Laying worries to rest over breast biopsy discord

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Karen Titus

May 2015—With the regularity of a pension fiscal crisis they appear: one study or another, in various journals, pointing out discrepancies in pathology findings. Editorials appear, the news jumps to the lay press, and suddenly the conversation feels hijacked.

The latest such study was published in JAMA in March (Elmore JG, et al. 2015;313:1122–1132). Participants interpreted 240 cases of breast biopsies (one slide/case); their diagnoses were compared to the reference interpretations from a three-member expert consensus panel. The three experts unanimously and independently agreed on the diagnosis in 75 percent of cases; the overall concordance rate between 115 randomly selected pathologists and the consensus panel was 75.3 percent. An accompanying editorial (Davidson NE, et al. 2015;313:1109–1110) called the findings “disconcerting.”

By now, it’s not news to anyone. “I guess everyone is aware of this article,” says Shi Wei, MD, PhD, head, section of surgical pathology, and associate professor of pathology, University of Alabama at Birmingham. While previous studies (most published in the 1990s) have looked at diagnostic disagreement among pathologists, this is the largest, with randomly selected cases. “It’s well designed,” says Dr. Wei, “but weighted heavily toward the interpretive concordance for the diagnoses of atypia and DCIS.”

Says Kenneth Bloom, MD, chief medical officer, In Vitro Diagnostics, GE Healthcare, Life Sciences: “I think it was a shock for some of my clinical colleagues—‘Oh my God.’ The initial read, without realizing the actual practice of pathology is quite different from the study design, is a shock.”

Dr. Wei uses similar language: “If you give the numbers to somebody who has no idea what we’re doing, I’m not surprised that some people would be shocked.”

Pathologists may not have been shocked, but they weren’t cheering the study, either. “The pathologists I’ve talked to have not viewed the study in a particularly good light,” says Jean Simpson, MD, president, Breast Pathology Consultants Inc., Nashville, Tenn., and adjunct professor of pathology, University of South Alabama, Mobile. “I think it makes them feel defensive.
“I talked to a pathologist yesterday,” she continues, “and he was going to give a talk to his clinical colleagues and assure them that they [his fellow pathologists] were on top of things.”

It’s possible that this study will, after its initial burst, eventually fade, like so many gorillas in the mist. But the study might be worth a closer look. Are there deeper issues to explore? What concerns have clinicians and patients raised, and how should pathologists respond?

“In the end, it’s a communication issue,” Dr. Bloom says.

It’s possible to see the study as a compliment, says Dr. Simpson, who also chairs the CAP Cancer Committee. “The lay public as well as many of our clinical colleagues think that anatomic diagnoses are straightforward and absolute,” she says. They may not always appreciate, for example, the differences between a core biopsy and a final excision, and why information from the former can be more launchpad than landing strip.

Given those lofty expectations, Dr. Simpson wasn’t necessarily surprised that her practice recently experienced an uptick in requests for case reviews, from patients and clinicians. “I suspect it’s as a result of the JAMA study.” Pathologists may feel under scrutiny and want confirmation that they’re on the right track, she hypothesizes, though she’s quick to add that their concerns might be groundless. Community pathologists, she says, “do just fine. They’re quite good at breast pathology.”

Dr. Simpson

The issue of trust—between pathologists, surgeons, oncologists, and radiologists—ripples beyond this study. “I’ve seen this go all sorts of ways,” says Dr. Bloom. “I’ve seen institutions where the pathologists lack expertise in breast disease and could actually use some help. And I’ve seen places that will read this [JAMA] study, and even though they’ve got world-class pathologists, they’ll say, ‘Oh, we need to send out everything for a second opinion.’”

Most of the consultations Dr. Simpson receives are from pathologists looking for guidance on cases involving atypical ductal hyperplasia and low-grade ductal carcinoma in situ. These same types of cases showed the least amount of concordance in the study. The participating pathologists agreed with the consensus diagnosis on 48 percent of the atypia cases. Overinterpretation of DCIS as invasive carcinoma occurred in three percent of cases; overinterpretation of atypias was noted in 17 percent; and overinterpretation of benign without atypia was seen in 13 percent. Underinterpretation of invasive breast cancer was noted in four percent of cases; underinterpretation of DCIS was seen in 13 percent; and underinterpretation of atypia was seen in 35 percent.

The study oversampled cases with atypia and DCIS to gain statistical precision for concordance in these categories. The breakdown was benign without atypia, 30 percent (10 percent nonproliferative and 20 percent proliferative without atypia); atypia, 30 percent; DCIS, 30 percent; and invasive carcinoma, 10 percent. “That’s not reality,” Dr. Wei says. “That’s not the percent in the real world.”