neuropathologists.” The lack of appropriate resources for molecular assays adds complication.

Advances in the field have improved matters for patients, pathologists, and oncologists, prompting the 2016 classification changes. “We call it an update,” says Dr. Hattab, explaining that the WHO has strict criteria for green-lighting a new, official revision.

Since the 2007 edition, “There has been an explosion of new information,” he says, “mostly in the form of molecular and genetic data on brain tumors that further allows us to subclassify certain entities. In a few cases, molecular testing has become the gold standard for such diagnoses.”

In a sense, the classification becomes a rallying cry: Splitters of the (neuropathology) world, unite!

“We are turning into more splitters than lumpers in some cases,” says Arie Perry, MD, professor of pathology and neurological surgery, and director of neuropathology and the neuropathology fellowship program, Department of Pathology, Division of Neuropathology, University of California, San Francisco.

The reasons for more specific categories are many.

One of the difficulties that emerged from the 2007 scheme, Dr. Perry says, is that in certain glioma types, including oligoastrocytoma, there was insufficient reproducibility among some pathologists, and some of the criteria were too vague. “It made it difficult to treat patients when they would go from one institution to another and get different diagnoses.”

David Louis, MD, pathologist-in-chief, Massachusetts General Hospital, and the Benjamin Castleman professor of pathology, Harvard Medical School, points out that the classification is not aimed strictly at patients and physicians. “Pathologists drive this, but the users are broad,” including researchers, epidemiologists, and payers, says Dr. Louis, lead editor of the 2016 CNS WHO classification. “All these constituencies are dependent on accurate classifications.”

For insurers, Dr. Perry adds, the consensus should make clear the justification for doing molecular testing. “If you’re not doing the testing, you can’t reach that particular diagnosis.”

By introducing molecular parameters into the WHO document for the first time, the authors restructured the classification of diffuse gliomas, medulloblastomas, and other embryonal tumors. This includes subdividing both the gliomas and the embryonal tumors to create cohorts that are as uniform as possible. For example, “Rather than just saying ‘diffuse astrocytoma,’ now you have to know if it’s IDH-mutant astrocytoma or IDH-wildtype,” says Dr. Perry, who helped author, with Dr. Louis, a summary of the classification (Louis DN, et al. Acta Neuropathol. 2016;131[6]:803–820). “They have different prognostic implications.”

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