Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2023;13(3):e2023193 1 Spaghetti Technique Versus Wide Local Excision for Lentigo Maligna Affecting the Head and Neck Regions: Surgical Outcome and Descriptive Analysis of 79 Cases from a Single Practice Cohort Manel Martinez-Molina1, Nina Richarz1, Ane Jaka1, Juli Bassas-Vila1, Verónica Mora-Fernández1, Ariadna Quer Pi-Sunyer 2, Sebastian Podlipnik3, José Manuel Carrascosa1, Aram Boada1 1 Department of Dermatology, Hospital University Germans Trias i Pujol, Badalona. Autonomous University of Barcelona, Barcelona, Spain 2 Department of Pathology, Hospital University Germans Trias i Pujol, Badalona, Barcelona, Spain 3 Department of Dermatology, Melanoma Unit, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain Key words: Lentigo maligna, Spaghetti technique, Wide local excision, Melanoma Citation: Martinez-Molina M, Richarz N, Jaka A, et al. Spaghetti Technique Versus Wide Local Excision for Lentigo Maligna Affecting the Head and Neck Regions: Surgical Outcome and Descriptive Analysis of 79 Cases From a Single Practice Cohort. Dermatol Pract Concept. 2023;13(3):e2023193. DOI: https://doi.org/10.5826/dpc.1303a193 Accepted: March 2, 2023; Published: July 2023 Copyright: ©2023 Martinez-Molina et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Manel Martinez Molina, Department of Dermatology, Hospital University Germans Trias i Pujol, Badalona. Autonomous University of Barcelona, Carretera de Canyet, w/n, PC: 08916, Badalona, Barcelona, Spain. Email: manel.martmol@gmail.com Introduction: Lentigo maligna is a subtype of melanoma in situ that typically affects the head and neck region with an increasing incidence. Margin-controlled techniques, such as spaghetti technique (ST), have gained popularity over wide local excision (WLE) with a margin of 5 mm. Objectives: To evaluate the outcomes of lentigo maligna cases in the head and neck area treated by either WLE or ST in a tertiary referral hospital. The secondary goal was to describe the demographic and clinical characteristics of our series. Methods: Cohort study of patients diagnosed with lentigo maligna on the head and neck region between January 2014 and February 2022 in a tertiary hospital. Results: In total, 79 lentigo maligna were studied, corresponding to 77 patients. Fifty-three lesions (67%) were treated with WLE and 26 (33%) with ST. The mean age of the patients was 73 years and 58% were men. Most of the tumors were located on the cheek (50%) and mean lesion diameter was 2.2 cm for the ST group and 1.2 cm for the WLE group. Mean duration follow-up was 44 months. There were two local recurrences in the WLE group (2/53; 3.7%) and none in the ST group. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2023;13(3):e2023193 Introduction Lentigo maligna (LM) is a subtype of melanoma in situ that typically appears on the sun-damaged skin of elderly patients [1]. The estimated risk of progression of LM to LM mel- anoma (LMM) is 3.5 % per year [2]. In recent years, the incidence of LM/LMM has increased in comparison to other melanoma subtypes [3,4]. A study of 8626 melanoma cases in Catalonia (Spain), showed a rise in the incidence of LMM, from 13.9% in 2008 to 22.6% in 2017 [5]. A 25-year study in the Netherlands mirrored this trend, with a rise in the incidence rate from 0.72 LM/100.000 person years in 1989 to 3.84 LM/100.000 patient years [6]. The estimated an- nual incidence in another recent study was 12 LM/100.000 persons. Surgical excision remains the treatment of choice for LM. Wide local excision (WLE) with 5-mm to 10-mm margins is the standard surgical management [8,9]. How- ever, 5-mm margins may be inadequate in some cases, with recurrence ranging from 6% to 20% [10,11], owing to subclinical peripheral spread and poor histological margin assessment. LM primarily affects the head and neck region and these margins are more difficult to achieve in areas with aesthetic and functional implications, such as the face. Margin-controlled techniques like Mohs micrographic sur- gery (MMS) evaluate 100% of the surgical margin, reducing the risk of recurrence, while preserving tissue in cosmetically sensitive sites. Owing to the difficulty of assessing atypical melanocytes in frozen sections in MMS, even with immu- nohistochemical staining, variations of MMS, such as slow Mohs (SM) and staged excision (SE) have gained popularity among surgeons [12]. SM and SE rely on permanent sec- tions and deferred histological examination. SM uses the same horizontal sectioning technique as MMS, but relies on formalin-fixed paraffin-embedded sections, instead of fro- zen sections. Following the intervention, the patient returns home. A few days later, depending on whether the margins are positive or not, an additional resection or a defect re- construction is performed. In SE, narrow margins are exam- ined in formalin-fixed permanent sections, without tumour debulking in the first stage. Debulking is performed in the final stage when all margins are clear. Among staged exci- sions, in both square technique and perimeter technique, a preoperative geometric-shaped excision is outlined adding safety margins to the clinically identified limits of the tumor, to check the periphery of this geometric figure before resec- tion [13,14]. In contrast, in the spaghetti technique (ST), a variation of SE first described by Gaudy-Marqueste et al, the intention is to define, step by step, as closely as possible the real - pathologically identified - shape of the LM, that will enable later its resection and reconstruction [15] (Table 1). Although MMS has been controversial for melanoma, because of concerns about the accuracy of detecting atypical Table 1. Staged excisions techniques: differences and similitudes. Square technique Perimeter technique Spaghetti technique Collarette technique Differences Excision of a 2-mm strip of skin in a square pattern. A variation of the square technique. Excision of a 2-mm strip of skin in a variety of geometric shapes (triangles, rectangles, or pentagons) to facilitate posterior reconstruction. Curved lines and rounded edges are used instead of straight lines, in order to define as closely as possible, the real pathologically shape of the tumor. It is identical to spaghetti technique. The only difference with ST is the use of dermoscopy to delineate tumor edges, in its original description by Kassi et al [37]. Similitudes • A double-bladed scalpel is used to remove a 2–4-mm strip surrounding the lesion. • The resulting linear defect is sutured. • The specimen is paraffin embedded and en face vertical sections containing 100 % of the peripheral margins are assessed. • If positive margins are identified, a procedure is repeated 5 mm beyond the corresponding involved segment and again sutured, until a tumor-free perimeter is achieved. • Resection of the central tumor and reconstruction is performed. Conclusions: Both WLE and ST are appropriate surgical approaches for lentigo maligna. ST offers an efficient alternative to Mohs surgery for treating lentigo maligna in the head and neck area, especially when guided by reflectance confocal microscopy. Original Article | Dermatol Pract Concept. 2023;13(3):e2023193 3 Figure 1. Spaghetti technique. (A) Lentigo maligna on the cheek area. (B) Skin markings prior to the first excision. (C) Resected “spaghetti” strip divided into segments and arranged in a circle before being sent for pathological study. (D) Suture of the resulting linear defect, leaving the tumor on site pending the results of histopathological study. (E) Tumor resection followed by flap reconstruction was performed when all “spaghetti” segments were tumor-free. melanocytes on frozen sections, a recent study showed a high diagnostic accuracy on frozen sections compared with perma- nent sections [16]. Another limitation of MMS is that immuno- histochemical staining is time-consuming for histotechnicians and can impair the flow of a Mohs practice [17]. In contrast, an advantage of ST over MMS is that it does not require specially trained MMS technicians, thus making it more accessible. Objectives The primary goal of the present study was to retrospectively evaluate the outcomes of LM cases in the head and neck area treated by either WLE or ST in a tertiary referral hospital. The secondary goal was to describe the demographic and clinical characteristics of our series. Methods This retrospective study included data from all the patients diagnosed with LM on the head or neck between January 2014 and February 2022 at a tertiary hospital in Spain (Germans Trias i Pujol Universitary Hospital in Badalona, Barcelona). The database included age at diagnosis, gender, phototype (I-II, III-IV, V-VI), tumor site (cheek, nose, perio- cular, perioral, scalp, forehead, ear, neck), clinical tumor greatest diameter (< or ≥ 2 cm), type of surgery (WLE or ST), number of stages required in ST (2 or ≥ 3) and in WLE (1 or 2), local and distant recurrence, and follow-up du- ration (months). We included patients with recurrent LM. These included LM that had reappeared after a prior cura- tive therapy, whether surgical or non-surgical (cryosurgery, laser therapy), performed in our hospital or elsewhere. Pa- tients with invasive melanoma (LMM) were excluded from the study. We also excluded cases in which the management chosen was therapeutic abstention. Histological diagnosis of LM was obtained by incisional biopsy prior to treatment. The surgical technique was chosen according to current guidelines, with ST being the preferred option in most LM cases in the recent years. When WLE was used, the margin of excision around the clinically apparent tumor was 5 mm. In the case of ST, a 2-mm strip of skin was resected, 2 mm to 3 mm beyond the clinically and der- moscopically defined outline of the lesion. The linear defect was sutured, and the patients discharged pending the results of histology. The narrow strip of resected skin was divided into appropriately sized segments, which were then pinned in a circular pattern reflecting their anatomic orientation. The number of segments varied depending on the size and morphology of the resected specimen (Figure 1). Each seg- ment was fixed in formol and analyzed in vertical in-face sec- tions by dermatopathologists. If a segment was positive for 4 Original Article | Dermatol Pract Concept. 2023;13(3):e2023193 lesion as reported by the patient ranged from 2 months to 25 years, and only 8 patients claimed a history of more than 10 years. Mean follow-up duration was 44 months (range 2 – 90 months). Local recurrence was diagnosed in 2 of 53 cases treated with WLE, at 12 and 39 months, respectively, (a mean interval of 25 months). Both cases were subsequently treated with ST. No local recurrences were observed in the ST group. Local recurrence-free survival at 30 and 60 months after di- agnosis was 98% and 95%, respectively, for the WLE group and 100% for lesions treated with ST (Figure 2). The differ- ence in local recurrence-free survival between WLE and ST groups was not significant (P = 0.33). Progression to LMM, distant metastases or death attributable to melanoma were not observed in any group. Ten patients died from other causes during the follow-up period. Conclusions In this study, we present a cohort of patients with LM on the head and neck treated with either WLE or ST, contributing the experience of one hospital to the literature on LM manage- ment. We found no significant difference in the frequency of local recurrence between WLE and ST. Two non-randomized studies have compared long-term outcomes for different sur- gical treatment modalities in LM, like the present study. Wall- ing et al reported a higher recurrence rate for MMS (36%) than for SE (8%) [20]. Walling et al attributed this significant local recurrence rate to the long follow-up period (mean al- most 10 years), arguing that most recurrences occur 3 to 5 years after treatment. Another possible explanation for the high recurrence rate in that study may be the small number (N = 14) of lesions treated with MMS. Hou et al reported a lower risk of recurrence with MMS (1.9%) than with WLE (5.9%), although the difference was not statistically significant [12]. Notably, in our series the recurrence rate for both sur- gical techniques was lower than that previously reported in the literature [10-12, 20-29]. Other studies have reported recurrence rates for WLE of between 6% and 20%, with a follow-up period of 36 to 90 months. Recurrence rates re- ported for MMS range from 0% to 6% with a follow-up pe- riod of 38 to 95 months, excluding the outlier of 36% in the study mentioned above. In the case of SE, recurrence rates were 2% to 10% with follow-up periods of between 32 and 95 months (Table 3). However, comparison with previous studies may be inaccurate because, the follow-up methods were not described in some cases and in others follow up was performed by general practitioners or was based on telephone reports by family members [30]. In our study, follow-up con- sisted of a physical examination carried out by one of the authors and local recurrence was confirmed by skin biopsy. Even though the recurrence rate was lower in the ST group than the WLE group, the difference was not statistically malignant cells, an additional strip excision was performed beyond the corresponding area. This step was repeated until all the segments of the ‘spaghetti’ were tumor free. In the last stage, resection of the tumor and reconstruction of the final defect (skin graft, flap, or primary closure) were performed at the same time. A major disadvantage of the ST is that the central tumor is not excised until the time of closure, so an unsuspected invasive melanoma would not be identified un- til after closure is complete [18]. This risk could be reduced by correlating the dermoscopy findings with the Breslow index and by performing a punch biopsy of the most sus- picious area of depth [19]. From 2019 onwards, reflectance confocal microscopy (RCM) was used to delineate excision margins before surgery in all cases of LM, whether the surgi- cal approach was WLE or ST. A descriptive analysis was carried out of the demo- graphic and clinical data. We compared the LM characteris- tics of the two groups (WLE and ST). The Student t test was used to analyze continuous variables and the Mann-Whitney U test when the data were not normally distributed. Com- parative variables were analyzed with the Chi2 test. A P value less than 0.05 was considered statistically significant. Local recurrence-free survival was assessed using Kaplan Meier analysis. For local recurrence-free survival, the time to an event (date of recurrence or last follow-up) was calculated from the date of histological diagnosis. Statistical analysis was performed using SPSS software version 28.0. The study was approved by the local Ethics Committee and patients gave written informed consent. Results Between January 2014 and February 2022, 81 lesions diag- nosed as LM affecting the head and neck region were iden- tified in 79 patients. Therapeutic abstention was the strategy chosen for two patients due to their advanced age (99 and 100 years-old respectively). In total, 79 LM corresponding to 77 patients were included in the study; 53 lesions were treated with WLE and 26 with ST. The characteristics of the study population are summarized in Table 2. The mean age of the patients was 73 years (range 43 – 95). Forty-two per- cent were women and 58% men. More than half of the pa- tients had skin phototype III-IV (52/79; 65.8%). Most of the tumors (75/79; 95%) were primary. At the time of diagnosis, three lesions in the ST group and one in the WLE group were recurrent. The most frequent site was the cheek (50%), fol- lowed by the forehead (12%), scalp (10%) and nose (10%). In the ST group, 54% of the lesions measured ≥ 2 cm. In contrast, only 17% of the LM treated with WLE measured ≥ 2 cm. Mean lesion size was 2.2 cm for the ST group and 1.2 cm for the WLE group. These differences were statisti- cally significant (P <0.05). The interval since first onset of the Original Article | Dermatol Pract Concept. 2023;13(3):e2023193 5 Table 2. Demographic and clinical characteristics of patients with lentigo maligna in the head and neck region by surgery type. Variable Spaghetti Technique Wide Lesion Excision Overall, N (%) P value No. of cases 26 (33%) 53 (67%) 79 (100%) Sex P>0.05 Female 12 (36.4%) 21 (63.6%) 33 (41.8%) Male 14 (30.4%) 32 (69.6%) 46 (58.2%) Average age 72.2 73.6 73 P>0.05 <70 years 9 (32.1%) 19 (67.9%) 28 (35.4%) P>0.05 ≥70 years 17 (33.3%) 34 (66.7%) 51 (64.5%) P>0.05 Skin phototype P>0.05 I-II 10 (40%) 15 (60%) 25 (31.6%) III-IV 15 (28.8%) 37 (71.2%) 52 (65.8%) V-VI 1 (50%) 1 (50%) 2 (2.5%) Site P>0.05 Centrofacial Cheek 16 (40%) 24 (60%) 40 (50.6%) Nose 3 (37.5%) 5 (62.5%) 8 (10.1%) Periocular 1 (50%) 1 (50%) 2 (2.5%) Perioral 1 (100%) 0 1 (1.3%) Peripheral Scalp 3 (37.5%) 5 (62.5%) 8 (10.1%) Forehead 2 (20%) 8 (80%) 10 (12.7%) Ear 0 (0%) 9 (100%) 9 (11.4%) Neck 0 (0%) 1 (100%) 1 (1.3%) Size P<0.05 <2 cm 12 (21.4%) 44 (78.6%) 56 (70.9%) ≥2 cm 14 (60.9%) 9 (39.1%) 23 (29.2%) Duration P<0.05 <5 years 15 (38.5%) 24 (61.5%) 39 (49.4%) ≥5 years 6 (27.3%) 16 (72.7%) 22 (27.8%) Unknown 5 (27.8%) 13 (72.2%) 18 (22.8%) Primary vs recurrent P<0.05 Primary 23 (30.7%) 52 (69.3%) 75 (94.9%) Recurrent 3 (75%) 1 (25%) 4 (5.1%) No. of stages ST WLE P<0.05 1 0 (0%) 51 (96%) 51 (65%) 2 21 (81%) 2 (4%) 23 (29%) ≥3 5 (19%) 0 (0%) 5 (6%) significant. Since the outcomes of both surgical techniques were similar in our study, we believe that additional factors should be considered before choosing the surgical approach, such as patient preference, tumor size, reconstruction options and the accessibility of margin-controlled techniques. In our hospital, collaboration with experienced dermatopatholo- gists with experience in ST and the use of paraffin-embedded sections has proved to be a fruitful strategy. Some authors have shown that the standard 5-mm mar- gins are often not sufficiently wide to ensure clear margins [31]. However, wide excisions margins (10 mm) are not al- ways acceptable because they can lead to morbidity in func- tional and cosmetically sensitive areas. Consequently, the site of the lesion, patient age and comorbidities must also be taken into account. The lower local recurrence rate observed in our WLE patients may be explained by the introduction 6 Original Article | Dermatol Pract Concept. 2023;13(3):e2023193 Figure 2. Local recurrence-free survival after wide local excision vs spaghetti technique. Table 3. Summary of studies reporting surgically treated lentigo maligna, by surgery typea. Treatment Study Recurrence rate (%) Mean follow-up (months) Mean time to recurrence (months) Wide local excision Pittman (1979) 9% (2/22) 38 - Tsang (1994) 6% (1/18) 36 - Osborne (2002) 20% (16/81) 43 - Hou (2015) 6% (16/269) 95 - Mohs micrographic surgery Robinson (1994) 6% (1/16) 60 96 Cohen (1998) 0% (0/26) 57 - Bhardwaj (2006) 1% (1/158) 38 - Walling (2007) 36% (5/14) 117 50 Bene (2008) 1% (1/116) 63 48 Gambichler (2014) 2% (3/124) 55 - Hou (2015) 2% (3/154) 95 - Staged excision Bub (2004) 4% (2/55) 57 54 Walling (2007) 8% (3/36) 95 24 Lee (2008) 10% (3/31) 42 48 Abdelmalek (2012) 2% (4/225) 32 15 De Vries (2016) 4% (4/100) 60 62 aLentigo maligna melanoma cases were excluded of RCM in our hospital, which allowed preoperative identi- fication of surgical margins in vivo. Moreover, RCM guid- ance contributed to the low number of stages (‘spaghetti’) needed to achieve clearance in the ST group (2 stages in 21 patients vs >3 stages in 5 patients). Advantages of RCM guided ST for LM, especially in functional and aesthetic areas, has also been reported by Couty et al [32]. A major drawback of RCM is that is limited to few centers. In addi- tion, RCM adds further cost (device, maintenance, specific training) in the diagnostic performance of melanoma. It is also a time-consuming procedure. Finally, our low recurrence rate could also be attribut- able to the short mean follow-up duration (44 months), since some authors have suggested that recurrence occurs later in LM than other melanoma subtypes [33,34]. A major limitation of this study is its retrospective and non-randomized design, which means that the comparison between the WLE and ST groups cannot be precise. We nonetheless consider it to be of interest to report the out- comes for these 2 surgical techniques to reflect a real-world practice scenario. In terms of descriptive findings, our cohort is in line with those previously reported [32,35]. A predominance of male patients (58%) was observed in our registry, as previously widely described [34]. Interestingly, mean tumor size was 16 mm, which is not especially large for slow-growing and ill-defined lesions. The clinical findings and tumor character- istics did not differ significantly between the two groups. It is noteworthy that the tumors treated by ST were larger in diameter than those treated with WLE and that this differ- ence was statistically significant. ST was the preferred treat- ment for recurrent LM. Both larger diameter tumours and recurrent tumours were considered high risk by Hou et al [12], and MMS was the surgical approach chosen for those LM. Even though treatment was individualized in our study group in accordance with current guidelines and patient preference, larger and recurrent LM were more likely to be treated by ST. The results of this study provide real-world insight into the surgical treatment of LM in the head and neck area, com- paring WLE and ST. While some authors have concluded that margin-controlled techniques are the preferred treatment for LM, to our knowledge, none of them have compared the outcomes of WLE and ST. To date, in the absence of data from randomized clinical trials and comparative studies on the preferred surgical approach in different cases of LM, this Original Article | Dermatol Pract Concept. 2023;13(3):e2023193 7 11. Tsang RW, Liu FF, Wells W, Payne DG. Lentigo maligna of the head and neck. Results of treatment by radiotherapy. Arch Der- matol. 1994;130(8):1008-1102. PMID: 8053696. 12. Hou JL, Reed KB, Knudson RM, et al. Five-year outcomes of wide excision and Mohs micrographic surgery for primary len- tigo maligna in an academic practice cohort. Dermatol Surg. 2015;41(2):211-218. DOI: 10.1097/DSS.0000000000000248. PMID: 25590473. 13. 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