Melanoma Research 2007, 17: Received 1 April 2007 Accepted 24 August 2007

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1 Original article 365 Sentinel node-guided evaluation of drainage patterns for melanoma of the helix of the ear Thomas Shpitzer a, Haim Gutman b, Yoav Barnea d, Adam Steinmetz c, Dan Guttman a, Dean Ad-El a, Shlomo Schneebaum f, Hedva Lerman e, Genady Lievshitz e and Eyal Gur d The head and neck region, and especially the ear and its helix, is notorious for its ambiguous pattern of lymphatic drainage. Therefore, the primary nodal drainage basins in melanoma of the helix of the ear are often unpredictable. The aim of the study was to examine the value of sentinel lymph node biopsy in melanoma of the helix of the ear and to describe the natural history of the disease. Fifteen consecutive patients (14 men) with primary melanoma of the helix of the ear (median thickness, 1.2 mm; range, ) underwent preoperative lymphoscintigraphy, followed by intraoperative lymphatic mapping, using blue dye in combination with a hand-held gamma probe and sentinel lymphadenectomy. The melanomas were characterized by low mitotic rate, low lymphocytic infiltrate, low spontaneous-regression rate, and mostly epitheloid cell type. In one patient, preoperative lymphoscintigraphy failed to demonstrate the draining nodes. The sentinel lymph nodes were identified and retrieved in all patients during surgery. In 13 patients (87%), they were found in the upper jugular lymphatic basin (level IIA); none were found in the retroauricular region. All sentinel lymph nodes were tumor-negative. At a median follow-up of 39 months (range, 12 73), all 15 patients were disease-free. In conclusion, sentinel lymph node biopsy for helix melanoma is an excellent alternative to elective lymph node neck dissection and superficial parotidectomy, with a high success rate and low morbidity. Melanoma of the helix of the ear has an indolent natural history. Melanoma Res 17: c 2007 Wolters Kluwer Health Lippincott Williams & Wilkins. Melanoma Research 2007, 17: Keywords: ear, helix, malignant melanoma, sentinel node Departments of a Otolaryngology-Head and Neck Surgery, b Surgery, c Nuclear Medicine, Rabin Medical Center, Petah Tiqwa, Departments of d Plastic Surgery, e Nuclear Medicine and f Radio-Isotope Guided Surgery Unit of Surgery A, Tel Aviv Sourasky Medical Center, Tel Aviv; all affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Correspondence to Thomas Shpitzer, MD, Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Beilinson Campus, Petah Tiqwa 49100, Israel Tel: ; fax: ; thomas-s@zahav.net.il Received 1 April 2007 Accepted 24 August 2007 Introduction About 15 20% of all cutaneous melanomas occur in the head and neck region; of these, 7 15% appear on the external ear [1 4]. The head and neck, and especially the ear, are notorious for their ambiguous and variable lymphatic drainage patterns. Melanomas of the ear have the potential to metastasize to preauricular or postauricular sites, to anterior or posterior cervical chains, and to the parotid gland [5,6]. Lymphatic mapping and sentinel lymph node biopsy are used to guide the surgeon to the appropriate lymph node basin(s) and to accurately stage the tumor without the need for elective lymph node dissection (ELND). Lymphatic mapping, however, poses unique problems in the head and neck region: 1. The lymphatic drainage is difficult to visualize with lymphoscintigraphy, because the sentinel nodes often lie in close proximity to the injection site. 2. The tracers, especially the blue dye, travel rapidly c 2007 Wolters Kluwer Health Lippincott Williams & Wilkins 3. The sentinel nodes may be small and located in sites that are not easily accessible, for example, the parotid gland [7]. 4. The number of sentinel nodes is high, and they may be located in more than one basin within the neck. The aim of this study was to explore the value of preoperative lymphoscintigraphy, intraoperative lymphatic mapping, sentinel node identification, and histopathology in the management of melanoma of the helix of the ear and to describe the natural history of the disease. Patients and methods We reviewed the charts of all patients treated for melanoma of the helix of the ear in two tertiary-care, university-affiliated centers between November 1998 and July Fifteen patients met the study criteria. Patients with melanoma of the external ear at sites other than the helix (such as the external auditory canal) were excluded. At Rabin Medical Center, seven patients underwent sentinel node mapping with intradermal injection of 2 mci (74 MBq) technetium-99m ( 99m Tc)- labeled nanocolloid (Nycomed Amersham Sorin Srl,

2 366 Melanoma Research 2007, Vol 17 No 6 Milan, Italy) containing less than 80 nm particles at four sites around the primary lesion or its biopsy scar (total 0.4 ml) 1 day before surgery. The patients were scanned in the supine position with an SP-4 gamma camera with a high-resolution collimator (ELSCINT Ltd, Haifa, Israel). Dynamic images were obtained at 15 frames/min for 15 min after injection, followed by static images 1 2 h later. Additional oblique and lateral views were obtained to separate the injection site from the various basins in the neck. After the lymphatic channels and/or sentinel nodes were visualized, they were marked on the patient s skin. At Sourasky Medical Center, eight patients underwent preoperative lymphoscintigraphy with the hybrid single photoemission computed tomography/low-dose computed tomography system using 99m Tc-rhenium colloid (TCK-17, CIS International, Gif-sur-Yvette, Cedex, France) [8]. Intraoperative lymphatic mapping was performed in all patients using an intradermal injection of ml patent blue V 2.5% dye (Guerbet, 9360-Aulnay-Sous-Bois, France) and a gamma-detecting probe (Neo-probe 1000 or 2000, Neoprobe Corporation, Dublin, Ohio, USA). The preoperatively marked or intraoperatively detected hot sites were explored, and the sentinel nodes retrieved. The blue-stained lymphatic channels were carefully dissected up to the point at which they drained into a lymph node. These nodes, as well as all blue-stained nodes and all radioactive nodes, were sampled. The sentinel nodes were submitted for total node processing, serial sectioning, and paraffin-embedded hematoxylin and eosin staining. All hematoxylin and eosin-negative sentinel nodes underwent immunohistochemistry study for HMB45 and S100 protein. At Sourasky Medical Center, the nodes from the eight patients were also evaluated intraoperatively. At both centers, if metastases are detected in a sentinel node, formal lymph node dissection and parotidectomy are offered in a second session, according to the standards of the American Academy of Otolaryngology [9]. Results The study group included 14 men and one woman aged years (median 55 years). Melanoma thickness ranged from 0.70 to 1.5 mm in 10 patients; mm in three patients, and greater than 4 mm in two patients (median 1.2 mm; mean 2.13 mm). Superficial spreading melanoma was the most common histopathologic type (33%). Ulceration was present in one lesion. The pathological characteristics are shown in Table 1. Preoperative lymphoscintigraphy Forty-five sentinel nodes were detected by lymphoscintigraphy in 14 of the 15 patients (average, three nodes/ patient; range 1 5). In one patient, lymphoscintigraphy failed to visualize the sentinel node. The number of sentinel nodes and drainage patterns is shown in Table 2. In 11 patients, melanomas drained to upper jugular lymph nodes (level II) and in seven patients, to lower jugular lymph nodes (level III and/or IV). More than one basin (median 2, range 1 5) was identified in 12 of the 15 patients. Intraoperative lymphatic mapping Sentinel lymph nodes were identified and retrieved in all patients during surgical exploration. In the patient in whom preoperative lymphoscintigraphy failed, the sentinel node was located by dye within the wide localexcision surgical field. A total of 48 sentinel nodes were retrieved (average three nodes/patient; range 1 7). Their locations are listed in Table 3. Twenty sentinel lymph nodes in 13 patients (87%) were found in the upper jugular lymphatic basin (level IIA); none were found in the retroauricular region. Figure 1 illustrates the anatomic distribution of the intraoperative lymphatic mapping findings. Table 1 Pathological characteristics of melanoma of the helix of the ear in 15 patients Breslow thickness Lymphocytic tumor (mm) Clark level Tumor ulceration Mitotic rate a infiltrate Cell type Regression No High Low Epitheloid + spindle No No Low Low Epitheloid Yes No Low Non brisk Epitheloid No No High Low/non-brisk Epitheloid No No Low Low Epitheloid + spindle No No Low Low Epitheloid + spindle Focal No Interm. Non-brisk Epitheloid No No Interm. Non-brisk Epitheloid No No Interm. Brisk Epitheloid No No Low Low Epitheloid No No Interm. Non-brisk Epitheloid No No Low Low Epitheloid No Yes Low Non-brisk Epitheloid No No N/A N/A N/A No No Interm. Non-brisk Epitheloid No a High > 6 mm 2, intermediate 2 6 mm 2, low < 1 mm 2.

3 Ear helix melanoma Shpitzer et al. 367 Table 2 Location and number of preoperative lymphoscintigraphically demonstrated sentinel nodes Total no. of sentinel nodes on scintigraphy Location Neck (level I) Neck (level II) Neck (level III) Neck (level IV) Neck (level V) Retroauricular Parotid gland Not found Table 3 Location and number of sentinel nodes excised Total no. of sentinel nodes on scintigraphy Location Neck (level I) Neck (level IIA) Neck (level III) Neck (level IV) Neck (level V) Retroauricular Parotid gland Surgical treatment All sentinel lymph nodes in all patients were tumornegative. The surgical approach to the primary melanoma varied. Ten patients underwent full-thickness wedge resection of the helix with primary closure, and five needed local reconstruction. No further surgical or other treatment was necessary. Clear margins were achieved in all patients. The minimal margins exceeded 1 cm in all patients. Follow-up At a median follow-up time of 39 months (range, months), all 15 patients were disease-free. One patient had postoperative paresis of the spinal accessory nerve, which resolved after 4 months. Two patients had dehiscence of the operated helix, one of whom required secondary plastic surgery. No other procedure-related complications were encountered. Discussion A large proportion of patients with cutaneous head and neck melanoma do not benefit from prophylactic regional lymphadenectomy because of the presence of histologically negative nodes [10]. Additionally, a considerable number of patients die of a disseminated disease despite findings of negative neck nodes on radical neck dissection [11]. Therefore, sentinel lymph node biopsy provides an excellent alternative to ELND. The status of the sentinel lymph node may serve as a guide for complete lymph node dissection and adjacent therapies. The falsenegative incidence for sentinel lymph node biopsy is low ( < 5%) [12,13]. This option is particularly attractive for melanoma of the head and neck, and especially the external ear, where the lymphatic drainage is often ambiguous. In these cases, preoperative lymphoscintigraphy is a critical component of the procedure. Studies have shown that the combination of blue dye injection with intraoperative hand-held gamma-probe evaluation identifies the sentinel lymph node in > 90% of patients with head and neck melanoma [5,14,15]. The use of both techniques is crucial, because the blue dye staining is not as vivid in the neck as in the axilla or groin [16]. The identification of tiny radioactive nodes is facilitated by the blue staining of the channel or the node itself.

4 368 Melanoma Research 2007, Vol 17 No 6 Fig. 1 revealed a low mitotic rate, low spontaneous-regression, and epitheloid cell type. The lymphocytic infiltrates, however, were modest in all patients. I=2 9 II=20 III = 9 V=3 IV=5 It is not unusual for lymphatic drainage of the ear to localize to the preauricular or parotid lymph nodes. Pockaj et al. [17] noted that 64% of external ear melanomas occur on the helix. In seven of their 10 patients (70%), the sentinel node was located in the parotid region. In our series, which focused on primary melanoma of the helix, the sentinel node was found in the parotid region in only four patients (27%). Although the sentinel nodes in the parotid region tend to be small and are usually situated within the substance of the gland, sentinel lymph node biopsy can still be performed successfully and with low morbidity [19 21], because 90% of the lymph nodes are located in the superficial portion of the gland, above the parotid duct and the facial nerve [22]. Sentinel lymph node biopsy in these cases spares patients the morbidity associated with superficial parotidectomy. Anatomical distribution of the intraoperative lymphatic mapping in patients with melanoma of the helix of the ear. In the present report of 15 patients with a primary melanoma of the helix, although lymphatic drainage was notoriously ambiguous, all patients had at least one sentinel lymph node intraoperatively at levels II or III of the neck. Other reports have also noted the success of sentinel lymph node biopsy in patients with melanoma of the ear [12,17,18]. All 48 sentinel lymph nodes identified in this cohort were negative for metastatic disease, regardless of the thickness of the primary melanoma, and no further lymph node dissection was performed. No false-negative cases were detected during follow-up. Wagner et al. [5] reported a 17% rate of regional metastatic disease for head and neck melanomas, which was within the 12 36% range cited in other studies. The absence of SLN micrometastatic disease in the present series of helix melanoma may have been attributable to the small sample size. Alternatively, it may represent a unique natural history of melanoma in the helix location. This assumption is further supported by the study of Pockaj et al. [17], wherein none of the 10 patients with melanoma of the external ear who underwent sentinel lymph node biopsy had pathologically positive lymph nodes. Furthermore, after median follow-up of 39 months, none of our patients had regional or other recurrences. On pathologic study, helix melanoma in our series mostly In conclusion, despite the ambiguous lymphatic drainage patterns of the ear helix, in patients with melanoma, the sentinel nodes can be identified by preoperative lymphoscintigraphy and intraoperative lymphatic mapping. As most of the sentinel nodes draining the helix (all in our cohort) do not contain metastases, sentinel lymph node biopsy offers an excellent alternative to ELND and superficial parotidectomy, with a high success rate and low morbidity. The indolent natural history of helix melanoma, as demonstrated in this series may be of clinical importance and needs further validation in larger databases. Acknowledgement No conflict of interest exists. References 1 Urist MM, Balch CM, Soong SJ, Milton GW, Shaw HM, McGovern VJ, et al. Head and neck melanoma in 534 clinical stage 1 patients. A prognostic factors analysis and results of surgical treatment. Ann Surg 1984; 200: Byers RM, Smith JL, Russel N, Rosenberg V. Malignant melanoma of the external ear: review of 102 cases. Am J Surg 1980; 140: Cole DJ, MacKay GJ, Walker BF, Wooden WA, Murray DR, Coleman JJ III. Melanoma of the external ear. J Surg Oncol 1992; 50: O Brien CJ, Coates AS, Petersen-Schaefer K, Shannon K, Thompson JF, Milton GW, et al. Experience with 99 cutaneous melanoma of the head and neck over 30 years. Am J Surg 1991; 162: Wagner JD, Park HM, Coleman JJ III, Love C, Hayes JT. Cervical sentinel lymph node biopsy for melanomas of the head and neck and upper thorax. Arch Otolaryngol Head Neck Surg 2000; 126: Wells KE, Cruse CW, Daniels S, Berman C, Norman J, Reintgen DS. The use of lymphoscintigraphy in melanoma of the head and neck. Plast Reconstr Surg 1994; 93: O Brien CJ, Uren RF, Thompson JF, Howman-Giles RB, Petersen-Schaefer K, Shaw HM, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg 1995; 170:

5 Ear helix melanoma Shpitzer et al Even-Sapir E, Lerman H, Lievshitz G, Khafif A, Fliss D, Schwartz A, et al. Lymphoscintigraphy for sentinel node mapping using a hybrid SPECT/CT system. J Nucl Med 2003; 44: Robbins KT. Pocket guide to neck dissection classification and TNM staging of head and neck cancer. Alexandria, Virginia: American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., Balch CM. The role of elective lymph node dissection in melanoma: rationale, results and controversies. J Clin Oncol 1988; 1: Jonk A, Strobbe LJA, Kroon BBR, Mooi WJ, Hart AA, Nieweg OE, et al. Cervical lymph node metastasis from cutaneous melanoma of the head and neck: a search for prognostic factors. Eur J Surg Oncol 1998; 24: Gershenwald JE, Thompson W, Mansfield PE, Lee JE, Colome MI, Tseng C, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 1999; 17: Morton DL, Thompson JF, Essner R, Elashoff R, Stern SL, Nieweg OE, et al. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Ann Surg 1999; 230: Alex JC, Krag DN, Harlow SP, Meijer S, Loggie BW, Kutin J, et al. Localization of regional lymph nodes in melanoma of the head and neck. Arch Otolaryngol Head Neck Surg 1998; 124: Shpitzer T, Segal K, Schachter J, Harduff R, Guttman D, Ulanovski D, et al. Sentinel node guided surgery for melanoma in the head and neck region. Melanoma Res 2004; 14: Stadelman WK, McMasters K, Digenis AG, Reintgen DS. Cutaneous melanoma of the head and neck: advances in evaluation and treatment. Plast Reconstr Surg 2000; 105: Pockaj BA, Jaroszewski PE, DiCando DJ, Hentz JG, Buchel EW, Gray RJ, et al. Changing surgical therapy for melanoma of the external ear. Ann Surg Oncol 2003; 10: Cole MD, Jakowatz J, Evans GR. Evaluation of nodal patterns for melanoma of the ear. Plast Reconstr Surg 2003; 112: Ollila DW, Foshag LJ, Essner R, Stern SL, Morton DL. Parotid region lymphatic mapping and sentinel lymphadenectomy for cutaneous melanoma. Ann Surg Oncol 1999; 6: Wells KE, Stadelman WK, Rapaport DP, Hamlin R, Cruse CW, Rientgen D. Parotid selective lymphadenectomy in malignant melanoma. Ann Plast Surg 1999; 43: Lin D, Kashani-Sabet M, Singer MI. Role of the head and neck surgeon in sentinel lymph node biopsy for cutaneous head and neck melanoma. Laryngoscope 2005; 115: McKean ME, Lee K, McGregor IA. The distribution of lymph nodes in and around the parotid gland: an anatomical study. Br J Plast Surg 1985;38:1 5.