Pathologists' diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study

Abstract

Objective To quantify the accuracy and reproducibility of pathologists' diagnoses of melanocytic skin lesions.Design Observer accuracy and reproducibility study.Setting 10 US states.Participants Skin biopsy cases (n=240), grouped into sets of 36 or 48. Pathologists from 10 US states were randomized to independently interpret the same set on two occasions (phases 1 and 2), at least eight months apart.Main outcome measures Pathologists' interpretations were condensed into five classes: I (eg, nevus or mild atypia); II (eg, moderate atypia); III (eg, severe atypia or melanoma in situ); IV (eg, pathologic stage T1a (pT1a) early invasive melanoma); and V (eg, ≥pT1b invasive melanoma). Reproducibility was assessed by intraobserver and interobserver concordance rates, and accuracy by concordance with three reference diagnoses.Results In phase 1, 187 pathologists completed 8976 independent case interpretations resulting in an average of 10 (SD 4) different diagnostic terms applied to each case. Among pathologists interpreting the same cases in both phases, when pathologists diagnosed a case as class I or class V during phase 1, they gave the same diagnosis in phase 2 for the majority of cases (class I 76.7%; class V 82.6%). However, the intraobserver reproducibility was lower for cases interpreted as class II (35.2%), class III (59.5%), and class IV (63.2%). Average interobserver concordance rates were lower, but with similar trends. Accuracy using a consensus diagnosis of experienced pathologists as reference varied by class: I, 92% (95% confidence interval 90% to 94%); II, 25% (22% to 28%); III, 40% (37% to 44%); IV, 43% (39% to 46%); and V, 72% (69% to 75%). It is estimated that at a population level, 82.8% (81.0% to 84.5%) of melanocytic skin biopsy diagnoses would have their diagnosis verified if reviewed by a consensus reference panel of experienced pathologists, with 8.0% (6.2% to 9.9%) of cases overinterpreted by the initial pathologist and 9.2% (8.8% to 9.6%) underinterpreted.Conclusion Diagnoses spanning moderately dysplastic nevi to early stage invasive melanoma were neither reproducible nor accurate in this large study of pathologists in the USA. Efforts to improve clinical practice should include using a standardized classification system, acknowledging uncertainty in pathology reports, and developing tools such as molecular markers to support pathologists' visual assessments.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. All authors had financial support from the National Cancer Institute for the submitted work. RLB reports a financial relationship with Myriad Genetics outside of the submitted work, and GML reports grants from Fred Hutchinson Cancer Research Center during the conduct of the study.

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Figures

Fig 1 Diagnostic terms given to example case by 36 pathologists who each independently interpreted the same glass slide (top image 5× magnification, bottom image 10× magnification)

Fig 2 Participant interpretive variation on each of 240 cases, with cases organized based on the MPATH-Dx consensus reference diagnosis class

Fig 3 Comparison of accuracy (discordance rates of over-interpretation rate and under-interpretation rate) by all three reference diagnoses

Fig 4 Population level predicted proportions of cutaneous melanocytic biopsy interpretations that would be verified by the consensus reference panel or would be classified as over-interpretations or under-interpretations