Lasers in Surgery and Medicine
Lentigo Maligna Melanoma With a History of Cosmetic Treatment: Prevalence, Surgical Outcomes, and Considerations Brian P. Hibler, MD,1 Karen L. Connolly, MD,1,2 Erica H. Lee, MD,1 Anthony M. Rossi, MD,1 and Kishwer S. Nehal, MD1 1 Memorial Sloan Kettering Cancer Center, Dermatology Service, 16 E. 60th Street, 4th Floor Dermatology, New York, New York 10022 2 Lincoln Hospital, Dermatology Service, 234 E. 149th Street, Bronx, New York 10451
Introduction: Lentigo maligna (LM) is melanoma in situ on sun-damaged skin and presents diagnostic challenges due to overlapping features with benign pigmented lesions. Cosmetic treatments may be inadvertently performed on LM. The aim of this study is to estimate the prevalence of LM with prior cosmetic treatment, and evaluate surgical outcomes. Study Design and Methods: Retrospective review of biopsy-proven LM presenting over a 10-year-period (2006– 2015). Prior cosmetic treatment and biopsies were recorded. Records were reviewed for demographic data, clinical characteristics, and surgical outcomes. Results: 37/503 (7.4%) patients with LM reported prior cosmetic therapy. Most (95%) were on the head and neck; mean size 1.9 cm. Most patients reported cryotherapy (73%), followed by laser (29.7%), topical bleaching agents (18.9%), and electrodessication, and/or curettage (5.3%). Ten patients (27%) received two or more modalities. Eight patients (21.6%) reported prior benign biopsies. Six patients (16%) had invasive disease, two on initial biopsy and 4/34 (11.7%) upstaged upon excision. Average margin for clearance was 9.1 mm. Conclusion: Prior cosmetic treatment of LM is not uncommon, and may delay diagnosis and obscure borders, resulting in wider surgical margins. Clinicians should consider a biopsy confirming the benign nature of equivocal lesions prior to cosmetic treatment. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc. Key words: benign; pigmented lesion; melanoma; lentigo maligna; solar lentigo; seborrheic keratosis; laser; cosmetic; cryotherapy; staged excision INTRODUCTION Lentigo Maligna and LM Melanoma (LM/LMM) are subtypes of melanoma occurring on chronically sundamaged skin, mainly on the head and neck, and its annual incidence is increasing [1,2]. LM can be diagnostically challenging, even for experienced dermatologists, due to overlapping features with benign pigmented lesions, such as macular seborrheic keratosis, pigmented actinic ß 2017 Wiley Periodicals, Inc.
keratosis, and solar lentigines [3]. Benign solar lentigines are present in an estimated 90% of lighter Fitzpatrick phototype individuals over age 60, and are a common cosmetic concern prompting elective treatment [4]. Misdiagnosis can have important consequences, as procedures used to treat benign pigmented lesions may be inadvertently performed on LM. As such, there have been reported cases of patients referred for cosmetic removal of benign pigmented lesions that were found to be LM on histological evaluation [5]. There is an aging population with a growing interest in cosmetic procedures and focus on decreasing the signs of aging, complicated by increasing rates of skin cancer. Cosmetic treatments including cryotherapy, laser therapy, or topical bleaching agents are used commonly to treat clinical pigmentation, but may obfuscate the subsequent detection of malignancy due to dyspigmentation or scarring, delaying diagnosis [6–8]. The actual incidence of LM previously treated cosmetically as benign pigmented lesions is unknown, and difficult to assess due to the indolent natural history of LM development. It is also unknown if cosmetic treatment of lesions that were later identified as LM result in worse clinical outcomes.
Abbreviations: LM, lentigo maligna; LMM, lentigo maligna melanoma; RCM, reflectance confocal microscopy Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Selected for the Dr. Richard E. Fitzpatrick Clinical Research and Innovations Award, ASLMS 37th Annual Conference, San Diego, CA, April 7, 2017. This study was granted an IRB waiver by the Memorial Sloan Kettering Cancer Center IRB. Contract grant sponsor: National Cancer Institute; Contract grant number: P30 CA008748. Correspondence to: Kishwer S. Nehal, MD, Memorial Sloan Kettering Cancer Center, Dermatology Service, 16 E. 60th Street, 4th Floor Dermatology, New York, NY 10022. E-mail: [email protected] Accepted 14 May 2017 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22691
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OBJECTIVE
Previous Biopsy Characteristics
The aim of this study is to determine the prevalence of biopsy-proven LM that presented for definitive treatment following a history of cosmetic treatment, and to evaluate if prior cosmetic treatment complicates management and prognosis.
Eight patients (8/37; 21.6%) reported a history of benign biopsy, with three patients having multiple prior benign biopsies (Table 1). The biopsies were performed between 1 month and 8 years prior to LM diagnosis. Benign biopsy diagnoses included seborrheic keratosis, nevus, solar lentigo, and lichen planus-like keratosis.
METHODS Following Institutional Review Board approval, a prospectively collected database of all biopsy-proven LM/ LMM presenting to a dermatologic surgery practice at a cancer center for management between 2006 and 2015 was retrospectively reviewed. Upon initial presentation, patients were asked if they had received prior cosmetic treatment of their biopsy-proven LM/LMM (including cryotherapy, laser treatments, electrodessication and/or curettage, or topical bleaching creams). Patients were also asked if they had a history of prior biopsy from the lesion. Outside pathology reports for prior benign biopsies were obtained. For any LM/LMM with a history of prior cosmetic treatment, records were reviewed for demographic data along with presenting clinical characteristics and surgical outcomes. All patients underwent surgical excision with a staged technique and rush paraffin-embedded permanent sectioning with serial sections for extent of residual LM and presence or absence of invasive tumor as previously described [9]. Pathology reports were reviewed, including final depth of invasion. Cases that were previously treated solely with surgical excision or with topical imiquimod were excluded. RESULTS Clinical Characteristics Five hundred three patients meeting inclusion criteria were treated for biopsy-proven LM/LMM from 2006 to 2015. Of these, 37 patients (7.4%) reported a history of prior cosmetic treatment of their lesion (Table 1). The average age of patients with prior cosmetic treatment was 61 (range: 34–81), with 17 men (46%) and 20 women (54%). All patients had Fitzpatrick phototype I–III. Of the most common locations, seventeen lesions presented on the cheek (45.9%), followed by eight on the forehead (21.6%) and five on the nose (13.5%). Overall, 35/37 (95%) were located on the head, with the other two on the extremities. The mean size of the lesion on presentation was 1.9 cm, ranging from 0.3 to 5.5 cm in longest clinical diameter. Cosmetic Treatments Prior cosmetic treatment included cryotherapy, laser, topical bleaching agents, and electrodessication and/or curettage. The majority of patients reported prior treatment with cryotherapy (73%, n ¼ 27) either alone or in combination with other treatments, followed by laser treatment (29.7%, n ¼ 11), topical bleaching agents (18.9%, n ¼ 7), and electrodessication and/or curettage (5.3%, n ¼ 3). Ten patients (27%) were treated with two or more treatment modalities (Table 1).
Histopathologic Characteristics: Overall, six patients (6/37; 16.2%) had invasive disease either on biopsy or excision. Two cases were diagnosed as LMM on initial biopsy, and four of the remaining 34 cases treated surgically (11.7%) were initially diagnosed as LM on biopsy but revealed an invasive component upon complete excision. Depths of invasive disease ranged from 0.2 mm to 1.25 mm (Table 1). Surgical Outcomes All patients except one were treated with staged surgical excision for complete margin control. One patient was treated at an outside institution. The average margin needed to clear the lesion was 9.1 mm (range 3–23 mm). Fifteen of 36 patients (42%) treated with staged surgical excision required at least 10 mm margins. The mean number of stages to clear the lesion was 2.1 (range 1–5). The average clinical lesion size in longest diameter for the six invasive lesions was 2.98 cm (0.9–5.5 cm). The average margins were 11.33 mm, with 2.2 stages to clear the lesion. For the lesion with depth 1.25 mm (focal Clark IV involvement), lymphoscintigraphy was attempted but a dominant nodal basin was not identified. Considering the subset of non-invasive lesions, the average clinical lesion size was 1.71 cm (0.3–4.5 cm). The average margin for noninvasive lesions was 8.63 mm, with 2.0 stages required for clearance. DISCUSSION There is an aging population with growing interest in cosmetic procedures to reverse the signs of aging. In this study the prevalence of LM/LMM reported to have been previously treated cosmetically as a benign pigmented lesion was 7.4%. As the incidence of LM/LMM continues to increase, providers must be aware of lesions not responding to conventional treatments, and be cautious of presumed benign pigmented lesions that deviate morphologically prior to treating cosmetically. The average age in our series (61) is lower than the reported 65–70 years [9–12], reflecting both the increased interest in cosmetic procedures among younger individuals and that the incidence of melanoma in situ is increasing, with a faster rate in younger populations [13]. Interestingly, nearly 50% of the patients in our series were male, which reflect current trends that more men are seeking cosmetic procedures [14]. Notably, over a quarter of patients were treated with multiple modalities, suggesting multiple clinic visits or time points to reassess the lesion. Although the setting and qualifications of providers performing cosmetic treatments in this study is not known, the
COSMETIC TREATMENT OF LM
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TABLE 1. Clinical Characteristics, Prior Treatment, and Surgical Outcomes of Cosmetically Treated Lentigo Maligna
Age/ Gender
Total margins (mm)
Total stages
EDC Cryo Cryo, Bleaching Cryo Cryo Cryo Cryo Cryo Laser Laser, Cryo, Bleaching Laser
10 11 13
2 3 3
8 8 7 5 7 5 8
2 2 1 1 2 1 2
14
3
Laser, Cryo Cryo Laser, Cryo Cryo Cryo Cryo
3
1
12 5
2 1
6 11 5
2 3 1
Cryo, Bleaching Laser Cryo Cryo, Bleaching Cryo, Bleaching EDC
15
3
8 8 8
2 2 1
5
2
6
2
Laser, Bleaching Laser Bleaching Laser
5
1
15 8 10
3 2 2
Cryo Cryo Cryo Cryo Laser
10 15 5 13 5
3 3 1 3 1
Cryo Cryo
8 10
2 2
Site
Size (cm)
Prior benign biopsy (time from prior biopsy to diagnosis)
Prior treatment
34/F 42/F 43/F
Cheek Forehead Cheek
2.0 2.5 0.5
No No No
44/M 47/F 48/F 49/M 50/F 51/F 51/F
Forehead Cheek Earlobe Nose Nose Periorbital Cheek
2 1 1.5 0.4 0.3 0.8 2.6
No No No No No No No
53/M
Cheek
0.9
No
53/F
Cheek
3
Yes—Macular SK (2 years)
54/M 56/F
Scalp Cheek
3.5 0.8
Yes—SK (n/a)a No
57/F 59/M 60/M
Extremity Periorbital Forehead
2.3 0.7 0.6
60/F
Cheek
5.5
No No Yes—Junctional nevus/Blue nevus (3 years) Yes—benign NOS (4 years)a
64/F 65/M 65/F
Cheek Cheek Cheek
2.1 1.1 3.5
No No Yes—benign NOS (4 years)a
66/M
Nose
1
No
66/M
Forehead
0.8
67/F
Nose
2
Yes—Solar elastosis, SK; Atypical proliferation of enlarged melanocytes and SL (3 years) No
67/F 69/M 69/M
Cheek Forehead Forehead
2.1 1.1 4.5
70/M 70/F 71/F 73/M 74/M
Cheek Chin Cheek Forehead Forehead
2.1 2.1 1.2 1 2
76/M 80/M
Cheek Extremity
3 5.5
No No Yes—Solar lentigo and actinic keratosis (1 year); LPLK and inflamed SK (6 months) No No No No Yes—macular SK (8 years); inflamed SK (1 year); SL (1 month) No No
Other details Invasive 0.4 mm
Invasive 0.2 mm
Invasive; at least 0.2 mm, transected (biopsy)
Invasive 1.25 mm Clark IV
Invasive 0.3 mm (Continued)
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TABLE 1. (Continued)
Age/ Gender 81/F 81/F 56/M
Site
Size (cm)
Prior benign biopsy (time from prior biopsy to diagnosis)
Prior treatment
Cheek Cheek Nose
2.5 2 0.5
No No No
Cryo, EDC Cryo Laser, Cryo
Total margins (mm)
Total stages
12 23 n/a
2 5 n/a
Other details (biopsy) Invasion 0.65 mm Surgery not performed
M, male; F, female; EDC, electrodessication and curettage; Cryo, cryotherapy; SK, seborrheic keratosis; NOS, not otherwise specific; LPLK, lichen planus-like keratosis; SL, solar lentigo. a Original outside benign biopsy report not available.
findings reinforce that skin lesions should be evaluated by individuals appropriately trained in evaluating skin and cosmetic concerns. LM is an indolent form of melanoma that evolves slowly and is often present for years prior to diagnosis. These lesions have a slow rate of invasion, and controversy exists regarding management and optimal surgical margins. Early detection and adequate treatment with negative margins is important prior to progression to invasive melanoma. It has been well-established in the dermatology literature that standard 5 mm margins are inadequate for complete margin control in large series of LM [11,15–18]. In a previously published series from our institution utilizing the same staged surgical technique, the margins required for clearance of LM was 7.1 mm, and for LMM was 10.3 mm [9]. In the current study, the margins required for clearance of cosmetically treated LM were even wider (8.6 mm for LM, 11.3 mm for LMM). Moreover, 15/36 patients in this series (42%) required at least 10 mm margins. This suggests the clinical borders may have been obscured by prior therapies aimed at destroying surface pigment, or there may have been a delay in diagnosis while treating as a benign pigmented lesion allowing for further radial growth (Fig. 1). In the author’s experience, skip areas have been occasionally observed but the true incidence is unknown. Overall, the rate of upstaging from LM to invasive disease upon final excision (11.7%) was high but within the expected range compared with other recently reported rates of upstaging for LM and
melanoma in situ (4–11.7%) [15,19–21]. Thus, the prior cosmetic treatment did not appear to have an effect on overall prognosis, but the wider surgical margins resulted in larger defects creating reconstructive challenges and increased morbidity. Long-term follow-up is required to determine if these lesions have higher rates of recurrence, as there may have been interruption in contiguous tumor resulting from their prior cosmetic treatment. A review of the literature shows 13 previously reported cases of pigmented lesions initially treated cosmetically with cryotherapy and/or laser treatment, later diagnosed as LM/LMM [8,22–26] (Table 2). The ages range from 59 to 72, with seven males and six females. All were located on the head and neck except one on the upper arm. Those with a benign biopsy at some point prior to cosmetic treatment had the following results: pigmented actinic keratosis, melanocytic nevus, nevoid lentigo, and dysplastic nevus. Of the 13 reported cases, 8 were found to have invasive LMM (61.5%) on final excision and one patient had lymph node metastasis. Additional reports document other forms of melanoma, including nodular, amelanotic, and metastatic, occurring after prior laser or cosmetic treatment of presumed benign lesions [24–28]. Stankiewicz et al. describe three patients who presented for cosmetic removal of pigmented lesions, two referred by physicians, all found to be LM or melanoma in situ before any cosmetic intervention, underscoring the importance of careful evaluation of presumed benign pigmented lesions before treatment [5].
Fig. 1. Lentigo Maligna. (A) 70-year-old female with a poorly demarcated hyperpigmented patch on the chin. She reported treatment with cryotherapy and no prior biopsies. (B) Surgical defect after three stages of excision and 15 mm margins.
COSMETIC TREATMENT OF LM
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TABLE 2. Lentigo Maligna Cosmetically Treated as a Benign Pigmented Lesion Prior treatment modality
Age/Gender
Lee et al.[45]
1) 59/M
-Cheek
2) 71/M
-Cheek
Dummer[8]
64/F
-Forehead
-Alexandrite laser
Ikoma et al.[23]
70/F
- Laser Therapy NOS -n/a
Zipser et al.[24] a note 12 melanomas total in this series
1) 72/M
-Cutaneous lip -Forehead
-LMM (lymph node metastasis) -LM
-Laser Therapy NOS
-LMM
2) 66/M 3) 75/F 4) 59/F 68/M 1) 52/M 2) 66/F 3) 70/M 4) 71/F
-Cheek -Preauricular -Cheek -Cheek -Nose -Upper arm -Nose -Nose
-CO2 -CO2 -Er:YAG -Laser Therapy NOS -Laser Therapy NOS
Simionescu et al.[25] Delker et al.[26] a note 11 melanomas total in this series
Location
Histology before initial treatment
Study
-Cryotherapy, Qswitched Ruby Laser 694 nm -Q-switched Ruby Laser
-No
-Possible pigmented actinic keratosis -No
-Melanocytic nevus -n/a -n/a -n/a -No -Nevoid lentigo -Dysplastic nevus -No -No
Outcome -LMM (Breslow thickness 2.35 mm, Clark IV) -LM
-LM -LM -LMM -LMM -LM -LMM -LMM -LMM
M, male; F, female; NOS, not otherwise specific; CO2, Carbon dioxide; Er:YAG, Erbium:yttrium-aluminum-garnet; n/a, not available; LM, lentigo maligna; LMM, lentigo maligna melanoma. a For series containing multiple subtypes of melanoma, only cases of LM/LMM are summarized in this table.
When patients present for cosmetic treatment of a pigmented lesion on sun-damaged skin, they should be questioned regarding changes in size, color, shape, or other features that are now raising cosmetic concern about the lesion. While it is unreasonable to biopsy every pigmented lesion prior to cosmetic treatment, all warrant thorough clinical and dermoscopic evaluation. Yet, diagnostic accuracy as measured by the number needed to biopsy among dermatologists at two academic centers ranges from 15 to 17.4 for melanoma [29,30]. Recently, reflectance confocal microscopy (RCM) has seen an emerging role for non-invasively evaluating clinically equivocal pigmented facial lesions, including LM [31,32] (Table 3). RCM has acquired Coding Procedural Terminology (CPT) codes (96931–96936), providing reimbursement for image acquisition and interpretation. These images may be acquired longitudinally over time, allowing for repeat non-invasive assessment of areas of skin to guide management, and may help provide a story to the dermatopathologist aiding in biopsy interpretation. For large, clinically suspicious lesions on sun-damaged skin, a biopsy may be warranted. However, limited sampling via a punch biopsy showing solar lentigo or pigmented actinic keratosis does not exclude the diagnosis of LM [33]. In fact, eight patients in this study reported a history of prior benign biopsies. Sampling error may only reveal mild or moderate melanocytic atypia when LM is present in other areas of the lesion, especially when small, partial biopsies are taken in the interest of preserving
cosmesis (Fig. 2). Variations in size, number, and type of biopsy likely account for the varied rates of upstaging seen after LM diagnosis [21,34–36]. This is supported by the observation that institutions performing microstaging (removal of all clinically apparent residual lesion suspicious for invasive disease prior to staged excision) achieve lowest rates of deeper residual disease (3.8%) [37]. In the case of particularly large lesions, incisional biopsy or multiple mapping biopsies should be taken of the most deeply pigmented or thickest areas. Repigmentation After Cosmetic Treatment Cosmetic treatments for pigmented lesions (lasers, cryotherapy, chemical peels, electrodessication and curettage, and bleaching agents) target surface pigmentation to improve the cosmetic appearance, but ultimately obscure future clinical examination [38]. The prospect of early LMs being successfully treated with these destructive modalities is possible; however, at this time, neither cryosurgery or laser treatment is recommended for LM due to the high rate of recurrence, potential for adnexal invasive disease, and lack of controlled studies [39,40]. In the current study, 10 patients reported multi-modality treatments suggesting that the lesion did not respond to an initial treatment. Patients reported their cosmetic treatments occurred over months to years, but the exact time to repigmentation is not known. Clinical repigmentation or persistent pigmentation in lesions previously treated with destructive or
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TABLE 3. Clinical, Dermoscopic, and Reflectance Confocal Microscopy Features of Benign Pigmented Lesions and Lentigo Maligna[46–53] Seborrheic keratosis Clinical Tan or brown
Slightly raised
Pigmented actinic keratosis Irregularly pigmented macule or patch with foci of keratotic scale May have hues of pink, red, tan, brown, dark brown
Flat, rough (warty) surface
Solar lentigo Tan to brown macule or patch; even pigmentation Well-defined border
Variegated tan to dark brown macule or patch
Multiple lesions; may increase in size and number over time
Colors change as lesion evolves
Waxy, stuck-on appearance
Well-demarcated, round or oval Dermoscopy Milia-like cysts
Comedo-like openings Light brown finger-like structures Hairpin blood vessels Cerebriform appearance (gyri, sulci)
Lentigo maligna
Indistinct, irregular borders
May have grey areas of regression or amelanotic (pink) areas
Brown/grey pseudonetwork (variation in pattern and extent of involvement) Surface scale Slate-grey/dark brown dots and globules around follicular ostia Fine vessels Annular-granular pattern
Diffuse brown and opaque structureless areas
Rhomboidal structures
Sharply demarcated or moth-eaten borders Fingerprint-like structures
Annular-granular structures
Reticular pattern
Gray pseudo-network Homogenous areas of pigment
Increased density of dermal papillae surrounded by bright, monomorphic layer of cells (edged papillae) Regular honeycomb pattern Cord-like rete ridges
Atypical melanocytes in nests
Asymmetric pigmented follicular openings
Rhomboidal structures Reflectance Confocal Microscopy Regular epidermal honeycomb pattern
Dense, well-circumscribed dermal papillae Corneal plugs and cysts Melanophages
Atypical keratinocytes in epidermis, parakeratosis, and scale
Increased epidermal thickness Bright, small dermal papillae Dendritic cells
Dilated, round and linear blood vessels
ablative modalities should raise suspicion of potential LM, even with a history of prior benign biopsy. In our series, 29/37 (78%) of LM who received cosmetic treatment did not report a prior biopsy. Other studies have also reported a lack of histological diagnosis prior to treatment of lesions that were melanoma. In a series by Delker et al., 9/11 (82%) lesions that were melanoma had no biopsy prior to cosmetic treatment [26]. Four of these were stage IV disease, and one patient died of melanoma. In
Epidermal disarray Cord-like rete ridges Sheets of atypical, dentritic cells, often with perifollicular infiltration Large, round, pagetoid cells
another series by Zipser et al., 8/12 (67%) patients had no biopsy prior to cosmetic treatment, 2/12 (17%) were misdiagnosed on review, and only 2/12 (17%) had benign biopsies before treatment [24]. In their series, two patients had stage IV disease, and three died of metastatic melanoma. Gottschaller et al. describe a case of metastatic melanoma after a clinically diagnosed “lentigo simplex” was treated with CO2 laser, and review other cases of malignant melanoma after laser therapy [27]. While it has been shown in vitro that
COSMETIC TREATMENT OF LM
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Fig. 2. Lentigo Maligna Melanoma. (A) Red and brown hyperpigmented patch on the left malar cheek encroaching upon the lower eyelid, previously treated with cryotherapy and topical bleaching agents. The patient reported a benign biopsy 4 years prior. (B) Defect after three stages of excision and 15 mm margins. Invasive disease was detected to a depth of 1.25 mm.
low-level laser exposure alters expression of tumor suppressor (p16 gene) and adhesion molecules in melanoma cell lines [41–43], this mechanism has not been observed in humans. The aforementioned studies in conjunction with the current study demonstrate the potential pitfalls in foregoing histological confirmation of a suspected benign pigmented lesion prior to pursuing cosmetic treatment. Limitations Limitations of our current study include possible recall bias regarding which lesions were previously treated. Cryotherapy is routinely used for treatment of facial lesions, and while patients may not exactly recall which ones were treated, it is plausible that these lesions were previously frozen. Secondly, we cannot definitively conclude that a new diagnosis of LM in an area previously treated with cosmetic therapies is evidence that a missed diagnosis of LM occurred. A de novo melanoma or a collision tumor may occur. In the cases of a prior benign biopsy, the area chosen for biopsy may not have captured adequate melanocytic atypia or the foci of invasive disease for correct diagnosis. Another limitation is that this was a single center study; however, this allowed for consistency in surgical technique, histopathologic evaluation, and margin determination. Comparison of our series to others was limited by heterogeneity of lesions included in the study, varying surgical technique, absence of reporting rates of invasion or surgical margins, and an unknown number of patients with prior cosmetic treatment included in other series [10–12,19,44]. CONCLUSION Prior cosmetic treatment of LM/LMM presenting for definitive surgical treatment is not uncommon. Overall, the incidence of LM previously treated as a benign pigmented lesion (7.4%) along with the cases reviewed here highlight the need for improved technologies to evaluate suspected benign pigmented lesions or possible LM. The rate of invasive disease was 16%, and 42% of all cosmetically treated LM lesions required at least 10 mm margins, suggesting prior cosmetic treatment may have
obscured borders. Lesion assessment with dermoscopy, RCM, or other non-invasive imaging prior to any cosmetic treatments may aid in evaluation. Clinicians must maintain an awareness of possible alternate diagnoses of pigmented lesions, especially for those occurring on sundamaged skin of the head and neck or in cases of residual or recurrent pigmentation. Patients should be consented and educated that if lesions do not resolve, they should return to their dermatologist for follow-up. ACKNOWLEDGMENTS The authors would like to acknowledge the American Society for Laser Medicine and Surgery (ASLMS) for generously providing a travel grant to present this work at the 37th Annual ASLMS Conference. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. REFERENCES 1. Gaudy-Marqueste C, Madjlessi N, Guillot B, et al. Risk factors in elderly people for lentigo maligna compared with other melanomas: A double case-control study. Arch Dermatol 2009;145:418–423. 2. Greveling K, Wakkee M, Nijsten T, et al. Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989–2013. J Invest Dermatol 2016;136: 1955–1960. 3. Guitera P, Pellacani G, Crotty KA, et al. The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face. J Invest Dermatol 2010;130:2080–2091. 4. Rhodes AR, Harrist TJ, Momtaz TK. The PUVA-induced pigmented macule: A lentiginous proliferation of large, sometimes cytologically atypical, melanocytes. J Am Acad Dermatol 1983;9:47–58. 5. Stankiewicz K, Chuang G, Avram M. Lentigines, laser, and melanoma: A case series and discussion. Lasers Surg Med 2012;44:112–116. 6. Ferguson RE, Jr., Vasconez HC. Laser treatment of congenital nevi. J Craniofac Surg 2005;16:908–914. 7. Marghoob AA, Borrego JP, Halpern AC. Congenital melanocytic nevi: Treatment modalities and management options. Semin Cutan Med Surg 2007;26:231–240. 8. Dummer R. About moles, melanomas, and lasers: The dermatologist’s schizophrenic attitude toward pigmented lesions. Arch Dermatol 2003;139:1405–1406. 9. Hazan C, Dusza SW, Delgado R, et al. Staged excision for lentigo maligna and lentigo maligna melanoma: A
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HIBLER ET AL. retrospective analysis of 117 cases. J Am Acad Dermatol 2008; 58:142–148. Kunishige JH, Brodland DG, Zitelli JA. Surgical margins for melanoma in situ. J Am Acad Dermatol 2012;66:438–444. Wilson JB, Walling HW, Scupham RK, et al. Staged excision for lentigo maligna and lentigo maligna melanoma: Analysis of surgical margins and long-term recurrence in 68 cases from a single practice. J Clin Aesthet Dermatol 2016;9:25–30. Hou JL, Reed KB, Knudson RM, et al. Five-year outcomes of wide excision and Mohs micrographic surgery for primary lentigo maligna in an academic practice cohort. Dermatol Surg 2015;41:211–218. Higgins HW, 2nd, Lee KC, Galan A, et al. Melanoma in situ: Part I. Epidemiology, screening, and clinical features. J Am Acad Dermatol 2015;73:181–190, quiz 91–2. Keaney TC. Aging in the male face: Intrinsic and extrinsic factors. Dermatol Surg 2016;42:797–803. Abdelmalek M, Loosemore MP, Hurt MA, et al. Geometric staged excision for the treatment of lentigo maligna and lentigo maligna melanoma: A long-term experience with literature review. Arch Dermatol 2012;148:599–604. Felton S, Taylor RS, Srivastava D. Excision margins for melanoma In situ on the head and neck. Dermatol Surg 2016;42:327–334. Lawrence CM, Rahim R, Charlton F, et al. Prospective study of formalin-fixed Mohs surgery and haematoxylin and eosin stains with control contralateral biopsies for lentigo maligna: 5-year follow-up results. Br J Dermatol 2014;171:298–303. Kasprzak JM, Xu YG. Diagnosis and management of lentigo maligna: A review. Drugs Context 2015;4:212281. Gardner KH, Hill DE, Wright AC, et al. Upstaging from melanoma in situ to invasive melanoma on the head and neck after complete surgical resection. Dermatol Surg 2015;41: 1122–1125. Iorizzo LJ, 3rd, Chocron I, Lumbang W, et al. Importance of vertical pathology of debulking specimens during Mohs micrographic surgery for lentigo maligna and melanoma in situ. Dermatol Surg 2013;39:365–371. de Vries K, Greveling K, Prens LM, et al. Recurrence rate of lentigo maligna after micrographically controlled staged surgical excision. Br J Dermatol 2016;174:588–593. Lee H, Sowerby LJ, Temple CL, et al. Carbon dioxide laser treatment for lentigo maligna: A retrospective review comparing 3 different treatment modalities. Arch Facial Plast Surg 2011;13:398–403. Ikoma N, Umezawa Y, Mabuchi T, et al. Lentigo maligna occurring in a patient with the past history of laser therapy. Tokai J Exp Clin Med 2008;33:75–77. Zipser MC, Mangana J, Oberholzer PA, et al. Melanoma after laser therapy of pigmented lesions-circumstances and outcome. Eur J Dermatol 2010;20:334–338. Simionescu O, Blum A, Grigore M, et al. Learning from mistakes: Errors in approaches to melanoma and the urgent need for updated national guidelines. Int J Dermatol 2016;55: 970–976. Delker S, Livingstone E, Schimming T, et al. Melanoma diagnosed in lesions previously treated by laser therapy. J Dermatol 2017;44:23–28. Gottschaller C, Hohenleutner U, Landthaler M. Metastasis of a malignant melanoma 2 years after carbon dioxide laser treatment of a pigmented lesion: Case report and review of the literature. Acta Derm Venereol 2006;86:44–47. Grob M, Senti G, Dummer R. Delay of the diagnosis of an amelanotic malignant melanoma due to CO2-laser treatment?case report and discussion. Praxis (Bern 1994) 1999;88: 1491–1494. Wilson RL, Yentzer BA, Isom SP, et al. How good are US dermatologists at discriminating skin cancers? A numberneeded-to-treat analysis. J Dermatolog Treat 2012;23:65–69. Nault A, Zhang C, Kim K, et al. Biopsy use in skin cancer diagnosis: Comparing dermatology physicians and advanced practice professionals. JAMA Dermatology 2015;151:899–902. Wurm EM, Curchin CE, Lambie D, et al. Confocal features of equivocal facial lesions on severely sun-damaged skin: Four case studies with dermatoscopic, confocal, and histopathologic correlation. J Am Acad Dermatol 2012;66:463–473.
32. Menge TD, Hibler BP, Cordova MA, et al. Concordance of handheld reflectance confocal microscopy (RCM) with histopathology in the diagnosis of lentigo maligna (LM): A prospective study. J Am Acad Dermatol 2016;74:1114–1120. 33. Somach SC, Taira JW, Pitha JV, et al. Pigmented lesions in actinically damaged skin. Histopathologic comparison of biopsy and excisional specimens. Arch Dermatol 1996;132: 1297–1302. 34. Huilgol SC, Selva D, Chen C, et al. Surgical margins for lentigo maligna and lentigo maligna melanoma: The technique of mapped serial excision. Arch Dermatol 2004;140: 1087–1092. 35. Bub JL, Berg D, Slee A, et al. Management of lentigo maligna and lentigo maligna melanoma with staged excision: A 5-year follow-up. Arch Dermatol 2004;140:552–558. 36. Agarwal-Antal N, Bowen GM, Gerwels JW. Histologic evaluation of lentigo maligna with permanent sections: Implications regarding current guidelines. J Am Acad Dermatol 2002;47:743–748. 37. Moyer JS, Rudy S, Boonstra PS, et al. Efficacy of staged excision with permanent section margin control for cutaneous head and neck melanoma. JAMA Dermatology 2017; 153:282–288. 38. Ortonne JP, Pandya AG, Lui H, et al. Treatment of solar lentigines. J Am Acad Dermatol 2006;54:S262–S271. 39. Arlette JP, Trotter MJ, Trotter T, et al. Management of lentigo maligna and lentigo maligna melanoma: Seminars in surgical oncology. J Surg Oncol 2004;86:179–186. 40. Zalaudek I, Horn M, Richtig E, et al. Local recurrence in melanoma in situ: Influence of sex, age, site of involvement and therapeutic modalities. Br J Dermatol 2003;148:703–708. 41. Van Leeuwen RL, Bastiaens MT, Grevelink JM. Management of nevus spilus with laser. Pediatr Dermatol 1997;14:155–156. 42. Chan HH, Xiang L, Leung JC, et al. In vitro study examining the effect of sub-lethal QS 755nm lasers on the expression of p16INK4a on melanoma cell lines. Lasers Surg Med 2003;32:88–93. 43. Sohn S, Kim S, Kang WH. Recurrent pigmented macules after q-switched alexandrite laser treatment of congenital melanocytic nevus. Dermatol Surg 2004;30:898–907; discussion 07. 44. Gambichler T, Kempka J, Kampilafkos P, et al. Clinicopathological characteristics of 270 patients with lentigo maligna and lentigo maligna melanoma: Data from a German skin cancer centre. Br J Dermatol 2014;171:1605–1607. 45. Lee PK, Rosenberg CN, Tsao H, et al. Failure of Q-switched ruby laser to eradicate atypical-appearing solar lentigo: Report of two cases. J Am Acad Dermatol 1998;38:314–317. 46. Braun RP, Rabinovitz HS, Krischer J, et al. Dermoscopy of pigmented seborrheic keratosis: A morphological study. Arch Dermatol 2002;138:1556–1560. 47. Chung HJ, McGuigan KL, Osley KL, et al. Pigmented solar (actinic) keratosis: An underrecognized collision lesion. J Am Acad Dermatol 2013;68:647–653. 48. Ahlgrimm-Siess V, Massone C, Scope A, et al. Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: A preliminary study. Br J Dermatol 2009; 161:1307–1316. 49. Ahlgrimm-Siess V, Cao T, Oliviero M, et al. Seborrheic keratosis: Reflectance confocal microscopy features and correlation with dermoscopy. J Am Acad Dermatol 2013;69: 120–126. 50. Peris K, Micantonio T, Piccolo D, et al. Dermoscopic features of actinic keratosis. J Dermatol 2007;5:970–976. 51. Ciudad C, Aviles JA, Suarez R, et al. [Diagnostic utility of dermoscopy in pigmented actinic keratosis]. Actas Dermosifiliogr 2011;102:623–626. 52. Moscarella E, Rabinovitz H, Zalaudek I, et al. Dermoscopy and reflectance confocal microscopy of pigmented actinic keratoses: A morphological study. J Eur Acad Dermatol Venereol 2015;29:307–314. 53. Richtig E, Hofmann-Wellenhof R, Kopera D, et al. In vivo analysis of solar lentigines by reflectance confocal microscopy before and after Q-switched ruby laser treatment. Acta Derm Venereol 2011;91:164–168.
Lentigo Maligna Melanoma With a History of Cosmetic Treatment: Prevalence, Surgical Outcomes, and Considerations Brian P. Hibler, MD,1 Karen L. Connolly, MD,1,2 Erica H. Lee, MD,1 Anthony M. Rossi, MD,1 and Kishwer S. Nehal, MD1 1 Memorial Sloan Kettering Cancer Center, Dermatology Service, 16 E. 60th Street, 4th Floor Dermatology, New York, New York 10022 2 Lincoln Hospital, Dermatology Service, 234 E. 149th Street, Bronx, New York 10451
Introduction: Lentigo maligna (LM) is melanoma in situ on sun-damaged skin and presents diagnostic challenges due to overlapping features with benign pigmented lesions. Cosmetic treatments may be inadvertently performed on LM. The aim of this study is to estimate the prevalence of LM with prior cosmetic treatment, and evaluate surgical outcomes. Study Design and Methods: Retrospective review of biopsy-proven LM presenting over a 10-year-period (2006– 2015). Prior cosmetic treatment and biopsies were recorded. Records were reviewed for demographic data, clinical characteristics, and surgical outcomes. Results: 37/503 (7.4%) patients with LM reported prior cosmetic therapy. Most (95%) were on the head and neck; mean size 1.9 cm. Most patients reported cryotherapy (73%), followed by laser (29.7%), topical bleaching agents (18.9%), and electrodessication, and/or curettage (5.3%). Ten patients (27%) received two or more modalities. Eight patients (21.6%) reported prior benign biopsies. Six patients (16%) had invasive disease, two on initial biopsy and 4/34 (11.7%) upstaged upon excision. Average margin for clearance was 9.1 mm. Conclusion: Prior cosmetic treatment of LM is not uncommon, and may delay diagnosis and obscure borders, resulting in wider surgical margins. Clinicians should consider a biopsy confirming the benign nature of equivocal lesions prior to cosmetic treatment. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc. Key words: benign; pigmented lesion; melanoma; lentigo maligna; solar lentigo; seborrheic keratosis; laser; cosmetic; cryotherapy; staged excision INTRODUCTION Lentigo Maligna and LM Melanoma (LM/LMM) are subtypes of melanoma occurring on chronically sundamaged skin, mainly on the head and neck, and its annual incidence is increasing [1,2]. LM can be diagnostically challenging, even for experienced dermatologists, due to overlapping features with benign pigmented lesions, such as macular seborrheic keratosis, pigmented actinic ß 2017 Wiley Periodicals, Inc.
keratosis, and solar lentigines [3]. Benign solar lentigines are present in an estimated 90% of lighter Fitzpatrick phototype individuals over age 60, and are a common cosmetic concern prompting elective treatment [4]. Misdiagnosis can have important consequences, as procedures used to treat benign pigmented lesions may be inadvertently performed on LM. As such, there have been reported cases of patients referred for cosmetic removal of benign pigmented lesions that were found to be LM on histological evaluation [5]. There is an aging population with a growing interest in cosmetic procedures and focus on decreasing the signs of aging, complicated by increasing rates of skin cancer. Cosmetic treatments including cryotherapy, laser therapy, or topical bleaching agents are used commonly to treat clinical pigmentation, but may obfuscate the subsequent detection of malignancy due to dyspigmentation or scarring, delaying diagnosis [6–8]. The actual incidence of LM previously treated cosmetically as benign pigmented lesions is unknown, and difficult to assess due to the indolent natural history of LM development. It is also unknown if cosmetic treatment of lesions that were later identified as LM result in worse clinical outcomes.
Abbreviations: LM, lentigo maligna; LMM, lentigo maligna melanoma; RCM, reflectance confocal microscopy Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Selected for the Dr. Richard E. Fitzpatrick Clinical Research and Innovations Award, ASLMS 37th Annual Conference, San Diego, CA, April 7, 2017. This study was granted an IRB waiver by the Memorial Sloan Kettering Cancer Center IRB. Contract grant sponsor: National Cancer Institute; Contract grant number: P30 CA008748. Correspondence to: Kishwer S. Nehal, MD, Memorial Sloan Kettering Cancer Center, Dermatology Service, 16 E. 60th Street, 4th Floor Dermatology, New York, NY 10022. E-mail: [email protected] Accepted 14 May 2017 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22691
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OBJECTIVE
Previous Biopsy Characteristics
The aim of this study is to determine the prevalence of biopsy-proven LM that presented for definitive treatment following a history of cosmetic treatment, and to evaluate if prior cosmetic treatment complicates management and prognosis.
Eight patients (8/37; 21.6%) reported a history of benign biopsy, with three patients having multiple prior benign biopsies (Table 1). The biopsies were performed between 1 month and 8 years prior to LM diagnosis. Benign biopsy diagnoses included seborrheic keratosis, nevus, solar lentigo, and lichen planus-like keratosis.
METHODS Following Institutional Review Board approval, a prospectively collected database of all biopsy-proven LM/ LMM presenting to a dermatologic surgery practice at a cancer center for management between 2006 and 2015 was retrospectively reviewed. Upon initial presentation, patients were asked if they had received prior cosmetic treatment of their biopsy-proven LM/LMM (including cryotherapy, laser treatments, electrodessication and/or curettage, or topical bleaching creams). Patients were also asked if they had a history of prior biopsy from the lesion. Outside pathology reports for prior benign biopsies were obtained. For any LM/LMM with a history of prior cosmetic treatment, records were reviewed for demographic data along with presenting clinical characteristics and surgical outcomes. All patients underwent surgical excision with a staged technique and rush paraffin-embedded permanent sectioning with serial sections for extent of residual LM and presence or absence of invasive tumor as previously described [9]. Pathology reports were reviewed, including final depth of invasion. Cases that were previously treated solely with surgical excision or with topical imiquimod were excluded. RESULTS Clinical Characteristics Five hundred three patients meeting inclusion criteria were treated for biopsy-proven LM/LMM from 2006 to 2015. Of these, 37 patients (7.4%) reported a history of prior cosmetic treatment of their lesion (Table 1). The average age of patients with prior cosmetic treatment was 61 (range: 34–81), with 17 men (46%) and 20 women (54%). All patients had Fitzpatrick phototype I–III. Of the most common locations, seventeen lesions presented on the cheek (45.9%), followed by eight on the forehead (21.6%) and five on the nose (13.5%). Overall, 35/37 (95%) were located on the head, with the other two on the extremities. The mean size of the lesion on presentation was 1.9 cm, ranging from 0.3 to 5.5 cm in longest clinical diameter. Cosmetic Treatments Prior cosmetic treatment included cryotherapy, laser, topical bleaching agents, and electrodessication and/or curettage. The majority of patients reported prior treatment with cryotherapy (73%, n ¼ 27) either alone or in combination with other treatments, followed by laser treatment (29.7%, n ¼ 11), topical bleaching agents (18.9%, n ¼ 7), and electrodessication and/or curettage (5.3%, n ¼ 3). Ten patients (27%) were treated with two or more treatment modalities (Table 1).
Histopathologic Characteristics: Overall, six patients (6/37; 16.2%) had invasive disease either on biopsy or excision. Two cases were diagnosed as LMM on initial biopsy, and four of the remaining 34 cases treated surgically (11.7%) were initially diagnosed as LM on biopsy but revealed an invasive component upon complete excision. Depths of invasive disease ranged from 0.2 mm to 1.25 mm (Table 1). Surgical Outcomes All patients except one were treated with staged surgical excision for complete margin control. One patient was treated at an outside institution. The average margin needed to clear the lesion was 9.1 mm (range 3–23 mm). Fifteen of 36 patients (42%) treated with staged surgical excision required at least 10 mm margins. The mean number of stages to clear the lesion was 2.1 (range 1–5). The average clinical lesion size in longest diameter for the six invasive lesions was 2.98 cm (0.9–5.5 cm). The average margins were 11.33 mm, with 2.2 stages to clear the lesion. For the lesion with depth 1.25 mm (focal Clark IV involvement), lymphoscintigraphy was attempted but a dominant nodal basin was not identified. Considering the subset of non-invasive lesions, the average clinical lesion size was 1.71 cm (0.3–4.5 cm). The average margin for noninvasive lesions was 8.63 mm, with 2.0 stages required for clearance. DISCUSSION There is an aging population with growing interest in cosmetic procedures to reverse the signs of aging. In this study the prevalence of LM/LMM reported to have been previously treated cosmetically as a benign pigmented lesion was 7.4%. As the incidence of LM/LMM continues to increase, providers must be aware of lesions not responding to conventional treatments, and be cautious of presumed benign pigmented lesions that deviate morphologically prior to treating cosmetically. The average age in our series (61) is lower than the reported 65–70 years [9–12], reflecting both the increased interest in cosmetic procedures among younger individuals and that the incidence of melanoma in situ is increasing, with a faster rate in younger populations [13]. Interestingly, nearly 50% of the patients in our series were male, which reflect current trends that more men are seeking cosmetic procedures [14]. Notably, over a quarter of patients were treated with multiple modalities, suggesting multiple clinic visits or time points to reassess the lesion. Although the setting and qualifications of providers performing cosmetic treatments in this study is not known, the
COSMETIC TREATMENT OF LM
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TABLE 1. Clinical Characteristics, Prior Treatment, and Surgical Outcomes of Cosmetically Treated Lentigo Maligna
Age/ Gender
Total margins (mm)
Total stages
EDC Cryo Cryo, Bleaching Cryo Cryo Cryo Cryo Cryo Laser Laser, Cryo, Bleaching Laser
10 11 13
2 3 3
8 8 7 5 7 5 8
2 2 1 1 2 1 2
14
3
Laser, Cryo Cryo Laser, Cryo Cryo Cryo Cryo
3
1
12 5
2 1
6 11 5
2 3 1
Cryo, Bleaching Laser Cryo Cryo, Bleaching Cryo, Bleaching EDC
15
3
8 8 8
2 2 1
5
2
6
2
Laser, Bleaching Laser Bleaching Laser
5
1
15 8 10
3 2 2
Cryo Cryo Cryo Cryo Laser
10 15 5 13 5
3 3 1 3 1
Cryo Cryo
8 10
2 2
Site
Size (cm)
Prior benign biopsy (time from prior biopsy to diagnosis)
Prior treatment
34/F 42/F 43/F
Cheek Forehead Cheek
2.0 2.5 0.5
No No No
44/M 47/F 48/F 49/M 50/F 51/F 51/F
Forehead Cheek Earlobe Nose Nose Periorbital Cheek
2 1 1.5 0.4 0.3 0.8 2.6
No No No No No No No
53/M
Cheek
0.9
No
53/F
Cheek
3
Yes—Macular SK (2 years)
54/M 56/F
Scalp Cheek
3.5 0.8
Yes—SK (n/a)a No
57/F 59/M 60/M
Extremity Periorbital Forehead
2.3 0.7 0.6
60/F
Cheek
5.5
No No Yes—Junctional nevus/Blue nevus (3 years) Yes—benign NOS (4 years)a
64/F 65/M 65/F
Cheek Cheek Cheek
2.1 1.1 3.5
No No Yes—benign NOS (4 years)a
66/M
Nose
1
No
66/M
Forehead
0.8
67/F
Nose
2
Yes—Solar elastosis, SK; Atypical proliferation of enlarged melanocytes and SL (3 years) No
67/F 69/M 69/M
Cheek Forehead Forehead
2.1 1.1 4.5
70/M 70/F 71/F 73/M 74/M
Cheek Chin Cheek Forehead Forehead
2.1 2.1 1.2 1 2
76/M 80/M
Cheek Extremity
3 5.5
No No Yes—Solar lentigo and actinic keratosis (1 year); LPLK and inflamed SK (6 months) No No No No Yes—macular SK (8 years); inflamed SK (1 year); SL (1 month) No No
Other details Invasive 0.4 mm
Invasive 0.2 mm
Invasive; at least 0.2 mm, transected (biopsy)
Invasive 1.25 mm Clark IV
Invasive 0.3 mm (Continued)
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TABLE 1. (Continued)
Age/ Gender 81/F 81/F 56/M
Site
Size (cm)
Prior benign biopsy (time from prior biopsy to diagnosis)
Prior treatment
Cheek Cheek Nose
2.5 2 0.5
No No No
Cryo, EDC Cryo Laser, Cryo
Total margins (mm)
Total stages
12 23 n/a
2 5 n/a
Other details (biopsy) Invasion 0.65 mm Surgery not performed
M, male; F, female; EDC, electrodessication and curettage; Cryo, cryotherapy; SK, seborrheic keratosis; NOS, not otherwise specific; LPLK, lichen planus-like keratosis; SL, solar lentigo. a Original outside benign biopsy report not available.
findings reinforce that skin lesions should be evaluated by individuals appropriately trained in evaluating skin and cosmetic concerns. LM is an indolent form of melanoma that evolves slowly and is often present for years prior to diagnosis. These lesions have a slow rate of invasion, and controversy exists regarding management and optimal surgical margins. Early detection and adequate treatment with negative margins is important prior to progression to invasive melanoma. It has been well-established in the dermatology literature that standard 5 mm margins are inadequate for complete margin control in large series of LM [11,15–18]. In a previously published series from our institution utilizing the same staged surgical technique, the margins required for clearance of LM was 7.1 mm, and for LMM was 10.3 mm [9]. In the current study, the margins required for clearance of cosmetically treated LM were even wider (8.6 mm for LM, 11.3 mm for LMM). Moreover, 15/36 patients in this series (42%) required at least 10 mm margins. This suggests the clinical borders may have been obscured by prior therapies aimed at destroying surface pigment, or there may have been a delay in diagnosis while treating as a benign pigmented lesion allowing for further radial growth (Fig. 1). In the author’s experience, skip areas have been occasionally observed but the true incidence is unknown. Overall, the rate of upstaging from LM to invasive disease upon final excision (11.7%) was high but within the expected range compared with other recently reported rates of upstaging for LM and
melanoma in situ (4–11.7%) [15,19–21]. Thus, the prior cosmetic treatment did not appear to have an effect on overall prognosis, but the wider surgical margins resulted in larger defects creating reconstructive challenges and increased morbidity. Long-term follow-up is required to determine if these lesions have higher rates of recurrence, as there may have been interruption in contiguous tumor resulting from their prior cosmetic treatment. A review of the literature shows 13 previously reported cases of pigmented lesions initially treated cosmetically with cryotherapy and/or laser treatment, later diagnosed as LM/LMM [8,22–26] (Table 2). The ages range from 59 to 72, with seven males and six females. All were located on the head and neck except one on the upper arm. Those with a benign biopsy at some point prior to cosmetic treatment had the following results: pigmented actinic keratosis, melanocytic nevus, nevoid lentigo, and dysplastic nevus. Of the 13 reported cases, 8 were found to have invasive LMM (61.5%) on final excision and one patient had lymph node metastasis. Additional reports document other forms of melanoma, including nodular, amelanotic, and metastatic, occurring after prior laser or cosmetic treatment of presumed benign lesions [24–28]. Stankiewicz et al. describe three patients who presented for cosmetic removal of pigmented lesions, two referred by physicians, all found to be LM or melanoma in situ before any cosmetic intervention, underscoring the importance of careful evaluation of presumed benign pigmented lesions before treatment [5].
Fig. 1. Lentigo Maligna. (A) 70-year-old female with a poorly demarcated hyperpigmented patch on the chin. She reported treatment with cryotherapy and no prior biopsies. (B) Surgical defect after three stages of excision and 15 mm margins.
COSMETIC TREATMENT OF LM
5
TABLE 2. Lentigo Maligna Cosmetically Treated as a Benign Pigmented Lesion Prior treatment modality
Age/Gender
Lee et al.[45]
1) 59/M
-Cheek
2) 71/M
-Cheek
Dummer[8]
64/F
-Forehead
-Alexandrite laser
Ikoma et al.[23]
70/F
- Laser Therapy NOS -n/a
Zipser et al.[24] a note 12 melanomas total in this series
1) 72/M
-Cutaneous lip -Forehead
-LMM (lymph node metastasis) -LM
-Laser Therapy NOS
-LMM
2) 66/M 3) 75/F 4) 59/F 68/M 1) 52/M 2) 66/F 3) 70/M 4) 71/F
-Cheek -Preauricular -Cheek -Cheek -Nose -Upper arm -Nose -Nose
-CO2 -CO2 -Er:YAG -Laser Therapy NOS -Laser Therapy NOS
Simionescu et al.[25] Delker et al.[26] a note 11 melanomas total in this series
Location
Histology before initial treatment
Study
-Cryotherapy, Qswitched Ruby Laser 694 nm -Q-switched Ruby Laser
-No
-Possible pigmented actinic keratosis -No
-Melanocytic nevus -n/a -n/a -n/a -No -Nevoid lentigo -Dysplastic nevus -No -No
Outcome -LMM (Breslow thickness 2.35 mm, Clark IV) -LM
-LM -LM -LMM -LMM -LM -LMM -LMM -LMM
M, male; F, female; NOS, not otherwise specific; CO2, Carbon dioxide; Er:YAG, Erbium:yttrium-aluminum-garnet; n/a, not available; LM, lentigo maligna; LMM, lentigo maligna melanoma. a For series containing multiple subtypes of melanoma, only cases of LM/LMM are summarized in this table.
When patients present for cosmetic treatment of a pigmented lesion on sun-damaged skin, they should be questioned regarding changes in size, color, shape, or other features that are now raising cosmetic concern about the lesion. While it is unreasonable to biopsy every pigmented lesion prior to cosmetic treatment, all warrant thorough clinical and dermoscopic evaluation. Yet, diagnostic accuracy as measured by the number needed to biopsy among dermatologists at two academic centers ranges from 15 to 17.4 for melanoma [29,30]. Recently, reflectance confocal microscopy (RCM) has seen an emerging role for non-invasively evaluating clinically equivocal pigmented facial lesions, including LM [31,32] (Table 3). RCM has acquired Coding Procedural Terminology (CPT) codes (96931–96936), providing reimbursement for image acquisition and interpretation. These images may be acquired longitudinally over time, allowing for repeat non-invasive assessment of areas of skin to guide management, and may help provide a story to the dermatopathologist aiding in biopsy interpretation. For large, clinically suspicious lesions on sun-damaged skin, a biopsy may be warranted. However, limited sampling via a punch biopsy showing solar lentigo or pigmented actinic keratosis does not exclude the diagnosis of LM [33]. In fact, eight patients in this study reported a history of prior benign biopsies. Sampling error may only reveal mild or moderate melanocytic atypia when LM is present in other areas of the lesion, especially when small, partial biopsies are taken in the interest of preserving
cosmesis (Fig. 2). Variations in size, number, and type of biopsy likely account for the varied rates of upstaging seen after LM diagnosis [21,34–36]. This is supported by the observation that institutions performing microstaging (removal of all clinically apparent residual lesion suspicious for invasive disease prior to staged excision) achieve lowest rates of deeper residual disease (3.8%) [37]. In the case of particularly large lesions, incisional biopsy or multiple mapping biopsies should be taken of the most deeply pigmented or thickest areas. Repigmentation After Cosmetic Treatment Cosmetic treatments for pigmented lesions (lasers, cryotherapy, chemical peels, electrodessication and curettage, and bleaching agents) target surface pigmentation to improve the cosmetic appearance, but ultimately obscure future clinical examination [38]. The prospect of early LMs being successfully treated with these destructive modalities is possible; however, at this time, neither cryosurgery or laser treatment is recommended for LM due to the high rate of recurrence, potential for adnexal invasive disease, and lack of controlled studies [39,40]. In the current study, 10 patients reported multi-modality treatments suggesting that the lesion did not respond to an initial treatment. Patients reported their cosmetic treatments occurred over months to years, but the exact time to repigmentation is not known. Clinical repigmentation or persistent pigmentation in lesions previously treated with destructive or
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TABLE 3. Clinical, Dermoscopic, and Reflectance Confocal Microscopy Features of Benign Pigmented Lesions and Lentigo Maligna[46–53] Seborrheic keratosis Clinical Tan or brown
Slightly raised
Pigmented actinic keratosis Irregularly pigmented macule or patch with foci of keratotic scale May have hues of pink, red, tan, brown, dark brown
Flat, rough (warty) surface
Solar lentigo Tan to brown macule or patch; even pigmentation Well-defined border
Variegated tan to dark brown macule or patch
Multiple lesions; may increase in size and number over time
Colors change as lesion evolves
Waxy, stuck-on appearance
Well-demarcated, round or oval Dermoscopy Milia-like cysts
Comedo-like openings Light brown finger-like structures Hairpin blood vessels Cerebriform appearance (gyri, sulci)
Lentigo maligna
Indistinct, irregular borders
May have grey areas of regression or amelanotic (pink) areas
Brown/grey pseudonetwork (variation in pattern and extent of involvement) Surface scale Slate-grey/dark brown dots and globules around follicular ostia Fine vessels Annular-granular pattern
Diffuse brown and opaque structureless areas
Rhomboidal structures
Sharply demarcated or moth-eaten borders Fingerprint-like structures
Annular-granular structures
Reticular pattern
Gray pseudo-network Homogenous areas of pigment
Increased density of dermal papillae surrounded by bright, monomorphic layer of cells (edged papillae) Regular honeycomb pattern Cord-like rete ridges
Atypical melanocytes in nests
Asymmetric pigmented follicular openings
Rhomboidal structures Reflectance Confocal Microscopy Regular epidermal honeycomb pattern
Dense, well-circumscribed dermal papillae Corneal plugs and cysts Melanophages
Atypical keratinocytes in epidermis, parakeratosis, and scale
Increased epidermal thickness Bright, small dermal papillae Dendritic cells
Dilated, round and linear blood vessels
ablative modalities should raise suspicion of potential LM, even with a history of prior benign biopsy. In our series, 29/37 (78%) of LM who received cosmetic treatment did not report a prior biopsy. Other studies have also reported a lack of histological diagnosis prior to treatment of lesions that were melanoma. In a series by Delker et al., 9/11 (82%) lesions that were melanoma had no biopsy prior to cosmetic treatment [26]. Four of these were stage IV disease, and one patient died of melanoma. In
Epidermal disarray Cord-like rete ridges Sheets of atypical, dentritic cells, often with perifollicular infiltration Large, round, pagetoid cells
another series by Zipser et al., 8/12 (67%) patients had no biopsy prior to cosmetic treatment, 2/12 (17%) were misdiagnosed on review, and only 2/12 (17%) had benign biopsies before treatment [24]. In their series, two patients had stage IV disease, and three died of metastatic melanoma. Gottschaller et al. describe a case of metastatic melanoma after a clinically diagnosed “lentigo simplex” was treated with CO2 laser, and review other cases of malignant melanoma after laser therapy [27]. While it has been shown in vitro that
COSMETIC TREATMENT OF LM
7
Fig. 2. Lentigo Maligna Melanoma. (A) Red and brown hyperpigmented patch on the left malar cheek encroaching upon the lower eyelid, previously treated with cryotherapy and topical bleaching agents. The patient reported a benign biopsy 4 years prior. (B) Defect after three stages of excision and 15 mm margins. Invasive disease was detected to a depth of 1.25 mm.
low-level laser exposure alters expression of tumor suppressor (p16 gene) and adhesion molecules in melanoma cell lines [41–43], this mechanism has not been observed in humans. The aforementioned studies in conjunction with the current study demonstrate the potential pitfalls in foregoing histological confirmation of a suspected benign pigmented lesion prior to pursuing cosmetic treatment. Limitations Limitations of our current study include possible recall bias regarding which lesions were previously treated. Cryotherapy is routinely used for treatment of facial lesions, and while patients may not exactly recall which ones were treated, it is plausible that these lesions were previously frozen. Secondly, we cannot definitively conclude that a new diagnosis of LM in an area previously treated with cosmetic therapies is evidence that a missed diagnosis of LM occurred. A de novo melanoma or a collision tumor may occur. In the cases of a prior benign biopsy, the area chosen for biopsy may not have captured adequate melanocytic atypia or the foci of invasive disease for correct diagnosis. Another limitation is that this was a single center study; however, this allowed for consistency in surgical technique, histopathologic evaluation, and margin determination. Comparison of our series to others was limited by heterogeneity of lesions included in the study, varying surgical technique, absence of reporting rates of invasion or surgical margins, and an unknown number of patients with prior cosmetic treatment included in other series [10–12,19,44]. CONCLUSION Prior cosmetic treatment of LM/LMM presenting for definitive surgical treatment is not uncommon. Overall, the incidence of LM previously treated as a benign pigmented lesion (7.4%) along with the cases reviewed here highlight the need for improved technologies to evaluate suspected benign pigmented lesions or possible LM. The rate of invasive disease was 16%, and 42% of all cosmetically treated LM lesions required at least 10 mm margins, suggesting prior cosmetic treatment may have
obscured borders. Lesion assessment with dermoscopy, RCM, or other non-invasive imaging prior to any cosmetic treatments may aid in evaluation. Clinicians must maintain an awareness of possible alternate diagnoses of pigmented lesions, especially for those occurring on sundamaged skin of the head and neck or in cases of residual or recurrent pigmentation. Patients should be consented and educated that if lesions do not resolve, they should return to their dermatologist for follow-up. ACKNOWLEDGMENTS The authors would like to acknowledge the American Society for Laser Medicine and Surgery (ASLMS) for generously providing a travel grant to present this work at the 37th Annual ASLMS Conference. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. REFERENCES 1. Gaudy-Marqueste C, Madjlessi N, Guillot B, et al. Risk factors in elderly people for lentigo maligna compared with other melanomas: A double case-control study. Arch Dermatol 2009;145:418–423. 2. Greveling K, Wakkee M, Nijsten T, et al. Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989–2013. J Invest Dermatol 2016;136: 1955–1960. 3. Guitera P, Pellacani G, Crotty KA, et al. The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face. J Invest Dermatol 2010;130:2080–2091. 4. Rhodes AR, Harrist TJ, Momtaz TK. The PUVA-induced pigmented macule: A lentiginous proliferation of large, sometimes cytologically atypical, melanocytes. J Am Acad Dermatol 1983;9:47–58. 5. Stankiewicz K, Chuang G, Avram M. Lentigines, laser, and melanoma: A case series and discussion. Lasers Surg Med 2012;44:112–116. 6. Ferguson RE, Jr., Vasconez HC. Laser treatment of congenital nevi. J Craniofac Surg 2005;16:908–914. 7. Marghoob AA, Borrego JP, Halpern AC. Congenital melanocytic nevi: Treatment modalities and management options. Semin Cutan Med Surg 2007;26:231–240. 8. Dummer R. About moles, melanomas, and lasers: The dermatologist’s schizophrenic attitude toward pigmented lesions. Arch Dermatol 2003;139:1405–1406. 9. Hazan C, Dusza SW, Delgado R, et al. Staged excision for lentigo maligna and lentigo maligna melanoma: A
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