Histologic Outcomes of Excised Moderate and Severe Dysplastic Nevi

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1 Histologic Outcomes of Excised Moderate and Severe Dysplastic Nevi MARIA V. ABELLO-POBLETE, MD, LILIA M. CORREA-SELM, MD, DANIELLE GIAMBRONE, BS, FRANK VICTOR, MD, FAAD, AND BABAR K. RAO, MD, FAAD* BACKGROUND Dysplastic nevi (DN) have been a matter of controversy since their initial description in 1978 because of differences in the clinical and histological terminology, and large studies on histological outcomes of excising moderate to severely DN have not previously been described. OBJECTIVE severe DN. To determine the clinical characteristics of DN and histologic outcomes of excised moderate and METHODS Retrospective chart review of patients with DN or Clark s nevi at the Dermatology Department at Rutgers Robert Wood Johnson Medical School in Somerset, New Jersey, from January 2009 to June Three hundred ninety-three lesions from 380 patients were included in this study. MAIN OUTCOME MEASURE Histologic results of excised moderate and severe DN. RESULTS Thirty-four percent of DN were excised because of the presence of moderate or severe atypia, personal history of melanoma, or both. None of the excised lesions showed evidence of melanoma; 81.6% of excisions showed scar or granulation tissue. Only 14% of excised lesions were found to have residual lesions, and 4.4% showed recurrent nevi. CONCLUSION In 134 excisions of moderate to severe DN, no melanoma was identified. Most of the excisions showed scar or granulation tissue. The rate of residual lesions after shave biopsy of moderate or severe DN was lower than after punch biopsy. The authors have indicated no significant interest with commercial supporters. Dysplastic nevi (DN) have been a controversial entity since their initial description in 1978 due to differences in the clinical and histological terminology, as well as the varied approach in management of these lesions. 1 Over the past 4 decades, DN have been called several names, including BK moles, 1 Clark s nevi, atypical moles, and nevi with architectural disorder. 2,3 Only a small percentage of DN progress to melanoma, 4,5 but their presence indicates a risk that is 10 to 15 times greater than in individuals without them. 6,7 This risk increases further as the number of nevi (benign or dysplastic) increases 8,9 or in the presence of a personal or family history of melanoma. 6 Despite evidence linking DN with risk of melanoma, controversy surrounds their true malignant potential and appropriate management. 5 9 After initial biopsy, further treatment depends in large part on the pathology report. Pathology reports of DN typically indicate degree of atypia and involvement of margins. There is no standardized system used in the histologic description of DN, which creates clinical ambiguity because what one pathologist may refer to as severe dysplasia *All authors are affiliated with the Rutgers-Robert Wood Johnson Medical School, Somerset, New Jersey 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: Dermatol Surg 2014;40:40 45 DOI: /dsu

2 A BELLO-POBLETE ET AL another may call melanoma in situ, and these two entities are managed differently. Despite this lack of consistency, clinicians make management decisions based on these pathology reports. With severe dysplasia on initial biopsy, most dermatologists excise the lesion because the distinction between severe dysplasia and melanoma in situ is imprecise and because of the potential evolution to melanoma. With mild to moderate dysplasia on initial biopsy, clinical management is less straightforward. Some dermatologists would not treat further, whereas others would monitor or completely excise the lesion. The need for excision of DN based on degree of atypia and margin involvement has been evaluated in previous studies. A study by Ackerman showed no signs of melanoma on excision biopsies of DN. 10,11 A recent study of 115 patients showed no development of melanoma at the site of previously removed DN with or without positive margins, with average follow-up of 17.4 years. 12 A 2-year follow-up study demonstrated that only 3% of DN recurred on physical examination, and none were consistent with severe DN or melanoma on excision. 13 Furthermore, positive margins were found not to be associated with recurrent lesions in a 5-year follow-up study. 14 Despite studies like these that find no melanoma and a low rate of recurrent lesions upon excision of DN, a survey of 145 fellows of the American Academy of Dermatology found that 53% excise incompletely removed DN in the majority of cases 15. Among 45% of responders, the most common reason for excising an incompletely removed DN was a finding of moderate or severe cytologic atypia. 15 More data on clinical outcomes is needed to guide clinicians in making appropriate decisions regarding management and follow-up for patients with DN. We conducted a retrospective chart review to evaluate clinical characteristics of biopsied DN and histologic outcomes of excisions of biopsy-proven moderate to severe DN. Objectives A retrospective chart review was conducted to determine clinical features of biopsied DN and histologic outcomes of excisions of biopsy-proven moderate or severe DN. Methods The biopsy log at the Dermatology Department at Robert Wood Johnson Medical School was reviewed from January 2009 and June 2012 to identify patients with DN or Clark s nevi. The diagnosis of DN was based on the final histologic diagnosis written in the official pathology report on file. Additional data, including age, sex, location of lesion, degree of dysplasia, and results of excision, were obtained retrospectively from the electronic medical record. Descriptive statistical analysis was conducted using Microsoft Excel (Microsoft Corp., Redmond, WA). Values, including means, standard deviations, and percentages, were obtained for patient age, sex, location of lesion, degree of atypia, and histologic outcomes of excised moderate and severe DN. Our protocol met the ethical guidelines of the 1975 Declaration of Helsinki, and institutional review board approval was obtained for this study. Results Demographic Characteristics From January 2009 to June 2012, 393 DN or Clark s nevi (based on histopathologic diagnosis) were identified in 380 patients. Mean patient age was 46, and there was a slight predominance of men (56.5%) (Table 1). Most of the 393 DN were located on the back, followed by the chest, abdomen, and lower extremities. These were the most prevalent sites for both sexes (Table 1). The majority of DN were considered mild in terms of atypia and were classified as 40:1:JANUARY

3 HISTOLOGICAL O UTCOMES O F EXCISED M ODERATE AND SEVERE D YSPLATIC NEVI TABLE 1. Patient Characteristics Characteristic Male Female Age, mean standard deviation Sex, n (%) 200 (56.5) 154 (43.5) Location of nevi, n (%) Head and neck 8 (4.2) 9 (4.4) Chest or abdomen 39 (20.6) 45 (22.1) Back 89 (47.1) 96 (47.1) Upper extremities 11 (5.9) 17 (8.3) Lower extremities 42 (22.2) 37 (18.1) Total 189 (100) 204 (100) junctional or compound (Table 2). Involvement of margins on initial biopsy was present in 76.5% (75/98) of moderate DN and 100% (16/16) of severe DN (Table 2). Thirty-four percent (134/393) of lesions were excised because of the presence of moderate to severe atypia, history of melanoma, or both (Table 3). Time between initial diagnosis and excision ranged from 2 to 16 weeks, with the majority of excisions occurring after 4 weeks. Melanoma was not detected in any of the excisions; 81.6% of excisions showed scar or granulation tissue. Fourteen percent (16/114) of the excised lesions had residual nevi, and 4.4% (5/114) had recurrent nevi (Table 4). Of the 16 excisions that showed residual nevi, 12 were initially biopsied using punch technique, and of the five excisions that showed recurrent nevi, four were initially biopsied using punch technique (Table 5). Discussion In this retrospective chart review, melanoma was not detected in 134 excisions of moderate to severe DN. TABLE 3. Reason for Excision of Nevi Reasons n (%) Moderate to severe dysplasia 89 (66.5) Family history of melanoma 20 (14.9) Both 25 (18.6) TABLE 4. Histopathologic Diagnosis of Excised Moderate to Severe Dysplastic Nevi (DN)* Diagnosis n (%) Scar 93 (81.6) Residual nevi 16 (14.0) Recurrent nevi 5 (4.4) *Excised mild DN excluded. The lack of melanoma and low rate of recurrent and residual lesions observed in excisions of moderate and severe DN emphasize the clinical dilemma regarding management of these lesions. Justification for excision includes the risk of malignant transformation, which is not substantiated in this and other studies Although DN and associated syndromes increase the risk of melanoma, 2 clinical management with excision is questionable given the uncertain risk of melanoma and the invasiveness of the procedure. Considering that the incidence of melanoma arising from a DN is approximately 1:3,000 per year, 15 that the majority of DN will remain stable or regress, 4,16,17 and that the recurrence of excised lesions is low even with positive margins on initial biopsy, 12 there seems to be little justification for excision of DN rather than noninvasive clinical monitoring. Another factor worth considering when deciding whether to excise a biopsy-proven DN is the number TABLE 2. Margin Involvement Severity of Dysplasia Total Positive Margins Negative Margins Not Reported Mild 262 (70) 200 (76.4) 12 (4.6) 50 (19.1) Moderate 98 (26) 75 (76.5) 14 (14.3) 9 (10.2) Severe 16 (4) 16 (100) 0 (0) 0 (0) 42 DERMATOLOGIC SURGERY

4 A BELLO-POBLETE ET AL TABLE 5. Biopsy Technique and Results of Excision Technique Scar or Granulation Tissue, n Residual Nevi, n Recurrent Nevi, n Punch Shave Not reported needed to treat (NNT) for melanoma, defined as the average number of lesions (pigmented lesions, nevi, DN) excised for every melanoma prevented. Many studies have been done in Australia, with values of 23, 18 29, 19 and 4 20 reported (the first two for general practitioners, the last for dermatologists), and in the United Kingdom, where a value of 6 was reported. 21 A study was done in the United States among dermatologists assessing the NNT before and after the introduction of dermoscopy; a large drop in NNT was noted after the intervention. 22 Careful selection of which lesions to biopsy is challenging as we consider the poor correlation between clinical dysplasia and histopathologic dysplasia Even worse, some benign nevi could show histopathologic signs of dysplasia. 25,27,28 Given our findings, we suggest the following as a comprehensive approach to a patient with a clinically suspicious nevus. Initial assessment should include noninvasive management, including clinical examination, dermoscopy, total body photography, and possibly confocal microscopy, depending on individual preferences. Dermatologists use total body photography to determine which lesions have changed over time Subtle changes in nevi are easier to identify using high-resolution images, which assist in the detection, diagnosis, and treatment of melanomas in the early stages. 30 Dermoscopy is used to improve identification of worrisome melanocytic lesions. 32,33 Its use along with total body photography has been associated with lower biopsy rate and early melanoma detection. 31,34,35 Furthermore, computed assisted dermoscopy objectively records subtle changes in size, color, or shape. 36,37 With proper training, dermoscopy allows physicians to choose appropriate lesions for biopsy and should be used for evaluation of all melanocytic lesions. 38 Confocal microscopy is a novel, noninvasive tool that allows in vivo evaluation of lesions at a cellular level. 39,40 It is useful in the diagnosis and monitoring of melanocytic lesions. 41,42 If the above noninvasive evaluative methods reveal suspicious findings, lesions should be biopsied to exclude melanoma. The results of this study suggest that excision of a moderate or severe DN is not necessary to prevent melanoma, although its retrospective nature, single site, and small sample size limit this study. Larger studies with long-term clinical and histopathologic follow-up are needed to determine the true recurrence rate of incompletely excised moderate to severe DN. Given the prevalence of DN and the continued ambiguity related to optimal clinical management, further studies should be conducted to elucidate the benefits of excision of moderate and severe DN. Acknowledgment We are indebted to Ms. Stephanie Okwundi for her help gathering the data for this study. References 1. Reimer RR, Clark WH Jr, Greene MH, Ainsworth AM, et al. Precursor lesions in familial melanoma. A new genetic preneoplastic syndrome. JAMA 1978;239(8): Tucker MA. Atypical melanocytic nevi. In: Wolff K, Goldsmith LA, Katz SI, Gilcrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick s dermatology in general medicine. New York, NY: McGraw-Hill; pp NIH Consensus conference. Diagnosis and treatment of early melanoma. JAMA 1992;268(10): Tucker MA, Fraser MC, Goldstein AM, Struewing JP, et al. A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families. Cancer 2002;94(12): Halpern AC, Guerry D 4th, Elder DE, Trock B, et al. Natural history of dysplastic nevi. J Am Acad Dermatol 1993;29(1): :1:JANUARY

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6 A BELLO-POBLETE ET AL microscopy of streaks in melanocytic lesions. Arch Dermatol 2007;143(6): Curiel-Lewandrowski C, Williams CM, Swindells KJ, Tahan SR, et al. Use of in vivo confocal microscopy in malignant melanoma: an aid in diagnosis and assessment of surgical and nonsurgical therapeutic approaches. Arch Dermatol 2004;140(9): Carrera C, Palou J, Malvehy J, Segura S, et al. Early stages of melanoma on the limbs of high-risk patients: clinical, dermoscopic, reflectance confocal microscopy and histopathological characterization for improved recognition. Acta Derm Venereol 2011;91(2): Pellacani G, Scope A, Ferrari B, Pupelli G, et al. New insights into nevogenesis: in vivo characterization and follow-up of melanocytic nevi by reflectance confocal microscopy. J Am Acad Dermatol 2009;61(6): Address correspondence and reprint requests to: Maria V. Abello-Poblete, MD, 15 Blyman Court, Robbinsville, New Jersey 09690, or myronmd1030@yahoo.com 40:1:JANUARY