Clin Plastic Surg 32 (2005) Melanoma. Maurice Y. Nahabedian, MD, FACS

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1 Clin Plastic Surg 32 (2005) Melanoma Maurice Y. Nahabedian, MD, FACS Division of Plastic and Reconstructive Surgery, Johns Hopkins University, 601 North Caroline Street 8152C, Baltimore, MD 21287, USA The incidence of cutaneous melanoma continues to increase worldwide. According to current figures from the American Cancer Society, invasive melanoma ranks fifth in men and seventh in women among the most common cancers in the United States [1,2]. Approximately 95,000 people will be diagnosed with melanoma in the United States in Of these, approximately 40,000 cases will be in situ and 55,000 will be invasive. This figure represents a 4% increase in incidence compared with the 2003 statistics. It is estimated that invasive melanoma will be diagnosed in nearly 30,000 men and 25,000 women and that nearly 8000 deaths will be attributed to melanoma this year. This figure represents 80% of all deaths due to skin cancer. Survival is directly related to staging, with 5-year survival rates that range from 95% for stage I melanoma to 2% for stage IV melanoma. Evaluation of the suspected melanoma In light of the increasing incidence of melanoma, public awareness has improved. Patients with pigmented skin lesions are seeking attention with increased frequency. The vast majority of these pigmented skin lesions are benign and normally would not require treatment. The decision about which skin lesions require biopsy is clinically challenging and can sometimes be difficult because of the wide range address: mnahabed@jhmi.edu and variety. The clinical criterion that is currently used in the evaluation of a suspected melanoma is the ABCD algorithm (Table 1). The differential diagnosis for the pigmented lesion is extensive and includes but is not limited to compound nevi, junctional nevi, pigmented basal cell carcinoma, and an array of keratoses. Melanoma can present in an amelanotic form and can be mistaken for a benign lesion. Therefore, it has become customary practice to perform a biopsy on any lesion in which there has been a change in appearance or behavior. Changes in appearance may include changes in border irregularity, tone, color, and size. Changes in behavior may include bleeding, itching, and altered texture. Biopsy of the suspected melanoma Various biopsy techniques are used, including incisional, punch, excisional, and shave. The indications for each are based on the clinical characteristics and location of the lesion. For suspicious lesions measuring less than 1 cm in diameter and located on most skin surfaces on the body, an excisional biopsy with a 1- to 2-mm margin is recommended, because a re-excision can be performed, if necessary, with appropriate margins of excision. For suspicious lesions measuring greater than 1 cm in diameter, an incisional or punch biopsy is usually performed to avoid disruption of the lymphatic channels around the lesion in the event of a future sentinel lymph node biopsy. Re-excision of a pathologically confirmed melanoma can then be planned with appropriate margins. A shave biopsy has no role in a lesion that is suspicious for melanoma /05/$ see front matter D 2005 Elsevier Inc. All rights reserved. doi: /j.cps plasticsurgery.theclinics.com

2 250 nahabedian Table 1 The ABCD criteria for evaluation of a lesion with characteristics of melanoma Criterion Characteristic A Asymmetry Uneven growth rate B Border Irregular C Color Variation and shading D Diameter Large (> 6 mm) Occasionally, following biopsy of a pigmented skin section, the final pathology report will return as atypical nevi. The pathologic interpretation and clinical significance of these lesions is controversial. Common descriptive phrases include cytologic atypia and architectural disorder [3]. Cytologic atypia refers to the variability in the size and shape of the melanocytic nuclei and is graded as mild, moderate, or severe. Architectural disorder refers to the lentiginous growth pattern of the melanocytes along the rete ridges. Although these lesions are not referred to as melanoma, they are considered premalignant, and re-excision is often recommended. Complete excision with a 5-mm margin is recommended for lesions demonstrating severe cytologic atypia with architectural disorder. Lesions demonstrating mild to moderate cytologic atypia do not usually require reexcision as long as the margins of excision are clear. Although there is no conclusive proof that these lesions will eventually become melanoma, the presence of similar cells has been demonstrated in true melanomas; hence, complete excision is usually recommended [4]. The pathologic interpretation of melanoma has various components. These include radial growth phase, vertical growth phase, Breslow thickness, and Clark level of invasion. Radial growth is demonstrated when the nest of melanoma cells within the epidermis exceeds that in the dermis. Vertical growth is demonstrated when the nests of melanoma cells in the papillary dermis exceed that in the epidermis. This pattern is commonly demonstrated with nodular melanoma and is significant for an increased propensity for metastases. Breslow level refers to the thickness of the melanoma in millimeters and is measured from the granular layer of the epidermis to the base of the tumor. Clark level refers to the layer of invasion and includes the epidermis, papillary dermis, papillary reticular junction, reticular dermis, and subcutaneous fat. The current American Joint Committee on Cancer classification incorporates this criterion only for the thin and invasive melanoma measuring less than 1 mm in thickness [5]. Excision of the melanoma The appropriate margin of excision for a confirmed melanoma has a long history of controversy but is currently well defined (Table 2). The margin of excision is based on the thickness of the melanoma. Excision margins greater than 2 cm are currently deemed unnecessary in most cases. This recommendation is based on several well-designed prospective studies that have demonstrated that margins of 3 cm, 4 cm, and 5 cm for melanomas that exceed 1 mm in thickness do not result in improved local control or survival compared with a 2-cm margin [6 8]. Lens et al [9] reviewed four randomized controlled trials comparing narrow with wide excision and found no difference with regard to recurrence or survival. However, in a recent prospective study that compared excision margins of 1 cm and 3 cm in patients with invasive melanoma of at least 2 mm in thickness, an excision margin of 1 cm was associated with a significantly greater risk (P = 0.05) of locoregional recurrence [10]. No statistically significant difference was seen in overall survival. The number of patients, median age, and median thickness were similar in the two groups (447 versus 453 patients; 57 versus 58 years of age; tumor thickness of 3.0 mm versus 3.1 mm). The role of Mohs micrographic surgery in the surgical management of melanoma has generated controversy. Advocates of the Mohs technique argue that it has the benefit of limiting the margin of excision. This limitation is especially important in critical areas with aesthetic importance, such as the face [11]. However, the current recommendations for margins of excision, based on years of investigation and prospective studies, do not support the concept of minimal margins. For less aggressive forms of melanoma, such as lentigo maligna on the face, Mohs may be useful and appropriate in some circumstances; however, its use for invasive melanoma is not recommended. The risks of tumor implantation, false negative margins due to suboptimal melanocytic staining, and inadequate margins limit the use and benefit of this technique. Table 2 Current recommended margins of excision for melanoma Thickness of melanoma Margin of excision Melanoma in situ 5 mm < 1 mm 1 cm 1 2 mm 1 2 cm 2 4 mm 2 cm >4 mm 2cm

3 Melanoma excision and closure based on anatomic location Most melanomas are excised in an elliptic fashion and closed primarily. This pattern holds especially true for the melanoma located on the trunk or extremities. Occasionally, larger defects that are not amenable to primary closure will require more advanced reconstructive techniques, such as adjacent tissue rearrangement, skin graft, or free tissue transfer. These procedures are not commonly needed for most melanoma defects that are located on the trunk or extremity. However, there are certain anatomic sites where the excision and reconstruction are more complicated because of skin thickness, complex anatomy, and proximity to important structures [12]. These areas are discussed separately. Ear melanoma 251 Melanoma arising on the ear can be difficult to manage because of proximity of the skin to the underlying cartilage and contour issues. Options for surgical management of the primary tumor have included wedge resection, Mohs resection, partial amputation, skin and subcutaneous resection with preservation of the perichondrium, and total amputation [13]. In general, for a melanoma in situ, the skin is excised with a 5-mm margin, and cartilage excision is usually not necessary. The defect is repaired by Fig. 2. Outline of the wedge excision. primary closure (when possible) or by using a fullthickness skin graft. Management of the invasive melanoma is more complicated. For melanoma located on the helical rim, a wedge excision, including skin and cartilage, is usually necessary (Figs. 1 4). The acquired defect is repaired by primary closure, when possible, or by local advancement flaps, such as the Antia-Buch procedure or the chonchal trans- Fig. 1. A melanoma involving the posterior helical rim of the ear. Fig. 3. Immediate closure of the helical rim defect.

4 252 nahabedian Fig. 4. Six-month follow-up demonstrating natural contour with minimal distortion of the ear. position flap [14]. For melanoma located in the chonchal region, the lesion is excised; it usually includes the underlying cartilage but not the posterior skin. These defects are repaired using a full-thickness skin graft. Eyelid The eyelid is a challenging structure, primarily because of its complex anatomy and function. The dermal component of eyelid skin is much thinner than other cutaneous regions of the body; hence, melanomas involving the eyelid tend to be more invasive. The excision usually includes the anterior lamellar structures (skin, orbicularis oculi) and may also include the posterior lamellar structures (tarsal plate, orbital fat, conjunctiva). The width and extent of the excision depends on the thickness of the melanoma. Esmaeli et al [15] recently demonstrated that a 5-mm margin of excision is adequate for thin melanomas involving the eyelid. The margin of excision did not have a statistically significant effect on local, regional, or distant recurrence, whereas the Breslow thickness did. Reconstruction of the acquired eyelid defect is based on its size and location [14]. In general, for defects that are less than 25% of the lid margin, primary closure of the skin and tarsus is possible. For defects that exceed 25% of the lid margin, more sophisticated techniques tend to be necessary. These techniques can include cartilage grafts from the ear or nose to reconstruct the tarsus, transposition skin and muscle flaps from the opposing eyelid, and complex adjacent tissue rearrangements using Mustarde flaps. composed of skin of variable thickness, subcutaneous fat, cartilage, bone, and nasal lining. The cutaneous surface of the upper two thirds of the nose is thin, nonsebaceous, and mobile, whereas the lower third of the nose is thick, sebaceous, and relatively nonmobile. The supportive structure of the upper two thirds of the nose is primarily nasal bone, whereas the lower third is cartilage. Excision of melanoma involving the nose can result in a substantial defect that is difficult to close. Given the complexity of the reconstruction, delayed reconstruction is usually recommended for defects that will require techniques more extensive than primary closure. This measure is taken to ensure pathologic confirmation of clear margins. The temporary management of the open defect can include local wound care using Xeroform gauze (Tyco Healthcare Group, LP, Mansfield, MA) or Allograft. The reconstructive technique is usually based on the size of the acquired defect [14]. Small defects measuring less than 5 mm are usually closed primarily with minimal distortion. However, larger defects may require more complex reconstructive techniques to maintain the natural nasal contour. Fullthickness skin grafts may be used; however, they may result in a patch-like appearance with some contour irregularity. Adjacent tissue rearrangement in the form of a unilobe or bilobe flap is useful for defects ranging in diameter from 5 mm to 2 cm (Figs. 5 8). These flaps are commonly based in the upper two thirds of the nose, where the skin is mobile and easily Nose Melanoma arising on the nose can pose a surgical challenge. The nose is a highly complex structure Fig. 5. Melanoma in situ involving the dorsal aspect of the nose.

5 melanoma 253 Fig. 6. The acquired defect and outline of a unilobe transposition flap. rearranged. The thick and sebaceous nature of the lower nasal skin makes it difficult to mobilize. These flaps are usually performed in a single stage. Defects exceeding 2 cm usually require remote flaps, such as the midline forehead flap or the Bishop-Meider flap. These procedures are usually completed in two to three stages. Total nasal reconstruction is a highly specialized operation that often includes free-tissue transfer for bulk and lining, cartilage support grafts, and local flaps for skin resurfacing. These procedures often require five to six operations to complete. Hands and feet Acral lentiginous melanoma commonly affects the plantar surface of the foot and the dorsum of the hand and foot. Plantar melanoma can occur in individuals with all degrees of skin pigmentation. These melanomas are less common than those that occur on the trunk and extremities and are often associated with a poor prognosis because of delayed diagnosis. The surgical management of these melanomas includes excisional biopsy followed by definitive resection [16]. Closure of the acquired defect is obtained by Fig. 8. Six-month follow-up demonstrating an acceptable aesthetic outcome. primary closure when possible, skin graft, local rotation flap, or free tissue transfer (Figs. 9 and 10) [14]. Local control is usually obtained for lesions measuring less than 1.5 mm with a 1-cm margin of resection. For lesions exceeding 1.5 mm in thickness, regional or systemic disease has been demonstrated in greater than 50%. Subungual melanoma The subungual melanoma will usually present as a narrow, pigmented streak that extends vertically from the proximal nail fold to the distal edge of the nail. The differential diagnosis includes trauma, as well as hematopoetic and vascular disorders. The initial Fig. 7. The flap is inset with minimal distortion. Fig. 9. Acral lentiginous melanoma involving the plantar surface in an African American man.

6 254 nahabedian Sentinel lymph node biopsy Fig. 10. One-year follow-up following excision and skin graft. evaluation includes a thorough history and physical examination, followed by a biopsy. The biopsy technique first involves a digital nerve block, using 1% lidocaine with or without bupivacaine (Marcaine), followed by total or partial removal of the nail plate. The sterile and germinal matrix are thoroughly inspected for areas of abnormal pigmentation. A biopsy is performed on any area of abnormal pigmentation using a 3-mm punch; however, other techniques may be used. If no abnormal pigmentation is observed, then a 3-mm, full-thickness punch biopsy of the germinal matrix is completed. It is important to perform a biopsy on that portion of the matrix that is in line with the pigmented streak. On completion, the nail plate is reapplied to prevent desiccation of the matrix. The confirmation of subungual melanoma calls for aggressive treatment. Amputation of the distal digit is usually required [16]. The level of amputation (proximal or distal interphalangeal joint) is determined by the thickness of the melanoma. In general, melanomas that are less than 2 mm in thickness require amputation at the level of the distal interphalangeal joint, and thicker melanomas require amputation at the level of the proximal interphalangeal joint. Evaluation of the regional lymph node basin is often required for these tumors. Despite this treatment, nodal metastases have been demonstrated in 46% of patients within 1 year [16]. The sentinel lymph node biopsy (SLNB) represents a significant advance in the management of melanoma [17]. The sentinel lymph node is defined as the first lymph node in a lymphatic basin that receives afferent lymph flow from the primary tumor site. The likelihood that the sentinel lymph node is negative while another lymph node in the same basin is positive is low. Successful identification and removal of the sentinel lymph node provides accurate staging of the entire nodal basin. The sentinel lymph node will occasionally demonstrate some degree of pigmentation; however, it is important to recognize that the lymph node pigmentation may not be due to melanoma [18]. SLNB is currently recommended for patients with invasive melanoma with a thickness that ranges from 1to4mm[19,20]. The use of SLNB in patients with melanoma that is less than 1 mm or greater than 4 mm in thickness is controversial and is reviewed later in this article. It is important to remember that SLNB is a diagnostic and not a therapeutic tool. The principal advantage of SLNB is that it significantly reduces the incidence of lymphedema, because a total lymphadenectomy is usually not necessary. Technique of sentinel lymph node biopsy Two methods of SLNB are in current use, one using the blue dye and the other the radiolabeled isotope Technetium 99 [21]. Both are sensitive techniques that can successfully identify a sentinel lymph node in most cases. Both the blue dye and the radioisotope techniques involve an intradermal injection of the material at the peripheral margin of the melanoma. The agents enter the dermal lymphatic and migrate to the regional lymph node basin. This process usually takes at least 20 minutes and can last as long as 24 hours. The excision of the melanoma and the SLNB should preferably be completed during the same operation. With the blue dye technique, temporary staining of the dermal lymphatic is observed, leading to the sentinel lymph node. This lymph node is then surgically excised. With the radioisotope technique, a gamma probe is positioned over the regional lymph node, and the radioactivity is quantitated. A count of at least 6000 units over baseline is usually necessary to qualify a lymph node as sentinel. Occasionally, more than one lymph node is detected using these techniques. All suspicious lymph nodes should be removed (Figs ). The anatomic location of the melanoma should be considered in preparation for an SLNB, because of

7 melanoma 255 Fig. 13. The sentinel lymph node is excised. Note the areas of pigmentation secondary to nodal metastases. Fig. 11. Subungual melanoma of the thumb. the anatomy and distribution of the lymphatic pathways [22]. For melanoma located on the upper or lower extremity, SLNB is straightforward, because the lymphatic pathways are constant and drain proximally into the inguinal and axillary lymph node basin. Generally, the excision and the SLNB are performed simultaneously. However, in some cases a pigmented lesion is completely excised that on histologic analysis demonstrates an invasive melanoma with a thickness between 1 and 4 mm. In these situations, a delayed SLNB is possible, despite the disrupted lymphatics and scar. The blue dye or radioisotope is injected proximal to the incision in the direction of the regional lymph node basin. Fig. 12. Localization of an axillary lymph node following lymphoscintigraphy. The SLNB procedure has simplified the operative management for melanomas located on the trunk and head and neck region [19 21]. In the past, for patients without palpable adenopathy, it was difficult to determine which nodal basin was at risk for regional metastases. For truncal melanoma, the lymphatic channels can drain into the axillary or inguinal lymph node basins. For head and neck melanoma, the lymphatics can drain into the cervical, supraclavicular, submandibular, parotid, and retroauricular lymph node basins. The SLNB technique has facilitated management by accurately assessing the lymphatic pathway [23]. However, the sensitivity and specificity of a delayed SLNB for previously excised melanomas located in the trunk, head, and neck region are compromised by the circumferentially disrupted lymphatic pathways. Sentinel lymph node biopsy for the invasive melanoma less than 1 mm The use of SLNB for the thin invasive melanoma is controversial [24]. This debate stems from studies demonstrating a low risk for regional metastases in these cases, a minimal survival or therapeutic advantage from SLNB, and potential morbidity [25,26]. The 5-year survival for patients with stage I melanoma ranges from 91% to 95%. However, recent evidence supports the use of SLNB in patients with invasive melanoma measuring less than 1 mm. Corsetti et al [27] have demonstrated a recurrence rate of 18.4% in patients with melanoma less than or equal to 1 mm at 3-year follow-up. Bedrosian et al [28] have demonstrated sentinel lymph node metastases in 5.6% of patients with melanoma less than 1 mm in thickness. These studies demonstrate the existence of a subset of patients with thin invasive melanoma that displays a more aggressive and po-

8 256 The indications for axillary lymphadenectomy have changed over the years. The most common indication today is for patients with a positive lymph node biopsy, usually using the sentinel technique. The dissection preserves the long thoracic and thoraconahabedian tentially lethal behavior. Current indications for identifying patients at high risk for regional metastases include any T-1 melanoma (<1 mm) associated with ulceration, regression on histologic evaluation, a positive deep margin on initial biopsy, a Clark level of invasion that extends to the reticular dermis or subcutaneous fat (IV or V), and a previous history of melanoma [24]. Exceptions to these criteria include the indication of SLNB for Clark level III invasion in patients with acral lentiginous melanoma and for a thickness of 0.9 mm in patients with superficial spreading or nodular melanoma, because these lesions are associated with an increased propensity for metastases. Sentinel lymph node biopsy for the invasive melanoma greater than 4 mm The benefit of SLNB for invasive melanoma greater than 4 mm in thickness is controversial [29,30], because the long-term survival is generally poor and the local recurrence is higher than in melanoma of less than 4 mm. Carlson et al [29] state that the pathologic status of the sentinel lymph node is a strong independent prognostic factor for survival and that SLNB should routinely be performed. Caraco et al [30], however, have demonstrated no significant difference in the 3-year survival curves between patients with thick melanomas who were nodepositive and node-negative following SLNB. Although SLNB is not routinely performed for melanomas greater than 4 mm in thickness, further studies appear warranted. Lymphadenectomy With the increasing use of the SLNB technique, lymphadenectomy for stages II, III, and IV melanoma has become less frequent. In patients with a negative sentinel lymph node, total lymphadenectomy is usually not necessary. However, in patients in whom the sentinel lymph node is positive, a lymphadenectomy is usually performed. In patients in whom a lymph node is palpable, a fine needle aspiration of the lymph node is performed. Histologic confirmation of melanoma is followed by a lymphadenectomy. The need for an elective lymph node dissection (ELND) is controversial [31,32]. Recently, the number of these procedures performed has significantly declined, after it was demonstrated in four large, prospective, randomized clinical trials that ELND failed to show any survival advantage in patients with intermediate-thickness melanoma (1 4 mm). ELND is currently not recommended in patients with thick melanoma (>4 mm), because of the high risk for regional and distant metastatic disease (60% 70%). In addition, ELND without lymphoscintigraphy in the head and neck region may be misdirected in up to 50% of cases, because of the variability in lymphatic pathways. The technique of lymphadenectomy varies based on the anatomic location. The principal lymphatic basins are located in the cervical neck, axillary, and inguinal territories. The number of lymph nodes removed ranges from 10 to 50 and is dependent on the anatomic location. The details of the operative procedures are beyond the scope of this article, and the reader is referred elsewhere [33 35]. However, the salient features will be discussed. Neck The lymph nodes in the cervical region have five distinct locations based on the sternomastoid muscle. They are recognized as level I through level V lymph node basins. Within the neck, four types of lymphadenectomy can be performed. These include the radical neck dissection (RND), modified (functional) radical neck dissection (MRND), extended radical neck dissection (ERND), and selective neck dissection (SND). The difference between the RND and the MRND is that the sternomastoid muscle, internal jugular vein, spinal accessory nerve, and nerves of the cervical plexus are preserved with the latter. Candidates for RND include patients with multiple or large (>3-cm) lymph nodes, soft tissue involvement, or tumor in the posterior triangle and those who have undergone failed radiation therapy. Functional neck dissection is recommended for patients with a positive sentinel lymph node and those with a palpable lymph node less than 3 cm. The ERND is considered when there is involvement of the suboccipital or retroauricular lymph nodes. The SND, also called the supraomohyoid neck dissection, removes lymph nodes located above the omohyoid muscle and primarily in the submental and submandibular triangles. Axilla

9 melanoma 257 dorsal nerves and generally includes 10 to 20 lymph nodes. Lymphedema of the upper extremity has been demonstrated in 15% to 20% of patients who have a complete axillary lymphadenectomy and in approximately 1% following sentinel lymphadenectomy. Inguinal Indications for inguinal lymphadenectomy include the histologic demonstration of melanoma in a sentinel or palpable lymph node. The dissection can include the superficial or deep lymph nodes. The lymph node chain is generally located along the path of the femoral vessels. Complications of inguinal lymphadenectomy include infection in 10% to 15% and lower-extremity lymphedema in 20%. Management of recurrent melanoma Recurrent melanoma is associated with a decreased survival. The site of recurrence may be the primary location, in transit, regional lymph node basin, or a distant organ. The recurrence risk is based on stage at presentation, presence of ulceration, margin of excision, and extent of operation [36]. Prognostic factors associated with a poor survival include tumor vascularity, tumor thickness, mitotic index, ulceration, and microsatellites [37,38]. Karakousis et al [39] have demonstrated a 3.8% overall rate of local recurrence with a progressive increase based on the thickness of the melanoma. This increase was 2.3% for the 1- to 2- mm melanoma, 4.2% for the 2- to 3-mm melanoma, and 11.7% for the 3- to 4-mm melanoma. Balch [35] has demonstrated that the risk for regional nodal recurrence is 25% for patients with a primary melanoma that measures between 0.76 mm and 1.5 mm and 60% for patients with a primary melanoma that measures between 1.5 mm and 4 mm. Recent studies have evaluated the role of the immune system in the prediction of recurrence. Currently, there is no method of identifying patients with occult melanoma who are at higher risk for recurrence. Kelly et al [40] have studied tumor-associated antigen (TA90) and immune complexes (IC) that circulate in the sera of patients with melanoma. Gupta [41] had previously demonstrated that, in patients with stage IV melanoma, the levels of TA90 are high and the levels of TA90-IC are low, whereas, in patients with stage I melanoma, the levels of TA90 are low and the levels of TA90-IC are high. Using ELISA, it was demonstrated that TA90-IC was elevated in 77% of patients who developed recurrent melanoma. The 5-year survival was 84% for patients without detectable levels of TA90-IC and 36% for patient with detectable levels of TA90-IC (P = ). This technique detected recurrence an average of 19 months sooner than routine clinical and radiologic examination. In the case of a patient with recurrent melanoma, management decisions can be difficult. Options for surgical management include complete resection, lymphadenectomy, and isolated limb perfusion. However, in deciding on the appropriate treatment, one should consider the tumor biology, patient expectations, and whether the procedure is curative or palliative [42]. Predictors of survival following metastatic resection include the site of metastasis, the number of metastases, and the disease-free interval [42]. The most common sites of recurrence of melanoma include the skin, the subcutaneous tissue, and the lymph node basin. Resection of the recurrence that is confined to these areas is usually performed without morbidity and results in a 5-year survival rate of 5% to 38% [42]. Other, less common sites of recurrence include the lung (15% 36%), the brain (8% 15%), the gastrointestinal tract (2% 4%), and the adrenal gland. Although surgical resection is possible and is sometimes indicated for these locations, other therapies are also considered, such as radiation, chemotherapy, and isolated limb perfusion. Isolated limb perfusion (ILP) has been a therapeutic option for nearly 50 years [43]. It has traditionally been used for in-transit melanoma, bulky recurrent disease, or melanoma that is confined to an extremity [44]. The technique involves isolation of the vascular compartment of the extremity, cannulation of the artery and vein, and perfusion of the extremity with high concentrations of chemotherapeutic agents, such as melphalan, tumor necrosis factor, or cis-platinum. The perfusate can be heated to take advantage of the tumoricidal effect of regional hyperthermia [45]. Isolated limb perfusion has traditionally been recommended to patients as a last resort to avoid amputation. Various centers worldwide have used ILP with reasonable success. The median complete response (CR) is approximately 50% using melphalan, and the overall response (OR) rate is approximately 85% [46,47]. When tumor necrosis factor is added to the treatment, the median CR and OR increase to 75% and 95%, respectively. Based on these studies, it appears that ILP is useful in certain situations. Complications include skin erythema, myopathy, peripheral neuropathy, and lymphedema. For additional information about ILP, the reader is referred elsewhere [46,47].

10 258 Sober AJ, et al, editors. Cutaneous melanoma. 4th edition. St Louis (MO)7 Quality Medical Publishing; p [15] Esmaeli B, Youssef A, Nederi A, et al. Margins of excision for cutaneous melanoma of the eyelid skin: the Collaborative Eyelid Skin Melanoma Group report. Ophthal Plast Reconstr Surg 2003;19(2): [16] Tseng JF, Tanabe KK, Gadd MA, et al. Surgical management of primary cutaneous melanoma of the hands and feet. Ann Surg 1997;225(5): [17] Morton DL, Wen DR, Wong JH, et al. Management of early stage melanoma by intraoperative lymphatic mapping and selective lymphadenectomy: an alternative to routine lymphadenectomy or watch and wait. Surg Oncol Clin North Am 1992;1: [18] Rozen S, Nahabedian MY. Melanoma and decorative tattoos: is a black sentinel lymph node unequivocally metastatic? Plast Reconstr Surg 2004;113(4): [19] Thompson JF. The Sydney melanoma unit experience of sentinel lymphadenectomy for melanoma. Ann Surg 2001;8(9S):44 7. [20] McMasters KM, Reintgen DS, Ross MI, et al. Sentinel lymph node biopsy for melanoma: controversy despite widespread acceptance. J Clin Oncol 2001;19(11): [21] Villa G, Agnese G, Bianchi P, et al. Mapping the sentinel lymph node in malignant melanoma by blue dye, lymphoscintigraphy, and intraoperative gamma probe. Tumori 2000;86(4): [22] Uren RF. Lymphatic drainage of the skin. Ann Surg Oncol 2004;11(3S): [23] Chao C, Wong SL, Edwards MJ, et al. Sentinel lymph node biopsy for head and neck melanomas. Ann Surg Oncol 2003;10(1):21 6. [24] Nahabedian MY, Tufaro AP, Manson PN. Sentinel lymph node biopsy for the T-1 (thin) melanoma. Is it necessary? Ann Plast Surg 2003;50: [25] Muller MG, van Leeuwen PA, van Diest PJ, et al. No indication for performing sentinel node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm. Melanoma Res 2001;11(3): [26] 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(6): [27] Corsetti RL, Allen HM, Wanebo HJ. Thin < or =1 mm level III and IV melanomas are higher risk lesions for regional failure and warrant sentinel lymph node biopsy. Ann Surg Oncol 2000;7: [28] 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: [29] Carlson GW, Murray DR, Hestley A, et al. Sentinel lymph node mapping for thick (>4mm) melanoma: should we be doing it? Ann Surg Oncol 2003;10(4): [30] Caraco C, Celentano E, Lastoria S, et al. Sentinel lymph node biopsy does not change melanomanahabedian Summary The surgical management of melanoma continues to evolve. A large body of information serves as a foundation for the oncologic principles, surgical excisions, and reconstructive methodologies that are currently in use. This article serves as a guide for the physician considering surgical management of the melanoma patient. References [1] American Academy of Dermatology Skin cancer fact sheet. Available at: [2] American Cancer Society Facts and figures. Available at: [3] Rozycki JL, Barrett TL. The dysplastic nevus. Curr Probl Dermatol 2003;15(5): [4] Nahabedian MY, Tufaro AP. Skin lesions: evaluation, diagnosis, and management. In: Cameron JL, editor. Current surgical therapy. 7th edition. St. Louis (MO)7 CV Mosby; p [5] Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19(16): [6] Balch CM, Soong SJ, Smith T, et al. Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1 4 mm melanomas. Ann Surg Oncol 2001;8(2): [7] Cohn-Cedermark G, Rutqvist LE, Andersson R, et al. Long-term results of a randomized study by the Swedish melanoma study group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of mm. Cancer 2000;89(7): [8] Cascinelli N. Margin of resection in the management of primary melanoma. Semin Surg Oncol 1998;14: [9] Lens MB, Dawes D, Goodacre T, et al. Excision margins in the treatment of primary cutaneous melanoma. Arch Surg 2002;137: [10] Thomas JM, Newton-Bishop J, A Hern R, et al. Excision margins in high-risk malignant melanoma. N Engl J Med 2004;350(8): [11] Zitelli JA, Brown C, Hanusa BH. Mohs micrographic surgery for the treatment of primary cutaneous melanoma. J Am Acad Dermatol 1997;37(2): [12] Narayan D, Ariyan S. Surgical management of the primary melanoma. Clin Plast Surg 2000;27(3): [13] Pockaj BA, Jaroszewski DE, DiCaudo DJ, et al. Changing surgical therapy for melanoma of the external ear. Ann Surg Oncol 2003;10(6): [14] Nahabedian M, Wagner JD. Complex closure of melanoma excisions. In: Balch CM, Houghton AN,

11 melanoma 259 specific survival among patients with Breslow thickness greater than four millimeters. Ann Surg Oncol 2004;11(3S): [31] Lens MB, Dawes M, Goodacre T, et al. Elective lymph node dissection in patients with melanoma: a systematic review and meta-analysis of randomized controlled trials. Arch Surg 2002;137(4): [32] Cascinelli N, Morabito A, Santinami M, et al. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomized trial. Lancet 1998;351: [33] Medina JE, Byers RM. Supraomohyoid neck dissection: rationale, indications, and technique. Head Neck 1989;11: [34] DeSanto LW, Beahrs OH. Modified and complete neck dissection in the treatment of squamous cell carcinoma of the head and neck. Surg Gynecol Obstet 1988;167: [35] Balch CM. Surgical management of regional lymph nodes in cutaneous melanoma. J Am Acad Dermatol 1980;3: [36] Mann GB, Coit DG. Does the extent of operation influence the prognosis in patients with melanoma metastatic to inguinal nodes? Ann Surg Oncol 1999; 6(3): [37] Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001;19(16): [38] Kashani-Sabet M, Sagebiel RW, Ferreira CMM, et al. Tumor vascularity in the prognostic assessment of primary cutaneous melanoma. J Clin Oncol 2002; 20(7): [39] Karakousis CP, Balch CM, Urist MM, et al. Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial. Ann Surg Oncol 1996;3(5): [40] Kelley MC, Gupta RK, Hseuh EC, et al. Tumor associated antigen TA90 immune complex assay predicts recurrence and survival after surgical treatment of stage I III melanoma. J Clin Oncol 2001;19: [41] Gupta RK. Circulating immune complexes in malignant melanoma. Dis Markers 1988;6: [42] Allen PJ, Coit DG. The surgical management of metastatic melanoma. Ann Surg Oncol 2002;9(8): [43] Creech O, Krementz ET, Ryan RF, et al. Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit. Ann Surg 1958;148: [44] dewilt JHW, Thompson JF. Is there a role for isolated limb perfusion with tumor necrosis factor in patients with melanoma? Ann Surg Oncol 2004;11(2): [45] Wile AG, Nahabedian MY, Plumley DA, et al. Experimental hyperthermic isolation-perfusion using cis-platinum. Cancer Res 1983;43: [46] Kroon BB, Fraker DL, Vrouenraets BC, et al. Isolated limb perfusion: results and complications. In: Thompson JF, Morton DL, Kroon BB, editors. Textbook of melanoma. London7 Martin Dunitz; p [47] Fraker DL. Management of in-transit melanoma of the extremity with isolated limb perfusion. Curr Treat Options Oncol 2004;5(3):