INTRODUCTION. Abbreviations used: ALM: acral lentiginous melanoma LM: lentigo maligna MM: melanoma MMS: Mohs micrographic surgery SS: staged surgery

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The spaghetti technique : An alternative to Mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma) Caroline Gaudy-Marqueste, MD, PhD, a Anne-Sophie Perchenet, MD, b Anne-Marie Taséi, MD, c Nika Madjlessi, MD, a Guy Magalon, MD, PhD, b Marie-Aleth Richard, MD, PhD, a and Jean-Jacques Grob, MD, PhD a Marseille, France Background: Lentigo maligna (LM) and acral lentiginous melanoma (ALM) are often large and clinically ill defined. The surgical challenge is to spare tissue while still achieving clear margins. Objective: We sought to provide a retrospective assessment of a two-phase surgical technique for lentiginous melanomas (MM) not suitable for en bloc resection. Methods: In the first phase, a narrow band of skin, the spaghetti, is resected just beyond the clinical outline of the MM, immediately sutured, and sent for pathological examination without removing the MM. The same procedure is repeated beyond the segments which are shown to be not tumor free and so forth until the minimal tumor-free perimeter is outlined. No operative wound is left between operative sessions. In the second phase, the MM resection and reconstruction are performed at the same time. Results: In 21 patients with LM (n = 16) or ALM (n = 5), the mean operative defect size was 27.5 cm 2 (range, 1.97-108.4 cm 2 ). The mean number of steps in the procedure was 1.55 (1-4). Grafts were used for reconstruction in all cases. The relevance of the spaghetti -defined outline was confirmed in 19 of 21 patients. After a median follow-up period of 25.36 months (range, 0-72 months), the local control rate was 95.24% with one case (4.76%) of in-transit invasive recurrence after 48 months. Limitations: This study was performed at a single center and included a limited number of patients. The follow-up time was relatively brief. Conclusion: The spaghetti technique is simple and reliable for LM and ALM. Unlike Mohs surgery, it does not require specific training of surgeons or pathologists. Unlike staged surgery, it does not leave patients with an open wound on the face or soles before final reconstruction. ( J Am Acad Dermatol 2011;64:113-8.) Key words: lentiginous melanomas; margins assessment; surgery. INTRODUCTION The lentiginous subtypes of melanoma (MM), namely lentigo maligna (LM) and acral lentiginous MM (ALM), share common characteristics: (1) the lentiginous phase can be very subtle with little or no Abbreviations used: ALM: acral lentiginous melanoma LM: lentigo maligna MM: melanoma MMS: Mohs micrographic surgery SS: staged surgery From the Service de Dermatologie, Hôpital Ste Marguerite, a Service de Chirurgie Plastique, Hôpital La Conception, b and the Service d Anatomopathologie, Hôpital La Timone, Université de la Méditerranée. c Funding sources: None. Conflict of interest: None declared. This work was presented as an oral communication during the 7th International Conference on Adjuvant Therapy of Melanoma e 4th European Association of Dermato-Oncology Congress, Marseille, June 19-21, 2008. Reprint requests: Dr Caroline Gaudy-Marqueste, Dermatology Department, Ste Marguerite Hospital, 270 Blvd Ste Marguerite, 13009 Marseille, France. E-mail: Caroline.Gaudy@mail.ap-hm.fr. 0190-9622/$36.00 ª 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.03.014 113

114 Gaudy-Marqueste et al JAM ACAD DERMATOL JANUARY 2011 pigmentation and can thus go undetected for months to years before they become nodular or ulcerate and (2) because of clinically ill-defined and not always pigmented peripheral margins, their extent tends to be underestimated, with a risk of insufficient resection. Margins of at least 10 mm are therefore usually recommended for complete excision of LM, even for in situ lesions. 1-6 LM and ALM grow on skin areas with major aesthetic or functional implications (face, soles), which accounts for the tendency to minimize resection, in a conscious or unconscious manner, increasing the risk of insufficient margins. Recurrences are therefore frequent, unless a precise control of limits is performed, either by the techniques of Mohs micrographic surgery (MMS) or CAPSULE SUMMARY staged surgery (SS). MMS uses frozen horizontal sections and gives good results in terms of safety and tissue sparing. 2-8 MMS can be performed in 1 day, but is complex and requires specific training; thus it is not considered cost-effective in many countries. Multi-step variants of MMS with paraffin sections require days or weeks with open wounds. Various SS procedures have been described in the literature. 9,10 When SS is applied to large LMs or ALMs, additional tissue excisions are often needed until tumor-free margins can be obtained, allowing for secondary reconstruction. Patients thus remain with an open wound on the face or soles with a potential major functional, social, and psychological impact. In the search for a technique more simple than MMS applicable to large LMs and ALMs, combining minimal resection with margin control and avoiding a prolonged open wound, we designed a two-phase procedure based on the sampling of a spaghettilike band of tissue to ascertain margins before tumor removal. This procedure helps to determine the most likely shape and extension of LMs and ALMs before they are resected, so that the patient has a single procedure with immediate reconstruction. Herein we report our retrospective experience. METHODS Indications We used the so-called spaghetti technique in patients with ALM or LM who were initially referred for SS. Indications included ill-defined borders, large size of lesion, or reconstruction issues. d d d Lentiginous melanomas are often large and clinically ill defined. Surgical assessment of margins before resection is recommended to avoid incomplete resection and to spare tissue. The spaghetti technique is a simple way to evaluate margins and does not require special surgical or dermatopathology training. Technique Phase I: Outlining the limits of the MM. After biopsy confirmation of the LM or ALM diagnosis and the obtaining of a provisional Breslow thickness, a 2- mm strip of skin, the so-called spaghetti, is resected under local anesthesia, 3 to 5 mm beyond the clinically apparent perimeter of the tumor (Fig 1). The resulting linear defect is immediately sutured without ablation of the central area including the MM (Fig 1). The spaghetti is further divided into anatomically identified segments and sent for dermatopathologic examination. Each segment is analyzed along its longitudinal axis, in en-face sections. When a segment of the spaghetti is tumor positive, the procedure is repeated 5 mm beyond the corresponding involved segment and again sutured, as shown in Fig 1, B, so that no operative wound is left between sessions. The procedure is repeated as often as necessary until the last segment of spaghetti is found to be tumor free. The smallest peripheral area free of any tumor is outlined by the most external line of sutures of the successive spaghetti procedures (see Fig 2) and thus defines the central area to be resected. Fig 3 represents the first phase of the procedure showing clinical pictures together with the histologic examination. Fig 4 represents a phase I procedure photographic sequence. Phase II. Resection of the tumor and reconstruction. The optimal surgical reconstruction to be applied is determined by the final shape of the area to be resected. Resection of the central area and reconstruction (graft or flap) are performed at the same time. The final tumor specimen is analyzed with serial vertical sections. Review of the cases. The medical records of all patients treated by this technique between 2002 and 2008 in our Dermatology department were retrospectively reviewed. Clinical, surgical, and histologic data were recorded, including demographic data (age and sex), the tumor location and thickness, the number of steps required in the procedure, the margin status on the final excision report, and the recurrence rate. RESULTS Patients Twenty-one patients (4 men and 17 women) underwent the spaghetti procedure. Mean age at diagnosis was 71 years (range, 53-90 years).

JAM ACAD DERMATOL VOLUME 64, NUMBER 1 Gaudy-Marqueste et al 115 Fig 1. A, First step of the procedure. Resection of the spaghetti and immediate suture of the defect. B, New spaghetti procedure is performed beyond the nonetumor-free segments until tumor-free margins are obtained. C, Second step: Resection of the entire area including the tumor and immediate reconstruction of the defect. Tumor characteristics Twenty one lentiginous MMs were treated, including 16 LMs (76.2%) and 5 ALMs (23.8%). All the LMs were located on the face: 8 on the cheek, 3 on the ear, one on the temple, one on the eyebrow, one on the nose, one on the inferior eyelid, and one on the inferior lip. All the ALMs were located on the soles. Surgical data Mean size of the resected area in phase II was 27.54 cm 2 (range, 1.97-108.33 cm 2 ). Reconstruction used grafts in all cases. No immediate complications occurred. Pathological data The mean number of spaghetti steps during phase I was 1.55 (range, 1-4). Several steps were required in 9 cases. After final excision, 10 MM were found to be in situ, whereas 11 were invasive, with a mean thickness of 1.90 mm (range, 0.65-10). The limits of the central skin specimen including the MM

116 Gaudy-Marqueste et al JAM ACAD DERMATOL JANUARY 2011 Fig 2. Determination of tumor margins before tumor resection following 3 spaghetti procedures. were tumor free in 15 cases, thus supporting the efficacy of the technique. A focus of intraepithelial MM was found close to the limits of the central part of the resection in 6 cases (30%), raising doubts about the validity and safety of the tumor-free limit defined by the spaghetti procedure. Therefore, these 6 patients were offered an extra 5-mm skin resection beyond the last suspect limit after reconstruction. One patient refused this additional resection. A focus of intraepithelial MM was found again in one case. The samples were tumor free in the 4 remaining cases, thus confirming the spaghetti -defined limit. The relevance of the spaghetti technique to define tumor extension could thus be confirmed by pathological examination in 19 of the 21 patients and remained uncertain in one case. Follow-up After a mean follow-up of 25.36 months (maximum 72 months) after the final surgical procedure, the local control rate was 95.24%. In one case (4.76%), an in-transit invasive recurrence was observed after 48 months. DISCUSSION We describe our experience with an easy and safe two-phase method, the spaghetti technique, which is well adapted to the specific problems of margin control and potential aesthetic sequelae encountered in the resection of lentiginous MMs. The concept of pathological control of the margins before resection of MM has also been applied in the so-called square technique 10,11 or perimeter technique. 12 The two strategies are, however, somewhat different. In the square or perimeter technique, the geometric shape (square, triangle, pentagons) for an optimal resection is determined a priori by adding safety margins to the clinically identified limits of the lentiginous MM, and the objective is to check the periphery of this geometric figure before resection. In the spaghetti technique, the objective is to define, step by step as closely as possible, the real (pathologically defined) shape and extension of the lentiginous MM, which in turn will allow, a posteriori, determination of the optimal shape and size of the resection for reconstruction. The spaghetti technique for LM and ALM has many advantages. The first is safety. The clinical limits of LM and ALM are often misleading and underestimated, as shown by a mean of 1.55 (up to 4) successive samplings of spaghetti before a tumor-free strip is found. This is in line with previous studies in LM showing a mean of 1.67 (up to 5) stages in SS of LM. 13 Safety is also linked to the comprehensive longitudinal en face dermatopathologic control of the periphery. As compared to serial sections, the use of en face sections minimizes the risk of missing a radial extension of MM between sections. However, these sections may sometimes be difficult to interpret 14 since they do not allow an assessment of the change in density from the center to the periphery, or an estimation of the difference between LM and a background of severely sun damaged skin. When compared to MMS, the use of paraffin sections is more reliable than frozen ones. As a whole, the safety of the spaghetti technique is supported by the confirmation of the spaghetti -defined limits as shown by the serial sections of the final excision, in 90.45% of patients (19/21) and by a 95% control rate after a median of 2 years. This follow-up period is too short, however, to draw firm conclusions. The risk of seeding of the wound is only theoretical as the spaghetti technique is performed in the in situ part of the lentiginous MM and as the surgery is performed after the last positive strip and within a few weeks. Like MMS, the spaghetti technique guarantees the sparing of tissue, due to the step-by-step centrifugal process following closely the tumor-free margin of the MM. This is especially crucial for lesions on the face and soles. As compared to SS, as well as to the perimeter or square technique, the sparing of tissue is probably optimized. In contrast to MMS, the technique can be performed by any surgeon and pathologist without any additional training. The overall spaghetti procedure is of greater duration than classic MMS using frozen sections, but probably similar to MMS using paraffin sections. 15 When compared with the usual SS, the spaghetti technique, as well as the square technique, are much more comfortable for patients, who do not have open wounds on the face or the soles for several days or weeks during the different steps leading to margin control.

JAM ACAD DERMATOL VOLUME 64, NUMBER 1 Gaudy-Marqueste et al 117 Fig 3. Outlining limits of a lentiginous melanoma: Resection of the spaghetti, division into anatomically defined segments, suture of the defect (upper panel ). Macroscopic appearance of the spaghetti segment together with histologic sections (lower panel ). Fig 4. Photographic sequence of the first step of the spaghetti procedure.

118 Gaudy-Marqueste et al JAM ACAD DERMATOL JANUARY 2011 Finally, outlining the true shape of LM and ALM prior to resection allows for a single surgical resection with immediate reconstruction. It also allows a choice of the most suitable graft or flap, combining safety, simplicity, minimal resection and management of comfort, function, and aesthetics. REFERENCES 1. Huilgol SC, Selva D, Chen C, Hill DC, James CL, Gramp A, et al. Surgical margins for lentigo maligna and lentigo maligna melanoma: the technique of mapped serial excision. Arch Dermatol 2004;140:1087-92. 2. Zitelli JA, Brown CD, Hanusa BH. Surgical margins for excision of primary cutaneous melanoma. J Am Acad Dermatol 1997; 37:422-9. 3. Zalla MJ, Lim KK, Dicaudo DJ, Gagnot MM. Mohs micrographic excision of melanoma using immunostains. Dermatol Surg 2000;26:771-84. 4. Cohen LM, McCall MW, Zax RH. Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. A follow-up study. Dermatol Surg 1998;24:673-7. 5. Robinson JK. Margin control for lentigo maligna. J Am Acad Dermatol 1994;31:79-85. 6. Agarwal-Antal N, Bowen GM, Gerwels JW. Histologic evaluation of lentigo maligna with permanent sections: implications regarding current guidelines. J Am Acad Dermatol 2002;47: 743-8. 7. Bhardwaj SS, Tope WD, Lee PK. Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma using Mel-5 immunostaining: University of Minnesota experience. Dermatol Surg 2006;32:690-6. 8. Temple CL, Arlette JP. Mohs micrographic surgery in the treatment of lentigo maligna and melanoma. J Surg Oncol 2006;94:287-92. 9. Bub JL, Berg D, Slee A, Odland PB. Management of lentigo maligna and lentigo maligna melanoma with staged excision: a 5-year follow-up. Arch Dermatol 2004;140:552-8. 10. Johnson TM, Headington JT, Baker SR, Lowe L. Usefulness of the staged excision for lentigo maligna and lentigo maligna melanoma: the square procedure. J Am Acad Dermatol 1997;37:758-64. 11. Anderson KW, Baker SR. Management of early lentigo maligna and lentigo maligna melanoma of the head and neck. Facial Plast Surg Clin North Am 2003;11:93-105. 12. Mahoney MH, Joseph M, Temple CL. The perimeter technique for lentigo maligna: an alternative to Mohs micrographic surgery. J Surg Oncol 2005;91:120-5. 13. Hazan C, Dusza SW, Delgado R, Busam KJ, Halpern AC, Nehal KS. Staged excision for lentigo maligna and lentigo maligna melanoma: a retrospective analysis of 117 cases. J Am Acad Dermatol 2008;58:142-8. Epub 2007 Oct 29. 14. Prieto VG, Argenyi ZB, Barnhill RL, Duray PH, Elenitsas R, From L, et al. Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions? Am J Clin Pathol 2003; 120:203-8. 15. Stonecipher MR, Leshin B, Patrick J, White WL. Management of lentigo maligna and lentigo maligna melanoma with paraffinembedded tangential sections: utility of immunoperoxidase staining and supplemental vertical sections. J Am Acad Dermatol 1993;29:589-94.