Atypical nevi

Published on 19/03/2015 by admin

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Atypical nevi

Julia Newton-Bishop

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

The term ‘atypical nevi’ refers to clinically diagnosed lesions, defined as nevi that are more than 5 mm in diameter with an irregular or diffuse edge and variable color. Biologically such nevi are believed to be melanocytic neoplasms that result from more protracted proliferation (leading to a stromal reaction) than do banal benign melanocytic nevi. Histologically, atypical nevi are characterized by elongated rete ridges, bridging of melanocytes between rete ridges, a predominance of single melanocytes over nested melanocytes, and a dermal inflammatory reaction with papillary dermal fibroplasia. Although these histological changes are characteristic there may be a lack of correlation between the clinical and histological features, which has lead to controversy which has largely been unhelpful. Suffice it to say that the entity remains an important one, that it is clinically diagnosed but there are characteristic histological correlates which are variable in degree.

I use the term ‘atypical nevi’ to mean nevi that others might call dysplastic nevi.

Atypical nevi may be considered more of a marker of patients at higher risk of melanoma than as frequent precursors of melanoma. The indication for excision is to exclude melanoma, not to make a diagnosis of an atypical nevus. There is no role for prophylactic excision of atypical nevi with a banal dermoscopic appearance except perhaps when a single atypical nevus appears in an individual who is older than the usual age for such nevi (over 50 years). It is important to note that two-thirds of melanomas do not arise from previous nevi even in the atypical mole syndrome, so that removing all atypical nevi does not prevent melanoma. It is mandatory to perform total body skin examinations in patients at risk for melanoma, looking for the ‘ugly duckling nevus,’ which stands out as different from that patient’s typical ‘signature nevi.’ The mnemonic ABCDE has been used as a clinical aid (asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution or change in a lesion), but in practice most experts make the diagnosis based upon a global clinical examination. This is similar to a child who recognizes her written name without understanding the meaning of the individual letters.

Some authorities advocate grading atypical nevi as mild, moderate, or severe atypical nevi (NIH Consensus Conference. Diagnosis and treatment of early melanoma. JAMA 1992; 268: 1314–1319). Others have argued that such grading has poor reproducibility, and therefore they do not grade the severity of the atypia. The majority of dermatopathologists prefer to grade the architectural and the cytologic atypia separately. It is not uncommon for severely atypical nevi to cause diagnostic difficulty. Histopathologists may report that such a lesion is of unknown malignant potential and recommend that the lesion best be treated as melanoma with a wide local excision as for melanoma.

It is common to have a single atypical nevus. In a mildly atypical nevus, with a bland dermoscopic appearance, the risk of malignant change under the age of 50 years is very small. Such nevi therefore should not be excised. It is then important to educate the patient how to monitor the lesion and to give that patient information booklets with photographs of atypical nevi and melanoma so that the patients knows what to look for. Merely asking the patient to ‘keep an eye out for change’ is insufficient.

Where the atypical nevus shows more markedly atypical features, and especially in older individuals, then the lesion should probably be excised. In such cases, taking a photograph and reviewing is rarely helpful as one usually feels no less comfortable to leave alone on review than at first visit; the hypothesis is that, if an atypical nevus is single, the patient’s risk can be removed by an excision of the lesion. If an atypical nevus causes concern then it should be excised in its entirety rather than sampled incisionally. Although data have been published to suggest that there is a low rate of clinical recurrence after biopsy of benign moderately ‘dysplastic’ nevi, sampling is risky as sample error may lead to examination of a less atypical portion of the tumor. For the patient and the clinician, complete excision is a safer approach as melanocyte pathology is difficult to interpret and the pathologist could make an error in this grey area – it is better to have excised the lesion completely in the face of ambiguity. Incisional biopsy may furthermore stimulate proliferation of melanocytes to lead to a clinically and histologically concerning lesion, known as a pseudo-melanoma; if there is enough clinical concern to sample such a nevus, an experienced clinician will be sampling a lesion with some clinically worrisome features thereby supporting the argument that a complete excision is desirable.

Patients with increased numbers of banal nevi and/or multiple clinically atypical nevi are said to have the atypical mole syndrome and require different management. These patients have a melanoma risk that cannot be removed by excision of nevi. The key components of good treatment are:

image Taking a detailed family history to determine if cases of melanoma have occurred in the family. Risk estimation is strongly modified by family history (see www.genomel.org)

image Education about monitoring of nevi

image Follow-up/supervision in clinic, for a period whose length is determined by risk estimation based upon family or personal history of melanoma, the competency of the patient in self examination and the clinical phenotype

image Excision of atypical nevi where it is necessary to exclude melanoma

image Education about ensuring sufficient sun protection without becoming vitamin D depleted. Sunburn avoidance is crucial in that sunburn is established to be associated with melanoma risk in multiple studies. Sunbathing, independently of sunburn may also increase risk so should be avoided in those with atypical moles.

Management strategy

The strategy is essentially to excise clinically atypical nevi if there is a reasonable suspicion of malignancy whilst avoiding excessive numbers of procedures. The history of the lesion, the appearance to the naked eye, and the dermoscopic appearance are all important. Clinically atypical nevi, which are behaving in an unusual fashion, should prompt a decision to excise such lesions. Examples include a new atypical nevus over the age of 50 or a lesion which looks like an atypical nevus which has grown rapidly in the previous 6 months. Dermoscopy has been shown to increase diagnostic accuracy. Although anecdotal reports in the literature have utilized topical tretinoin, imquimod, laser surgery, or cryosurgery, these modalities cannot be advocated for treating atypical nevi.

Treatment strategies for atypical nevi:

image Single nevi

image Multiple nevi

Specific investigations

imageDermoscopy: change in appearance B
imageDermoscopy influencing decision to treat B
imageDermoscopy in patients under follow-up for increased risk of melanoma B
imageConfocal microscopy: a pilot study C
imageMobile teledermatology B

The details of how to perform dermoscopy and the criteria for atypical nevi and melanoma are beyond the scope of this book, but there are increasing numbers of dermoscopy teaching sites on the Intranet including www.genomel.org, and an Interaction Atlas of Dermoscopy CD from Medisave.

Variables predicting change in benign melanocytic nevi undergoing short-term dermoscopic imaging.

Menzies SW, Stevenson ML, Altamura D, Byth K. Arch Dermatol 2011; 147: 655–9.

In this study from the Sydney Melanoma Diagnostic Centre, the authors reviewed 2497 benign melanocytic nevi over 2.5 to 4.5 months and documented a change in 16%. Change in dermoscopic features was most common under the age of 18 and over the age of 65 years. Dermoscopy may increase diagnostic accuracy and there may be a combination of signs that allow dermatologists to make the diagnosis of melanoma with confidence. In patients under surveillance, change alone may be sufficient to cause concern and indeed short-term surveillance is commonly used to ensure that melanomas are not being missed. Therefore, a melanocytic lesion that looks benign, but displays some atypical features, may be reviewed at 3 to 4 months, with the advice that if there is change after this period of time the lesion should be excised. This study attempted to determine how often clinically normal moles change dermoscopically at different ages. The high frequency of change under the age of 18 years was expected as nevi are evolving in this age group, and it would be reasonable to conclude that dermoscopic change per se would not be sufficient to prompt excision of nevi in this age group. The authors did not speculate as to why change was also more common in the elderly. An interpretation of this paper would be that change is common: that short term dermoscopic review which detects new specific features of melanoma is likely to be of higher predictive value rather than change alone.

Impact of digital dermoscopy analysis on the decision to follow up or to excise a pigmented skin lesion: a multicentre study.

Burroni M, Wollina U, Torricelli R, Gilardi S, Dell’Eva G, Helm C, et al. Skin Res Technol 2011; 17: 451–60.

In this study of 3227 patients treated in four European dermatology units, dermosocpy images were stored and analysed using a computerized tool called the DB-DM-MIPS System (Biomips Engineering, S.R.L., Siena, Italy). The management (review versus excise) was investigated and the predictive positive value (the probability that a lesion indicated as suspect in that center proved to be a melanoma) of the clinicians was compared. The centers varied in the proportion of excised lesions which proved to be dysplastic or atypical nevi (ranging from 15% to 81%) but the proportion of excised very thin melanomas (<0.75 mm) was very similar in all centers. The predictive positive value ranged from 4% to 30%. Higher levels of excision did not correspond with greater numbers of melanomas excised.

Dermoscopy with computerized image analysis using a common system in this study was associated with considerable variation in ‘interventionism’; however, the proportion of thin melanomas excised appeared to be the same. Thus approaches to management (not surprisingly) appeared to be variable even when the clinicians were using a similar tool, but in this study at least there appeared to be no difference in melanoma detection rates.

Impact of dermoscopy on the management of high-risk patients from melanoma families: a prospective study.

van der Rhee JI, Bergman W, Kukutsch NA. Acta Derm Venereol 2011; 91: 428–31.

Dermoscopy is widely used. In this prospective study the authors attempted to assess the effect of dermoscopy on management of individuals from melanoma families in follow-up. The study related to only 132 patients in whom two melanomas were detected over a period of 18 months, but this proportion is not unexpected in a study of this sort. Dermoscopy was (perhaps surprisingly) only performed in 37% of patients. Use of dermoscopy did not result in changed diagnosis from melanoma to non-melanoma or vice versa. Seven lesions were diagnosed clinically as melanoma and all were judged to be suspicious of melanoma using dermoscopy, although only two were confirmed histologically to be malignant. Use of dermoscopy significantly reduced the number of excisions performed in this study; however, while dermoscopy did not increase sensitivity it increased specificity, in contrast to previous studies.

Application of mobile teledermatology for skin cancer screening.

Lamel SA, Haldeman KM, Ely H, Kovarik CL, Pak H, Armstrong AW. J Am Acad Dermatol 2012; 11: 957–69.

This study from California used an intelligent phone and ClickDerm (Click Diagnostics, Boston, MA) designed to facilitate remote diagnostics. The outcomes demonstrated concordance between the two dermatologists taking part and the agreement between the ‘in person’ diagnoses and the teledermatologist’s diagnoses. Overall the concordance in terms of decisions made was high at 81% but a lack of concordance was greater for older patients and for dysplastic or atypical nevi.

The development of intelligent phones and ‘Apps’ has had an impact on imaging/monitoring nevi. Most ‘Apps’ remain to be evaluated but this paper describes a form of teledermatology using mobile phones.This study highlights the possibilities for use of digital imaging but also the potential risks in teledermatology of melanocytic nevi.

First-line therapies

imageLate diagnosis of melanomas: an assessment of the associations B
imageNumber of melanocytic lesions excised per melanoma detected B
imageUK melanoma treatment guidelines  
imageMargins of excision for atypical nevi B

A decade of melanomas: identification of factors associated with delayed detection in an academic group practice.

Goodson AG, Florell SR, Boucher KM, Grossman D. Dermatol Surg 2011; 37: 1620–30.

The study was a retrospective study of 572 melanomas excised in the 10-year period 1999 to 2008 in new patients to the practice and in established patients. Established patients were less likely to have thicker lesions removed than new patients; however, there were significant numbers of established patients who had tumors thicker than 1 mm. Only 3% of melanomas were diagnosed as a result of change in photographic appearance on review in the pigmented lesion clinic. The interval for follow-up did not predict the depth of melanoma, suggesting that increasing surveillance might not address the problem of late diagnosis. These melanomas were thinner, however. Thicker primaries were more likely to be present on the trunk and extremities than other sites; these lesions were commonly clinically diagnosed by the dermatologist as non-melanoma skin cancers. The crucial therapy for melanocytic lesions is detection and excision of melanoma; this study reports an attempt to understand why melanomas are sometimes diagnosed late in a large office practice. The authors reflect on the difficulties around early detection: surveillance of high-risk individuals results in the identification of thinner tumors, although many of the more aggressive tumors mimic non-melanoma skin cancers. This explains why I argue for prompt full excision of all new skin cancers.

The number of benign moles excised for each malignant melanoma: the number needed to treat.

Sidhu S, Bodger O, Williams N, Roberts DL. Clin Exp Dermatol 2012; 37: 6–9.

In this retrospective study, 4691 lesions were examined in a 5-year period by nine dermatologists working in the UK NHS serving a population of 600 000. The key metric was the ‘number needed to treat’ which was the number of benign or dysplastic nevi and melanomas excised for every melanoma: interpreted as a measure of diagnostic accuracy. The number needed to treat ranged from 4.9 to 11.3, overall 6.3. More benign nevi were removed in female patients. The authors compared their results with reported measures elsewhere which ranged from 29.9 to 4; 6/7 of the other studies reported had higher values than this UK study. The authors suggest that this ratio might be a useful quality measure for the pigmented lesion clinic.

Excision of some atypical nevi to exclude melanoma is required, but efficient use of healthcare resources and avoidance of unnecessary scarring requires that excision of excessive numbers of nevi should be avoided.

Revised U.K. guidelines for the management of cutaneous melanoma.

Marsden JR, Newton-Bishop JA, Burrows L, Cook M, Corrie PG, Cox NH, et al. Br J Dermatol 2010; 163: 238–56.

The approach to excision of atypical nevi remains somewhat controversial. The UK perspective is clear however: that all suspicious melanocytic lesions should be excised in their entirety. Thus if atypical nevi are being excised to exclude melanoma then this would be the approach taken. The text is as follows: A lesion suspected to be melanoma, or where melanoma needs to be excluded, should be photographed, and then excised completely. The axis of excision should be orientated to facilitate possible subsequent wide local excision; generally on the limb this will be along the long axis. The excisional biopsy should include the whole tumour with a clinical margin of 2 mm of normal skin, and a cuff of fat. This allows confirmation of the diagnosis by examination of the entire lesion, such that subsequent definitive treatment can be based on Breslow thickness.

Incisional or punch should be avoided since it may lead to incorrect diagnosis due to sampling error, and make accurate pathological staging of the lesion impossible. Many perform shave excisions which may be a reasonable option if performed adequately and if the lesion is re-excised if necessary after pathology review. Shave biopsy was however assessed in the paper discussed below. The UK guidelines continue: ‘For the same reasons partial removal of nevi for diagnosis must be avoided and partial removal of a melanocytic nevus may result in a clinical and pathological picture very like melanoma (pseudomelanoma). This gives rise to needless anxiety and is avoidable. Incisional or punch biopsy is occasionally acceptable, for example in the differential diagnosis of lentigo maligna on the face or of acral melanoma, but there is no place for either incisional or punch biopsy outside the skin cancer multidisciplinary service.’

Dysplastic naevi: to shave, or not to shave? A retrospective study of the use of the shave biopsy technique in the initial management of dysplastic naevi.

Armour K, Mann S, Lee S. Australas J Dermatol 2005; 46: 70–5.

The management of atypical (dysplastic) nevi is a controversial subject. This study sought to assess the usefulness of the shave biopsy technique in the initial management of dysplastic nevi, and to demonstrate the advantages over the punch biopsy technique. The authors, from Sydney, New South Wales, reported a retrospective observational study of histopathology specimens examined in one histopathology practice over a 14-month period. Patients who had a clinical diagnosis of ‘dysplastic naevus’, which had initially been biopsied using either a shave or punch biopsy, and then followed up with a full-thickness elliptical excision, were included in the study. Histopathological concordance between the shave and punch biopsy specimens and their respective follow-up elliptical excisions was compared. The authors found that 21 of 22 (95.5%) shave biopsies were concordant with their respective excision specimens, and that 29 of 41 (70.7%) punch biopsies were concordant with their respective elliptical excision specimens. Of the shave biopsy specimens reviewed, 66% showed that the dysplastic nevi were completely excised with the initial biopsy, compared with 21.2% of the punch biopsy specimens. The authors concluded that the findings confirm that shave biopsies provide accurate diagnostic information in the assessment of dysplastic nevi. Shave biopsies enable the entire lesion to be submitted for histopathological assessment, improving the chances of an accurate diagnosis.

Clinical decision making based on histopathologic grading and margin status of dysplastic nevi.

Duffy KL, Mann DJ, Petronic-Rosic V, Shea CR. Arch Dermatol 2012; 148: 259–60.

There is some evidence within the US that the perspective of most dermatologists is that clear excision of atypical nevi is important. A survey of US dermatologists carried out in 2009 suggested that the majority considered that histological evidence of clear excision of a dysplastic nevus is necessary where there is moderate (81%) to severe (95%) atypia and 21% thought this was still important for mild atypia.

Thus the dermatologists considered that histological evidence of dysplasia would influence further management and that re-excision was necessary if the dysplasia was reported as moderate or severe. Whilst differentiation according to the degree of dysplasia seems at one level reasonable, the difficulty is that within a nevus there may be marked histological variation and that not re-excising a mildly atypical nevus is associated with some risk of leaving a more dysplastic component in place. In my view it is always preferable to aim for full excision at first pass.

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