Type 2 tumors, Dr. Reuter continues, are morphologically distinct in that they’re more likely to have eosinophilic cytoplasm, high nuclear grade, and prominent nucleoli. But these tumors share an overlapping morphology with other types of tumors, including high-grade Type 1 papillary renal cell carcinomas. Others with overlapping morphology include tumors associated with fumarate hydratase deficiency, as well as those with translocations of either the TFE-3 or TFE-B gene.
(At this point, a wandering mind in search of lighter fare might find itself thinking that RCC classifications mimic the morphing partnerships behind the Great American Songbook. Who wrote what—Rodgers and Hart? Rodgers and Hammerstein? Kern and Hammerstein?)
In simpler terms, says Dr. Reuter, “Type 2 papillary renal carcinoma is a less-than-pure entity. In fact, it’s not an entity.” Given the encompassing nature of this category, “When confronted with this morphology, a pathologist must consider the differential diagnosis.” The answer can help guide therapy, especially for tumors that might qualify for checkpoint inhibitors, for example. And if a familial cancer is implicated, genetic counseling for family members is in order. “These are lethal tumors,” he warns.
The ongoing confusion is understandable—and widespread. “These tumors,” Dr. Reuter says, “comprise a very large percentage of the cases that people like myself and others get in consultation.”
He credits academic pathologists for educating colleagues in the last five to 10 years, spreading the word about modern classifications and molecular correlates “every chance they get.” Nonetheless, he says, that doesn’t obviate the fact that some of these tumors are rare, nor that the many subclassifications can be confusing. “For that reason it’s not unusual for these tumors that are not absolutely the classic examples to be submitted for second opinions by practicing pathologists.”
It can be hard for pathologists, especially in community practice, to keep all these entities straight when the frequency is low, says Michelle Hirsch, MD, PhD, associate professor of pathology, Harvard Medical School, and chief of the Genitourinary Pathology Division and staff pathologist in the Women’s and Perinatal Division at Brigham and Women’s Hospital. There are at least 10 rare renal tumor subtypes that account for only a few percent of all cases. “You’re talking less than one percent for each of these tumor subtypes. So if you’re in a small practice where you’re not seeing a nephrectomy that often, then you’re definitely unlikely to see these unusual subtypes.” (Although none of these are as rare as Aline Kuragina, who apparently shows up only once in War and Peace, and whose husband, naturally, spells his surname Kuragin.)
Dr. Hirsch’s advice: Stay caught up with reading and attend CME conferences. “At least if you’ve heard about or seen these less common tumors in a lecture, you can seek help from somebody who sees these tumors more frequently or in greater volume.”
Picking up the phone can also be helpful. “If I’m really struggling with a tumor,” says Dr. Hansel, “I call the urologists to get a sense of either their impression of the radiology or how the surgery was—was it difficult to get out? I’m very honest about what I’m struggling with. I feel that sort of communication across the board is very helpful.”