Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Histological Peripheral Margins and Recurrence of Melanoma In Situ Treated with Wide Local Excision

Histological Peripheral Margins and Recurrence of Melanoma In Situ Treated with Wide Local Excision Hindawi Journal of Skin Cancer Volume 2020, Article ID 8813050, 8 pages https://doi.org/10.1155/2020/8813050 Research Article Histological Peripheral Margins and Recurrence of Melanoma In Situ Treated with Wide Local Excision Francisco S. Moura , Lucy E. Homer , and Stuart W. McKirdy Department of Plastic & Reconstructive Surgery, Royal Preston Hospital, PR29HT, Fulwood, UK Correspondence should be addressed to Francisco S. Moura; francisco.serraemoura@nhs.net Received 31 July 2020; Revised 3 October 2020; Accepted 11 October 2020; Published 29 October 2020 Academic Editor: Mark Lebwohl Copyright © 2020 Francisco S. Moura et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. *e incidence of melanoma in situ (MIS) is increasing faster compared to invasive melanoma. Despite varying international practice, a minimum of 5 mm surgical excision margin is currently recommended in the UK. *ere is no clear guidance on the minimum histological peripheral clearance margins. Aim. *is study compares the histological peripheral clearance margins of MIS using wide local excision (WLE) to the rate of recurrence and progression to invasive disease. Methods. A retrospective single-center review was performed over a 5-year period. Inclusion criteria consisted of MIS diagnosis, ≥16 years of age, and treatment with WLE with curative intent. *ose patients with a recurrence of a previous MIS or with a reported focus of invasion/regression were also included. Clinicopathological data and follow-up were recorded. Results. 167 MIS were identified in 155 patients, 80% of which were lentigo maligna subtype. Of patients with completely excised MIS on histology (>0 mm), 9% had recurrence with a median time to recurrence of 36 months. *ree (1.8%) cases recurred as invasive disease. Age, MIS site, MIS subtype, and histological evidence of foci of invasion/regression did not predict recurrence nor progression to invasive disease (p> 0.05). *e recurrence rate of MIS with a histological excision margin ≤3.0 mm was 13% compared to 3% in those with histology margins of >3.0 mm (p � 0.049). Conclusion. A histological peripheral clearance of at least 3.0 mm is advocated to achieve lower recurrence rates. *e follow-up duration should be reviewed due to the median recurrence occurring at 36 months in our cohort. Cumulative work on MIS needs to be collated and completed in a large multicenter study with a long follow- up period. chronic exposure to ultraviolet radiation and primarily af- 1. Introduction fects the head and neck region. Cutaneous melanoma is one of the fastest rising cancer Surgical intervention by wide local excision (WLE) is the diagnoses in recent years [1]. *is is owed to an aging most widely used first-line therapy for MIS. However, no population and increased exposure to risk factors in- prospective RCTs have been performed, aiming to optimize cluding sun exposure and immunosuppression [1]. margin control. Moreover, there is no international con- Melanoma in situ (MIS) is a noninvasive lesion that sensus on the optimal excision margin. *e National In- accounts for up to 27% of all melanomas [2] and its stitute of Health and Care Excellence (NICE) guidelines in incidence is increasing faster compared to invasive the UK currently recommends a minimum surgical excision melanoma. margin of 5 mm [7] and recommend discharging the patient MIS is characterized by an increased number of atypical at the first outpatient clinic follow-up if the lesion has been intraepidermal melanocytes [3, 4]. *is entity represents a histologically excised. *e most recent guidance from the precursor of invasive melanoma. Lentigo maligna (LM) is American Association of Dermatology (AAD) recommends the most common subtype of MIS accounting for 79% to a 5 to 10 mm surgical margin, recognizing that LM may 83% of all MIS tumors [5, 6]. It is associated specifically with require a larger than 5 mm margin [8]. Numerous reports 2 Journal of Skin Cancer (lentiginous) growth of atypical melanocytes in the basal have indicated that the current standards, particularly a surgical 5 mm margin, are inadequate for the management layer, with or without some pagetoid ascent. Immunohis- tochemistry using Melan-A antibody staining aids in the of MIS [9–22]. Importantly, there is no current guidance on the minimal histological margin clearance that should be diagnosis of MIS. achieved in the treatment of MIS when excised by WLE. Follow-up was recorded as the time of discharge from *is study aims to evaluate the impact of the histological the clinic after the WLE. As per UK guidance [7], most peripheral clearance margins of MIS on the recurrence and patients (regardless of the first episode, recurrence, histo- progression to invasive disease when treated with WLE. *e logical evidence of foci of invasion/regression, or histological novelty of this study is the heterogeneity of the study clearance margin) with complete histological excision were population. In addition to those patients that present with discharged from the clinic at their first appointment at their first episode of MIS, prior studies have not incorpo- approximately 6 weeks to 12 weeks postoperatively. At discharge, patients are educated and strongly advised to rated cases that are treated as MIS in which the histology reports a potential regression and/or focus of invasion, as contact our center if there are any concerns regarding re- currence. Patients are not discharged if they have a pref- well as those that present with a recurrence of MIS. erence to continue follow-up in the clinic and have other lesions that require close monitoring or issues with delayed 2. Methodology wound healing. A 5-year period following all patients’ *e principles of the Declaration of Helsinki were followed, discharge was examined to check for possible recurrences. and given the retrospective nature of this study, no formal Recurrence was defined as those patients that had a further patient consent was required. Royal Preston Hospital is the biopsy-proven pathological diagnosis of MIS at the same tertiary center for plastic surgery for the Lancashire region in site. the UK serving a population of 1.7 million people. All pa- To analyze the relationship between recurrence rate and the histological peripheral clearance, subjects were catego- tients with a diagnosis of melanoma in this region of the UK are referred to our center. A single-center retrospective rized into the following groups as proposed by the Cancer Outcomes and Services Dataset in the UK (advised by the study was carried out to analyze patients with a diagnosis of MIS treated by wide local excision alone at our unit over a 5- RCPath, UK, and supported by the NICE, UK) [23]: year period between 1 January 2009 and 1 January 2014. (i) Clearance by more than 5 mm Selection criteria included patients above the age of 16 years (ii) Clearance at or by more than 1 mm, but less than or with a pathological diagnosis of MIS. *ese patients were equal to 5 mm identified through our pathological database using a SNOMED pathology code (M87422). Patients with primary (iii) Clearance by less than 1 mm, but the tumor does not MIS, recurrence of MIS, or a reported possible focus of reach the margin invasion or regression (but treated primarily as MIS) were (iv) Margin involved included in this study. In our unit, patients with MIS are To identify a minimum peripheral histological clearance treated with WLE only and not with Mohs micrographic margin associated with a lower recurrence rate, the pe- surgery (MMS). Exclusion criteria included any patient that ripheral margins of all subjects and their recurrence rates was not treated with curative intent or that had any other were analyzed. *is commenced with a 1 mm peripheral forms of treatment such as radiotherapy or other topical margin and gradually increased by 1 mm until a statistically treatments. Further exclusion criteria included those which significant (p< 0.05) difference in recurrence was noted. had a simultaneous diagnosis of invasive melanoma at the Statistical analyses were performed using Fisher’s exact same site and were treated instead as an invasive disease. test for analyzing contingency tables and Kruskal–Wallis for Patient case notes (including operation notes, follow-up comparison of nonparametric medians. *ese were carried letters, and histopathological reports) were all carefully out on StatsDirect statistical software (version 3.1.2), with a studied by two authors (FM and LH). Clinicopathological statistical significance at p< 0.05. data collection comprised patient demographics, anatomical site of the lesion, melanoma subtype, evidence of invasion or regression in histology, histological excision margins, 3. Results number of surgical interventions to achieve histological clear margins, recurrence, and progression to invasion. During the 5-year study period, 155 patients with 167 Generally, WLE is carried out with a 5 mm surgical cases of MIS met the inclusion criteria. *e cohort had a margin in our unit as per national guidelines [7]. Histo- mean age of 72 years (range 36–95 years) of which 72 logical analyses of MIS specimens were performed as per the (46%) patients were male. *e median follow-up time was standard set by the Royal College of Pathology (RCPath) 8 months (interquartile range (IQR) 3–30 months). [23]. *e specimens are fixed with formalin and bread sliced. *e most common site of MIS was the head and neck *e thickness is dependent on the size of the specimen. (138 cases, 83%) followed by the upper limb (13 cases, 8%) Typically, they are sliced into 3-4 mm thick cuts, and the (Figure 1). *e anatomical distribution did not vary with nearest margins are further transversely sliced and exam- gender (p � 0.14). Primary MIS represented 84% (140 ined. A constellation of morphological criteria is used to cases) of subjects whilst recurrent cases were 5% (9 cases) diagnose MIS including observation of a contiguous (Table 1). Most MIS subtypes within our cohort were LM Journal of Skin Cancer 3 3.6 Scalp and neck Face Upper limb 7.8 Trunk 3.6 Lower limb 0 1020304050607080 Percentage of MIS cases (%) Figure 1: Percentage of MIS cases per body region. No statistically significant difference between gender and body site of MIS was identified (p � 0.14). Table 1: Different lesion types of MIS. Lesion type Subjects (n) % of MIS subjects 140 84 Primary (120 LM; 12 SS-MIS; 8 both LM and SS-MIS) 9 5 Recurrent (7 LM; 2 both LM and SS-MIS) 18 11 MIS with invasive foci or regression (7 LM; 6 SS-MIS; 5 both LM and SS-MIS) Average BT depth of MIS with reported foci of invasion 0.47 mm (80%, 134 cases) whilst the remaining were superficial recurrence and recurrence-free (8 months vs. 13 months, spreading MIS (SS-MIS) (11%, 18 cases) or had evidence p � 0.5). of both SS-MIS and LM (9%, 15 subjects) (Figure 2). 160 (96%) subjects were completely excised at first surgery 4. Discussion (Figure 3). *e recurrence rate was 9% (15/167) with a median time *e incidence of MIS is growing faster compared to invasive to recurrence of 36 months (IQR 25–53) (Supplement Ta- melanoma [24]. *is is most likely due to improved public ble 1). *ree patients (1.8%) had recurrence with evidence of awareness, diagnosis, and increasing efficiency of referral invasive melanoma. *e only site of recurrence was the head services [24]. *is is particularly relevant to countries such as and neck region with 15 cases (100%) (Figure 4(a)) the UK with a significant population with Fitzpatrick 1–3 (p � 0.04). *ere was no difference in recurrence amongst skin type [25] which increases the risk of developing cu- LM (8%, 11/134) and non-LM (12%, 4/33) MIS subtypes taneous melanoma [26]. Even though skin types were not (p � 0.49) (Figure 4(b)). Similarly, there was no difference in individually assessed in our dataset, it is important to rec- the recurrence rate if a patient had a reported focus of ognize that our study population likely falls within Fitz- invasion/regression and/or recurrence (p � 0.27) patrick 1–3 skin type. *erefore, this limits the (Figure 4(c)). *e rate of recurrence decreased with in- generalizability of the results of this study, making it most creasing histological peripheral margins (p � 0.037) applicable to those populations with lighter skin tones. (Figure 4(d)). *e recurrence rate of lesions with a histo- Sun exposure is one of the principal risk factors for logical peripheral margin of ≤3.0 mm was 14% (13/103) cutaneous melanoma [27, 28]. Subsequently, the head and compared to 3% (2/64) in those lesions with a histological neck region, besides being more visible to patients and their margin of >3.0 mm (p � 0.049). *ere was a statistically relatives, is the most common site of MIS as seen within our significant difference in median follow-up time between study. All recurrences in our study were limited to the head those with and without risk factors (28 months vs. 7.5 and neck region. Yet again, this is explained by the increased months, p � 0.001). However, there was no statistically exposure of the head and neck region to the patient and their significant difference in follow-up between those with relatives. Moreover, if most cases of MIS are in the head and 4 Journal of Skin Cancer LM and SS-MIS 9% SS-MIS 11% Lentigo maligna 80% Figure 2: Distribution of different subtypes of MIS. LM: lentigo maligna; MIS: melanoma in situ; SS-MIS: superficial spreading melanoma in situ. 20 13 111 11 00 0 First Second ird Fourth Number of WLE attempts to complete MIS excision (histology margin > 0 mm) LM SS-MIS LM and SS-MIS Figure 3: Number of WLE attempts to excise MIS (histology clearance >0 mm) per subtype. LM: lentigo maligna; MIS: melanoma in situ; SS-MIS: superficial spreading melanoma in situ. explanations for this high recurrence rate. In this study, we neck region in the first instance, then the probability of a recurrence in this area is logically higher as well. Although have included heterogeneous cases (recurrence or evidence 5 mm is the standard excision margin for MIS in the UK, the of regression or foci of invasion), whilst in other studies, this operating surgeon may be more forgiving when excising an has not been the case. Yet, no statistically significant dif- MIS from a less cosmetically sensitive area such as a limb as ference was noted in recurrence amongst those cases with compared to the face, thus increasing the clearance margins risk factors (recurrence, evidence of regression, and/or foci and reducing recurrences. of invasion) and those cases that were seemingly risk-free. Of One of the most prominent findings of our study was the note, the median follow-up duration for those with risk high rate of recurrence of 9%, especially compared to other factors was longer which could mean that a recurrence could studies evaluating MIS recurrence with WLE treatment have been picked up on consultation if it had occurred (Table 2) [27, 29, 31, 32]. *ere are several potential before discharge. *e difference in follow-up duration could Number of subjects Journal of Skin Cancer 5 Scalp and neck Lm and SS-MIS (same sample) Face 120 Upper limb 13 SS-MIS alone 14 Trunk 10 LM alone 128 Lower limb 6 050 100 150 0 50 100 150 Number of MIS cases Number of MIS cases Recurrence Recurrence Nonrecurrence Nonrecurrence (a) (b) 160 100 35 77 40 80 50 10 2 4 5 23 8 0 0 Risk factors including prior No prior recurrence >0 mm to >1 mm to < 5 mm ≥5 mm or no recurrence, invasive foci/ nor foci of ≤ 1 mm (clear) evidence regression, association with invasion/regression (clear but close) (complete ivasion excision) Histological clearance Recurrence Nonrecurrence Recurrence Nonrecurrence (c) (d) Figure 4: Comparison of recurrence and nonrecurrence following MIS excision. (a) Comparison of recurrence and nonrecurrence per body region. *ere was a statistically significant difference in the face compared to other sites of the body (p � 0.004). (b) Comparison of recurrence and nonrecurrence per MIS subtype. *ere was no difference in recurrence depending on the MIS subtype (p � 0.49). (c) Comparison of recurrence and nonrecurrence per presence (recurrent lesion, evidence of invasive foci, and regression) or absence of risk factors. *ere was no difference in recurrence with or without the presence of risk factors (p � 0.27). (d) Comparison of recurrence and nonrecurrence per histological peripheral clearance margin. *ere was a reduced risk of recurrence with increasing histological peripheral margins (p � 0.04). LM: lentigo maligna; MIS: melanoma in situ; SS-MIS: superficial spreading melanoma in situ. Table 2: Comparison of recurrence rates amongst studies using retrospective study, patients were not actively followed up wide local excision. for a set period and instead encouraged to self-present if they were concerned about a recurrence. As a result, the recur- Study No. of MIS subjects Recurrence rate (%) rence rate in our study could be underestimated, and Joyce et al. [26] 410 2.2 similarly, the 36-month average time for recurrence in our Nosrati et al. [29] 385 5.7 study may be an overestimation. *is could have been Hou et al. [30] 269 5.9 Akhtar et al. [31] 192 2.9 prevented if a clinical specialist had assessed all subjects Current study 167 9.0 regularly. Many studies suggest that a 5 mm surgical margin is inadequate [9–22]. *e AAD currently recommends a be explained by factors including patients being followed up 5 mm–1 cm surgical margin for MIS [8]. Garcia et al. [13] for other diseases, delayed wound healing, or patient and reported a 13.1 mm mean surgical margin in their serial disk clinician preference. In addition to the inherent bias of a staged excisions with zero recurrences over three months of Number of MIS cases Proportion (%) 6 Journal of Skin Cancer recurrence amongst those with and without evidence of foci follow-up. However, one should recognize that MIS typically affects the head and neck area and that such a wide margin of of invasion. In the UK, the mainstay of treatment for MIS is WLE. excision is not always pragmatic. Despite no recurrences in their study [13], our data indicate a median recurrence at 36 MMS is an additional surgical option for MIS which is not months which raises the questions if our study populations routinely offered to patients with a diagnosis of MIS in the are comparable and if future studies should encompass a UK. Compared to WLE, MMS offers the possibility of total longer follow-up period. margin evaluation and has been associated with decreased *e surgical margins used for WLE for each subject were rates of recurrence [33]. Other recent studies contradict not reported in this study. Hence, no inferences can be made these findings by suggesting no differences in overall sur- vival, cancer-specific survival, and recurrence rates amongst to compare the surgical excision margins with both the histological margins and the recurrence rate, even if these patients treated with MMS and WLE [29, 39]. *ere is a misconception that MMS is more costly than WLE, but cases are generally known to be excised with a 5 mm surgical margin [7]. One could argue that a histological peripheral recent preliminary work [34] would imply that MMS is more cost-effective than WLE, particularly with an increased in- margin of 3.0 mm is broadly similar to a 5 mm surgical excision margin once the specimen shrinks postexcision. cidence of skin cancers [1]. Such findings are important to Yet, no reliable scientific conclusions can be derived from the National Health System in the UK which is a fully such a variable relationship. Furthermore, the subclinical publicly funded healthcare system. extension of MIS adds to the complexity of MIS excision as it An area that warrants attention is that recurrence may is not visible to the operating surgeon unless the surgeon relate to both a wide subclinical extension of atypical me- uses MMS or reflectance confocal microscopy (RCM). lanocytes and the limitations associated with histological margin assessment of WLE samples. RCM has, and will, Some groups have questioned the need for 1 cm surgical margins for all types of MIS as per the AAD guidelines [8] become a more common adjunct to the clinical exam, dermoscopy, and histopathology assessment [40]. In MMS, and instead support that only the LM subtype requires this wider margin [33, 34]. LM has been reported to have dif- the entire margin is examined whereas in standard patho- logical assessment this is reported to range from 0.5% to 5% ferences in behavior and outcomes compared to non-LM MIS due to a tendency towards subclinical peripheral ex- [41]. Should the decision be to continue managing patients tension and difficulty of histological diagnosis when located with MIS in the UK using WLE, a national consensus should in sun-damaged skin. A retrospective review of 192 cases of be reached to either advocate a minimal histological MIS found that LM required wider margins for complete clearance margin, a specific follow-up plan depending on excision than did non-LM MIS [31]. LM has a reported local said histological margins, or promote a more detailed his- recurrence rate of 5% by two years [9] and carries up to a tological analysis of specimens. We cannot overlook the increased workload that would result from the latter for 4.7% lifetime risk of developing an invasive melanoma [35]. Still, Kunishige et al. [22] propose that subclinical extension pathologists. Otherwise, surgeons should be rational in employing a 5–10 mm surgical margin as suggested by the of LM and MIS is similar and, as a result, propose the use of 9 mm surgical margins for all subtypes of MIS disease. *is is AAD [8] instead of the 5 mm UK guidance [7]. in keeping with our finding that no difference in recurrence rate was identified amongst different MIS subtypes 5. Conclusion (Figure 4(b)). Most lesions, regardless of their subtype and other More robust pathways for patients with a diagnosis of MIS histological features, were successfully excised as per his- are required. *is body of work supports that the histological tological report (>0 mm) at the first attempt of WLE (Fig- margins, particularly when using WLE as the means to ure 3). Importantly, our data demonstrate that an increased surgically remove MIS, play an important role in the surgical histological margin results in a lower rate of recurrence management of patients with MIS. *is study endorses that (Figure 4(d)). A statistically significant reduction in recur- UK guidelines should aim for a consensus for a minimum rence rate is seen when histological clearance exceeds histological clearance when MIS is treated by WLE. Our data 3.0 mm from 14% recurrence down to 3% recurrence indicate that a minimum histological margin of at least (p � 0.049). *e latter recurrence rate is comparable to 3.0 mm should be advocated to achieve lower recurrence recurrences in other studies, even when our dataset includes rates of MIS. Besides, the length of follow-up should be subjects with presumed risk factors, such as recurrence cases revised given the potential risk of recurrence and risk of and foci of invasion or regression, on top of the typical invasion, particularly if the histological margins fall short of primary cases of MIS (Table 1). 3.0 mm. *is is the first study to compare the impact of A Cochrane review has revealed that there is a lack of different risk factors such as recurrence, invasive foci, and high-quality evidence for the treatment of MIS and LM [32]. regression on recurrence. *ese did not have a statistically Despite this, studies have demonstrated that all MIS sub- significant impact on the rate of recurrence if complete types have a high incidence of invasive foci [35–37]. Meg- histological excision was achieved. We, therefore, emphasize ahed et al. [37] reported that 29% of all MIS subtypes had the need for further research into the histological peripheral invasive tumors. Because of this, some reports [38] advocate margins of MIS excised by WLE in which cumulative work the treatment of MIS as an early-stage invasive melanoma. must be collated and completed in a large multicenter study Our results demonstrate no significant difference in with a prolonged follow-up monitoring period. Journal of Skin Cancer 7 current state of diagnosis and treatment,” Dermatologic Abbreviations Surgery, vol. 32, no. 4, pp. 493–504, 2006. [7] National Institute for Health and Care Excellence, Melanoma: AAD: American Association of Dermatology Assessment and Management, National Institute for Health IQR: Interquartile range and Care Excellence, London, UK, 2015. LM: Lentigo maligna [8] S. M. Swetter, H. Tsao, C. K. Bichakjian et al., “Guidelines of MIS: Melanoma in situ care for the management of primary cutaneous melanoma,” MMS: Mohs micrographic surgery Journal of the American Academy of Dermatology, vol. 80, NICE: National Institute of Health and Care Excellence no. 1, pp. 208–250, 2019. RCM: Reflectance confocal microscopy [9] J. L. Bub, D. Berg, A. Slee, and P. B. Odland, “Management of RCPath: Royal College of Pathology lentigo, maligna and lentigo maligna melanoma with staged SS-MIS: Superficial spreading melanoma in situ excision: a 5-year follow-up,” Arch. Dermatol, vol. 140, no. 5, WLE: Wide local excision. pp. 552–558, 2004. [10] S. Felton, R. S. Taylor, and D. Srivastava, “Excision margins for melanoma in situ on the head and neck,” Dermatologic Data Availability Surgery, vol. 42, no. 3, pp. 327–334, 2016. *e data pertinent to the recurrences are available in [11] S. S. Jejurikar, G. H. Borschel, T. M. Johnson, L. Lowe, and D. L. Brown, “Immediate, optimal reconstruction of facial Supplementary Table 1. Additional information from the lentigo maligna and melanoma following total peripheral study is available upon reasonable request. margin control,” Plastic and Reconstructive Surgery, vol. 120, no. 5, pp. 1249–1255, 2007. Conflicts of Interest [12] S. C. Huilgol, D. Selva, C. Chen et al., “Surgical margins for lentigo maligna and lentigo maligna melanoma: the technique *e authors declare that there are no conflicts of interest. of mapped serial excision,” Archives of Dermatology, vol. 140, no. 9, pp. 1087–1092, 2004. Acknowledgments [13] D. Garcia, R. E. Eilers, and S. B. Jiang, “Recurrence rate of melanoma in situ when treated with serial disk staged exci- *e authors would like to acknowledge Mr. M Badawy sion: a case series,” Journal of Clinical and Investigative (senior clinical fellow in plastic surgery) and Dr. D Baishnab Dermatology, vol. 5, no. 1, pp. 01–04, 2017. for assisting with data collection and for explaining the [14] T. N. Bienert, M. J. Trotter, and J. P. Arlette, “Treatment of methods used to histologically examine MIS specimens, cutaneous melanoma of the face by mohs micrographic respectively. No writing assistance was utilized in the pro- surgery,” Journal of Cutaneous Medicine and Surgery: In- duction of this manuscript. corporating Medical and Surgical Dermatology, vol. 7, no. 1, pp. 25–30, 2003. [15] C. L. F. Temple and J. P. Arlette, “Mohs micrographic surgery Supplementary Materials in the treatment of lentigo maligna and melanoma,” Journal of Supplementary Table 1 (attached file) contains the histo- Surgical Oncology, vol. 94, no. 4, pp. 287–292, 2006. pathological details of the patient with recurrences. (Sup- [16] J. G. Albertini, D. M. Elston, L. F. Libow, S. B. Smith, and M. F. Farley, “Mohs micrographic surgery for melanoma,” plementary Materials) Dermatologic Surgery, vol. 28, no. 8, pp. 656–665, 2002. [17] M. J. Zalla, K. K. Lim, D. J. Dicaudo, and M. M. Gagnot, References “Mohs micrographic excision of melanoma using immu- nostains,” Dermatologic Surgery, vol. 26, no. 8, pp. 771–784, [1] H. K. Weir, T. D. *ompson, A. Soman, B. Møller, and S. Leadbetter, “*e past, present, and future of cancer inci- [18] G. M. Bricca, D. G. Brodland, D. Ren, and J. A. Zitelli, dence in the United States: 1975 through 2020,” Cancer, “Cutaneous head and neck melanoma treated with Mohs vol. 121, no. 11, pp. 1827–1837, 2015. micrographic surgery,” Journal of the American Academy of [2] M. Coory, P. Baade, J. Aitken, M. Smithers, G. R. C. McLeod, Dermatology, vol. 52, no. 1, pp. 92–100, 2005. and I. Ring, “Trends for in situ and invasive melanoma in [19] N. I. Bene, C. Healy, and B. M. Coldiron, “Mohs micrographic Queensland, Australia,” Cancer Causes Control, vol. 17, no. 1, surgery is accurate 95.1% of the time for melanoma in situ: a pp. 21–27, 2006. prospective study of 167 cases,” Dermatologic Surgery, vol. 34, [3] R. King, R. N. Page, P. B. Googe, and M. C. Mihm, “Lenti- no. 5, pp. 660–664, 2008. ginous melanoma: a histologic pattern of melanoma to be [20] J. K. Robinson, “Margin control for lentigo maligna,” Journal distinguished from lentiginous nevus,” Modern Pathology, of the American Academy of Dermatology, vol. 31, no. 1, vol. 18, no. 10, pp. 1397–1401, 2005. pp. 79–85, 1994. [4] Z. Tannous, L. Lerner, L. Duncan, M. Mihmjr, and T. Flotte, [21] L. M. Cohen, M. W. Mccall, and R. H. Zax, “Mohs micro- “Progression to invasive melanoma frommalignant mela- graphic surgery for lentigo maligna and lentigo maligna noma in situ, lentigo maligna type,” Human Pathology, vol. 31, no. 6, pp. 705–708, 2000. melanoma. A follow-up study,” Dermatologic Surgery, vol. 24, no. 6, pp. 673–677, 1998. [5] M. Kvaskoff, V. Siskind, and A. C. Green, “Risk factors for lentigo maligna melanoma compared with superficial [22] J. H. Kunishige, D. G. Brodland, and J. A. Zitelli, “Surgical margins for melanoma in situ,” Journal of the American spreading melanoma,” Archives of Dermatology, vol. 148, no. 2, pp. 164–170, 2012. Academy of Dermatology, vol. 66, no. 3, pp. 438–444, 2012. [23] “Standards and datasets for reporting cancers dataset for [6] J. K. McKenna, S. R. Florell, G. D. Goldman, and G. M. Bowen, “Lentigo maligna/lentigo maligna melanoma: histopathological reporting of primary cutaneous malignant 8 Journal of Skin Cancer melanoma and regional lymph nodes unique document [39] K. Phan and A. Loya, “Mohs micrographic surgery versus wide local excision for melanoma in situ: analysis of a na- number G125 document name dataset for histopathological reporting of primary cutaneous malignant melanoma and tionwide database,” International Journal of Dermatology, vol. 58, no. 6, pp. 697–702, 2019. regional lymph nodes,” 2008. [24] G. Bieliauskiene, A. S. S. Holm-Schou, P. A. Philipsen et al., [40] A. Waddell, P. Star, and P. Guitera, “Advances in the use of reflectance confocal microscopy in melanoma,” Melanoma “Measurements of sun sensitivity in five european countries Management, vol. 5, no. 1, p. MMT04, 2018. confirm the relative nature of fitzpatrick skin phototype [41] A. M. Demer, K. K. Vance, N. Cheraghi, H. C. Reich, and scale,” Photodermatology, Photoimmunology and Photo- P. K. Lee, “Benefit of mohs micrographic surgery over wide local medicine, vol. 36, no. 3, pp. 179–184, 2019. excision for melanoma of the head and neck,” Dermatologic [25] A. C. Walls, J. Han, T. Li, and A. A. Qureshi, “Host risk Surgery, vol. 45, no. 3, pp. 381–389, 2019. factors, ultraviolet index of residence, and incident malignant melanoma in situ among US women and men,” American Journal of Epidemiologyprevention, vol. 177, no. 9, pp. 997– 1005, 2013. [26] K. M. Joyce, C. W. Joyce, D. M. Jones et al., “An assessment of histological margins and recurrence of melanoma in situ,” Plastic and Reconstructive Surgery – Global Open, vol. 3, no. 2, [27] S. Gandini, F. Sera, M. S. Cattaruzza et al., “Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure,” European Journal of Cancer, vol. 41, no. 1, pp. 45–60, 2005. [28] V. Bataille and E. De Vries, “Melanoma - part 1: epidemiology, risk factors, and ,” BMJ-British medical journal, vol. 337, no. 7681, pp. 1287–1291, 2008. [29] A. Nosrati, J. G. Berliner, S. Goel et al., “Outcomes of mel- anoma in situ treated with mohs micrographic surgery compared with wide local excision,” JAMA Dermatology, vol. 153, no. 5, pp. 436–441, 2017. [30] J. L. Hou, K. B. Reed, R. M. Knudson et al., “Five-year outcomes of wide excision and Mohs micrographic surgery for primary lentigo maligna in an academic practice cohort,” Dermatologic Surgery, vol. 41, no. 2, pp. 211–218, 2015. [31] S. Akhtar, W. Bhat, A. Magdum, and P. R. W. Stanley, “Surgical excision margins for melanoma in situ,” Journal of Plastic, Reconstructive & Aesthetic Surgery, vol. 67, no. 3, pp. 320–323, 2014. [32] T. Tzellos, A. Kyrgidis, S. Mocellin, A. Chan, P. Pilati, and Z. Apalla, “Interventions for melanoma in situ, including lentigo maligna,” Cochrane Database of Systematic Reviews, vol. 12, 2014. [33] K. L. Duffy, A. Truong, G. M. Bowen et al., “Adequacy of 5 mm surgical excision margins for non-lentiginous melanoma in situ,” Journal of the American Academy of Dermatology, vol. 71, no. 4, pp. 835–838, 2014. [34] R. P. Johnson, N. Butala, M. Alam, and N. Lawrence, “A retrospective case-matched cost comparison of surgical treatment of melanoma and nonmelanoma skin cancer in the outpatient versus operating room setting,” Dermatologic Surgery, vol. 43, no. 7, pp. 897–901, 2017. [35] N. Agarwal-Antal, G. M. Bowen, and J. W. Gerwels, “His- tologic evaluation of lentigo maligna with permanent sections: implications regarding current guidelines,” Journal of the American Academy of Dermatology, vol. 47, no. 5, pp. 743– 748, 2002. [36] M. E. Dawn, A. G. Dawn, and S. J. Miller, “Mohs surgery for the treatment of melanoma in situ,” Dermatologic Surgery, vol. 33, no. 4, pp. 395–402, 2007. [37] M. Megahed, M. Schon, ¨ D. Selimovic, and M. P. Schon, ¨ “Reliability of diagnosis of melanoma in situ,” 2e Lancet, vol. 359, no. 9321, pp. 1921-1922, 2002. [38] J. H. Kunishige, D. G. Brodland, and J. A. Zitelli, “Larger surgical margins are required for lentigo maligna and other melanoma in situ,” Journal of the American Academy of Dermatology, vol. 67, no. 5, pp. 1069–1071, 2012. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Skin Cancer Hindawi Publishing Corporation

Histological Peripheral Margins and Recurrence of Melanoma In Situ Treated with Wide Local Excision

Loading next page...
 
/lp/hindawi-publishing-corporation/histological-peripheral-margins-and-recurrence-of-melanoma-in-situ-QV9XCkf7vV

References (49)

Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2020 Francisco S. Moura et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
2090-2905
eISSN
2090-2913
DOI
10.1155/2020/8813050
Publisher site
See Article on Publisher Site

Abstract

Hindawi Journal of Skin Cancer Volume 2020, Article ID 8813050, 8 pages https://doi.org/10.1155/2020/8813050 Research Article Histological Peripheral Margins and Recurrence of Melanoma In Situ Treated with Wide Local Excision Francisco S. Moura , Lucy E. Homer , and Stuart W. McKirdy Department of Plastic & Reconstructive Surgery, Royal Preston Hospital, PR29HT, Fulwood, UK Correspondence should be addressed to Francisco S. Moura; francisco.serraemoura@nhs.net Received 31 July 2020; Revised 3 October 2020; Accepted 11 October 2020; Published 29 October 2020 Academic Editor: Mark Lebwohl Copyright © 2020 Francisco S. Moura et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. *e incidence of melanoma in situ (MIS) is increasing faster compared to invasive melanoma. Despite varying international practice, a minimum of 5 mm surgical excision margin is currently recommended in the UK. *ere is no clear guidance on the minimum histological peripheral clearance margins. Aim. *is study compares the histological peripheral clearance margins of MIS using wide local excision (WLE) to the rate of recurrence and progression to invasive disease. Methods. A retrospective single-center review was performed over a 5-year period. Inclusion criteria consisted of MIS diagnosis, ≥16 years of age, and treatment with WLE with curative intent. *ose patients with a recurrence of a previous MIS or with a reported focus of invasion/regression were also included. Clinicopathological data and follow-up were recorded. Results. 167 MIS were identified in 155 patients, 80% of which were lentigo maligna subtype. Of patients with completely excised MIS on histology (>0 mm), 9% had recurrence with a median time to recurrence of 36 months. *ree (1.8%) cases recurred as invasive disease. Age, MIS site, MIS subtype, and histological evidence of foci of invasion/regression did not predict recurrence nor progression to invasive disease (p> 0.05). *e recurrence rate of MIS with a histological excision margin ≤3.0 mm was 13% compared to 3% in those with histology margins of >3.0 mm (p � 0.049). Conclusion. A histological peripheral clearance of at least 3.0 mm is advocated to achieve lower recurrence rates. *e follow-up duration should be reviewed due to the median recurrence occurring at 36 months in our cohort. Cumulative work on MIS needs to be collated and completed in a large multicenter study with a long follow- up period. chronic exposure to ultraviolet radiation and primarily af- 1. Introduction fects the head and neck region. Cutaneous melanoma is one of the fastest rising cancer Surgical intervention by wide local excision (WLE) is the diagnoses in recent years [1]. *is is owed to an aging most widely used first-line therapy for MIS. However, no population and increased exposure to risk factors in- prospective RCTs have been performed, aiming to optimize cluding sun exposure and immunosuppression [1]. margin control. Moreover, there is no international con- Melanoma in situ (MIS) is a noninvasive lesion that sensus on the optimal excision margin. *e National In- accounts for up to 27% of all melanomas [2] and its stitute of Health and Care Excellence (NICE) guidelines in incidence is increasing faster compared to invasive the UK currently recommends a minimum surgical excision melanoma. margin of 5 mm [7] and recommend discharging the patient MIS is characterized by an increased number of atypical at the first outpatient clinic follow-up if the lesion has been intraepidermal melanocytes [3, 4]. *is entity represents a histologically excised. *e most recent guidance from the precursor of invasive melanoma. Lentigo maligna (LM) is American Association of Dermatology (AAD) recommends the most common subtype of MIS accounting for 79% to a 5 to 10 mm surgical margin, recognizing that LM may 83% of all MIS tumors [5, 6]. It is associated specifically with require a larger than 5 mm margin [8]. Numerous reports 2 Journal of Skin Cancer (lentiginous) growth of atypical melanocytes in the basal have indicated that the current standards, particularly a surgical 5 mm margin, are inadequate for the management layer, with or without some pagetoid ascent. Immunohis- tochemistry using Melan-A antibody staining aids in the of MIS [9–22]. Importantly, there is no current guidance on the minimal histological margin clearance that should be diagnosis of MIS. achieved in the treatment of MIS when excised by WLE. Follow-up was recorded as the time of discharge from *is study aims to evaluate the impact of the histological the clinic after the WLE. As per UK guidance [7], most peripheral clearance margins of MIS on the recurrence and patients (regardless of the first episode, recurrence, histo- progression to invasive disease when treated with WLE. *e logical evidence of foci of invasion/regression, or histological novelty of this study is the heterogeneity of the study clearance margin) with complete histological excision were population. In addition to those patients that present with discharged from the clinic at their first appointment at their first episode of MIS, prior studies have not incorpo- approximately 6 weeks to 12 weeks postoperatively. At discharge, patients are educated and strongly advised to rated cases that are treated as MIS in which the histology reports a potential regression and/or focus of invasion, as contact our center if there are any concerns regarding re- currence. Patients are not discharged if they have a pref- well as those that present with a recurrence of MIS. erence to continue follow-up in the clinic and have other lesions that require close monitoring or issues with delayed 2. Methodology wound healing. A 5-year period following all patients’ *e principles of the Declaration of Helsinki were followed, discharge was examined to check for possible recurrences. and given the retrospective nature of this study, no formal Recurrence was defined as those patients that had a further patient consent was required. Royal Preston Hospital is the biopsy-proven pathological diagnosis of MIS at the same tertiary center for plastic surgery for the Lancashire region in site. the UK serving a population of 1.7 million people. All pa- To analyze the relationship between recurrence rate and the histological peripheral clearance, subjects were catego- tients with a diagnosis of melanoma in this region of the UK are referred to our center. A single-center retrospective rized into the following groups as proposed by the Cancer Outcomes and Services Dataset in the UK (advised by the study was carried out to analyze patients with a diagnosis of MIS treated by wide local excision alone at our unit over a 5- RCPath, UK, and supported by the NICE, UK) [23]: year period between 1 January 2009 and 1 January 2014. (i) Clearance by more than 5 mm Selection criteria included patients above the age of 16 years (ii) Clearance at or by more than 1 mm, but less than or with a pathological diagnosis of MIS. *ese patients were equal to 5 mm identified through our pathological database using a SNOMED pathology code (M87422). Patients with primary (iii) Clearance by less than 1 mm, but the tumor does not MIS, recurrence of MIS, or a reported possible focus of reach the margin invasion or regression (but treated primarily as MIS) were (iv) Margin involved included in this study. In our unit, patients with MIS are To identify a minimum peripheral histological clearance treated with WLE only and not with Mohs micrographic margin associated with a lower recurrence rate, the pe- surgery (MMS). Exclusion criteria included any patient that ripheral margins of all subjects and their recurrence rates was not treated with curative intent or that had any other were analyzed. *is commenced with a 1 mm peripheral forms of treatment such as radiotherapy or other topical margin and gradually increased by 1 mm until a statistically treatments. Further exclusion criteria included those which significant (p< 0.05) difference in recurrence was noted. had a simultaneous diagnosis of invasive melanoma at the Statistical analyses were performed using Fisher’s exact same site and were treated instead as an invasive disease. test for analyzing contingency tables and Kruskal–Wallis for Patient case notes (including operation notes, follow-up comparison of nonparametric medians. *ese were carried letters, and histopathological reports) were all carefully out on StatsDirect statistical software (version 3.1.2), with a studied by two authors (FM and LH). Clinicopathological statistical significance at p< 0.05. data collection comprised patient demographics, anatomical site of the lesion, melanoma subtype, evidence of invasion or regression in histology, histological excision margins, 3. Results number of surgical interventions to achieve histological clear margins, recurrence, and progression to invasion. During the 5-year study period, 155 patients with 167 Generally, WLE is carried out with a 5 mm surgical cases of MIS met the inclusion criteria. *e cohort had a margin in our unit as per national guidelines [7]. Histo- mean age of 72 years (range 36–95 years) of which 72 logical analyses of MIS specimens were performed as per the (46%) patients were male. *e median follow-up time was standard set by the Royal College of Pathology (RCPath) 8 months (interquartile range (IQR) 3–30 months). [23]. *e specimens are fixed with formalin and bread sliced. *e most common site of MIS was the head and neck *e thickness is dependent on the size of the specimen. (138 cases, 83%) followed by the upper limb (13 cases, 8%) Typically, they are sliced into 3-4 mm thick cuts, and the (Figure 1). *e anatomical distribution did not vary with nearest margins are further transversely sliced and exam- gender (p � 0.14). Primary MIS represented 84% (140 ined. A constellation of morphological criteria is used to cases) of subjects whilst recurrent cases were 5% (9 cases) diagnose MIS including observation of a contiguous (Table 1). Most MIS subtypes within our cohort were LM Journal of Skin Cancer 3 3.6 Scalp and neck Face Upper limb 7.8 Trunk 3.6 Lower limb 0 1020304050607080 Percentage of MIS cases (%) Figure 1: Percentage of MIS cases per body region. No statistically significant difference between gender and body site of MIS was identified (p � 0.14). Table 1: Different lesion types of MIS. Lesion type Subjects (n) % of MIS subjects 140 84 Primary (120 LM; 12 SS-MIS; 8 both LM and SS-MIS) 9 5 Recurrent (7 LM; 2 both LM and SS-MIS) 18 11 MIS with invasive foci or regression (7 LM; 6 SS-MIS; 5 both LM and SS-MIS) Average BT depth of MIS with reported foci of invasion 0.47 mm (80%, 134 cases) whilst the remaining were superficial recurrence and recurrence-free (8 months vs. 13 months, spreading MIS (SS-MIS) (11%, 18 cases) or had evidence p � 0.5). of both SS-MIS and LM (9%, 15 subjects) (Figure 2). 160 (96%) subjects were completely excised at first surgery 4. Discussion (Figure 3). *e recurrence rate was 9% (15/167) with a median time *e incidence of MIS is growing faster compared to invasive to recurrence of 36 months (IQR 25–53) (Supplement Ta- melanoma [24]. *is is most likely due to improved public ble 1). *ree patients (1.8%) had recurrence with evidence of awareness, diagnosis, and increasing efficiency of referral invasive melanoma. *e only site of recurrence was the head services [24]. *is is particularly relevant to countries such as and neck region with 15 cases (100%) (Figure 4(a)) the UK with a significant population with Fitzpatrick 1–3 (p � 0.04). *ere was no difference in recurrence amongst skin type [25] which increases the risk of developing cu- LM (8%, 11/134) and non-LM (12%, 4/33) MIS subtypes taneous melanoma [26]. Even though skin types were not (p � 0.49) (Figure 4(b)). Similarly, there was no difference in individually assessed in our dataset, it is important to rec- the recurrence rate if a patient had a reported focus of ognize that our study population likely falls within Fitz- invasion/regression and/or recurrence (p � 0.27) patrick 1–3 skin type. *erefore, this limits the (Figure 4(c)). *e rate of recurrence decreased with in- generalizability of the results of this study, making it most creasing histological peripheral margins (p � 0.037) applicable to those populations with lighter skin tones. (Figure 4(d)). *e recurrence rate of lesions with a histo- Sun exposure is one of the principal risk factors for logical peripheral margin of ≤3.0 mm was 14% (13/103) cutaneous melanoma [27, 28]. Subsequently, the head and compared to 3% (2/64) in those lesions with a histological neck region, besides being more visible to patients and their margin of >3.0 mm (p � 0.049). *ere was a statistically relatives, is the most common site of MIS as seen within our significant difference in median follow-up time between study. All recurrences in our study were limited to the head those with and without risk factors (28 months vs. 7.5 and neck region. Yet again, this is explained by the increased months, p � 0.001). However, there was no statistically exposure of the head and neck region to the patient and their significant difference in follow-up between those with relatives. Moreover, if most cases of MIS are in the head and 4 Journal of Skin Cancer LM and SS-MIS 9% SS-MIS 11% Lentigo maligna 80% Figure 2: Distribution of different subtypes of MIS. LM: lentigo maligna; MIS: melanoma in situ; SS-MIS: superficial spreading melanoma in situ. 20 13 111 11 00 0 First Second ird Fourth Number of WLE attempts to complete MIS excision (histology margin > 0 mm) LM SS-MIS LM and SS-MIS Figure 3: Number of WLE attempts to excise MIS (histology clearance >0 mm) per subtype. LM: lentigo maligna; MIS: melanoma in situ; SS-MIS: superficial spreading melanoma in situ. explanations for this high recurrence rate. In this study, we neck region in the first instance, then the probability of a recurrence in this area is logically higher as well. Although have included heterogeneous cases (recurrence or evidence 5 mm is the standard excision margin for MIS in the UK, the of regression or foci of invasion), whilst in other studies, this operating surgeon may be more forgiving when excising an has not been the case. Yet, no statistically significant dif- MIS from a less cosmetically sensitive area such as a limb as ference was noted in recurrence amongst those cases with compared to the face, thus increasing the clearance margins risk factors (recurrence, evidence of regression, and/or foci and reducing recurrences. of invasion) and those cases that were seemingly risk-free. Of One of the most prominent findings of our study was the note, the median follow-up duration for those with risk high rate of recurrence of 9%, especially compared to other factors was longer which could mean that a recurrence could studies evaluating MIS recurrence with WLE treatment have been picked up on consultation if it had occurred (Table 2) [27, 29, 31, 32]. *ere are several potential before discharge. *e difference in follow-up duration could Number of subjects Journal of Skin Cancer 5 Scalp and neck Lm and SS-MIS (same sample) Face 120 Upper limb 13 SS-MIS alone 14 Trunk 10 LM alone 128 Lower limb 6 050 100 150 0 50 100 150 Number of MIS cases Number of MIS cases Recurrence Recurrence Nonrecurrence Nonrecurrence (a) (b) 160 100 35 77 40 80 50 10 2 4 5 23 8 0 0 Risk factors including prior No prior recurrence >0 mm to >1 mm to < 5 mm ≥5 mm or no recurrence, invasive foci/ nor foci of ≤ 1 mm (clear) evidence regression, association with invasion/regression (clear but close) (complete ivasion excision) Histological clearance Recurrence Nonrecurrence Recurrence Nonrecurrence (c) (d) Figure 4: Comparison of recurrence and nonrecurrence following MIS excision. (a) Comparison of recurrence and nonrecurrence per body region. *ere was a statistically significant difference in the face compared to other sites of the body (p � 0.004). (b) Comparison of recurrence and nonrecurrence per MIS subtype. *ere was no difference in recurrence depending on the MIS subtype (p � 0.49). (c) Comparison of recurrence and nonrecurrence per presence (recurrent lesion, evidence of invasive foci, and regression) or absence of risk factors. *ere was no difference in recurrence with or without the presence of risk factors (p � 0.27). (d) Comparison of recurrence and nonrecurrence per histological peripheral clearance margin. *ere was a reduced risk of recurrence with increasing histological peripheral margins (p � 0.04). LM: lentigo maligna; MIS: melanoma in situ; SS-MIS: superficial spreading melanoma in situ. Table 2: Comparison of recurrence rates amongst studies using retrospective study, patients were not actively followed up wide local excision. for a set period and instead encouraged to self-present if they were concerned about a recurrence. As a result, the recur- Study No. of MIS subjects Recurrence rate (%) rence rate in our study could be underestimated, and Joyce et al. [26] 410 2.2 similarly, the 36-month average time for recurrence in our Nosrati et al. [29] 385 5.7 study may be an overestimation. *is could have been Hou et al. [30] 269 5.9 Akhtar et al. [31] 192 2.9 prevented if a clinical specialist had assessed all subjects Current study 167 9.0 regularly. Many studies suggest that a 5 mm surgical margin is inadequate [9–22]. *e AAD currently recommends a be explained by factors including patients being followed up 5 mm–1 cm surgical margin for MIS [8]. Garcia et al. [13] for other diseases, delayed wound healing, or patient and reported a 13.1 mm mean surgical margin in their serial disk clinician preference. In addition to the inherent bias of a staged excisions with zero recurrences over three months of Number of MIS cases Proportion (%) 6 Journal of Skin Cancer recurrence amongst those with and without evidence of foci follow-up. However, one should recognize that MIS typically affects the head and neck area and that such a wide margin of of invasion. In the UK, the mainstay of treatment for MIS is WLE. excision is not always pragmatic. Despite no recurrences in their study [13], our data indicate a median recurrence at 36 MMS is an additional surgical option for MIS which is not months which raises the questions if our study populations routinely offered to patients with a diagnosis of MIS in the are comparable and if future studies should encompass a UK. Compared to WLE, MMS offers the possibility of total longer follow-up period. margin evaluation and has been associated with decreased *e surgical margins used for WLE for each subject were rates of recurrence [33]. Other recent studies contradict not reported in this study. Hence, no inferences can be made these findings by suggesting no differences in overall sur- vival, cancer-specific survival, and recurrence rates amongst to compare the surgical excision margins with both the histological margins and the recurrence rate, even if these patients treated with MMS and WLE [29, 39]. *ere is a misconception that MMS is more costly than WLE, but cases are generally known to be excised with a 5 mm surgical margin [7]. One could argue that a histological peripheral recent preliminary work [34] would imply that MMS is more cost-effective than WLE, particularly with an increased in- margin of 3.0 mm is broadly similar to a 5 mm surgical excision margin once the specimen shrinks postexcision. cidence of skin cancers [1]. Such findings are important to Yet, no reliable scientific conclusions can be derived from the National Health System in the UK which is a fully such a variable relationship. Furthermore, the subclinical publicly funded healthcare system. extension of MIS adds to the complexity of MIS excision as it An area that warrants attention is that recurrence may is not visible to the operating surgeon unless the surgeon relate to both a wide subclinical extension of atypical me- uses MMS or reflectance confocal microscopy (RCM). lanocytes and the limitations associated with histological margin assessment of WLE samples. RCM has, and will, Some groups have questioned the need for 1 cm surgical margins for all types of MIS as per the AAD guidelines [8] become a more common adjunct to the clinical exam, dermoscopy, and histopathology assessment [40]. In MMS, and instead support that only the LM subtype requires this wider margin [33, 34]. LM has been reported to have dif- the entire margin is examined whereas in standard patho- logical assessment this is reported to range from 0.5% to 5% ferences in behavior and outcomes compared to non-LM MIS due to a tendency towards subclinical peripheral ex- [41]. Should the decision be to continue managing patients tension and difficulty of histological diagnosis when located with MIS in the UK using WLE, a national consensus should in sun-damaged skin. A retrospective review of 192 cases of be reached to either advocate a minimal histological MIS found that LM required wider margins for complete clearance margin, a specific follow-up plan depending on excision than did non-LM MIS [31]. LM has a reported local said histological margins, or promote a more detailed his- recurrence rate of 5% by two years [9] and carries up to a tological analysis of specimens. We cannot overlook the increased workload that would result from the latter for 4.7% lifetime risk of developing an invasive melanoma [35]. Still, Kunishige et al. [22] propose that subclinical extension pathologists. Otherwise, surgeons should be rational in employing a 5–10 mm surgical margin as suggested by the of LM and MIS is similar and, as a result, propose the use of 9 mm surgical margins for all subtypes of MIS disease. *is is AAD [8] instead of the 5 mm UK guidance [7]. in keeping with our finding that no difference in recurrence rate was identified amongst different MIS subtypes 5. Conclusion (Figure 4(b)). Most lesions, regardless of their subtype and other More robust pathways for patients with a diagnosis of MIS histological features, were successfully excised as per his- are required. *is body of work supports that the histological tological report (>0 mm) at the first attempt of WLE (Fig- margins, particularly when using WLE as the means to ure 3). Importantly, our data demonstrate that an increased surgically remove MIS, play an important role in the surgical histological margin results in a lower rate of recurrence management of patients with MIS. *is study endorses that (Figure 4(d)). A statistically significant reduction in recur- UK guidelines should aim for a consensus for a minimum rence rate is seen when histological clearance exceeds histological clearance when MIS is treated by WLE. Our data 3.0 mm from 14% recurrence down to 3% recurrence indicate that a minimum histological margin of at least (p � 0.049). *e latter recurrence rate is comparable to 3.0 mm should be advocated to achieve lower recurrence recurrences in other studies, even when our dataset includes rates of MIS. Besides, the length of follow-up should be subjects with presumed risk factors, such as recurrence cases revised given the potential risk of recurrence and risk of and foci of invasion or regression, on top of the typical invasion, particularly if the histological margins fall short of primary cases of MIS (Table 1). 3.0 mm. *is is the first study to compare the impact of A Cochrane review has revealed that there is a lack of different risk factors such as recurrence, invasive foci, and high-quality evidence for the treatment of MIS and LM [32]. regression on recurrence. *ese did not have a statistically Despite this, studies have demonstrated that all MIS sub- significant impact on the rate of recurrence if complete types have a high incidence of invasive foci [35–37]. Meg- histological excision was achieved. We, therefore, emphasize ahed et al. [37] reported that 29% of all MIS subtypes had the need for further research into the histological peripheral invasive tumors. Because of this, some reports [38] advocate margins of MIS excised by WLE in which cumulative work the treatment of MIS as an early-stage invasive melanoma. must be collated and completed in a large multicenter study Our results demonstrate no significant difference in with a prolonged follow-up monitoring period. Journal of Skin Cancer 7 current state of diagnosis and treatment,” Dermatologic Abbreviations Surgery, vol. 32, no. 4, pp. 493–504, 2006. [7] National Institute for Health and Care Excellence, Melanoma: AAD: American Association of Dermatology Assessment and Management, National Institute for Health IQR: Interquartile range and Care Excellence, London, UK, 2015. LM: Lentigo maligna [8] S. M. Swetter, H. Tsao, C. K. Bichakjian et al., “Guidelines of MIS: Melanoma in situ care for the management of primary cutaneous melanoma,” MMS: Mohs micrographic surgery Journal of the American Academy of Dermatology, vol. 80, NICE: National Institute of Health and Care Excellence no. 1, pp. 208–250, 2019. RCM: Reflectance confocal microscopy [9] J. L. Bub, D. Berg, A. Slee, and P. B. Odland, “Management of RCPath: Royal College of Pathology lentigo, maligna and lentigo maligna melanoma with staged SS-MIS: Superficial spreading melanoma in situ excision: a 5-year follow-up,” Arch. Dermatol, vol. 140, no. 5, WLE: Wide local excision. pp. 552–558, 2004. [10] S. Felton, R. S. Taylor, and D. Srivastava, “Excision margins for melanoma in situ on the head and neck,” Dermatologic Data Availability Surgery, vol. 42, no. 3, pp. 327–334, 2016. *e data pertinent to the recurrences are available in [11] S. S. Jejurikar, G. H. Borschel, T. M. Johnson, L. Lowe, and D. L. Brown, “Immediate, optimal reconstruction of facial Supplementary Table 1. Additional information from the lentigo maligna and melanoma following total peripheral study is available upon reasonable request. margin control,” Plastic and Reconstructive Surgery, vol. 120, no. 5, pp. 1249–1255, 2007. Conflicts of Interest [12] S. C. Huilgol, D. Selva, C. Chen et al., “Surgical margins for lentigo maligna and lentigo maligna melanoma: the technique *e authors declare that there are no conflicts of interest. of mapped serial excision,” Archives of Dermatology, vol. 140, no. 9, pp. 1087–1092, 2004. Acknowledgments [13] D. Garcia, R. E. Eilers, and S. B. Jiang, “Recurrence rate of melanoma in situ when treated with serial disk staged exci- *e authors would like to acknowledge Mr. M Badawy sion: a case series,” Journal of Clinical and Investigative (senior clinical fellow in plastic surgery) and Dr. D Baishnab Dermatology, vol. 5, no. 1, pp. 01–04, 2017. for assisting with data collection and for explaining the [14] T. N. Bienert, M. J. Trotter, and J. P. Arlette, “Treatment of methods used to histologically examine MIS specimens, cutaneous melanoma of the face by mohs micrographic respectively. No writing assistance was utilized in the pro- surgery,” Journal of Cutaneous Medicine and Surgery: In- duction of this manuscript. corporating Medical and Surgical Dermatology, vol. 7, no. 1, pp. 25–30, 2003. [15] C. L. F. Temple and J. P. Arlette, “Mohs micrographic surgery Supplementary Materials in the treatment of lentigo maligna and melanoma,” Journal of Supplementary Table 1 (attached file) contains the histo- Surgical Oncology, vol. 94, no. 4, pp. 287–292, 2006. pathological details of the patient with recurrences. (Sup- [16] J. G. Albertini, D. M. Elston, L. F. Libow, S. B. Smith, and M. F. Farley, “Mohs micrographic surgery for melanoma,” plementary Materials) Dermatologic Surgery, vol. 28, no. 8, pp. 656–665, 2002. [17] M. J. Zalla, K. K. Lim, D. J. Dicaudo, and M. M. Gagnot, References “Mohs micrographic excision of melanoma using immu- nostains,” Dermatologic Surgery, vol. 26, no. 8, pp. 771–784, [1] H. K. Weir, T. D. *ompson, A. Soman, B. Møller, and S. Leadbetter, “*e past, present, and future of cancer inci- [18] G. M. Bricca, D. G. Brodland, D. Ren, and J. A. Zitelli, dence in the United States: 1975 through 2020,” Cancer, “Cutaneous head and neck melanoma treated with Mohs vol. 121, no. 11, pp. 1827–1837, 2015. micrographic surgery,” Journal of the American Academy of [2] M. Coory, P. Baade, J. Aitken, M. Smithers, G. R. C. McLeod, Dermatology, vol. 52, no. 1, pp. 92–100, 2005. and I. Ring, “Trends for in situ and invasive melanoma in [19] N. I. Bene, C. Healy, and B. M. Coldiron, “Mohs micrographic Queensland, Australia,” Cancer Causes Control, vol. 17, no. 1, surgery is accurate 95.1% of the time for melanoma in situ: a pp. 21–27, 2006. prospective study of 167 cases,” Dermatologic Surgery, vol. 34, [3] R. King, R. N. Page, P. B. Googe, and M. C. Mihm, “Lenti- no. 5, pp. 660–664, 2008. ginous melanoma: a histologic pattern of melanoma to be [20] J. K. Robinson, “Margin control for lentigo maligna,” Journal distinguished from lentiginous nevus,” Modern Pathology, of the American Academy of Dermatology, vol. 31, no. 1, vol. 18, no. 10, pp. 1397–1401, 2005. pp. 79–85, 1994. [4] Z. Tannous, L. Lerner, L. Duncan, M. Mihmjr, and T. Flotte, [21] L. M. Cohen, M. W. Mccall, and R. H. Zax, “Mohs micro- “Progression to invasive melanoma frommalignant mela- graphic surgery for lentigo maligna and lentigo maligna noma in situ, lentigo maligna type,” Human Pathology, vol. 31, no. 6, pp. 705–708, 2000. melanoma. A follow-up study,” Dermatologic Surgery, vol. 24, no. 6, pp. 673–677, 1998. [5] M. Kvaskoff, V. Siskind, and A. C. Green, “Risk factors for lentigo maligna melanoma compared with superficial [22] J. H. Kunishige, D. G. Brodland, and J. A. Zitelli, “Surgical margins for melanoma in situ,” Journal of the American spreading melanoma,” Archives of Dermatology, vol. 148, no. 2, pp. 164–170, 2012. Academy of Dermatology, vol. 66, no. 3, pp. 438–444, 2012. [23] “Standards and datasets for reporting cancers dataset for [6] J. K. McKenna, S. R. Florell, G. D. Goldman, and G. M. Bowen, “Lentigo maligna/lentigo maligna melanoma: histopathological reporting of primary cutaneous malignant 8 Journal of Skin Cancer melanoma and regional lymph nodes unique document [39] K. Phan and A. Loya, “Mohs micrographic surgery versus wide local excision for melanoma in situ: analysis of a na- number G125 document name dataset for histopathological reporting of primary cutaneous malignant melanoma and tionwide database,” International Journal of Dermatology, vol. 58, no. 6, pp. 697–702, 2019. regional lymph nodes,” 2008. [24] G. Bieliauskiene, A. S. S. Holm-Schou, P. A. Philipsen et al., [40] A. Waddell, P. Star, and P. Guitera, “Advances in the use of reflectance confocal microscopy in melanoma,” Melanoma “Measurements of sun sensitivity in five european countries Management, vol. 5, no. 1, p. MMT04, 2018. confirm the relative nature of fitzpatrick skin phototype [41] A. M. Demer, K. K. Vance, N. Cheraghi, H. C. Reich, and scale,” Photodermatology, Photoimmunology and Photo- P. K. Lee, “Benefit of mohs micrographic surgery over wide local medicine, vol. 36, no. 3, pp. 179–184, 2019. excision for melanoma of the head and neck,” Dermatologic [25] A. C. Walls, J. Han, T. Li, and A. A. Qureshi, “Host risk Surgery, vol. 45, no. 3, pp. 381–389, 2019. factors, ultraviolet index of residence, and incident malignant melanoma in situ among US women and men,” American Journal of Epidemiologyprevention, vol. 177, no. 9, pp. 997– 1005, 2013. [26] K. M. Joyce, C. W. Joyce, D. M. Jones et al., “An assessment of histological margins and recurrence of melanoma in situ,” Plastic and Reconstructive Surgery – Global Open, vol. 3, no. 2, [27] S. Gandini, F. Sera, M. S. Cattaruzza et al., “Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure,” European Journal of Cancer, vol. 41, no. 1, pp. 45–60, 2005. [28] V. Bataille and E. De Vries, “Melanoma - part 1: epidemiology, risk factors, and ,” BMJ-British medical journal, vol. 337, no. 7681, pp. 1287–1291, 2008. [29] A. Nosrati, J. G. Berliner, S. Goel et al., “Outcomes of mel- anoma in situ treated with mohs micrographic surgery compared with wide local excision,” JAMA Dermatology, vol. 153, no. 5, pp. 436–441, 2017. [30] J. L. Hou, K. B. Reed, R. M. Knudson et al., “Five-year outcomes of wide excision and Mohs micrographic surgery for primary lentigo maligna in an academic practice cohort,” Dermatologic Surgery, vol. 41, no. 2, pp. 211–218, 2015. [31] S. Akhtar, W. Bhat, A. Magdum, and P. R. W. Stanley, “Surgical excision margins for melanoma in situ,” Journal of Plastic, Reconstructive & Aesthetic Surgery, vol. 67, no. 3, pp. 320–323, 2014. [32] T. Tzellos, A. Kyrgidis, S. Mocellin, A. Chan, P. Pilati, and Z. Apalla, “Interventions for melanoma in situ, including lentigo maligna,” Cochrane Database of Systematic Reviews, vol. 12, 2014. [33] K. L. Duffy, A. Truong, G. M. Bowen et al., “Adequacy of 5 mm surgical excision margins for non-lentiginous melanoma in situ,” Journal of the American Academy of Dermatology, vol. 71, no. 4, pp. 835–838, 2014. [34] R. P. Johnson, N. Butala, M. Alam, and N. Lawrence, “A retrospective case-matched cost comparison of surgical treatment of melanoma and nonmelanoma skin cancer in the outpatient versus operating room setting,” Dermatologic Surgery, vol. 43, no. 7, pp. 897–901, 2017. [35] N. Agarwal-Antal, G. M. Bowen, and J. W. Gerwels, “His- tologic evaluation of lentigo maligna with permanent sections: implications regarding current guidelines,” Journal of the American Academy of Dermatology, vol. 47, no. 5, pp. 743– 748, 2002. [36] M. E. Dawn, A. G. Dawn, and S. J. Miller, “Mohs surgery for the treatment of melanoma in situ,” Dermatologic Surgery, vol. 33, no. 4, pp. 395–402, 2007. [37] M. Megahed, M. Schon, ¨ D. Selimovic, and M. P. Schon, ¨ “Reliability of diagnosis of melanoma in situ,” 2e Lancet, vol. 359, no. 9321, pp. 1921-1922, 2002. [38] J. H. Kunishige, D. G. Brodland, and J. A. Zitelli, “Larger surgical margins are required for lentigo maligna and other melanoma in situ,” Journal of the American Academy of Dermatology, vol. 67, no. 5, pp. 1069–1071, 2012.

Journal

Journal of Skin CancerHindawi Publishing Corporation

Published: Oct 29, 2020

There are no references for this article.