(Click arrow for video.) With this tissue sample, the interpretations of 36 pathologists ranged from “common nevus,” the technical term for a benign mole, to invasive melanoma. The consensus reference panel judged it to be a Class III melanoma in situ.
Every year, millions of Americans have a suspicious mole or skin lesion biopsied and sent to a pathologist to learn whether it is a potentially deadly melanoma. The pathologist’s interpretation is important: If the lesion is judged to be benign, no treatment may be recommended, but if malignant, the patient will typically undergo surgery and possibly other treatments.
New research indicates that pathologists are likely to agree when lesions are benign or highly malignant, but often disagree when gray-area lesions are less obviously characterized. What’s more, the pathologists in the study not only often disagreed with the interpretations of a consensus reference panel of experts, they also often disagreed with their own interpretations when shown the same biopsy samples eight or more months later.
The study appears June 28 in The BMJ (British Medical Journal). Its lead author was Dr. Joann G. Elmore, a professor of medicine at the University of Washington School of Medicine in Seattle.
“We found that pathologists’ interpretations of biopsies for certain gray-area lesions indicate that accuracy and reproducability can be affected,” Elmore said. “These findings underscore how challenging it may be to make these judgements in clinical practice. Such interpretations could be improved by using a standardized classification system, which could reduce the risk of misdiagnosis and inappropriate treatment.”
The investigation involved 187 experienced pathologists in 10 states, who had volunteered to participate. In the study’s first phase, each was asked to review and interpret 48 cases randomly selected from 240 skin biopsies. In the second phase, 118 of the pathologists viewed the same set of slides that they had interpreted before but shuffled in a different order. At least eight months had passed between the first and second viewings of the slides.
The pathologists’ interpretations were then organized with the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) histology form, which placed each interpretation into one of five diagnostic classes:
I) benign lesions that require no further treatment;
II) moderately abnormal lesions in which the removal of a small margin of tissue around the lesion is suggested;
III) severely abnormal lesions, including melanoma in situ, in which a slightly larger margin is suggested;
IV) early stage invasive melanoma, in which case a margin ≥1 cm is recommended;
(V) higher stage invasive melanoma, in which case a wide excision, ≥1cm, is recommended with possible additional treatment, including sentinel lymph node biopsy and adjuvant radiation or chemotherapy.
The researchers found that the participating pathologists agreed with the consensus panel’s interpretation in 92 percent of the benign Class I cases and in 72 percent of the Class V higher-stage invasive melanomas. However, participants agreed with the panel’s consensus diagnosis in 25 percent of the Class II cases, 40 percent of the Class III cases and 43 percent of the Class IV cases.
“This low level of diagnostic precision is of clinical concern,” the researchers wrote. “Although diagnostic discordance has been described in other areas of clinical medicine, including pathologists diagnosing breast biopsies and radiologists interpreting mammograms, the findings reported here are more pronounced than in other fields of medicine.”
Dr. Michael Piepkorn, a UW clinical professor of dermatology and senior author of the study, offered this context:
"The findings reflect the emerging realization that a large gray zone of intermediate moles exists between common moles and fully developed melanoma. The diagnostic processes developed over past generations of pathologists do not reliably discriminate between the intermediate moles that are clinically harmless versus those that harbor changes that will worsen over time and ultimately become malignant.”
In an associated opinion piece also in The BMJ, Elmore emphasized that "the diagnostic variability that we found does not mean that pathologists are the problem.” She added that "pathologists embrace this responsibility with the utmost skill and thoughtful commitment.”
In addition to adopting more standardized classification systems, physicians could communicate to patients that there are limits to medical professionals’ ability to classify skin lesions, the researchers wrote. “We propose adding standardized statements to pathology reports reminding readers that melanocytic lesions are challenging to interpret and that variability exists among pathologists, especially in the middle diagnostic classes,” they wrote.
Invasive melanoma kills more than 9,000 Americans a year.
This work was supported by the National Cancer Institute (R01 CA151306, R01 CA201376, and K05 CA104699).