Do we need to rethink the diagnoses melanoma <i>in situ</i> and severely dysplastic naevus?

Abstract

Dear Editor, Many countries have seen a dramatic increase in the reported incidence of cutaneous melanoma in recent decades, largely driven by increased diagnoses of melanoma in situ and thin invasive melanoma. The incidences of thick and metastatic melanomas, and melanoma mortality have remained relatively stable. While ageing populations could be causing some true increase in melanoma incidence, much of this increase may represent overdiagnosis: diagnosis of lesions that would never have caused harm if left undetected and untreated.1 If it occurs, melanoma overdiagnosis may result in potential psychological and physical harms to individuals, as well as significant costs to the healthcare system from procedures and long-term surveillance.1-3 The use of new diagnostic labels (e.g. ‘melanocytic neoplasm’)2 and/or the recalibration of diagnostic thresholds for the diagnosis of melanoma in situ could reduce these harms.4, 5 These strategies could also be applied to the diagnosis of severely dysplastic naevus, whereby the diagnostic label and apparent equivalence to melanoma in situ in the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema (with associated treatment recommendations)6 may also cause substantial anxiety for patients and clinicians.3 We undertook a search and review of the published evidence to support or reject a change to the diagnostic thresholds and/or terminology used for these low-risk melanocytic lesions and provide a detailed report on our findings,7 which we summarize here. Three lines of evidence were evaluated (Table 1). First was evidence on the natural history of these lesions, which we found was sparse as both melanoma in situ and severely dysplastic naevus are usually managed with excision. We found four studies on natural history, all at high risk of bias. One statistical modelling study estimated that at most 3.5% of lentigo maligna (a type of melanoma in situ) may progress to lentigo maligna melanoma (a type of invasive melanoma) each year. Three retrospective studies reported on patients with severely dysplastic naevi who were observed following incomplete excision. None of the collective 127 patients with positive or close margins developed an invasive melanoma at the same site as the severely dysplastic naevus, or metastases, after follow-up periods of between 6 months and 29.9 years. Second was evidence on the reliability of diagnostic criteria for the two types of lesions. We found 14 reproducibility studies, three of which were at low risk of bias. The largest of these, by Elmore et al.,8 found poor reproducibility for diagnoses of melanoma in situ and severely dysplastic naevus (MPATH-Dx class III), with 40% agreement between study pathologists and an expert panel consensus, 45% interobserver agreement, and 60% intraobserver agreement. Other studies also demonstrated poor reproducibility for diagnoses of both melanoma in situ and severely dysplastic naevus. Third was evidence of diagnostic drift in the diagnostic threshold over time, such that a more ‘malignant’ diagnostic label would now be applied even though the same melanocytic lesion was judged benign previously. We found two studies providing evidence on diagnostic drift, both at high risk of bias. These provided evidence of a downward shift of the diagnostic thresholds, and expansion of disease definitions, for both melanoma in situ and severely dysplastic naevus. The first retrospective study compared the original diagnoses made for 40 melanocytic lesions in 1988–1990 against diagnoses made by dermatopathologists in 2008–2009 who were blinded to the original diagnoses. Of the 40 lesions, 29 were diagnosed as severely dysplastic naevi and 11 as superficial spreading melanomas in 1998–1990. The mean proportion upgraded to melanoma in 2008–2009 was seven of 40 (18%), with no lesions downgraded. In another study, 1179 lesions originally diagnosed as junctional or compound naevus in 1980–1989 were re-reviewed in 2011–2012. Using contemporary histopathological criteria, 117 of 1179 (10%) were reclassified as dysplastic naevi (seven severely dysplastic naevi, 42 moderately dysplastic naevi, and 66 mildly dysplastic naevi; two excluded). These studies both suggest an implicit lowering of the diagnostic thresholds for melanoma and severely dysplastic naevus over time, causing expansion of the disease definition. In summary, sparse natural history evidence suggests uncertain but likely low risk of progression from melanoma in situ to invasive melanoma, and negligible risk of progression from severely dysplastic naevus to invasive melanoma. These types of lesions may be better conceptualized as risk factors for, rather than obligate precursors to, invasive melanoma. There is strong evidence of low reproducibility for diagnosis of both types of lesions, and some evidence that disease definitions have expanded over time. Our review supports the need for robust discussion, in both clinical and pathology communities, on the benefits and downsides of changing diagnostic thresholds and/or terminology to address potential overdiagnosis. Such discussions could be facilitated through an international summit on the topic, which would inform the next steps towards achieving change in policy and practice for pathology diagnosis. Caitlin R Semsarian: Data curation (lead); formal analysis (equal); investigation (lead); project administration (equal); writing – original draft (lead); writing – review and editing (equal). Tara Ma: Data curation (equal); formal analysis (supporting); investigation (equal); project administration (equal); writing – review and editing (supporting). Brooke Nickel: Conceptualization (equal); methodology (equal); project administration (supporting); writing – review and editing (supporting). Richard Scolyer: Formal analysis (equal); writing – review and editing (equal). Peter Ferguson: Formal analysis (equal); writing – review and editing (equal). Peter Soyer: Formal analysis (equal); writing – review and editing (equal). Lisa Parker: Formal analysis (equal); writing – review and editing (equal). Alexandra Barratt: Formal analysis (supporting); writing – review and editing (equal). John F Thompson: Formal analysis (equal); writing – review and editing (equal). Katy JL Bell: Conceptualization (lead); data curation (equal); formal analysis (equal); funding acquisition (lead); investigation (equal); methodology (equal); project administration (equal); supervision (lead); writing – original draft (supporting); writing – review and editing (lead).

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