March 21, 2016
2 min read

Pathologists often disagree when diagnosing atypia, DCIS

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Pathologists reviewing biopsy slides were less likely to confirm an initial diagnosis of atypia or ductal carcinoma in situ than a diagnosis of invasive breast cancer, according to the results of a population study.

“Results of the B-Path (Breast Pathology) Study, an evaluation of diagnostic agreement among pathologists interpreting breast biopsy specimens, indicated marked variability across diagnostic categories,” Joann G. Elmore, MD, MPH, professor of medicine and adjunct professor of epidemiology at University of Washington School of Medicine, and colleagues wrote. “These results raise concerns that interpretations of breast biopsy specimens in clinical practice may be inaccurate.”

Joann Elmore

Joann G. Elmore

Elmore and colleagues sought to assess the effect of diagnostic variability among U.S. pathologists. Their study included data from 115 practicing pathologists, representing 6,900 total interpretations from 240 women undergoing breast biopsy between the ages of 50 and 59 years.

For each biopsy, a single representative slide was analyzed to estimate the number of biopsies that would be verified if the same slide were interpreted by a three-person reference group.

The researchers used B-Path Study results, as well as data on the prevalence of biopsy diagnoses for women aged 50 to 59 years in the Breast Cancer Surveillance Consortium, to establish predictive values.

Elmore and colleagues found that the use of one representative slide per case led to verification by reference consensus diagnosis in 92.3% (95% CI, 91.4-93.1) of breast biopsy diagnoses.

Overinterpretation occurred in 4.6% (95% CI, 3.9-5.3) of cases and underinterpretation occurred in 3.2% (95% CI, 2.7-3.6).

Verification concordance remained high for cases of invasive breast cancer (97.7%; 95% CI, 96.5-98.7) and benign disease without atypia (97.1%; 95% CI, 96.7-97.4).

However, verification rates for precancerous atypia and noninvasive ductal carcinoma in situ (DCIS) — which is often called “stage zero breast cancer” — varied more widely.

For atypia, the researchers saw a 53.6% overinterpretation and an 8.6% underinterpretation in the reference consensus. DCIS had an overinterpretation rate of 18.5% and an underinterpretation rate of 11.8%.

The researchers acknowledged limitations of their study, including the use of only one slide per biopsy and the reliance on film mammography alone, which may not represent more recent advances in screening science. Further, they noted that their results may not be generalizable to women in other age groups or to unscreened women.

“Efforts to reduce diagnostic variability need to be considered and evaluated and might include educational programs, improved diagnostic techniques or second-review policies,” Elmore and colleagues wrote. “Alternatively, women with borderline breast lesions that are difficult to categorize, such as atypical ductal hyperplasia and low-grade DCIS, may benefit from revised guidelines for clinical treatment and management, given the degree of diagnostic variability and biological overlap between these diagnostic categories.”

Laura Esserman

Laura Esserman

These study results raise questions not only of diagnosis, but of the conception of cancer itself, Alexander Borowsky, MD, associate professor of pathology and laboratory medicine at University of California, Davis, and Laura Esserman, MD, MBA, professor of surgery and radiology and director of the Carol Franc Buck Breast Cancer Center at University of California San Francisco Helen Diller Family Comprehensive Cancer Center, wrote in an accompanying editorial.

“We must invest effort in developing methods to better distinguish true cancer from indolent pseudocancer or its precursors,” Borowsky and Esserman wrote. “As we become better able to identify indolent lesions, we may be better able to classify their precursors as indolent lesions of epithelial origin and safely avoid overtreatment. The B-Path Study further emphasizes the need to redefine ‘cancer’ and avoid using the term for lesions that are not destined to kill the patient.” – by Cameron Kelsall

Disclosure: The NCI provided funding for this study. Elmore and three other researchers report grants from the NCI during the conduct of this study. The other researchers, Borowsky and Esserman report no relevant financial disclosures.