Home » Blog » Clinical Articles » Dysplastic naevi: the controversy continues

Dysplastic naevi: the controversy continues

Key Points

 

Dysplastic naevus: the controversy since the 1970s

The entity of dysplastic naevus has been shrouded in controversy since first described in the 1970s.1 This appears to be due to:

  1. Interobserver differences between histopathologists in applying the previous three tier grading system for dysplasia
  2. Perceived risk of progression to melanoma, and
  3. The possibility of benign entities simulating melanoma, all of which contribute to uncertainty and variability in management.2,3

Dysplastic naevi are benign neoplasms of melanocytes.3

Dysplasia in melanocytes may occur de novo or in association with either congenital dermal naevi or common dermal naevi. It is probable that dysplasia arising in pre-existing naevi results from successive acquisition of genetic abnormalities.3 Both common naevi and dysplastic naevi demonstrate BRAF or NRAS mutations.3

It was at one time proposed that there is a step-wise model of tumour progression from dysplastic naevi through mild, to moderate, then severe dysplasia, and finally melanoma.4 However, there is no evidence that dysplastic naevi are, in fact, common precursors of melanoma.4 In actuality, the most common naevus remnant found in association with melanoma is the common acquired naevus.4

Given the large number of dysplastic naevi, compared with the comparatively small number of melanomas arising in association with dysplastic naevi, it seems that the rate of progression from dysplastic naevus to melanoma is extremely low.4 Dysplastic naevi seen associated with melanomas have an increased incidence of TERT promoter mutations, a common early genetic event in the evolution of melanoma in situ.3 This suggests that some dysplastic naevi are an intermediate entity between benign naevus and melanoma.3

There is a lack of data examining the frequency of similar genetic alterations in non-melanoma associated dysplastic naevi; thus, although the risk of progression is very low, it is suggested that naevi with high grade dysplasia or added genetic events (e.g. TERT promoter mutation) are considered for complete excision.3

It has been suggested that dysplastic naevi represent a marker of increased risk for an individual developing melanoma.5

It is difficult to establish the risk of melanoma at a separate site in patients with dysplastic naevi, as the reported incidence of dysplastic naevi in fair-skinned individuals varies widely (between 2% and 50%).4

One study has demonstrated that only the diameter of the dysplastic naevus had a significant association with a personal history of melanoma,6 whilst another study has shown that individuals with many naevi, whether common or dysplastic, have an increased risk of developing melanoma.7 Thus it would seem that two factors are associated with an individual’s risk of developing melanoma: a large number of common or dysplastic naevi (>100) and the larger size of the naevi (>4.4mm).6

It is generally agreed that there is low interobserver agreement between pathologists when grading dysplastic naevi, particularly in those lesions exhibiting moderate atypia to early in situ melanoma.8,9 This leads to uncertainty with regard to management of these lesions, especially if there is margin involvement.

In 2017, Wall et al.2 conducted a survey investigating the management of dysplastic naevi by Australian dermatologists. This survey demonstrated that, similarly to comparable studies reported within the USA and Canada, most dermatologists would re-excise a moderately or severely dysplastic naevus with involved margins.2

There is, however, variability in Australian dermatologists’ approaches to severely dysplastic naevi (clinically concerning for melanoma) which are completely excised on biopsy, with 44% re-excising with a 5mm margin, and the remainder considering no further treatment necessary.2 In addition, whilst between 5-12% of US and Canadian dermatologists re-excise mildly dysplastic naevi involving margins, that rate in Australian dermatologists is 49%.2

A consensus statement released by Kim et al.10 in 2015 identified a critical gap in knowledge with regard to management of dysplastic naevi with involved margins. This consensus statement recommended that mildly to moderately dysplastic naevi with clear histologic margins need no re-excision.

If a biopsy report reveals severe dysplasia with positive margins, re-excision to achieve a 2-5mm clinical margin is recommended. The statement suggested that mildly dysplastic naevi with positive histologic margins after biopsy (and no residual pigment) may be observed, and while observation may be a reasonable option for moderately dysplastic naevi with positive histologic margins (and no clinical pigment), more data are required to make a definitive recommendation.10

A further multi-centre retrospective cohort study in 2018 by Kim et al.11 suggests that close observation is a reasonable management approach for moderately dysplastic naevi with positive histologic margins. No specific recommendations are made regarding a severely dysplastic naevus with clear margins on biopsy.

 

WHO redefines melanocytic naevi

The World Health Organisation (WHO) released their new Classification of Skin Tumours in 2018.3 They define dysplastic naevus as ‘a subset of melanocytic naevi that are clinically atypical and characterized histologically by architectural disorder and cytological atypia, always involving their junctional component.10

Diagnostic criteria for dysplastic naevi traditionally include a division of cytoarchitectural atypia into mild, moderate and severe categories.3 Pathologists often further subdivide these categories into ‘mild to moderate’ and ‘moderate to severe’ to reflect the histological field effect often perceived in these lesions.

Lentiginous junctional or compound naevi (previously labelled mildly dysplastic naevi) are not associated with increased melanoma risk/progression to melanoma, and are also common within the population.3 The WHO consensus meeting working group recommends against the continued use of the term ‘mildly dysplastic naevus’ and instead recommends the use of low grade and high grade dysplasia.

So, where are we now with these new recommendations regarding the grading of dysplastic naevi, and what are the management implications? It seems that the new WHO recommendations support the view that biopsies of the previously known mildly dysplastic naevi need no further treatment, having removed the entity from their classification.

It would appear that there is agreement that dysplastic naevi with high grade dysplasia (previous severely dysplastic naevi) with involved margins requires re-excision to achieve a 2-5mm clinical margin of clearance.

However, there appears to be no recommendations or clear consensus regarding whether these high grade dysplastic (previous severely dysplastic) naevi require re-excision, if initially excised with clear margins, albeit less than 2mm.

With regard to dysplastic naevi with low grade dysplasia (previous moderately dysplastic naevi), there is a slowly growing body of evidence to suggest that it may be reasonable for these cases to be observed if they were excised with clinically clear margins/no residual clinical pigment is observed, despite histologically involved margins.

Given the current variation in clinical management of these lesions, as well as the continued lack of interobserver agreement between histopathologists when diagnosing these lesions, more data may be required before this recommendation is accepted.

In conclusion, as the consensus statement by Kim et al.10 recommends, the decision to re-excise dysplastic naevi should be based on both the clinical and histologic findings.

If the prebiopsy level of clinical concern is high, re-excision should be considered if the biopsy reveals positive margins, even if the level of histopathological dysplasia is low.

In addition, there may be clinical scenarios warranting re-excision of a mildly, mildly-moderately/moderately dysplastic lesion (now known as lentiginous junctional/compound naevi and dysplastic naevus with low grade dysplasia respectively), including patient preference.10

 

References:

  1. Duffy K, Grossman D. The dysplastic nevus: from historical perspective to management in the modern era. J Am Acad Dermatol. 2012;67 (1): 1. E1-18. DOI: 10.1016/j.jaad.2012.03.013
  2. Wall N, De’Ambrosis B, Muir J. The management of dysplastic naevi: a survey of Australian dermatologists. Australasian Journal of Dermatology. 2017;58:304-307. DOI: 10.1111/ajd.12720
  3. Elder DE, Massi D, Scolyer RA, Willemze R, editors (2018). WHO classification of skin tumours. 4th Ed. Lyon: IARC.
  4. Busam KJ, Gerami P, Scolyer RA (2019). Pathology of Melanocytic Tumors. 1st Ed. Philadelphia: Elsevier.
  5. Elder DE. Dysplastic naevi: an update. Pathology. 2010;56(1):112-120.
  6. Xiong M, Rabkin M, Piepkorn M, Barnhill R, Argenyi Z, et al. Diameter of dysplastic naevi is a more robust bio marker of increased melanoma risk than degree of histologic dysplasia: a case-controlled study. J Am Acad Dermatol. 2014;71(6):12578.e4. DOI: https://doi.org/10.1016/j.jaad.2014.07.030
  7. Holly EA, Kelly JW, et al. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol. 1987;17:459-468. DOI: https://doi.org/10.1016/S0190-9622(87)70230-8
  8. Hiscox B, Hardin MR, Orengo IF, Rosen T, Mir M, Diwan AH: Recurrence of moderately dysplastic nevi with positive histological margins. J Am Acad Dermatol . 2017;76:527530.  DOI: 10.1016/j.jaad.2016.09.009
  9. Stefanato C. The “Dysplastic Nevus” Conundrum: A look back, a peek forward. Dermatopathology. 2018;5:53-57. DOl: https://doi.org/10.1159/000487924 
  10. Kim C, Swetter S, Curiel-Lewandrowski C, Grichnik J, Grossman D, et al. Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi. JAMA Dermatol. 2015;151(2):212218. DOI: 10.1001/jamadermatol.2014.2694
  11. Kim C, Berry E, Marchetti M, Swetter S, Liam G, et al. Risk of subsequent cutaneous melanoma in moderately dysplastic nevi excisional biopsies but with positive histologic margins. JAMA Dermatology. 2018;154(12):1401-1408 DOI: 10.1001/jamadermatol.2018.3359

 

– General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.