Diagnosing Melanomas Is Not Easy

Nick Mulcahy

June 28, 2017

There are notable levels of inaccuracy and disagreement among US pathologists when diagnosing suspected melanomas, according to results of a new study.

Importantly, for melanoma in situ and early-stage invasive melanoma, which together are more common than all other melanomas combined, the diagnoses by the physicians participating in the study were "neither reproducible nor accurate," report the authors, led by Joann Elmore, MD, MPH, an internist and epidemiologist at the University of Washington School of Medicine in Seattle.

However, pathologists are not at fault here, especially for these two categories of melanomas, which are among the "intermediate" types of lesions, Dr Elmore told Medscape Medical News.

"Our findings reflect the difficulty of the gray zone of intermediate lesions and highlight that our current diagnostic processes are limited by our technology," she wrote in an email.

In addition, currently, there are insufficient criteria for distinguishing these intermediate lesions, she said.

The new study was published online June 28 in BMJ.

Overall, the findings confirm previous studies, which have included small numbers of specimens and pathologists. The new study is the first population-level evaluation of pathologists' work in this area.

The investigators recruited 187 pathologists from 10 states who interpret melanocytic lesions as part of their job. Nearly 75% of the pathologists were community based, most were not certified or trained in dermapathology, and nearly half had a caseload of fewer than 10% of melanomalike lesions per month. They were asked to interpret the same set of skin biopsy specimens (n = 36-48) on two separate occasions (phases 1 and 2).

The study authors acknowledged that there were more cases of "difficult to interpret" intermediate lesions than are found in routine clinical practice.

All of the cases had already been reviewed by a panel of three expert dermapathologists, who established a "consensus reference diagnosis" for each biopsy specimen.

Study participants' interpretations were assigned to one of five classes: I, mild atypia; II, moderate atypia; III, severe atypia or melanoma in situ; IV, early invasive melanoma; and V, invasive melanoma. Classes II-IV are considered intermediate.

The investigators measured accuracy by comparing the pathologists' determinations with the expert panel's determination.

The pathologists were most accurate when assessing class I mild lesions (92%) and class V high-stage invasive melanoma (72%).

But accuracy suffered in the intermediate classes, with concordance with the experts less than 50%.

The pathologists were only accurate with 25% of the class II moderately atypical lesions; 40% of class III severely atypical lesions and melanoma in situ; and 43% of class IV early-stage invasive melanoma.

Hong Wu, MD, PhD, director of dermatopathology at Fox Chase Cancer Center in Philadelphia, Pennsylvania, pointed out that with respect to misclassifications, it is "most important to avoid misdiagnosing an invasive melanoma (especially as T1b or above) as benign; and in the other direction, a benign nevus as an invasive melanoma (especially as a class V lesion).

"This is [most important] because misinterpretation between class I/II and class V lesions will lead to very different treatment and follow-up of the patient," he explained.

Misinterpretation between class I/II and class V lesions will lead to very different treatment and follow-up. Dr Hong Wu

Dr Wu, who was not involved in the study, took a deep dive into the study data and found some results that he took "most seriously."

He highlighted that among patients classified with invasive melanoma (class IV or V) by study pathologists, an estimated 16% would be reclassified downward as having benign lesions (class I or II) by the experienced consensus panel.

Furthermore, among patients classified with benign lesions (I or II) by study pathologists, an estimated 0.5% would be classified as having invasive melanoma (IV or V) by the experienced consensus panel, Dr Wu said.

The study also yielded another troublesome insight about the pathologists when they described biopsy samples as class II-IV (ie, intermediate). There was a lack of reproducibility of the pathologists' interpretations of the same case on two different occasions, which was part of the study design. The concordance between the pathologists' first and second diagnoses ranged from 35.2% to 63.2% for these intermediate cases.

At a population level, the study authors estimate that 82.8% of pathologists' diagnoses would be verified if reviewed by a consensus reference panel of experienced pathologists, with 8% of cases overinterpreted by the initial pathologist and 9% underinterpreted.

To make this population-level estimate, the team performed a calculation that changed the prevalence of skin biopsy classifications to reflect the distribution found in clinical practice. The study authors acknowledged that their study sample of lesions included more cases that were intermediate and thus "more difficult to determine."

Looking to the future, the study authors hope that "reliable and objective techniques" can be developed to support pathologists' visual assessments of melanocytic lesions.

The study was supported by the National Cancer Institute. Dr Elmore and Dr Wu have disclosed no relevant financial relationships.

BMJ. 2017;357:j2813.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

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