Management of Dysplastic Nevi: The Role of Complete Surgical Excision

Kavitha K. Reddy, MD
Director of Dermatologic Surgery
Department of Dermatology
Boston University School of Medicine

Gary S. Rogers, MD
Professor of Dermatology
Beverly Hospital Cancer Center
Lahey Health System
Boston, Massachusetts

Atypical moles, also called dysplastic nevi (DN), are considered by many to reside in the grey portion of the spectrum between benign nevi and melanoma. Because of the difficulty of assessing the behavior of an individual DN, and the association with an increased overall risk of melanoma, physicians and patients have grappled with the choice between observation and surgical excision.1 In the absence of a reliable predictive test or formal management guidelines, many physicians elect complete surgical excision of DN. The prevalence of DN is believed to be at least 8-10 percent in susceptible populations,2,3 posing a large health burden. An improved understanding of their role in and relationship with melanoma thus remains an important objective.

In pursuit of this goal, our research team examined detailed outcomes of surgical excision of DN, as well as the association of DN with melanoma.1 This pivotal data was analyzed for clinically relevant measures and sorted by grade of atypia, forming the first published evidence of specific DN excision outcomes.

Diagnosis and Current Practices

Clinically, atypical moles exhibit border or color irregularity, have a variable and often larger size than ordinary moles (5-15 mm), and are often found in patients with numerous nevi (often >50-100).4 Clark, Lynch and Elder originally described the clinical and histologic characteristics of these distinctive-appearing nevi in a portion of melanoma-prone families and sporadically in individuals prone to melanoma.5,6 Biopsy of either normal-appearing nevi or clinically atypical nevi reveals a subset with histologic features of atypia, such as atypical melanocytic hyperplasia, lamellar or eosinophilic fibrosis, and lymphocytic inflammatory response; these are termed nevi with architectural disorder, or dysplastic nevi.4 Some prefer to name these Clark’s nevi, noting that the term “dysplastic” may imply that all DN have significant malignant potential.7 Unifying diagnostic criteria have not been established to date for atypical or dysplastic nevi, but a number of groups have suggested criteria.4,8

The presence of clinically atypical nevi and/or histological dysplasia in nevi is associated with increased overall melanoma risk.9 Due to this increased risk, management includes counseling on skin cancer prevention and detection, as well as regular full-body skin examinations. Further management of a biopsied DN having a positive histologic margin has remained variable. As our study and others have demonstrated, in the absence of significant guidance as to risk, there has been substantial inter-physician variability in recommendations for observation or excision, and a standard of care has not been established.1,10 In our study sample of 580 DN, after biopsies reporting DN with a positive histologic margin, those with mild histologic dysplasia were most often observed (only 12 percent received excision), those with moderate dysplasia were variably excised (63 percent), and the vast majority of those with severe dysplasia (82 percent) received excision. Not surprisingly, nevi reported to have moderate histologic dysplasia represent the most nebulous portion of the DN spectrum, and management has been correspondingly ambiguous.1

Surgical Excision after Biopsy

In our study of 580 dysplastic nevi and 216 primary cutaneous melanomas, biopsied DN demonstrated a number of key characteristics (Figure 1).1 Positive histologic margins were more frequently reported as the grade of DN increased. In addition, biopsied DN with a positive histologic margin were treated with subsequent complete excision more frequently as the grade of DN increased.1 Changes in diagnosis upon excision of biopsied DN and rates of associated melanoma were examined. Primary cutaneous melanomas were also reviewed and analyzed to determine the type and depth of melanoma, rate of DN-associated melanoma, and grade of associated DN.1

The study outcomes provide evidence suggesting that mildly and moderately dysplastic nevi may generally behave differently than moderately-to-severely and severely dysplastic nevi.1 Of biopsy-diagnosed DN, two were found to harbor melanoma upon re-excision; both were moderately-to-severely dysplastic nevi. A 3.1 percent rate of melanoma was diagnosed on excision of DN with moderate-to-severe dysplasia. In contrast, there was not any instance in the study of a biopsy-diagnosed mildly or moderately dysplastic nevus containing melanoma upon excision.

Of 216 primary melanomas evaluated, a significant association with moderately-to- severely or severely DN was also evident. In cases where a grade of DN was specified, 93 percent of DN-associated melanomas showed moderately-to-severely or severely DN. Mildly and moderately dysplastic nevi were found significantly less often (6 percent of the time when a grade was specified) in DN-associated melanoma.

Our data suggest that excision of biopsy-diagnosed DN with moderate-to-severe and/or severe dysplasia may offer measurable benefits in the early detection and possible prevention of associated melanoma.1 The data also suggest that routine excision of biopsy-diagnosed DN with mild or moderate dysplasia may have significantly less benefit.1 As it is standard practice to remove the entire clinically visible nevus during biopsy, our findings are most generalizable to cases where the lesion has been clinically removed with the initial biopsy. The data further suggest that pathologist-issued recommendations for routine complete excision of clinically removed DN with mild or moderate dysplasia may be unnecessary. Based on these data, further examination is encouraged of the risks and benefits of excision in the management of these common skin lesions.1


Figure 1. Characteristics of biopsied dysplastic nevi

Key Considerations

Investigation of outcomes of the excision of DN represents a milestone in our understanding of DN and raises important questions for discussion.

DN generally receive more aggressive management by both pathologists and clinicians in cases of positive margins and with increasing grades of atypia.1,10 In our study, as the grade of DN increased, positive histologic margins were more frequently reported, and DN with a positive histologic margin were more often treated with complete excision.1 While the majority of dysplastic nevi are considered benign lesions, increasing concern about diagnostic accuracy and risk of transformation appears correlated with higher grade of atypia. Our study confirms the validity of these concerns in cases of DN with moderate-to-severe atypia and severe atypia, for which excision provides a measurable benefit in melanoma diagnosis and possible melanoma prevention.1 In addition, the data reveal that mildly and moderately dysplastic nevi appear to have a high degree of diagnostic accuracy on biopsy and a significantly lower association with melanoma, so excision offers fewer benefits.1

Many pathology reports routinely contain comments that DN with moderate or greater atypia and a positive histologic margin should be completely excised to confirm the diagnosis.11 It has been informally reported in the literature that many pathologists may increase the reported DN grade when a positive margin is found,12 suggesting pathologists’ desire to view a completely excised DN with negative histologic margins before feeling confident in the rendered diagnosis. Our study suggests that such diagnostic concerns may be appropriate in cases of biopsy-diagnosed DN with a severely atypical component, which show a significant rate of melanoma upon complete excision. However, greater confidence in the biopsy diagnosis of clinically removed mildly and moderately dysplastic nevi may be warranted, since in our study none revealed severe atypia or melanoma upon complete excision.1 Based on these data, pathologist-issued comments advising routine complete excision to confirm the diagnosis of biopsied mildly and moderately dysplastic nevi with negative clinical margins and a positive histologic margin may be unnecessary.

Recent studies have further examined rates of melanoma diagnosis upon excision of dysplastic nevi, supporting many of these findings. In a study of 77 histologically dysplastic acral nevi having mild to severe atypia, none revealed melanoma upon excision.13 A study of 134 cases of biopsied nevi with histologically moderate or severe dysplasia similarly did not find melanoma upon excision.14

Inter-observer diagnostic variability among pathologists remains a consideration.11 Uniform guidelines and improved diagnostic concordance should be a priority, with specimens optimally interpreted by a board-certified dermatopathologist. Potential inter-observer variability does not appear likely to justify routine re-excision of every biopsy-diagnosed moderately dysplastic nevus for fear of pathologic misdiagnosis. Diagnostic limitations in this regard should be improved through continued research and development of uniform guidelines of care.

In assessing the risk of transformation of a DN, Tsao and colleagues have estimated an overall rate of 1 in 10,000 for an “average” atypical nevus, based on rates of association of atypical nevi with melanoma that are consistent with our data.1,15 Risk stratification by grade of atypical nevus appears prudent. Our study data provide evidence suggesting that if DN are in some cases precursor lesions to melanoma, moderately-to-severely and severely dysplastic nevi may be more likely to transform than mildly or moderately dysplastic nevi.1 

Though concerns exist that the biologic behavior of any individual DN is not possible to predict, most agree that wholesale removal of DN is not warranted.12 Similarly, the routine re-excision of all incompletely excised DN in an individual or population of patients may not be necessary.  Presumably, DN selected for biopsy may have appeared clinically more suspicious than the patient’s other nevi, but there is not any evidence that clinical selection of a DN for biopsy correlates with an increased risk of future transformation.12,16 In our study, there were not any cases of melanoma arising at the site of a previously biopsied DN.1 Two studies have followed patients with incompletely excised DN for 5 and 17 years, respectively, and similarly failed to find melanoma at the site of a biopsied DN, suggesting that risk of melanoma development at the site of a biopsied DN is very low.17,18

Finally, the risk that a recurrent benign mole or recurrent DN may appear as a pseudo-melanoma, resulting in unnecessary surgery, appears low based on available literature.19 Further data would be valuable, as there are few published cases. Recurrence of DN after biopsy has been reported as 3.6 percent, similar to the 3.3 percent recurrence rate found for benign nevi.20 Biopsy margin positivity does not appear to influence the recurrence rate, indicating that to prevent recurrent nevi, re-excision of both typical and atypical nevi having either negative or positive biopsy margins would be considered.20 Shave removals are associated with a higher risk of recurrence, and punch excisions sampling the entire clinical lesion may be considered optimal when seeking to prevent recurrence.20

Continued evaluation of the primary characteristics of atypical nevi and their related clinical outcomes will
assist physicians and patients in making appropriate treatment decisions about these challenging lesions, as well as aid in improving melanoma prevention and detection efforts.

Clinical Recommendations

In advising patients who have a biopsy diagnosis of dysplastic nevus with a positive margin, discussion about the generally benign nature of most DN, relevant concerns and uncertainties about the ultimate behavior of some nevi, especially high-grade DN, and review of treatment choices is encouraged (Figure 2). By explaining the association with an increased overall risk of melanoma at any site, physicians can help moderate excessive fears about a particular individual nevus, while encouraging appropriate monitoring of the entire skin surface for any suspicious or changing lesions and providing education on melanoma-preventive behaviors.

For patients with DN containing a severely atypical component (moderately-to-severely and severely dysplastic nevi), the increased association with melanoma and increased rate of melanoma diagnosis upon excision may be reviewed to support general management by excision. In cases of moderately dysplastic nevi, our study data suggest the possibility of generally benign behavior that may be similar to that of mildly dysplastic nevi. This evidence supports the commonly accepted management method of periodic observation for mildly dysplastic nevi with a positive margin, and suggests that observation represents a similarly reasonable option for moderately dysplastic nevi. Reliable evidence for most mildly or moderately dysplastic nevi behaving as true precursor lesions progressing to melanoma at a higher rate than typical benign nevi remains lacking or insufficient.4 However, until further evidence and diagnostic tests can be developed to improve our understanding of DN, each lesion should be considered in the context of the individual patient, with excision considered if deemed appropriate by the patient and treating physician.

While histologic classification into categories of mild, moderate, and severe atypia appears to provide some guidance as to melanoma risk, future improved classification by genetic or biologic characteristics may allow us to improve risk stratification and thereby improve the balance of risks and benefits of surgical excision.  Ultimately, by collecting evidence to guide management of atypical nevi, we will improve our melanoma prevention and treatment efforts while also limiting unnecessary procedures and surgical complications.

Figure 2. Clinical management of dysplastic nevi.  *Melanoma in situ

References

  1. Reddy KK, Farber MJ, Bhawan J, Geronemus RG, Rogers GS. Atypical (dysplastic) nevi: outcomes of surgical excision and association with melanoma. JAMA Dermatol 2013; 149(8):928-934.
  2. Piepkorn M, Meyer LJ, Goldgar D, et al. The dysplastic melanocytic nevus: a prevalent lesion that correlates poorly with clinical phenotype. J Am Acad Dermatol 1989; 20(3):407-415.
  3. Steijlen PM, Bergman W, Hermans J, et al. The efficacy of histopathological criteria required for diagnosing dysplastic naevi. Histopathology 1988; 12(3):289-300.
  4. Duffy K, Grossman D. The dysplastic nevus: from historical perspective to management in the modern era: part I. Historical, histologic, and clinical aspects. J Am Acad Dermatol 2012; 67(1):1.e1-16; quiz 17-8. doi: 10.1016/j.jaad.2012.02.047.
  5. Elder DE, Goldman LI, Goldman SC, et al. Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma. Cancer 1980; 46(8):1787-1794.
  6. Clark WH, Jr., Reimer RR, Greene M, et al. Origin of familial malignant melanomas from heritable melanocytic lesions. ‘The B-K mole syndrome’. Arch Dermatol 1978; 114(5):732-738.
  7. Metcalf JS, Maize JC. Clark’s nevus. Semin Cutan Med Surg 1999; 18(1):43-46.
  8. NIH Consensus Conference. Diagnosis and treatment of early melanoma. JAMA  1992; 268(10):1314-1319.
  9. Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur J Cancer 2005; 41(1):28-44.
  10. Tripp JM, Kopf AW, Marghoob AA, Bart RS. Management of dysplastic nevi: a survey of fellows of the American Academy of Dermatology. J Am Acad Dermatol 2002; 46(5):674-682.
  11. Elston D, McNiff J, Maize J, Sr. Histologically dysplastic nevi that extend to a specimen border. J Am Acad Dermatol 2013; 68(4):682-683.
  12. Elston D. Practical advice regarding problematic pigmented lesions. J Am Acad Dermatol 2012; 67(1):148-155.
  13. Bronsnick T, Kazi N, Kirkorian AY, Rao BK. Outcomes of biopsies and excisions of dysplastic acral nevi: a study of 187 lesions. Dermatol Surg 2014; 40(4):455-459.
  14. Abello-Poblete MV, Correa-Selm LM, Giambrone D, et al. Histologic outcomes of excised moderate and severe dysplastic nevi. Dermatol Surg 2014; 40(1):40-45.
  15. Tsao H, Bevona C, Goggins W, Quinn T. The transformation rate of moles (melanocytic nevi) into cutaneous melanoma: a population-based estimate. Arch Dermatol 2003; 139(3):282-288.
  16. Skender-Kalnenas TM, English DR, Heenan PJ. Benign melanocytic lesions: risk markers or precursors of cutaneous melanoma? J Am Acad Dermatol 1995; 33(6):1000-1007.
  17. Hocker TL, Alikhan A, Comfere NI, Peters MS. Favorable long-term outcomes in patients with histologically dysplastic nevi that approach a specimen border. J Am Acad Dermatol 2013; 68(4):545-551.
  18. Kmetz EC, Sanders H, Fisher G, et al. The role of observation in the management of atypical nevi. South Med J 2009; 102(1):45-48.
  19. King R, Hayzen BA, Page RN, et al. Recurrent nevus phenomenon: a clinicopathologic study of 357 cases and histologic comparison with melanoma with regression. Mod Pathol 2009; 22(5):611-617.
  20. Goodson AG, Florell SR, Boucher KM, Grossman D. Low rates of clinical recurrence after biopsy of benign to moderately dysplastic melanocytic nevi. J Am Acad Dermatol 2010; 62(4):591-596.