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Original Article

No Recurrence in Primary Invasive Stage 1a and 1b Melanoma and Melanoma in Situ Treated With Serial Disk Staged Excision

Ahn, Grace Sora BS; Pousti, Bobak MD; Singh, Gaurav MD, MPH; Elsensohn, Ashley MD; Jiang, Shang I Brian MD*

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doi: 10.1097/DSS.0000000000003357
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Abstract

The surgical treatment of invasive melanoma (IM) and melanoma in situ (MIS) has been debated, with ongoing discussion regarding the various treatment modalities and ideal margins needed for optimal outcomes. The incidence of melanoma continues to rise, with an estimated 100,350 new cases of IM diagnosed in the United States in 2020.1 Lentigo maligna (LM), in particular, needs treatment clarification. Previously labeled a relatively benign melanoma subtype, LM has been shown to hold similar prognosis as other melanoma forms with a lifetime risk up to 4.7% of progressing to invasive disease.2,3

The 5-mm margin has been well-studied for MIS.4–9 The American Academy of Dermatology (AAD), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend 5-mm to 1-cm margins for MIS with the wider surgical margin suggested particularly for the LM subtype.4,10,11 There are multiple surgical techniques currently recommended for both IM and MIS. Among those are serial staged excision (SSE), Mohs micrographic surgery (MMS), and standard wide local excision (WLE). Mohs micrographic surgery and SSE have recently demonstrated better margin control compared with WLE.12–15 Much recent literature has come out to highlight the benefit of MMS in the treatment of melanoma, particularly at academic centers and with the use of immunohistochemistry—there are also retrospective studies demonstrating the superiority of MMS not only regarding recurrence rates but also regarding survival in large cohorts of patients.16–21 There has been some recent critique on the retrospective and heterogeneous nature of these MMS studies.22 Overall, however, there seems to be benefit of complete margin control using the MMS technique. Here, SSE is considered as an alternative to Mohs, allowing another modality for margin assessment prior to wound closure.

One SSE technique is the serial disk staged technique, which has shown low recurrence rates.5 The decision to use vertical “bread loafing” sectioning allows for the examination of the evolution of cell changes as they progress to the margins, especially important when considering the difficulties in interpreting LM in the background of sun-damaged skin.23,24 This technique was previously studied as part of a case series and was concluded to be a simple, accessible, alternative to WLE and MMS while comparable in efficacy to other SSE techniques.

The purpose of this study is to identify the recurrence rates and optimal surgical margin of MIS and invasive stage 1 melanoma using a serial disk staged excision technique with rush permanent processing and “bread loafing” microscopic analysis.

Materials and Methods

Data Collection

Two hundred seventy patients at the University of California San Diego Dermatologic Surgery Unit with MIS and Stage 1a or 1b IM treated with SSE between March 2010 and December 2019 were included. The primary outcome was clinical recurrence at the original surgical site. Age at diagnosis, age at excision, sex, skin type, pathology reports, tumor location, tumor dimensions, excision and repair dimensions, number of required stages, complications, recurrences, follow-up duration, preoperative size, postoperative size, and adverse outcomes were collected. Adverse outcomes were identified as any complication requiring additional medical or surgical intervention and included skin infections, postoperative bleeding, flap necrosis, graft loss, and wound dehiscence. The surgical margins were determined by taking the difference between the preoperative and postoperative excision dimensions. Continuous data were analyzed with t-test distributions. Institutional review board approved this study.

Surgical Technique

The staged excision utilizes a simple disk staged excision with 90° angles. A notch is marked at 12 o'clock for the initial stage and a three-suture marking technique for subsequent stages. Initial margins are 5 mm to the superficial/mid-fat for MIS and 10 mm to the muscular fascia for IM (stage T1a or T1b). Pathology is sent for rush permanent sections with 24-hour turnaround. The excision specimen is bread-loafed with 3-mm intervals with 1 or 2 slides per interval segment. All slides are reviewed by the board-certified dematopathologist. En-face margin assessment was not utilized.

Histopathologic Definition

Diagnoses were rendered by a board-certified dermatopathologist. Dermatopathologists of the University of California examined all the specimens, to include internal and externally referred cases.

Results

From March 1, 2010, to December 31, 2019, 321 patients underwent SSE of either superficially IM (Stage 1a or 1b) or MIS. Two patients with MIS were excluded from this study due to previous primary excisions at outside institutions. Forty-nine patients were excluded due to inadequate follow-up duration, determined to be less than 10 months. Ultimately, 270 patients were included, including 63 with IM and 207 with MIS (Tables 1 and 2).

TABLE 1. - Patient Demographics and Lesion Characteristics of MIS Cohort
Serial Staged Excision for MIS
Variable n (SD or %)
No. of MIS cases 207
Sex
 Male 138 (67%)
 Female 69 (33%)
Fitzpatrick
 I 2 (1%)
 II 202 (98%)
 III 3 (1%)
Lesion location
 Head and neck 133 (64%)
  Cheek 41 (20%)
  Chin/jawline 6 (3%)
  Forehead 8 (4%)
  Nose 5 (2%)
  Neck 22 (11%)
  Scalp 21 (10%)
  Ear 10 (5%)
  Eyelid 5 (2%)
  Temple 11 (5%)
  Lip 4 (2%)
 Torso and extremities 74 (36%)
  Back 9 (4%)
  Leg 20 (10%)
  Foot/ankle 6 (3%)
  Arm 20 (10%)
  Shoulder 7 (3%)
  Hand 1 (1%)
  Chest 11 (5%)
Age at excision (yrs) Mean 68.7, median 70 (range 22–96)
Preoperative size (mm) Mean 14.7 (SD 16.5) 
Postoperative size (mm) Mean 25.8 (SD 23.1) 
Final surgical margin (mm) Mean 12.1 (SD 12.2) 
Stages needed for histologically clear margin Mean 1.28 (range 1–3) 
Follow-up duration (mo) Mean 36.5, median 33 (range 10–92) 
Complications 5
Recurrences 0
MIS, melanoma in situ.

TABLE 2. - Patient Demographics and Lesion Characteristics of IM cohort
Serial Staged Excision for IM
Variable n (SD or %)
No. of IM cases 63
Sex
 Male 43 (68%)
 Female 20 (32%)
Fitzpatrick
 I 2 (3%)
 II 61 (97%)
 III 0
Lesion location
 Head and neck 35 (56%)
  Cheek 8 (13%)
  Chin/jawline 1 (2%)
  Forehead 2 (3%)
  Nose 1 (2%)
  Neck 9 (14%)
  Scalp 6 (10%)
  Ear 4 (6%)
  Eyelid 1 (2%)
  Temple 3 (5%)
 Torso and extremities 28 (44%)
  Back 10 (16%)
  Leg 8 (13%)
  Foot/ankle 3 (5%)
  Arm 1 (2%)
  Shoulder 2 (3%)
  Hand 2 (3%)
  Chest 2 (3%)
Age at excision (yrs) Mean 43, median 68 (range 22–89)
Preoperative size (mm) Mean 14.8 (SD 18.2) 
Postoperative size (mm) Mean 33.5 (SD 23.0) 
Final surgical margin (mm) Mean 19.8 (SD 9.7) 
Stages needed for histologically clear margin Mean 1.16 (range 1–2) 
Follow-up duration (mo) Mean 33.7, median 26 (range 10–90) 
Complications 2
Recurrences 0
IM, invasive melanoma.

Invasive Melanoma (n = 63)

Average Breslow depth was 0.41 mm (SD 0.14). All lesions were staged as T1a except one T1b with a Breslow depth of 0.8 mm. Approximately 24% (15/63) of lesions were classified as LM melanoma with the average Breslow depth of these lesions being 0.34 mm (SD 0.12) compared with 0.43 (SD 0.14) for non-LM lesions (p = .0386). The difference between LM type and non-LM type, as they relate to preoperative size, number of stages, and margin size for histopathologic clearance, were not statistically significant.

The average preoperative size for IM was 14.8 mm (SD 18.2), margin size for histopathologic clearance was 19.8 mm (SD 9.7), and number stages needed for margin clearance was 1.16 (range, 1–2) with 12.7% (8/63) requiring more than 1 stage. Reasons for reexcision were pathology upstaging (n = 1), atypical junctional melanocytic proliferation at lateral margin (n = 3), residual IM at margin (n = 1), and residual MIS at margin (n = 3). Three percent (2/63) experienced complications, comprising 2 superficial infections requiring oral antibiotics. No recurrences were identified within this cohort.

Melanoma in Situ (n = 207)

The average preoperative size for MIS was 14.7 mm (SD 16.5), the margin size for histopathologic clearance was 12.1 mm (SD 12.2), and the number of stages needed for histologically clear margins was 1.29 (range, 1–3). Although 24% (50/207) of lesions required more than 1 stage, 3 stages were the maximum and required for only 4% (9/207) of patients. There was no correlation between preoperative lesion size and the number of stages. Five (2.4%) experienced complications; the most common (4/5) being superficial infection requiring oral antibiotics, with one patient requiring surgical intervention for primary graft loss. No recurrences were identified within this cohort.

Discussion

There were no recurrences within this series of 270 melanoma in situ or superficial (Stage T1a or T1b) IM with the variant of serial disk staged excision. This assuring lack of recurrence is similar to previously reported ranges for such staged techniques, between 0% and 12%, as summarized in Table 3.5,6,15,29,36–50 Likewise, the mean follow-up duration between 34 and 36 months for MIS and IM, respectively, provides a good window in identifying potential recurrence, similar to previously reported duration of 4.7 to 96 months.5,6,15,29,36–50

TABLE 3. - Prior Studies Summarizing Recurrence Rates of Serial Staged Excision for IM and MIS
Staged Excision Study Recurrence Rate Time to Recurrence (mo) Follow-up Duration (mo)
Walling 3 of 41 (7.3%) 24 96 ± 43.6
Bub 2 of 55 (3.6%) n/a 57
Huilgol 2 of 125 (1.6%) 12 38 ± 25
Johnson 0 of 35 (0%) n/a n/a
Hill and Gramp 1 of 38 (2.6%) 10 25
Anderson 1 of 150 (0.67%) <60 undefined n/a
Agarwal-Antal 0 of 93 (0%) n/a n/a
Malhotra 4 of 109 (3.7%) 12–40 32 ± 26
Mahoney 0 of 11 (0%) n/a 4.7
Jejurikar 0 of 51 (0%) n/a 31
Bosbous 1 of 59 (1.7%) n/a 26.4
Lee and Ryman 3 of 31 (9.7%) 48 42
Joyce 9 of 410 (2.2%) 29.6 23
de Vries 4 of 100 (4%) 37–77 60
Patel 1 of 21 (4.8%) 24 n/a
Lawrence 4 of 56 (12%) 52.8 60 minimum
Gaudy-Marqueste 0 of 20 (0%) 48 25.36
Möller 0 of 49 (0%) n/a 14
Garcia and Jiang 0 of 29 (0%) n/a 31.5
IM, invasive melanoma; MIS, melanoma in situ.

Histopathologic clearance in this series of 207 MIS lesions required an average margin of 12.1 mm with 79% of lesions cleared utilizing a margin of 10 mm or less. This is similar to prior studies showing a clearance rate of 74.5% and 97% utilizing a 10- and 12-mm margin, respectively.25,26 Additionally, shown through multiple prior studies as well as results of the current study, oftentimes, these margins are not adequate for margin control and disease clearance.7,25,27–29 Lack of recurrence with the above margins suggests that the current recommendations for MIS excision may be too conservative, leading to a higher than desired recurrence rate. Alternatively, larger margins than standard recommendations may also support the use of margin control techniques such as SSE and MMS.

A unique aspect of this study is its assessment of SSE for superficially IM (T1a and T1b). The NCCN, AAD, and ESMO guidelines recommend clinical margins based on Breslow depth (BD). All of the excised IM lesions were <1 mm in BD and thus correlate with recommended clinical margins of at least 1.0 cm and a maximum excision margin of 2 cm recommended in Europe.30 As stated previously, a margin of 1.0 cm has shown to be insufficient in acquiring margin control for a significant portion of MIS lesions. Notably, the average margin size for IM was just less than 2 cm, roughly 1 cm larger than the aforementioned guidelines. Prior studies have confirmed that a 10-mm margin for invasive disease is often insufficient. One study including more than 260 IMs with an average BD of 0.46 mm demonstrated that only approximately half of their excisions were clear of disease after 10 mm or less margins.29 Invasive melanoma in Europe has also shown favorable survival outcomes associated with 3-cm excision margins compared with 1 cm.31 Such results may advocate caution when following minimum margin recommendations because many lesions may need advanced sections and further excision for adequate disease management.

The LM variants of both MIS and IM provide additional challenges given their pattern of growth and subclinical spread, with prior literature suggesting the need for wider margins than what are currently recommended.26,32–36 In patient sample of this study, no significant difference in initial lesion size was identified between LM and non-LM type MIS lesions. Invasive LM type melanoma lesions on average had a decreased Breslow depth when compared with non-LM IM (p = .038). Even so, there was no clinical difference in the number of stages or margin size for disease clearance between the 2.

Although WLE was long believed to be standard of care treatment for both MIS and IM, an ever-growing body of literature has suggested benefits with either MMS or SSE surgical technique.5,6,15,29,36–50 Current literature affirms these comparisons. A recent 10-year retrospective study demonstrated that MMS for MIS or thin IM decreased local recurrence rate compared with WLE.51 An additional 10-year retrospective review of “modified” MMS with permanent sectioning identified a 0% to 2% recurrence rate in those with MIS as well as an estimated 99% (95% confidence interval, 97.7%–99.6%) melanoma-specific survival.52 A recent cohort study of more than 70,000 patients treated for thin (T1) melanoma echoed this sentiment, demonstrating a modest survival benefit (Hazard Ratio, HR 0.86) for MMS compared with WLE.53 Such benefits become even more evident on anatomically complex locations, such as the head, neck, and acral surfaces. A recent study addressing acral melanoma found just that, illustrating a local recurrence of 3.7% using MMS with permanent processing compared with 10.7% with WLE.54 These results, in addition to the results of the present study, demonstrate how both MMS and SSE provide effective treatment alternatives to WLE, particularly on anatomically complex locations.

Critics of SSE reference the multiday nature of the staged treatment course and the potential complications associated with maintaining open wounds between stages and subsequent delayed repair. Only a minority of patients in this study, 28% with MIS and 15% with IM, required an additional stage after their primary excision. As such, the majority of patients did not require lengthy, recurrent surgical sessions and were able to proceed with closure shortly after their primary excision. Additionally, this study found that even with an extended, multiday course requiring patients to address an open wound, the complication rate demanding additional intervention remained low. Only 2.4% (5/207) of MIS and 3.2% (2/63) of IM patients experienced complications—the most common being a superficial infection requiring oral antibiotics (6/7). These results are similar to prior analyses of dermatologic surgery complications, with identified rates between 1.6% and 6%.55–57 As such, this study demonstrates how SSE remains not only an effective but also a safe and logistically viable surgical method for the treatment of melanoma and its variants.

Comparison of the 2 tissue sparing modalities, SSE and MMS, is a more nuanced conversation, with multiple iterations of both modalities—MMS with traditional frozen sections, modified MMS in combination with permanent sections, and SSE with permanent sections. Logistically, MMS could offer a faster, single-day procedural experience when compared with SSE if the wound closure is not delayed due to processing of the permanent sections of the debulked central specimen. The counterargument to such claim is that the benefit SSE delay could result in better quality slides for histological evaluation with permanent sections compared with the frozen sections utilized during MMS. Concerns remain that utilizing frozen sections alone with Hematoxylin & Eosin (H&E) may make accurately identifying melanocytes more difficult, particularly in a background of sun-damaged skin or inflammatory infiltrate. This is often deemed a function of frozen processing's “freeze artifact” with H&E staining, leading to the alteration of melanocytes and vacuolization of keratinocytes.58,59 Prieto and colleagues identified the potential impact of such changes by confirming 66 discrepancies in IM cases between frozen and permanent sections. The majority of changed diagnoses in these cases led to negative frozen margins becoming positive in the permanent sections.60 Even so, other studies found that with experienced technicians, the sensitivity and specificity of frozen sections for MIS and LM may still be as high as 97% to 100% and 90% to 100%, respectively.61,62 Of further note, Mohs surgeons are using rapid immunohistochemical stains more often to accurately identify melanocytes with data demonstrating low local recurrence rates with immunostaining. The discrepancy in prior studies, in combination with the known underestimating of Breslow's depth by frozen processing, complicates the use of sole frozen sections, particularly if concerned for invasive disease.62

This study consists of a large single-institutional report on an SSE technique with a significant recurrence rate of 0% for both T1 melanomas and MIS. The following limitations are worth noting, namely, the cohort involved only a single institution review, and the patient population and physician skill set cannot fully translate to represent the recurrence rates achievable with a different patient population, surgeon, and dermatopathologist. Additionally, the academic center does not routinely biopsy prior surgical scar sites unless there is a suspicion for tumor recurrence. Clinical and histologic recurrence alongside longer follow-up are highly recommended in future studies. The conclusions of this study regarding the significant recurrence rate of serial disk staged SSE could benefit from the data that a prospective study involving a comparison group with either WLE or MMS could better illustrate the direct comparison of each technique for both melanoma and MIS lesions.

References

1. Huribert M. 2020 Melanoma Mortality Rates Decreasing Despite Ongoing Increase in Incidence. 2020. Available at: https://curemelanoma.org/blog/article/2020-melanoma-mortality-rates-decreasing-despite-ongoing-increase-in-incidence-rates#:∼:text=In%202020%20in%20the%20US,4%2C610%20men%20and%202%2C240%20women. Accessed March 1, 2021.
2. Collgros H, Rodriguez-Lomba E, Regio Pereira A, Lo SN, et al. Lentiginous melanoma (lentigo maligna and lentigo maligna melanoma) in Australia: clinicopathological characteristics, management and recurrence rates after 10-year follow-up at a tertiary centre. J Eur Acad Dermatol Venereol 2021;35:1315–22.
3. Navarrete-Dechent C, Aleissa S, Cordova M, Liopyris K, et al. Incompletely excised lentigo maligna melanoma is associated with unpredictable residual disease: clinical features and the emerging role of reflectance confocal microscopy. J Eur Acad Dermatol Venereol 2020;34:2280–7.
4. Welch A, Reid T, Knox J, Wilson ML. Excision of melanoma in situ on nonchronically sun-exposed skin using 5-mm surgical margins. J Am Acad Dermatol 2014;71:834–5.
5. Garcia D, Eilers RE, Jiang SB. Recurrence rate of melanoma in situ when treated with serial disk staged excision: a case series. J Clin Investig Dermatol 2017.
6. Möller MG, Pappas-Politis E, Zager JS, Santiago LA, et al. Surgical management of melanoma-in-situ using a staged marginal and central excision technique. Ann Surg Oncol 2009;16:1526–36.
7. Felton S, Taylor RS, Srivastava D. Excision margins for melanoma in situ on the head and neck. Dermatol Surg 2016;42:327–34.
8. Shin TM, Shaikh WR, Etzkorn JR, Sobanko JF, et al. Clinical and pathologic factors associated with subclinical spread of invasive melanoma. J Am Acad Dermatol 2017;76:714–21.
9. Glazer ES, Porubsky CF, Francis JD, Sobanko JF, et al. Treatment of head and neck melanoma in situ with staged contoured marginal excisions. Ann Plast Surg 2017;78:663–7.
10. Duffy KL, Truong A, Bowen GM, Andtbacka RHI, et al. Adequacy of 5-mm surgical excision margins for non-lentiginous melanoma in situ. J Am Acad Dermatol 2014;71:835–8.
11. Michielin O, van Akkooi ACJ, Ascierto PA, Dummer R, et al. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30:1884–901.
12. McKenna JK, Florell SR, Goldman GD, Bowen GM. Lentigo maligna/lentigo maligna melanoma: current state of diagnosis and treatment. Dermatol Surg 2006;32:493–504.
13. McLeod M, Choudhary S, Giannakakis G, Nourik K. Surgical treatments for lentigo maligna: a review. Dermatol Surg 2011;37:1210–28.
14. Kelley LC, Starkus L. Immunohistochemical staining of lentigo maligna during Mohs micrographic surgery using MART-1. J Am Acad Dermatol 2002;46:78–84.
15. Walling HW, Scupham RK, Bean AK, Ceilley RI. Staged excision versus Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol 2007;57:659–64.
16. Theunissen CCW, Lee MH, Murad FG, Waldman AH. Systematic review of the role of Mohs micrographic surgery in the management of early-stage melanoma of the head and neck. Dermatol Surg 2021;47:1185–9.
17. Cheraghlou S, Christensen SR, Leffell DJ, Girardi M. Association of treatment facility characteristics with Overall survival after Mohs micrographic surgery for T1a-T2a invasive melanoma. JAMA Dermatol 2021;157:531–9.
18. Miller CJ, Bichakjian CK. Mohs micrographic surgery for melanoma-do outcomes vary among treatment facilities?. JAMA Dermatol 2021;157:513–5.
19. Sharma AN, Foulad DP, Doan L, Lee PK, et al. Mohs surgery for the treatment of lentigo maligna and lentigo maligna melanoma—a systematic review. J Dermatolog Treat 2021;32:157–63.
20. Burnett ME, Brodland DG, Zitelli JA. Long-term outcomes of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities. J Am Acad Dermatol 2021;84:661–8.
21. Shin TM, Nugent S, Aizman L, Weiner DM, et al. Mohs micrographic surgery with MART-1 immunostaining has durable low local recurrence rates for in situ and invasive melanomas. J Am Acad Dermatol 2021;84:196–8.
22. Adalsteinsson JA, Stoj VJ, Algzlan H, Swede H, et al. Limitations in the literature regarding Mohs surgery and staged excision for melanoma: a critical review of quality and data reporting. J Am Acad Dermatol 2021:S0190-9622(21):00772-6.
23. Barlow RJ, White CR, Swanson NA. Mohs' micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ. Br J Dermatol 2002;146:290–4.
24. Fallowfield ME, Cook MG. Epidermal melanocytes adjacent to melanoma and the field change effect. Histopathology 1990;17:397–400.
25. Moyer JS, Rudy S, Boonstra PS, Kraft C, et al. Efficacy of staged excision with permanent section margin control for cutaneous head and neck melanoma. JAMA Dermatol 2017;153:282–8.
26. Kunishige JH, Doan L, Brodland DG, Zitelli JA. Comparison of surgical margins for lentigo maligna versus melanoma in situ. J Am Acad Dermatol 2019;81:204–12.
27. Clark GS, Pappas-Politis EC, Cherpelis BS, Messina JL, et al. Surgical management of melanoma in situ on chronically sun-damaged skin. Cancer Control 2008;15:216–24.
28. Raziano RM, Clark GS, Cherpelis BS, Sondak VK, et al. Staged margin control techniques for surgical excision of lentigo maligna. G Ital Dermatol Venereol 2009;144:259–70.
29. Johnson TM, Headington JT, Baker SR, Lowe L. Usefulness of the staged excision for lentigo maligna and lentigo maligna melanoma: the “square” procedure. J Am Acad Dermatol 1997;37:758–64.
30. Guillot B, Dalac S, Denis MG, Dupuy A, et al. French updated recommendations in Stage I to III melanoma treatment and management. J Eur Acad Dermatol Venereol 2017;31:594–602.
31. Costa Svedman F, Spanopoulos D, Taylor A, Amelio J, et al. Surgical outcomes in patients with cutaneous malignant melanoma in Europe—a systematic literature review. J Eur Acad Dermatol Venereol 2017;31:603–15.
32. Hou JL, Reed KB, Knudson RM, Mirzoyev SA, et al. Five-year outcomes of wide excision and Mohs micrographic surgery for primary lentigo maligna in an academic practice cohort. Dermatol Surg 2015;41:211–8.
33. Hazan C, Dusza SW, Delgado R, Busam KJ, et al. Staged excision for lentigo maligna and lentigo maligna melanoma: a retrospective analysis of 117 cases. J Am Acad Dermatol 2008;58:142–8.
34. Hilari H, Llorca D, Traves V, Villanueva A, et al. Conventional surgery compared with slow Mohs micrographic surgery in the treatment of lentigo maligna: a retrospective study of 62 cases. Actas Dermo-Sifiliográficas 2012;103:614–23.
35. Abdelmalek M, Loosemore MP, Hurt MA, Hruza G. 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.
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;47:743–8.
37. Bub JL, Berg D, Slee A, Odland PB. Management of lentigo maligna and lentigo maligna melanoma with staged excision: a 5-year follow-up. Arch Dermatol 2004;140:552–8.
38. Huilgol SC, Selva D, Chen C, Hill DC, et al. Surgical margins for lentigo maligna and lentigo maligna melanoma: the technique of mapped serial excision. Arch Dermatol 2004;140:1087–92.
39. Hill DC, Gramp AA. Surgical treatment of lentigo maligna and lentigo maligna melanoma. Australas J Dermatol 1999;40:25–30.
40. Anderson KW, Baker SR, Lowe L, Su L, et al. Treatment of head and neck melanoma, lentigo maligna subtype: a practical surgical technique. Arch Facial Plast Surg 2001;3:202–6.
41. Malhotra R, Chen C, Huilgol SC, Hill DC, et al. Mapped serial excision for periocular lentigo maligna and lentigo maligna melanoma. Ophthalmology 2003;110:2011–8.
42. Mahoney MH, Joseph M, Temple CL. The perimeter technique for lentigo maligna: an alternative to Mohs micrographic surgery. J Surg Oncol 2005;91:120–5.
43. Jejurikar SS, Borschel GH, Johnson TM, Lowe L, et al. Immediate, optimal reconstruction of facial lentigo maligna and melanoma following total peripheral margin control. Plast Reconstr Surg 2007;120:1249–55.
44. Bosbous MW, Dzwierzynski WW, Neuburg M. Staged excision of lentigo maligna and lentigo maligna melanoma: a 10-year experience. Plast Reconstr Surg 2009;124:1947–55.
45. Lee MR, Ryman WJ. Treatment of lentigo maligna with total circumferential margin control using vertical and horizontal permanent sections: a retrospective study. Australas J Dermatol 2008;49:196–201.
46. Joyce KM, Joyce CW, Jones DM, Donnellan P, et al. An assessment of histological margins and recurrence of melanoma in situ. Plast Reconstr Surg Glob Open 2015;3:e301.
47. de Vries K, Greveling K, Prens LM, Munte K, et al. Recurrence rate of lentigo maligna after micrographically controlled staged surgical excision. Br J Dermatol 2016;174:588–93.
48. Patel AN, Perkins W, Leach IH, Varma S. Johnson square procedure for lentigo maligna and lentigo maligna melanoma. Clin Exp Dermatol 2014;39:570–6.
49. Lawrence CM, Rahim R, Charlton F, Husain A. 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.
50. Gaudy-Marqueste C, Perchenet AS, Taséi AM, Madjlessi N, et al. The “spaghetti technique”: an alternative to Mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma). J Am Acad Dermatol 2011;64:113–8.
51. Demer AM, Vance KK, Cheraghi N, Reich HC, et al. Benefit of Mohs micrographic surgery over wide local excision for melanoma of the head and neck: a rational approach to treatment. Dermatol Surg 2019;45:381–9.
52. Heath M, Woody M, Leitenberger J, Latour E, et al. Invasive melanoma and melanoma in situ treated with modified Mohs micrographic surgery with en face permanent sectioning: a 10-year retrospective review. Dermatol Surg 2020;46:1004–13.
53. Cheraghlou S, Christensen SR, Agogo GO, Girardi M. Comparison of survival after Mohs micrographic surgery vs wide margin excision for early-stage invasive melanoma. JAMA Dermatol 2019;155:1252–9.
54. Seo J, Oh Y, Kim SK, Roh MR, et al. Slow Mohs micrographic surgery for acral melanoma treatment in Korean patients. Dermatol Surg 2021;47:e42–e46.
55. Amici JM, Rogues AM, Lasheras A, Gachie JP. A prospective study of the incidence of complications associated with dermatological surgery. Br J Dermatol 2005;153:967–71.
56. Cook JL, Perone JB. A prospective evaluation of the incidence of complications associated with Mohs micrographic surgery. Arch Dermatol 2003;139:143–52.
57. Merritt BG, Lee NY, Brodland DG, Zitelli JA, et al. The safety of Mohs surgery: a prospective multicenter cohort study. J Am Acad Dermatol 2012;67:1302–9.
58. Kroumpouzos G, Frank EW, Albertini JG, Krivo JM, et al. Lentigo maligna with spread onto oral mucosa. Arch Dermatol 2002;138:1216–20.
59. Robinson JK. Margin control for lentigo maligna. J Am Acad Dermatol 1994;31:79–85.
60. Prieto VG, Argenyi ZB, Barnhill RL, Duray PH, et al. Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions?. Am J Clin Pathol 2003;120:203–8.
61. Zitelli A, Mohs FE, Larson P, Snow S. Mohs micrographic surgery for melanoma. Derniatol Chi 1989;7:833–43.
62. Shafir R, Hiss J, Tsur H, Bubis JJ. Pitfalls in frozen section diagnosis of malignant melanoma. Cancer 1983;51:1168–70.
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