doi: 10.1111/1346-8138.12923
Journal of Dermatology 2015; 42: 861–866
ORIGINAL ARTICLE
Effects of non-amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma Yasuhiro NAKAMURA,1 Kuniaki OHARA,2 Akiko KISHI,2 Yukiko TERAMOTO,1 Sayuri SATO,1 Yasuhiro FUJISAWA,3 Manabu FUJIMOTO,3 Fujio OTSUKA,3 Nobukazu HAYASHI,2 Naoya YAMAZAKI,4 Akifumi YAMAMOTO1 1
Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Saitama, 2Department of Dermatology, Toranomon Hospital, 4Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, 3Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
ABSTRACT Subungual melanomas (SUM) are rare, and amputation is often required. Non-amputative wide local excision (WLE) of the nail unit with the periosteum of the distal phalanx, followed by skin graft, has been accepted for in situ or SUM of 0.5 mm or less thickness. However, previous reports have included a limited number of cases, and not all more than 0.5-mm thick SUM exhibit invasion or attachment to the distal phalanx. The aim of the present study was to investigate the local recurrence and prognosis for in situ, minimally invasive and invasive SUM that were treated using WLE. We retrospectively reviewed 50 patients with in situ (n = 48) or minimally invasive SUM (n = 2) (in situ or minimally invasive group) and 12 patients with more than 0.5-mm thick invasive SUM (invasive group) who were treated using WLE. All patients survived the follow-up period (24–207 months), although four patients with in situ SUM experienced local recurrence at the lateral margin and re-excision was required. In the invasive group, no patients experienced local recurrence, although one patient (8.3%) developed nodal metastasis at 86 months and regional lymph node dissection was required. WLE may provide acceptable local control for in situ and intermediate thickness SUM, without compromising the vital prognosis. However, a larger randomized prospective study with long-term follow up is required to evaluate adequately the risks associated with a nonamputative WLE for in situ and invasive SUM.
Key words:
amputation, distal phalanx, local recurrence, subungual melanoma, wide local excision.
INTRODUCTION Subungual melanomas (SUM) are rare, occurring in only 2–3% of all cutaneous melanomas in the Caucasian population,1 and in 8.7–20% of all cutaneous melanomas in the Asian or African populations.2,3 Unfortunately, the excision margin for SUM remains controversial, as preservation of the thumb and toe is critical to maintaining the patient’s quality of life. In addition, amputation at the interphalangeal joint of the thumb results in a 10% loss of function in the affected hand, while amputation at the metacarpophalangeal joint results in a 40% loss of function.4 Although amputation at various bone levels has been recommended, comparisons of the various amputation levels have not demonstrated any advantage for metacarpal amputation compared with metacarpophalangeal, proximal interphalangeal or distal amputation.5 In addition, the prognosis for patients with SUM does not depend on the amputation level, but rather on the time from the initial diagnosis to surgery.6–8
Recently, in situ SUM and minimally invasive SUM (defined as a tumor thickness [TT] of ≤0.5 mm)9 have been treated conservatively using non-amputative wide local excision (WLE), followed by skin graft (SG) coverage.9–13 In addition, other case reports have described two-step surgeries that used artificial dermis for tentative coverage of the defect after WLE, followed by SG coverage after histopathological confirmation of a negative surgical margin.14,15 However, each report only evaluated a small number of patients with in situ or minimally invasive SUM, and therefore the local control rate, relapse-free survival and overall survival for this procedure remains unclear. Interestingly, not all more than 0.5-mm thick SUM invade or attach to the bony surface of the distal phalanx, and nonamputative WLE can be applied to such cases. However, only a few cases of more than 0.5-mm thick SUM that were treated using non-amputative WLE have been reported,12,15,16 and information regarding the local control and prognosis remains unclear. Therefore, we conducted this multicenter retrospective
Correspondence: Yasuhiro Nakamura, M.D., Ph.D., Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. Email: [email protected] Received 2 March 2015; accepted 26 March 2015.
© 2015 Japanese Dermatological Association
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Y. Nakamura et al.
study to evaluate the effect of WLE on the local control and prognosis among patients with in situ or invasive SUM.
METHODS Patients This retrospective study included patients with in situ and invasive SUM who were initially treated using WLE, and were followed up at the Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center (2007– 2011), at the Department of Dermatology, University of Tsukuba (1998–2011), and at the Department of Dermatology, Toranomon Hospital (1996–2011). Over a minimum follow up of 24 months after the initial surgery, patient characteristics, including demographic, clinical, pathological, treatment and outcomes (e.g. local recurrence, nodal/distant metastasis and survival) were extracted from the patients’ medical records. The study was approved by the institutional review board or human research ethics committee at each participating institution. All patients with invasive SUM (without bone involvement according to hand or foot radiography), who had refused amputation and requested conservative management, underwent WLE, after being fully informed regarding the unconventional nature of WLE. In each case, the preoperative diagnosis of SUM was made by inspection, dermoscopy or incisional biopsy. The dermoscopic diagnosis was made by more than two well-experienced dermatologists at each institution. No patients had clinically palpable regional lymph nodes.
Surgery All surgeries were performed under digital block anesthesia, with a tourniquet on the metacarpophalangeal or metatarsophalangeal joint. WLE was performed by excising the entire nail unit (to the bone), with the periosteum of the distal phalanx, using a side margin of 5–10 mm, which included the two lateral nail folds, the proximal nail fold and the distal pulp of the finger or toe. After WLE, the defect was immediately covered using an SG, or tentatively covered using artificial dermis (Pelnac [Smith and Nephew Wound Management, Tokyo, Japan] or Terudermis [Terumo, Tokyo, Japan]). In cases when the artificial dermis was used, an SG was applied to the vascularized artificial dermis several weeks after confirmation of the negative surgical margin. Sentinel lymph node biopsy (SLNB) was offered to patients in whom more than 1-mm thick invasive SUM were suspected (according to visual inspection) or in whom more than 0.75-mm thick invasive SUM were confirmed using incisional biopsy.
Histological evaluation For histological evaluation, the nail unit was sectioned longitudinally at the thickest part of the tumor, and at the parts that were approximately 5 mm medial and lateral to the thickest part. In cases where the thickest part was indistinguishable, the nail unit was sectioned longitudinally at the melanonychia striata with the darkest color or at the midline of the nail. The longitudinally sectioned specimens from the medial and lateral
862
sides were sectioned transversely with a 5-mm width to evaluate the lateral surgical margins around the lateral nail folds. All specimens were treated routinely and stained using hematoxylin–eosin for analysis. In several specimens, immunohistochemical staining for HMB-45 and Melan-A expression was used to highlight melanoma cells at the lateral and deep margins.
RESULTS Patient characteristics In this study, we enrolled 50 patients with in situ (48 patients) or minimally invasive SUM (two patients) (the “in situ or minimally invasive” group) and 12 patients with more than 0.5-mm thick invasive SUM (the “invasive” group) who were treated using WLE; their characteristics are listed in Table 1. In the in situ or minimally invasive group, the thumb was the most commonly affected digit (20 patients, 40%) and 28 patients (56%) exhibited Hutchinson’s sign. Among cases in the invasive group, the thumb was also the most commonly affected digit (five patients, 41.7%). In the invasive group, all six patients who underwent SLNB exhibited negative surgical margins throughout the follow up. Two patients with 0.6-mm thick SUM underwent SLNB at the patient’s request and three patients with more than 0.75-mm thick SUM refused SLNB (Table 2).
Surgical margin Two in situ patients (4%) in the in situ or minimally invasive group and two patients (16.7%) in the invasive SUM group exhibited positive lateral surgical margins, which required additional excision. All four patients achieved margin clearance following the additional excision, and did not develop subsequent local recurrence or metastasis (follow up: 90, 120, 84 and 107 months, respectively). No patients exhibited positive deep surgical margins.
Local recurrence In the in situ or minimally invasive group, four (8%) patients developed local recurrences during the follow up. Three of the four recurrent tumors were in situ lesions and re-excision was followed by additional SG in these cases. The remaining patient developed an invasive lesion (thickness: 0.6 mm) and amputation was performed. All four patients remained free from disease in the follow up after the additional surgery (Table 3). In contrast, no patients in the invasive group developed local recurrences.
Metastasis and prognosis In both groups, all patients survived during the follow-up period (24–207 months). In the in situ or minimally invasive group, no patients developed nodal metastasis or distant metastasis over the follow-up period. In the invasive group, one patient with a 2.5-mm thick SUM and negative sentinel nodes exhibited epitrochlear lymph node metastasis, although no local recurrence was observed in the 86 months after the initial surgery. Epitrochlear and axillary lymph node dissection was also performed, and no recurrence or metastasis was observed during
© 2015 Japanese Dermatological Association
© 2015 Japanese Dermatological Association
– NED, no evidence of disease; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy; WLE, wide local excision.
Negative Done Negative – 67/M 12
First toe
2.6
+
5 mm
mm mm mm mm – – – + 65/M 62/M 79/M 45/F 8 9 10 11
Thumb Second finger Thumb Thumb
1.1 1.4 1.7 2.5
+ + + –
5 10 5 5
mm mm mm mm – – – – 0.7 0.8 0.8 1
+ + + –
5 5 5 5
67, NED
31, NED 40, NED 24, NED 93
– – – Interval node (upper arm) metastasis (86 months) – – – – – – Negative Negative Negative Not done Done Done Done
NED NED NED NED – – – – – – – – – – Negative – Not done Not done Done Not done
– – – – – – – Negative Negative Not done Done Done
Negative Negative Positive (lateral margin) Negative Negative Negative Positive (lateral margin) Negative Negative Negative Negative – – –
5 mm 5 mm 5 mm
SLNB
+ + +
Second toe Third finger First toe Thumb
No absolute guidelines exist to guide the management of SUM, although many dermatological surgeons perform conservative surgery to maximize the length of the affected digits. Therefore, the currently recommended treatment for in situ or minimally invasive SUM is considered WLE with a narrow surgical margin, followed by SG. Although this strategy is becoming more common, there is limited evidence available regarding this procedure, and the recommendation for this strategy is based on a number case reports and series (0.5-mm thick tumors) in a larger patient population. Regarding in situ lesions, Lazar et al.11 reported a series of nine patients with in situ SUM who were treated using WLE and full-thickness SG, and noted that no recurrence was observed after a mean follow-up period of 50.4 months. In contrast, High et al.10 reported that one of four patients developed local recurrence after 5 months and that this patient eventually required amputation. Similarly, Cohen et al.12 performed WLE for six patients with in situ SUM, although three patients exhibited positive margins after WLE and underwent immediate amputation. Among the three remaining patients, one patient developed local recurrence 18 months after WLE and required amputation. These cases are the only published cases in which WLE for in situ SUM led to a negative outcome. In contrast, only two of our 48 patients exhibited positive lateral surgical margins, and after they underwent additional nonamputative excision, no subsequent local recurrence or metastasis was observed. In addition, four patients developed local recurrences at the lateral margin and these patients survived without evidence of local recurrence after re-excision.
864
Unfortunately, there are much fewer reports regarding WLE for minimally invasive SUM, with only five cases reported in the published work. These were reported by Cohen et al.12 (one patient, TT: 0.2 mm), Sureda et al.9 (two patients, TT: 0.15 and 0.2 mm) and Debarbieux et al.19 (two patients, TT: 0.12 and 0.35 mm) (Table 4). However, among these cases, no local recurrence was reported during the short follow-up periods (0.5–29 months). In contrast, WLE for invasive SUM that are more than 0.5-mm thick is not generally accepted, and amputation is more commonly performed. This practice is based on the unique anatomy of the nail unit, given the minimal soft tissue between the nail unit and the bony surface of the distal phalanx. Interestingly, Kim et al.21 measured the matrix-tobone distances in cadavers and reported that the average distance for all digits was 0.90 mm. Therefore, owing to the short matrix-to-bone distance, WLE is considered insufficient to eradicate invasive SUM with a safe deep surgical margin. However, not all SUM invade or attach to the distal phalanx. In our previous study of the shortest tumor-to-bone distance in amputated specimens of invasive SUM, no bone attachment or invasion occurred in cases of less than 4-mm thick SUM, and the shortest tumor-to-bone distance was more than 0.9 mm in
© 2015 Japanese Dermatological Association
Wide local excision for subungual melanoma
Table 5. Details of more than 0.5-mm thick subungual melanoma treated by wide local excision Year
Author
Age/sex
Site
Tumor thickness
Follow up (months)
Recurrence
2007
Rayatt et al.16
49/N.S. 73/N.S. 50/N.S. 51/F
Thumb Thumb Thumb Thumb
0.9 mm 1.5 mm 3 mm 4 mm
77 118 85 88
2008 2010
Cohen et al.12 Smock et al.15
N.S. 44/M
N.S. Thumb
0.6 mm 1.2 mm
24 24
– – – Local recurrence (36 months) – –
N.S., not stated.
all specimens.22 These tumor-to-bone distances were similar to the matrix-to-bone distances reported by Kim et al.,21 despite the dermal invasion of the tumors in their cases. Therefore, we suggest that the patients with less than 4-mm thick invasive SUM may be candidates for non-amputative surgery.22 Interestingly, there are only a few reports of patients with a more than 0.5-mm thick SUM who were treated using WLE (Table 5). Rayatt et al.16 have reported four cases of invasive SUM (TT: 0.9, 1.5, 3 and 4 mm) treated using WLE, including one patient with a 4-mm thick SUM who experienced local recurrence at 36 months. Although this patient was treated using amputation thereafter, and remained free from disease, she later died of an unrelated cause at 88 months. The other patients did not experience local recurrence or metastasis, and two additional patients, reported by Cohen et al.12 and Smock et al.,15 also exhibited no evidence of disease at their 24-month follow ups. In another study, Moehrle et al.23 reported 31 cases of invasive SUM, with a median thickness of 1.68 mm. Most of these cases were treated using partial amputation of the distal phalanx, and only three cases underwent WLE, although more detailed information (e.g. TT, follow-up period and prognosis) was not reported. Our present study included 12 patients with more than 0.5-mm thick SUM who were treated using WLE, and the local control rate was 100%. Although the present study focused on the deep surgical margin, the lateral margin is another crucial factor for the successful application of WLE. Although no definitive evidence exists to indicate that Mohs micrographic surgery is beneficial in cutaneous melanoma, several authors have proposed this technique for the treatment of SUM.10,24,25 However, it is difficult to establish the histopathological criteria for complete excision in the acral lentiginous melanomas (which include SUM), as the melanoma cells are often scattered at the border of the lesion. Therefore, immunohistochemical staining (e.g. for HMB-45 and MART-1 expression) are often needed for accurate margin assessment, as well as the routine hematoxylin– eosin staining. In addition, using WLE to treat extensive diseases that produce an excessive horizontal skin defect, such as circumferential defect of the digital skin, can lead to SG failure and/or joint contracture. In these cases, amputation should still be considered, even if it appears possible to obtain a sufficiently deep margin.
© 2015 Japanese Dermatological Association
In conclusion, non-amputative WLE for in situ and intermediate-thickness SUM may provide an acceptable local control rate, without compromising the vital prognosis, and the revision surgery for local recurrence at the lateral margin would not compromise the prognosis of in situ disease. However, the present study has two limitations. First, the number of patients that we evaluated was relatively small, especially in the invasive SUM groups. In addition, we were unable to provide a rigorous comparative group of invasive SUM treated by amputation. A larger randomized prospective study with longterm follow up is needed to evaluate adequately the risks associated with a non-amputative WLE for in situ and invasive SUM.
ACKNOWLEDGMENT:
This work was partly supported by the National Cancer Center Research and Development Fund (26-A-4).
CONFLICT OF INTEREST:
None.
REFERENCES 1 Blessing K, Kernohan NM, Park KG. Subungual malignant melanoma: clinicopathological features of 100 cases. Histopathology 1991; 19: 425–429. 2 Takematsu H, Obata M, Tomita Y, Kato T, Takahashi M, Abe R. Subungual melanoma. A clinicopathologic study of 16 Japanese cases. Cancer 1985; 55 (11): 2725–2731. 3 Ishihara K, Saida T, Otsuka F, Yamazaki N. Statistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update. Int J Clin Oncol 2008; 13 (1): 33–41. 4 Chow WT, Bhat W, Magdub S, Orlando A. In situ subungual melanoma: digit salvaging clearance. J Plast Reconstr Aesthet Surg 2013; 66 (2): 274–276. 5 Haneke E. Ungual melanoma – controversies in diagnosis and treatment. Dermatol Ther 2012; 25: 510–524. 6 O’Leary JA, Berend KR, Johnson JL, Levin LS, Seigler HF. Subungual melanoma. A review of 93 cases with identification of prognostic variables. Clin Orthop Relat Res 2000; 378: 206–212. 7 Heaton KM, el-Naggar A, Ensign LG, Ross MI, Balch CM. Surgical management and prognostic factors in patients with subungual melanoma. Ann Surg 1994; 219: 197–204. 8 Park KG, Blessing K, Kernohan NM. Surgical aspects of subungual malignant melanomas. The Scottish Melanoma Group. Ann Surg 1992; 216 (6): 692–695. 9 Sureda N, Phan A, Poulalhon N, Balme B, Dalle S, Thomas L. Conservative surgical management of subungual (matrix derived) melanoma: report of seven cases and literature review. Br J Dermatol 2011; 165 (4): 852–858.
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10 High WA, Quirey RA, Guillen DR, Munoz G, Taylor RS. Presentation, histopathologic findings, and clinical outcomes in 7 cases of melanoma in situ of the nail unit. Arch Dermatol 2004; 140 (9): 1102– 1106. 11 Lazar A, Abimelec P, Dumontier C. Full thickness skin graft for nail unit reconstruction. J Hand Surg Br 2005; 30: 194–198. 12 Cohen T, Busam KJ, Patel A, Brady MS. Subungual melanoma: management considerations. Am J Surg 2008; 195 (2): 244–248. 13 Imakado S, Sato H, Hamada K. Two cases of subungual melanoma in situ. J Dermatol 2008; 35 (11): 754–758. 14 Hayashi K, Uhara H, Koga H, Okuyama R, Saida T. Surgical treatment of nail apparatus melanoma in situ: the use of Artificial dermis in reconstruction. Dermatol Surg 2012; 38 (4): 692–694. 15 Smock ED, Barabas AG, Geh JL. Reconstruction of a thumb defect with Integra following wide local excision of a subungual melanoma. J Plast Reconstr Aesthet Surg 2010; 63 (1): e36–e37. 16 Rayatt SS, Dancey AL, Davison PM. Thumb subungual melanoma: is amputation necessary? J Plast Reconstr Aesthet Surg 2007; 60 (6): 635–638. 17 Clarkson JH, McAllister RM, Cliff SH, Powell B. Subungual melanoma in situ: two independent streaks in one nail bed. Br J Plast Surg 2002; 55: 165–167. 18 Duarte AF, Correia O, Barros AM, Azevedo R, Haneke E. Nail matrix melanoma in situ: conservative surgical management. Dermatology 2010; 220: 173–175.
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19 Debarbieux S, Hospod V, Depaepe L, Balme B, Poulalhon N, Thomas L. Perioperative confocal microscopy of the nail matrix in the management of in situ or minimally invasive subungual melanomas. Br J Dermatol 2012; 167 (4): 828–836. 20 Haddock NT, Wilson SC, Shapiro RL, Choi M. Wide local en bloc excision of subungual melanoma in situ, maximizing functional and aesthetic outcome: a retrospective review. Ann Plast Surg 2014; 73: 640–644. 21 Kim JY, Jung HJ, Lee WJ et al. Is the distance enough to eradicate in situ or early invasive subungual melanoma by wide local excision? from the point of view of matrix-to-bone distance for safe inferior surgical margin in Koreans. Dermatology 2011; 223: 122–123. 22 Nakamura Y, Fujisawa Y, Teramoto Y et al. Tumor-to-bone distance of invasive subungual melanoma: an analysis of 30 cases. J Dermatol 2014; 41 (10): 872–877. 23 Moehrle M, Metzger S, Schippert W, Garbe C, Rassner G, Breuninger H. “Functional” surgery in subungual melanoma. Dermatol Surg 2003; 29: 366–374. 24 Banfield CC, Dawber RP, Walker NP, Stables GI, Zeina B, Schomberg K. Mohs micrographic surgery for the treatment of in situ nail apparatus melanoma: a case report. J Am Acad Dermatol 1999; 40 (1): 98–99. 25 Brodland DG. The treatment of nail apparatus melanoma with Mohs micrographic surgery. Dermatol Surg 2001; 27: 269–273.
© 2015 Japanese Dermatological Association
Journal of Dermatology 2015; 42: 861–866
ORIGINAL ARTICLE
Effects of non-amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma Yasuhiro NAKAMURA,1 Kuniaki OHARA,2 Akiko KISHI,2 Yukiko TERAMOTO,1 Sayuri SATO,1 Yasuhiro FUJISAWA,3 Manabu FUJIMOTO,3 Fujio OTSUKA,3 Nobukazu HAYASHI,2 Naoya YAMAZAKI,4 Akifumi YAMAMOTO1 1
Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Saitama, 2Department of Dermatology, Toranomon Hospital, 4Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, 3Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
ABSTRACT Subungual melanomas (SUM) are rare, and amputation is often required. Non-amputative wide local excision (WLE) of the nail unit with the periosteum of the distal phalanx, followed by skin graft, has been accepted for in situ or SUM of 0.5 mm or less thickness. However, previous reports have included a limited number of cases, and not all more than 0.5-mm thick SUM exhibit invasion or attachment to the distal phalanx. The aim of the present study was to investigate the local recurrence and prognosis for in situ, minimally invasive and invasive SUM that were treated using WLE. We retrospectively reviewed 50 patients with in situ (n = 48) or minimally invasive SUM (n = 2) (in situ or minimally invasive group) and 12 patients with more than 0.5-mm thick invasive SUM (invasive group) who were treated using WLE. All patients survived the follow-up period (24–207 months), although four patients with in situ SUM experienced local recurrence at the lateral margin and re-excision was required. In the invasive group, no patients experienced local recurrence, although one patient (8.3%) developed nodal metastasis at 86 months and regional lymph node dissection was required. WLE may provide acceptable local control for in situ and intermediate thickness SUM, without compromising the vital prognosis. However, a larger randomized prospective study with long-term follow up is required to evaluate adequately the risks associated with a nonamputative WLE for in situ and invasive SUM.
Key words:
amputation, distal phalanx, local recurrence, subungual melanoma, wide local excision.
INTRODUCTION Subungual melanomas (SUM) are rare, occurring in only 2–3% of all cutaneous melanomas in the Caucasian population,1 and in 8.7–20% of all cutaneous melanomas in the Asian or African populations.2,3 Unfortunately, the excision margin for SUM remains controversial, as preservation of the thumb and toe is critical to maintaining the patient’s quality of life. In addition, amputation at the interphalangeal joint of the thumb results in a 10% loss of function in the affected hand, while amputation at the metacarpophalangeal joint results in a 40% loss of function.4 Although amputation at various bone levels has been recommended, comparisons of the various amputation levels have not demonstrated any advantage for metacarpal amputation compared with metacarpophalangeal, proximal interphalangeal or distal amputation.5 In addition, the prognosis for patients with SUM does not depend on the amputation level, but rather on the time from the initial diagnosis to surgery.6–8
Recently, in situ SUM and minimally invasive SUM (defined as a tumor thickness [TT] of ≤0.5 mm)9 have been treated conservatively using non-amputative wide local excision (WLE), followed by skin graft (SG) coverage.9–13 In addition, other case reports have described two-step surgeries that used artificial dermis for tentative coverage of the defect after WLE, followed by SG coverage after histopathological confirmation of a negative surgical margin.14,15 However, each report only evaluated a small number of patients with in situ or minimally invasive SUM, and therefore the local control rate, relapse-free survival and overall survival for this procedure remains unclear. Interestingly, not all more than 0.5-mm thick SUM invade or attach to the bony surface of the distal phalanx, and nonamputative WLE can be applied to such cases. However, only a few cases of more than 0.5-mm thick SUM that were treated using non-amputative WLE have been reported,12,15,16 and information regarding the local control and prognosis remains unclear. Therefore, we conducted this multicenter retrospective
Correspondence: Yasuhiro Nakamura, M.D., Ph.D., Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. Email: [email protected] Received 2 March 2015; accepted 26 March 2015.
© 2015 Japanese Dermatological Association
861
Y. Nakamura et al.
study to evaluate the effect of WLE on the local control and prognosis among patients with in situ or invasive SUM.
METHODS Patients This retrospective study included patients with in situ and invasive SUM who were initially treated using WLE, and were followed up at the Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center (2007– 2011), at the Department of Dermatology, University of Tsukuba (1998–2011), and at the Department of Dermatology, Toranomon Hospital (1996–2011). Over a minimum follow up of 24 months after the initial surgery, patient characteristics, including demographic, clinical, pathological, treatment and outcomes (e.g. local recurrence, nodal/distant metastasis and survival) were extracted from the patients’ medical records. The study was approved by the institutional review board or human research ethics committee at each participating institution. All patients with invasive SUM (without bone involvement according to hand or foot radiography), who had refused amputation and requested conservative management, underwent WLE, after being fully informed regarding the unconventional nature of WLE. In each case, the preoperative diagnosis of SUM was made by inspection, dermoscopy or incisional biopsy. The dermoscopic diagnosis was made by more than two well-experienced dermatologists at each institution. No patients had clinically palpable regional lymph nodes.
Surgery All surgeries were performed under digital block anesthesia, with a tourniquet on the metacarpophalangeal or metatarsophalangeal joint. WLE was performed by excising the entire nail unit (to the bone), with the periosteum of the distal phalanx, using a side margin of 5–10 mm, which included the two lateral nail folds, the proximal nail fold and the distal pulp of the finger or toe. After WLE, the defect was immediately covered using an SG, or tentatively covered using artificial dermis (Pelnac [Smith and Nephew Wound Management, Tokyo, Japan] or Terudermis [Terumo, Tokyo, Japan]). In cases when the artificial dermis was used, an SG was applied to the vascularized artificial dermis several weeks after confirmation of the negative surgical margin. Sentinel lymph node biopsy (SLNB) was offered to patients in whom more than 1-mm thick invasive SUM were suspected (according to visual inspection) or in whom more than 0.75-mm thick invasive SUM were confirmed using incisional biopsy.
Histological evaluation For histological evaluation, the nail unit was sectioned longitudinally at the thickest part of the tumor, and at the parts that were approximately 5 mm medial and lateral to the thickest part. In cases where the thickest part was indistinguishable, the nail unit was sectioned longitudinally at the melanonychia striata with the darkest color or at the midline of the nail. The longitudinally sectioned specimens from the medial and lateral
862
sides were sectioned transversely with a 5-mm width to evaluate the lateral surgical margins around the lateral nail folds. All specimens were treated routinely and stained using hematoxylin–eosin for analysis. In several specimens, immunohistochemical staining for HMB-45 and Melan-A expression was used to highlight melanoma cells at the lateral and deep margins.
RESULTS Patient characteristics In this study, we enrolled 50 patients with in situ (48 patients) or minimally invasive SUM (two patients) (the “in situ or minimally invasive” group) and 12 patients with more than 0.5-mm thick invasive SUM (the “invasive” group) who were treated using WLE; their characteristics are listed in Table 1. In the in situ or minimally invasive group, the thumb was the most commonly affected digit (20 patients, 40%) and 28 patients (56%) exhibited Hutchinson’s sign. Among cases in the invasive group, the thumb was also the most commonly affected digit (five patients, 41.7%). In the invasive group, all six patients who underwent SLNB exhibited negative surgical margins throughout the follow up. Two patients with 0.6-mm thick SUM underwent SLNB at the patient’s request and three patients with more than 0.75-mm thick SUM refused SLNB (Table 2).
Surgical margin Two in situ patients (4%) in the in situ or minimally invasive group and two patients (16.7%) in the invasive SUM group exhibited positive lateral surgical margins, which required additional excision. All four patients achieved margin clearance following the additional excision, and did not develop subsequent local recurrence or metastasis (follow up: 90, 120, 84 and 107 months, respectively). No patients exhibited positive deep surgical margins.
Local recurrence In the in situ or minimally invasive group, four (8%) patients developed local recurrences during the follow up. Three of the four recurrent tumors were in situ lesions and re-excision was followed by additional SG in these cases. The remaining patient developed an invasive lesion (thickness: 0.6 mm) and amputation was performed. All four patients remained free from disease in the follow up after the additional surgery (Table 3). In contrast, no patients in the invasive group developed local recurrences.
Metastasis and prognosis In both groups, all patients survived during the follow-up period (24–207 months). In the in situ or minimally invasive group, no patients developed nodal metastasis or distant metastasis over the follow-up period. In the invasive group, one patient with a 2.5-mm thick SUM and negative sentinel nodes exhibited epitrochlear lymph node metastasis, although no local recurrence was observed in the 86 months after the initial surgery. Epitrochlear and axillary lymph node dissection was also performed, and no recurrence or metastasis was observed during
© 2015 Japanese Dermatological Association
© 2015 Japanese Dermatological Association
– NED, no evidence of disease; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy; WLE, wide local excision.
Negative Done Negative – 67/M 12
First toe
2.6
+
5 mm
mm mm mm mm – – – + 65/M 62/M 79/M 45/F 8 9 10 11
Thumb Second finger Thumb Thumb
1.1 1.4 1.7 2.5
+ + + –
5 10 5 5
mm mm mm mm – – – – 0.7 0.8 0.8 1
+ + + –
5 5 5 5
67, NED
31, NED 40, NED 24, NED 93
– – – Interval node (upper arm) metastasis (86 months) – – – – – – Negative Negative Negative Not done Done Done Done
NED NED NED NED – – – – – – – – – – Negative – Not done Not done Done Not done
– – – – – – – Negative Negative Not done Done Done
Negative Negative Positive (lateral margin) Negative Negative Negative Positive (lateral margin) Negative Negative Negative Negative – – –
5 mm 5 mm 5 mm
SLNB
+ + +
Second toe Third finger First toe Thumb
No absolute guidelines exist to guide the management of SUM, although many dermatological surgeons perform conservative surgery to maximize the length of the affected digits. Therefore, the currently recommended treatment for in situ or minimally invasive SUM is considered WLE with a narrow surgical margin, followed by SG. Although this strategy is becoming more common, there is limited evidence available regarding this procedure, and the recommendation for this strategy is based on a number case reports and series (0.5-mm thick tumors) in a larger patient population. Regarding in situ lesions, Lazar et al.11 reported a series of nine patients with in situ SUM who were treated using WLE and full-thickness SG, and noted that no recurrence was observed after a mean follow-up period of 50.4 months. In contrast, High et al.10 reported that one of four patients developed local recurrence after 5 months and that this patient eventually required amputation. Similarly, Cohen et al.12 performed WLE for six patients with in situ SUM, although three patients exhibited positive margins after WLE and underwent immediate amputation. Among the three remaining patients, one patient developed local recurrence 18 months after WLE and required amputation. These cases are the only published cases in which WLE for in situ SUM led to a negative outcome. In contrast, only two of our 48 patients exhibited positive lateral surgical margins, and after they underwent additional nonamputative excision, no subsequent local recurrence or metastasis was observed. In addition, four patients developed local recurrences at the lateral margin and these patients survived without evidence of local recurrence after re-excision.
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Unfortunately, there are much fewer reports regarding WLE for minimally invasive SUM, with only five cases reported in the published work. These were reported by Cohen et al.12 (one patient, TT: 0.2 mm), Sureda et al.9 (two patients, TT: 0.15 and 0.2 mm) and Debarbieux et al.19 (two patients, TT: 0.12 and 0.35 mm) (Table 4). However, among these cases, no local recurrence was reported during the short follow-up periods (0.5–29 months). In contrast, WLE for invasive SUM that are more than 0.5-mm thick is not generally accepted, and amputation is more commonly performed. This practice is based on the unique anatomy of the nail unit, given the minimal soft tissue between the nail unit and the bony surface of the distal phalanx. Interestingly, Kim et al.21 measured the matrix-tobone distances in cadavers and reported that the average distance for all digits was 0.90 mm. Therefore, owing to the short matrix-to-bone distance, WLE is considered insufficient to eradicate invasive SUM with a safe deep surgical margin. However, not all SUM invade or attach to the distal phalanx. In our previous study of the shortest tumor-to-bone distance in amputated specimens of invasive SUM, no bone attachment or invasion occurred in cases of less than 4-mm thick SUM, and the shortest tumor-to-bone distance was more than 0.9 mm in
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Wide local excision for subungual melanoma
Table 5. Details of more than 0.5-mm thick subungual melanoma treated by wide local excision Year
Author
Age/sex
Site
Tumor thickness
Follow up (months)
Recurrence
2007
Rayatt et al.16
49/N.S. 73/N.S. 50/N.S. 51/F
Thumb Thumb Thumb Thumb
0.9 mm 1.5 mm 3 mm 4 mm
77 118 85 88
2008 2010
Cohen et al.12 Smock et al.15
N.S. 44/M
N.S. Thumb
0.6 mm 1.2 mm
24 24
– – – Local recurrence (36 months) – –
N.S., not stated.
all specimens.22 These tumor-to-bone distances were similar to the matrix-to-bone distances reported by Kim et al.,21 despite the dermal invasion of the tumors in their cases. Therefore, we suggest that the patients with less than 4-mm thick invasive SUM may be candidates for non-amputative surgery.22 Interestingly, there are only a few reports of patients with a more than 0.5-mm thick SUM who were treated using WLE (Table 5). Rayatt et al.16 have reported four cases of invasive SUM (TT: 0.9, 1.5, 3 and 4 mm) treated using WLE, including one patient with a 4-mm thick SUM who experienced local recurrence at 36 months. Although this patient was treated using amputation thereafter, and remained free from disease, she later died of an unrelated cause at 88 months. The other patients did not experience local recurrence or metastasis, and two additional patients, reported by Cohen et al.12 and Smock et al.,15 also exhibited no evidence of disease at their 24-month follow ups. In another study, Moehrle et al.23 reported 31 cases of invasive SUM, with a median thickness of 1.68 mm. Most of these cases were treated using partial amputation of the distal phalanx, and only three cases underwent WLE, although more detailed information (e.g. TT, follow-up period and prognosis) was not reported. Our present study included 12 patients with more than 0.5-mm thick SUM who were treated using WLE, and the local control rate was 100%. Although the present study focused on the deep surgical margin, the lateral margin is another crucial factor for the successful application of WLE. Although no definitive evidence exists to indicate that Mohs micrographic surgery is beneficial in cutaneous melanoma, several authors have proposed this technique for the treatment of SUM.10,24,25 However, it is difficult to establish the histopathological criteria for complete excision in the acral lentiginous melanomas (which include SUM), as the melanoma cells are often scattered at the border of the lesion. Therefore, immunohistochemical staining (e.g. for HMB-45 and MART-1 expression) are often needed for accurate margin assessment, as well as the routine hematoxylin– eosin staining. In addition, using WLE to treat extensive diseases that produce an excessive horizontal skin defect, such as circumferential defect of the digital skin, can lead to SG failure and/or joint contracture. In these cases, amputation should still be considered, even if it appears possible to obtain a sufficiently deep margin.
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In conclusion, non-amputative WLE for in situ and intermediate-thickness SUM may provide an acceptable local control rate, without compromising the vital prognosis, and the revision surgery for local recurrence at the lateral margin would not compromise the prognosis of in situ disease. However, the present study has two limitations. First, the number of patients that we evaluated was relatively small, especially in the invasive SUM groups. In addition, we were unable to provide a rigorous comparative group of invasive SUM treated by amputation. A larger randomized prospective study with longterm follow up is needed to evaluate adequately the risks associated with a non-amputative WLE for in situ and invasive SUM.
ACKNOWLEDGMENT:
This work was partly supported by the National Cancer Center Research and Development Fund (26-A-4).
CONFLICT OF INTEREST:
None.
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