Sentinel Lymph Node Biopsy for the T1 (Thin) Melanoma: Is It Necessary?

Sentinel Lymph Node Biopsy for the T1 (Thin) Melanoma: Is It Necessary? Maurice Y. Nahabedian, MD Anthony P. Tufaro, MD Paul N. Manson, MD The use of sentinel lymph node biopsy for the T1 melanoma is controversial. Recent reports have demonstrated that certain T1 melanomas are at increased risk for early regional metastases and late recurrence when compared with all thin melanomas. The purpose of this study was to review the authors experience with wide excision and sentinel lymph node biopsy for certain patients with T1 melanoma. A retrospective analysis of 34 patients with T1 melanoma was completed over a 3-year period. Indications for sentinel lymph node biopsy included a Breslow thickness of less than or equal to 1 mm, a Clark level of III or IV, tumor ulceration, or tumor regression. Twenty-four patients met these criteria (13 men and 11 women). Mean age was 47.6 years (range, 23 88 years). Mean tumor thickness for all patients was 0.69 mm (range, 0.3 1.0 mm), 0.61 mm for the Clark level III patients (N 15), and 0.72 mm for the Clark level IV patients (N 9). Tumor ulceration was present in 1 patient and histological regression was present in 2 patients. Regional lymph node metastases were confirmed histologically in 2 of 24 patients (8.3%) in whom the thickness of the melanoma was 0.9 mm and 1 mm. Both patients have died of metastatic melanoma. No recurrence has been demonstrated in the remaining 22 patients at the 2 to 5-year follow-up. Current indications for sentinel lymph node biopsy for patients with T1 melanoma include tumors associated with Clark level IV or V invasion, ulceration, regression, a positive deep margin on initial biopsy, or previous melanoma. Acral lentiginous melanoma associated with at least a Clark level III invasion warrant sentinel lymph node biopsy. Superficial spreading or nodular melanoma larger than 0.9 mm should include sentinel lymph node biopsy regardless of other associated histological factors. Nahabedian MY, Tufaro AP, Manson PN. Sentinel lymph node biopsy for the T1 (thin) melanoma: is it necessary? Ann Plast Surg. 2003;50:601 606. From the Division of Plastic and Reconstructive Surgery, Johns Hopkins Medical Institutions, Baltimore, MD. Received Oct 5, 2002. Accepted for publication Oct 5, 2002. Address correspondence and reprint requests to Dr Nahabedian, Johns Hopkins Hospital, 601 North Caroline Street, 8152C, Baltimore, MD 21287; e-mail: mnahabed@jhmi.edu Current indications for sentinel lymph node biopsy (SLNB) in patients with invasive melanoma are based on the thickness of the lesion. 1 5 These lesions include the T2 melanoma (Breslow thickness, 1.01 2 mm) and the T3 melanoma (2.01 4 mm). However, its use for T1 melanoma ( 1 mm) is controversial. 6 10 This is primarily because the risk of regional metastases for the T1 melanoma is low, the therapeutic and survival advantage is small, and the potential morbidity of SLNB may outweigh the benefits. 11 13 However, there are several recent studies that have reported regional lymph node involvement at the time of primary excision as well as later recurrence in the patient with melanoma less than 1 mm in thickness. 11,14 17 Despite this, a general consensus regarding the necessity of SLNB in patients with T1 melanoma is lacking. Thus, it was the intent of this study to evaluate a series of patients with stage 1 and T1 melanoma to determine whether SLNB is necessary or beneficial. Methods A retrospective analysis of 34 patients with stage 1 and T1 melanoma was completed. The study interval was from June 1997 to November 2000. Indications for SLNB included Breslow thickness less than or equal to 1 mm, Clark level III or IV invasion, ulceration, and regression. SLNB was not performed in patients with melanoma in situ or Clark level II invasion. The criteria for SLNB was obtained in 24 patients (71%) and was not obtained in 10 patients (29%). Patients who met the criteria included 13 men and 11 women. Mean patient age was 47.6 years (range, 23 88 years). Mean tumor thickness was 0.69 mm (range, 0.3 1.0 mm). Melanomas were characterized based on clinical and histological features that included location, thickness (Breslow), level of invasion (Clark), ulceration, and regression. Tumor location included the trunk (N 8), ear (N 6), lower extremity (N 5), upper extremity (N 3), and scalp (N 2). A Clark level III invasion was Copyright 2003 by Lippincott Williams & Wilkins, Inc. 601

Annals of Plastic Surgery Volume 50 / Number 6 / June 2003 Location and Histological Factors Associated With the Melanoma Patient No. Age, yr Gender Location Breslow Thickness, mm Clark Level Regression Ulceration SLNB 1 46 M Ear 0.6 4 No No ( ) 2 71 M Ear 0.9 3 No No ( ) 3 66 F Finger 0.9 3 No No ( ) 4 32 F Lower leg 0.5 3 No No ( ) 5 26 F Lower leg 0.8 3 No No ( ) 6 66 F Shoulder 0.65 3 Yes No ( ) 7 35 M Chest 0.42 3 No No ( ) 8 35 F Leg 0.9 3 No No ( ) 9 31 F Abdomen 0.32 3 No No ( ) 10 45 F Back 0.95 4 No Yes ( ) 11 54 F Leg 0.44 3 No No ( ) 12 37 M Back 0.51 4 No No ( ) 13 23 F Knee 0.5 3 No No ( ) 14 34 M Back 0.5 3 No No ( ) 15 46 M Arm 1.0 3 No No ( ) 16 52 M Scalp 0.58 3 No No ( ) 17 67 M Ear 1.0 3 Yes No ( ) 18 34 F Back 0.4 4 No No ( ) 19 72 M Back 0.72 4 No No ( ) 20 68 M Scalp 0.3 4 No No ( ) 21 46 M Ear 0.8 3 No No ( ) 22 25 F Back 0.9 4 No No ( ) 23 31 M Ear 0.95 4 No No ( ) 24 61 M Ear 0.9 4 No No ( ) SLNB sentinel lymph node biopsy; M male; F female; ( ) negative; ( ) positive. present in 15 cases with a mean thickness of 0.61 mm (range, 1.0 0.32 mm). A Clark level IV invasion was present in 9 cases with a mean thickness of 0.72 mm (range, 0.95 0.30 mm). Histological evidence of tumor regression was demonstrated in 2 patients and ulceration was present in 1 patient. Localization of the sentinel lymph node used a radiocolloid tracer that involved the intradermal injection of technetium-99 metastable sulfur colloid. This technique has been demonstrated to be effective and accurate. 18,19 The injection sites varied based on the diameter of the lesion, but in general were made along the periphery of the tumor in a clockwise fashion at the 3, 6, 9, and 12-o clock positions. Immediately after injection, imaging was performed and continued until the sentinel lymph node was visualized (15 20 minutes). After visualization, the patient was transported to the operating room for SLNB. The C-Trak gamma probe (Prime Source Surgical, Birmingham, AL) was used to detect radioactivity at the delineated point within the lymph node basin. In general, the sentinel lymph node was excised 2 to 5 hours after injection of technetium- 99. This time interval is within the 6-hour halflife of technitium-99. The sentinel lymph node (or nodes) was excised. Complete removal of the sentinel node was confirmed by documenting no residual radioactivity activity within the lymph node basin. A closed suction drain was placed within the lymph node basin in all patients. The blue dye technique was not used in this series of patients. Results The radioactive lymph node was identified in all patients using the gamma probe. The data are presented in the Table. Regional lymph node metastases were demonstrated in 2 of 24 patients (8.3%). In these 2 patients, characteristics of the melanoma included location on the upper extremity, Clark level III invasion, and a Breslow thickness of 1 mm in the first patient; and Clark level III invasion and a Breslow thickness of 0.9 mm in the second patient. Neither patient demonstrated ulceration or regression on initial histological evaluation. Both patients with lymph node metastases died within 2 years of the initial diagnosis from systemic melanoma. No recur- 602

Nahabedian et al: Sentinel Lymph Node Biopsy for the T1 Melanoma Fig 1. The melanoma extends from the subungual region to the tip of the finger. rence of melanoma has been observed in the 22 patients without nodal involvement at the 2 to 5-year follow-up. No patient developed infection, lymphedema, or seroma after the SLNB. Patient 1 A 66-year-old woman presented with a pigmented lesion on the tip of her right fourth finger. The lesion had been present for 1 year. The biopsy specimen demonstrated a 1.0-mm Clark level III invasive melanoma. Physical examination demonstrated an area of irregular pigment at the distal aspect of the nail bed (Fig 1). No additional skin lesions or axillary adenopathy was appreciated. Operative management included amputation at the distal interphalangeal joint and right axillary SLNB. Pathology demonstrated that the thickness of the melanoma was 1 mm and metastatic melanoma was a single lymph node (Fig 2). Computed tomography of the head, Fig 2. The sentinel lymph node with a single metastatic focus is shown. chest, abdomen, and pelvis was negative. Subsequent operative management included a formal axillary lymph node dissection that demon- 603

Annals of Plastic Surgery Volume 50 / Number 6 / June 2003 strated no melanoma in 11 of 11 nodes. Adjuvant therapy was initiated; however, systemic metastases were documented and the patient died 2 years after the initial diagnosis. Patient 2 A 45-year-old man presented with a pigmented lesion on the right upper arm within a tattoo. The biopsy specimen demonstrated a 0.9-mm Clark level III invasive melanoma. Physical examination was notable for a well-healed incision, no axillary adenopathy, and no additional skin lesions. Operative management included wide excision and sentinel lymph node biopsy. Pathology demonstrated a no residual melanoma at the biopsy site and metastatic melanoma in the single sentinel lymph node. Computed tomography of the head, chest, abdomen, and pelvis was negative. Subsequent operative management included formal axillary lymph node dissection that demonstrated no additional melanoma in 21 of 21 lymph nodes. Adjuvant therapy was initiated; however, systemic metastases were documented and the patient died 18 months after the initial diagnosis. Discussion Patients with stage 1 melanoma are characterized as early stage with a low risk for metastases and mortality. Survival rates for these patients generally ranges from 91 to 95%. 12 These stage 1 melanomas are classified further as 1A and 1B. The stage 1A melanoma is a T1 lesion that is characterized by an absence of ulceration and a Clark level II or III invasion. The stage 1B melanoma is a T1 or T2 lesion that is characterized by either the presence of ulceration or a Clark level IV or V invasion. Traditional management for these patients with stage 1 and T1 melanoma includes wide excision without SLNB. However, there is an increasing body of evidence that supports SLNB for select patients with T1 melanomas despite the fact that a survival advantage may not be evident. The need for SLNB in the patient with T1 melanoma has been controversial. 8,17,20 Arguments against SLNB include a low risk for regional metastases, minimal therapeutic and survival advantage, and potential morbidity such as lymphedema. 10,13,21 Arguments for SLNB include identification of patients who are at an increased risk of early metastases and local recurrence. It is speculated that early identification may confer a therapeutic and survival advantage. 6 8,16,22,23 Previous studies that have shown that certain thin melanomas can be lethal may justify SLNB. 24,25 In addition, there may be psychosocial benefits to these patients by performing an SLNB as a means of alleviating fear resulting from factors such as a previous personal history or family history of melanoma. 26 Thus, it was the primary goal of this study to determine whether SLNB for the T1 melanoma is necessary and beneficial. This study evaluated various clinical and histological features of T1 melanomas to determine whether regional metastases were more likely. These included the Breslow thickness, Clark level of invasion, location, ulceration, and regression. Previous studies have demonstrated that regional metastases correlate with the thickness of the melanoma and that the risk for dissemination is low for melanomas smaller than 1 mm. 27 However, melanomas smaller than 1 mm that extend to regions of the dermis that contain vascular and lymphatic vessels do have the capacity to metastasize. Anatomic studies have demonstrated the presence of a subpapillary plexus of arterioles, postcapillary venules, and lymphatics at the junction of the papillary and reticular dermis. 28 These structures are present at the Clark III level. Although Clark s classification according to the new World Health Organization classification appears to be a less useful prognostic indicator for melanomas larger than 1 mm in thickness, it is still useful for thin melanomas. 12 Ulcerated melanomas are associated with higher regional spread and recurrence because of their aggressive biological nature. 12 Regression of a melanoma on histological analysis creates uncertainty regarding maximal thickness and may be associated with metastases. 15,29 Acral lentiginous melanoma is speculated to be distinct from the superficial spreading and nodular melanomas. The etiology does not appear to be related to ultraviolet irradiation or skin color, its behavior tends to be more aggressive, and its prognosis may be different. 12,25 604

Nahabedian et al: Sentinel Lymph Node Biopsy for the T1 Melanoma Various investigators have studied the metastatic potential of T1 melanomas. 7,17,22 25,30 Slingluff and colleagues 24,25 have studied prognostic factors in patients with thin melanomas and found that the metastatic risk is increased in male patients with at least a Clark level III invasion, ulcerated lesions, histological evidence of regression, and axial location. Corsetti and associates 22 demonstrated a local recurrence in 7 of 38 patients (18.4%) after wide excision alone for melanomas that were smaller than 1 mm in thickness with a Clark level of invasion of III or IV. Bedrosian and coworkers 30 demonstrated regional metastases in 4 of 71 patients (5.6%) after wide excision, and SLNB for melanomas smaller than 1 mm in thickness with a vertical growth phase. Muller and colleagues, 17 using SLNB for thin melanomas, demonstrated no regional spread in 75 patients in whom the melanoma was less than 0.9 mm in thickness. Our current indications for SLNB for patients with T1 melanoma include tumors associated with Clark level IV or V invasion, ulceration, regression, a positive deep margin on initial biopsy, or previous melanoma. Acral lentiginous melanoma differs from the superficial spreading and nodular melanoma in that a Clark level III invasion warrants SLNB. Superficial spreading or nodular melanoma exceeding 0.9 mm in thickness should include SLNB regardless of other associated histological factors. This study also demonstrated that certain T1 melanomas can be fatal despite early identification of regional metastases. Morbidity was not observed in any patient after SLNB. Based on the outcomes of this study, further investigation into the biology of certain T1 melanomas is warranted. Presented at the 19th annual meeting of the Northeastern Society of Plastic Surgeons; Bermuda; October 2 5, 2002. References 1 Balch CM, Houghton AN, Sober AJ, et al. Cutaneous Melanoma. St. Louis: Quality Medical Publishing; 1998. 2 Clary BM, Brady MS, Lewis JJ, et al. Sentinel lymph node biopsy in the management of patients with primary cutaneous melanoma: review of a large single institutional experience with an emphasis on recurrence. Ann Surg. 2001;233:250 258. 3 Wagner JD, Corbett L, Park HM, et al. Sentinel lymph node biopsy for melanoma: experience with 234 consecutive procedures. Plast Reconstr Surg. 2000;105:1956 1966. 4 Bachter D, Michl C, Buchels H, et al. The predictive value of the sentinel node in malignant melanomas. Recent Results Cancer Res. 2001;158:129 136. 5 Blaheta HJ, Schittek B, Breuninger H, et al. Detection of micrometastases in sentinel lymph nodes of patients with primary cutaneous melanoma. Recent Results Cancer Res. 2001;158:137 146. 6 Frahm SO, Schubert C, Parwaresch R, et al. High proliferative activity may predict early metastases of thin melanomas. Hum Pathol. 2001;32:1376 1381. 7 Pontikes LA, Temple WJ, Cassar SL. Influence of level and depth on recurrence rate in thin melanomas. Am J Surg. 1993;165:225 228. 8 Buttner P, Garbe C, Bertz J, et al. Primary cutaneous melanoma. Optimized cutoff points of tumor thickness and importance of Clark s level for prognostic classification. Cancer. 1995;75:2499 2506. 9 McMasters KM, Reintgen DS, Ross MI, et al. Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement. J Clin Oncol. 2001;19:2851 2855. 10 Reintgen DS, Rapaport DP, Tanabe KK, et al. Lymphatic mapping and sentinel lymphadenectomy. In: Balch CM, Houghton AN, Sober AJ, et al. eds. Cutaneous Melanoma. St. Louis: Quality Medical Publishing; 1998:227 244. 11 Cascinelli N, Belli F, Santinami M, et al. Sentinel lymph node biopsy in cutaneous melanoma: the WHO melanoma program experience. Ann Surg Oncol. 2000;7:469 474. 12 Balch CM, Buzaid AC, Soong SJ. Final version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma. J Clin Oncol. 2001;16:3635 3648. 13 Wrone DA, Tanabe KK, Cosimi AB, et al. Lymphedema after sentinel lymph node biopsy for cutaneous melanoma: a report of 5 cases. Arch Dermatol. 2000;136:511 514. 14 Park KGM, Blessing K, McLaren KM, et al. Study of thin ( 1.5 mm) malignant melanomas with poor prognosis. Br J Plast Surg. 1993;46:607 610. 15 Shaw HM, McCarthy SW, McCarthy WH, et al. Thin regressing malignant melanoma: significance of concurrent regional lymph node metastases. Histopathology. 1989;15:257 265. 16 Cook MG, Spatz A, Brocker EB, et al. Identification of histological features associated with metastatic potential in thin ( 1.0 mm) cutaneous melanoma with metastases. A study on behalf of the EORTC Melanoma Group. J Pathol. 2002;197:188 193. 17 Muller MG, van Leewen PA, van Diest PJ, et al. No indication for performing sentinel lymph node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm. Melanoma Res. 2001;11:303 307. 18 Temple CL, Scilley CG, Engel CJ, et al. Sentinel node biopsy in melanoma using technetium-99m rhenium colloid: the London experience. Ann Plast Surg. 2000;45: 491 499. 19 Harlow SP, Krag DN, Ashikaga T, et al. Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicenter study. Melanoma Res. 2001;11:45 55. 20 Owen SA, Sanders LL, Edwards LJ, et al. Identification of higher risk thin melanomas should be based on Breslow depth not Clark level IV. Cancer. 2002;91:983 991. 21 Fearfield LA, Rowe A, Francis N, et al. Clinico-pathological features of relapsing very thin melanoma. Exp Dermatol. 2001;26:686 695. 22 Corsetti RL, Allen HM, Wanebo HJ. Thin or 1mm 605

Annals of Plastic Surgery Volume 50 / Number 6 / June 2003 level III, IV melanomas are higher risk lesions for regional failure and warrant sentinel lymph node biopsy. Ann Surg Oncol. 2000;7:456 460. 23 Gershenwald JE, Colome MI, Lee JE, et al. Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol. 1998;16:2253 2260. 24 Slingluff CL, Vollmer RT, Reintgen DS, et al. Lethal thin malignant melanoma: identifying patients at risk. Ann Surg. 1988;208:150 161. 25 Slingluff CL, Seigler HF. Thin malignant melanoma: risk factors and clinical management. Ann Plast Surg. 1992;28:89 94. 26 Rayatt SS, Hettiaratchy SP, Key A, et al. Psychosocial benefits of sentinel lymph node biopsy in the management of cutaneous malignant melanoma. Br J Plast Surg. 2002; 55:95 99. 27 Vollmer RT. Malignant melanoma: a multivariate analysis of prognostic factors. Pathol Annu. 1989;24:383 407. 28 Holbrook KA, Wolff K. Structure and development of skin. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds. Dermatology in General Medicine. New York: McGraw Hill Book Company; 1987:93 131. 29 Demierre MF. Thin melanomas and regression, thick melanomas and older men. Arch Dermatol. 2002;138:678 682. 30 Bedrosian I, Faries MB, Guery D, et al. Incidence of sentinel lymph node metastases in patients with thin primary melanoma ( 1mm) with vertical growth phase. Ann Surg Oncol. 2000;7:262 267. Open Discussion Maurice Y. Nahabedian, MD Donald R. MacKay, MD (Hershey, PA): If I understand you correctly, the Breslow level at which you are now doing sentinel node biopsies is 0.9 mm. Is that correct? Dr Nahabedian: Yes, except for the acral lentiginous melanomas, which are a little bit different from the other types. It is similar to the desmoplastic melanoma, and its behavior is different. So for those patients, I ll go down to a Clark level III. In my experience I think the yield is going to be low. Dr MacKay: In your reading and researching this, did you find any evidence of a survival benefit in the patients that are getting sentinel node biopsies? Dr Nahabedian: I think a lot of it just depends on the thickness of the lesions. I have had a variety of patients who have died but presented with 3 to 4-mm melanomas and positive nodes. So I think there is benefit in some of the staging, but it s hard to say if the survival is really impacted by this. Steven P. Davison, MD (Washington, DC):Ifyou get a positive sentinel node biopsy, are you then doing a therapeutic node dissection or are you sending the patients directly for adjuvant or immunotherapy regimens? Dr Nahabedian: These 2 patients in this study went on to get a therapeutic node dissection. All patients who have had positive sentinel nodes have then gone on to have full node dissection and then were referred to the medical oncologist. Fouad Samaha, MD (Boston, MA): Are these nodes examined with special stains or merely with H&E staining? Dr Nahabedian: These were all positive on H&E staining. However, in cases when there is ambiguity, we will do some immune staining and things like that. 606