Practical Management of Atypical Melanocytic Lesions

Transcription

1 Practical Management of Atypical Melanocytic Lesions Caroline C. Kim, MD, Director Assistant Professor, Department of Dermatology Harvard Medical School Director, Pigmented Lesion Clinic Associate Director, Cutaneous Oncology Program Beth Israel Deaconess Medical Center, Boston, MA Forum 014: Pigmented Lesions, Shedding Light on the Darkness Summer AAD 2018 Meeting, Chicago, IL, July 27, 2018

2 Disclosures No relevant conflicts of interest Relationships Hoffmann-La Roche, Ltd. Investigator, Consultant

3 Overview: Practical Management of Atypical Melanocytic Lesions 1. Background 2. Examination of the atypical nevus patient 3. Management/ biopsy

4 Background: Atypical Nevi --First described in 1978: clinicopathologic entity, which identified patients at increased risk for melanoma Mole larger than 5 mm Variegated pigmentation Irregular borders Pathology features: Architecture: nests bridge rete ridges elongated rete ridge Cytology: larger, atypical cells larger nucleoli Host response: lymphocytic infiltrate Elder DE, Murphy GF. Melanocytic tumors of the skin. In: Rosai J, Sobin LH, eds. Atlas of Tumor Pathology; 3 rd series, part 2. Washington DC: Armed Froces Institute of Pathology; 1991

5 Atypical Nevi (Dysplastic Nevi) Background: 1992: National Institute of Health (NIH) Consensus Statement Paper Clinical term: Atypical nevus Pathologic term: Nevus with architectural disorder Dysplastic nevus

6 Atypical/ Dysplastic Nevi Significance: Increased risk of developing MM General population: ~1.93% lifetime risk Atypical nevi: ~2-12 x risk Atypical Mole Syndrome: --10 yr cumulative risk for developing MM 10.7% vs. 0.62% for controls Slade J, Marghoob AA, Salopek TG, et al. Atypical mole syndrome: risk factor for cutaneous malignant melanoma and implications fo rmanagement. J Am Acad Dermatol 1995; 32: Greene MH. Genetics of cutnaeous melanoma and nevi. Mayo Clin Proc 1997; 72: Marghoob AA, Kopf AW, Rigel DS et al. Risk of cutaneous malignant melanoma in patients with classic atypical-mole syndrome. A case-control study. Arch Derm 1994; 130(8):

7 Benign nevus Mild dysplasia Mod dysplasia Severe dysplasia Melanoma???

8 Atypical/ Dysplastic Nevi and Risk of Melanoma ~50-75% of melanomas arise de novo Similar rate may be observed of melanoma arising in association with dysplastic nevi (21-56%) vs. common nevi (44-79%) Actual transformation rate of dysplastic nevus cells into melanoma:???? Bevona et al. Archives of Dermatology. 139(12):1620-4, Dec Friedman RJ et al. The dysplastic nevus. Clin Dermatol. 2009; 27(1): Sagebiel RW.. J Invest Dermatol 1993;100:322S-5S. Marks R, Dorevitch AP, Mason G.. Australas J Derma- tol 1990;31: Crucioli V, Stilwell J. J Cutan Pathol 1982;9: Skender-Kalnenas TM, English DR, Heenan PJ. J Am Acad Dermatol 1995;33: Tsao et al. Arch Dermatol 2003; 139(3):282-2 Pampena R et al. A meta-analysis of nevus-associated melanoma: Prevalence and practical implications. J Am Acad Dermatol 2017 Nov; 77(5):

9 Examination of the Atypical Nevus Patient

10 Clinical Pearls Look for signatures and the ugly duckling!

11 Clinical Pearls Look for signatures and the ugly duckling Use dermoscopy

12 Epiluminesence Microscopy Clinical exam alone: 65-80% melanomas correctly diagnosed With dermoscopy: 70-95% Training necessary! Without training, dermoscopy decreased rate of melanoma detection Grin 1990, Miller and Ackerman 1992, Wolf 1998 Mayer 1997 Binder et al. 1997

13 Dermoscopy: Beauty and the Beast Benign patterns Malignant patterns Marghoob AA, Korzenko AJ, Changchien L, Scope A, Braun RP, Rabinovitz H. The beauty and the beast sign in dermoscopy. Dermatol Surg 2007; 33(11):

14 Clinical Pearls Look for signatures and the ugly duckling Use dermoscopy Beware of de novo and changing lesions

15 Clinical Pearls Look for signatures and the ugly duckling Use dermoscopy Beware of de novo and changing lesions A picture is worth a thousand words

16 Total Body Digital Photography -- can detect subtle changes and de novo lesions: detection of early melanoma --can reduce the number of lesions excised --can reduce patient anxiety Kelly JW, Yeatman JM, Regalia C, et al. A high incidence of melanoma found in patients with multiple dysplastic naevi by photographic surveillance. Med J Aust 1997; 167: Rhodes AR. Intervention strategy to prevent lethal cutaneous melanoma: use of dermatologic photography to aid surveillance of high-risk persons. J Am Acad Dermatol 1998; 39: Goodson et al. Comparative analysis of total body and dermatoscopic photogrphic monitoring of nevi in similar patient populations at risk for cutaneous melanoma. Dermatol Surg Jul; 36(7): Zakiya M et al. J Am Acad of Dermatol 2008; 58 (2): AB102 Canfield Scientific, Inc.

17 Total Body Digital Photography -- can detect subtle changes and de novo lesions: detection of early melanoma --can reduce the number of lesions excised Reviewed records of all patients in 2 pigmented lesion clinics who received TBP and had 2 or more f/u visits over at least 2 years. Before PLC/TBP vs. after PLC/TBP: --mean rate of of biopsies: 1.62 vs per year fold reduction in nevus biopsies Truong A, Strazzulla L, March J, Boucher KM, Nelson KC, Kim CC, Grossman D. Reduction in nevus biopsies in patients monitored by total body photography (JAAD 2016 March E pub ahead of print)

18 Diagnosis Future directions: Further development of diagnostic devices: --Multispectral imaging / computer analysis --Confocal microscopy --Automated change detection --Optical coherence tomography --Teledermoscopy --Smartphone applications --Artificial intelligence

19 Clinical Pearls Look for signatures and the ugly duckling Use dermoscopy Beware of de novo and changing lesions A picture is worth a thousand words Listen to the patient!

20 Management / Biopsy

21 Atypical Nevi Education: --significance of AN (avoid word precancerous ) --rationale for biopsy/excisions --self-skin exam: abcds, ugly duckling --sun protection --notify family members Caonline.amcancersoc.org Follow-up: q6 or 12 mo Decide if total body photography would be beneficial Consider sharing care with a local pigmented lesion clinic

22 Atypical Nevi When to biopsy? --Diagnosis of atypical nevus can be made clinically --Biopsy suspicious lesions concerning for melanoma --Removal also option for nevi in areas difficult to monitor

23 Biopsy Variable types of biopsies performed my.webmd.com

24 2011: American Academy Dermatology and NCCN Guidelines FROM THE ACADEMY Guidelines of care for the management of primary cutaneous melanoma Work Group: Christopher K. Bichakjian, MD, a Allan C. Halpern, MD (Co-chair), b Timothy M. Johnson, MD (Co-chair), a Table IV. Recommendations Antoinette Foote Hood, MD, c for biopsy James M. Grichnik, MD, PhD, d Susan M. Swetter, MD, e,f Hensin Tsao, MD, PhD, g Preferred Victoria Holloway biopsy technique Barbosa, is MD, narrow h Tsu-Yi excisional Chuang, biopsy MD, MPH, that i,j Madeleine Duvic, MD, k Vincent C. Ho, MD, l encompasses Arthur J. Sober, entire MD, breadth g Karl R. ofbeutner, lesion with MD, clinically PhD, m,n Reva Bhushan, PhD, o negative margins and Wendy to depth Smith sufficient Begolka, toms ensure o that Ann Arbor, Michigan; Newlesion York, is New notyork; transected, Norfolk, which Virginia; may be Miami, accomplished Florida; Palo by Alto, Los Angeles, Palm Springs, San Francisco, elliptical and Fairfield, or punch California; excisionboston, with sutures, Massachusetts; or shave Chicago and Schaumburg, Illinois; removal Houston, totexas; depth and belowvancouver, anticipated British planecolumbia, of lesion. Canada Partial sampling (incisional biopsy) is acceptable in select clinical circumstances such as facial or acral location, low clinical suspicion or uncertainty of diagnosis, or very large lesion. Repeat biopsy is recommended if initial biopsy specimen is inadequate for diagnosis or microstaging of primary lesion. NCCN Practice Guidelines in Oncology v Melanoma

25 High suspicion for melanoma: narrow excisional biopsy preferred 1-3 mm margins 2 mm margins in saucerization method: ~87% of excisional biopsies had clear pathologic margins Terushkin et al. A prospective study evaluating the utility of a 2-mm biopsy margin for complete removal of histologically atypical (dysplastic nevi). J Am Acad Dermatol 2017 Dec; 77(6):

26 Partial/incisional biopsy: Facial or acral areas Very large lesions Low suspicion Be aware of limitations of partial / incisional biopsy

27 Clinical Pearls Look for signatures and the ugly duckling Use dermoscopy Beware of de novo and changing lesions A picture is worth a thousand words Listen to the patient! Excisional biopsies for lesions suspicious for melanoma are preferred / be aware of limitations of partial biopsies.

28 Clinical Pearls Look for signatures and the ugly duckling Use dermoscopy Beware of de novo and changing lesions A picture is worth a thousand words Listen to the patient! Excisional biopsies for lesions suspicious for melanoma are preferred / be aware of limitations of partial biopsies. Think about your biopsy / think ahead

29 Dysplastic nevi: after the biopsy Pathology result: --grading system is variable dysplastic vs severely DN Mild, mod, severely DN Mild, mild-mod, mild-focal mod, mod-focal severe, mod-severe, severe No guidelines on indications for reexcision

30 Pathology interobserver variability: Pathologists diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study Elmore JG et al. BMJ Jun 28 Skin biopsy cases (n=240), Pathologists from 10 US states were randomized to independently interpret the same set on two occasions (phases 1 and 2), at least 8 months apart Diagnosed in 5 classes: I (eg, nevus or mild atypia) II (eg, moderate atypia) III (eg, severe atypia or melanoma in situ) IV (eg, pathologic stage T1a (pt1a) early invasive melanoma) V (eg, pt1b invasive melanoma). Reproducibility was assessed by intraobserver and interobserver concordance rates

31 Pathology interobserver variability: Pathologists diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study Elmore JG et al. BMJ Jun 28 Intraobserver concordance: highest for class I 76.7% and class V 82.6%). However, the intraobserver reproducibility was lower for class II (35.2%), class III (59.5%), and class IV (63.2%). Average interobserver concordance rates were lower, but with similar trends. Efforts to improve clinical practice should include using a standardized classification system, acknowledging uncertainty in pathology reports, and developing tools such as molecular markers to support pathologists' visual assessments.

32 Observation Fleming et al observed 5.5 years 1 (AIMP favor early MMIS) Mild: 131 Mod: 47 Severe: 7?: Hiscox et al Total 517 Eval. of reexcision Mild: 18 Mild-Mod: 146 Mod: 469 Mod-sev: 55 Sev: Total 713

33 Comparison between Chicago dermatologist study and 2014 New England dermatologists survey Observe or other 2009 Chicago positive margins Reexcise 2014 New England positive margins Mild 79% 21% Mod 19% 81% Mod-Sev Severe 5% 95% 95% 5% 39% 61% 5% 95% 0% 100% No consensus Duffy et al. Arch Dermatol. 2012; 148(2): Tong L, Wu P and Kim CC (JAAD 2016)

34 Other recent survey studies Management Strategies of Academic Pigmented Lesion Clinic Directors in the United States. Nelson KC et al. JAAD Jan 2018 Survey of pigmented lesion clinic directors in U.S. ; 40 directors identified, 38 responded (95%) Recommended management of moderate DN with + histologic margins, no clinical residual: No re-excision: 43%; 1-2 mm margins: 27%; 3-4 mm margins: 21%. A Survey Analysis on the Management of Moderately Dysplastic Nevi Among Academic Dermatologists Across the United States Tessitore et al. JAAD May 2018 Survey ed to 385 members of Association of Professors Dermatology 131 responses (34%) showed varied responses for scenarios Absence of visible pigment in a positive biopsy margin (lateral, deep or deep and lateral) markedly increased the percentage of respondents who chose clinical monitoring (45%, 40%, 37% respectively )

35 Mild + margins without pigment Observation Moderate + margins without pigment Observation may be reasonable, more data needed Severe + margins without pigment Monitor all biopsy sites for unusual regrowth Re-excision Pigmented Lesion Subcommittee MPWG/ECOG/SWOG

36 Need for large-scale data to further investigate role of observation vs. re-excision of dysplastic nevi Pigmented Lesion Subcommittee MPWG/ECOG/SWOG Multi-center study

37 Role of Observation for Excisionally Biopsied Moderately Dysplastic Nevi with Positive Histologic Margins and Risk of Development of Future Melanoma Caroline C. Kim, MD 1,#, Elizabeth G. Berry, MD 2,3*# and Suephy C. Chen, MD 2,3 On behalf of the Pigmented Lesion Subcommittee, Melanoma Prevention Working Group Beth Israel Deaconess Medical Center, Boston, MA 1, Emory University, Atlanta, GA 2, Atlanta VA Health Care System, Decatur, GA 3 # These authors contributed equally Presented at the Society of Investigative Dermatology Annual Meeting 2018

38 Recurrent Pigmentation Recurrent nevi: tend to develop within 8 months with pigmentation confined to scar Melanomas: tend to recur more than 20 months after biopsy, in patients older than 30 years, and with pigmentation crossing into normal skin Blum A et al. Recurrent melanocytic nevi and melanomas in dermoscopy: results of a multicenter study of the International Dermoscopy Society. JAMA Dermatol. 2014;150(2):

39 Summary Management of atypical nevus patients can be challenging Clinical pearls: Look for signatures and the ugly duckling Use dermoscopy Beware of de novo and changing lesions A picture is worth a thousand words Listen to the patient! Excisional biopsies for lesions suspicious for melanoma are preferred / be aware of limitations of partial biopsies. Think about your biopsy / think ahead Recurrent pigmentation Dysplastic nevi with positive margins: Recent data on observation of dysplastic nevi with positive margins: observation may be reasonable option for excisionally biopsied mildly and moderately DN without clinical residual pigment but with + histologic margins. Follow all biopsy sites clinically for any unusual regrowth, educate patients.

40 Thank you! Caroline C. Kim, MD, Director Assistant Professor, Department of Dermatology Harvard Medical School Director, Pigmented Lesion Clinic Associate Director, Cutaneous Oncology Program Beth Israel Deaconess Medical Center, Boston, MA