It is clear from the literature that patients with DN are at increased risk for developing melanoma.9–11
Although 20 to 50% of melanomas appear to arise from a pre-existing nevus,12–14
the annual risk of individual nevi transforming into a melanoma is extremely low – estimated to be only 1 in 200,000.15
The annual risk is higher for DN (estimated 1 in 10,000),16
raising the question of whether incompletely removed DN should be re-excised with clear margins to prevent potential evolution into melanoma. While most dermatologists would agree that DN demonstrating severe dysplasia should be re-excised given the risk of early or evolving melanoma, management of incompletely excised DN demonstrating mild or moderate dysplasia remains an open question. A key factor to consider is the likelihood of recurrence, which must be balanced against the cost of re-excision and risk associated with a surgical procedure, including a larger scar. To our knowledge, the present study of DN recurrence following biopsy involves the largest number of lesions and longest follow-up period reported in the literature.
We found very low (3–4%) recurrence rates for both BN and DN following biopsy, regardless of margin involvement, nevus subtype (junctional, compound, intradermal), or the presence of congenital features. We might have expected the recurrence rate of incompletely excised DN to be significantly higher than that of BN, given that DN are associated with increased proliferation and decreased senescence.17,18
In addition, we might have expected the recurrence rate to be higher for compound than intradermal lesions since nevus cells are more likely to be proliferative and less differentiated in a compound nevus. The recurrence rates we observed were much lower than those seen in previous studies.4–7
Our lower recurrence rates are unlikely to be due to differences in follow-up times, since our follow-up period was greater than that in most of the other studies. A more likely explanation is that we may perform deeper and broader shave biopsies of clinically atypical nevi in our high-risk patients in an attempt to remove nevi completely, while earlier studies primarily examined recurrence of BN removed for cosmetic purposes, where a more superficial shave biopsy may have been done to minimize scarring.
We also might have expected the presence of congenital features to be associated with nevus recurrence, given that nevus cells in congenital nevi tend to extend deeper into the skin through their involvement with vascular and follicular structures. However, since we did not re-biopsy the nevus sites in this study, it is possible that some cases lacking clinical evidence of recurrence might demonstrate residual nevus cells beneath the scar. Even if we did find nevus persistence in some sites upon histologic examination, however, the lack of visibly apparent change over time would suggest limited clinical significance. It is also possible that clinically apparent nevus in the biopsy scar may represent pigmentation in keratinocytes or melanophages rather than persistent or recurrent nevus cells.
Although there was an association between positive margin and recurrence, it was not statistically significant (P=0.17 for all DN and BN combined, P=0.11 for DN), perhaps due to the low numbers of recurrences. Lack of greater association of recurrence with margin involvement was somewhat surprising, given that positive margin is the justification often used for re-excision of DN.8
Failure of nevi with positive margins to recur suggests that in most cases, residual nevus cells in the biopsy wound are not of sufficient number (or do not have the capacity) for regeneration and pigment production.
The only statistically significant association found with nevus recurrence was biopsy method, with shave technique being significantly associated with recurrence. One potential explanation for a higher recurrence rate with shave biopsies compared to punch biopsies is that nevus recurrence may be more likely to originate from a deep rather than lateral margin – which indeed we observed in most recurrent nevi in this study (). Since shave biopsies are generally more superficial than punch biopsies, they would be more likely to have a positive deep margin. Another explanation for the association between shave technique and recurrence is that lesions that are shaved tend to be much larger than those selected for punch biopsy, where the diameter of the punch tool (usually <6 mm) necessarily limits application of punch biopsies to small lesions. Larger lesions may contain more proliferative cells or be more likely to recur from residual cells for other reasons that are presently unclear.
One of the factors complicating management of DN is potential variability in histologic interpretation. In one study addressing interobserver variation in histologic diagnosis of atypical nevi, lesions interpreted as DN by an expert panel were diagnosed as melanoma by other pathologists in 21% of cases.19
Conversely, lesions originally diagnosed as thin or in situ
melanomas were re-read as DN in 12% of the cases.19
In our study, all of the histologic slides were re-reviewed by the same dermatopathologist to limit interobserver variation. In addition, routine histologic evaluation of punch or shave biopsies typically involves examination of only a fraction of the lesion to determine degree of atypia and margin involvement, leading some to propose that all DN should undergo excisional biopsy to obtain the most accurate diagnosis.20
A recent study from our institution, however, found that in a majority of biopsied nevi the histologic findings were homogeneous such that the diagnostic information in one section could be extrapolated to the remainder of the specimen.21
We recognize the possibility that some lesions may have had unrecognized margin involvement, and that the degree of dysplasia may have been underestimated. However, this information would not have affected the low rate of clinical recurrence that was observed.
Our results are consistent with those of Kmetz et al,22
who found that no melanomas developed over a 5-year period following biopsy of 55 atypical nevi (26 lesions with at least one positive margin and 29 with clear margins) that were not re-excised. Based on these findings, the authors recommended observation as a safe alternative to re-excision for incompletely removed atypical nevi.22
In order to fully answer the question of whether incompletely removed DN with mild or moderate dysplasia should be re-excised, longer follow-up of more lesions is required. We still believe that nevi with severe dysplasia should be re-excised to ensure complete removal, given that such lesions may represent evolving melanoma or potentially later interpreted as melanoma given the possibility of interobserver variation among pathologists19
as noted above. However, our data suggest that lesions which demonstrate only mild or moderate dysplasia may not need to be re-excised given their low likelihood of recurrence, and can be followed clinically for evidence of recurrence or development of any concerning features.