H ead a nd N ec k M el an om a Jerry Cheriyan, MD, MRCSa, Jessica Wernberg, Andrew Urquhart, MDc
MD
b,
*,
KEYWORDS Head and neck melanoma (HNM) Parotidectomy Sentinel lymph node Treatment of primary lesion Treatment of draining lymph node KEY POINTS Wide local excision is the mainstay in the treatment of the primary lesion with consideration given to specific anatomic constraints in head and neck melanoma (HNM). Sentinel lymph node biopsy (SLNB) is considered in all lesions with ulceration, mitoses greater than or equal to 1/mm2, stage1B or higher, and in all high-risk nonmetastatic melanoma. Lymphatic drainage patterns in the head and neck can be atypical and may involve the parotid gland. Higher rate of locoregional recurrence has been reported in SLN-negative patients in HNM compared with cutaneous melanoma elsewhere. Location of primary, SLNB status, node-positive disease, and the drainage pattern determines the extent of neck dissection and parotidectomy. Reconstructive strategy must be considered in multidisciplinary teams with reconstructive surgeons for large head and neck defects.
INTRODUCTION Epidemiology
It is estimated that melanoma of the head and neck comprises 6% to 25% of all cutaneous melanomas.1–3 Head and neck melanoma (HNM) is uncommon in patients under 30 years of age and is usually seen in adults older than 70 years.4 Men are at higher risk of developing HNM than women,5–7 and the incidence of melanoma of the face and neck is two times greater in men than in women, although the differences
Funding Support: None. Conflict of Interest: The authors have nothing to disclose. a Department of General Surgery, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA; b Department of General Surgery/Surgical Oncology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA; c Department of Otolaryngology/Head and Neck Surgery, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA * Corresponding author. E-mail address: [email protected] Surg Clin N Am 94 (2014) 1091–1113 http://dx.doi.org/10.1016/j.suc.2014.07.011 surgical.theclinics.com 0039-6109/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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are smaller in younger age groups.8 Sixty to 90% of HNMs occur on the face,3,9 with the scalp, neck, and ears less commonly involved (Fig. 1).10–14 The higher incidence of HNM in relation to total body surface area may be explained by the fact that the head and neck area is more affected by increased exposure to ultraviolet radiation and the higher density of melanocytes in the head and neck.3,15 Risk factors for HNM include the following: Continuous (occupational) sun exposure Higher levels of occupational sun exposure, whereas extremity melanoma was associated with a higher total sun exposure16,17 Lighter skin17,18 Increased number of sunburns Nevus count, although a positive association between nevus counts to HNM is weaker than that between nevus counts and trunk or extremity melanoma17 CLINICAL PRESENTATION History
As with cutaneous melanoma at any site on the body, early detection and diagnosis of HNM are vital for effective and timely therapeutic intervention. Approximately half of the time, melanoma is self-discovered, with 26% discovered by medical providers and the rest by family members or others.19 The most common presenting symptom is color change or growth of a preexisting lesion.20 Other presenting symptoms include itching, bleeding, ulceration, and pain, or paresthesias that would be a manifestation of late symptoms, occurring in thick melanomas.20 Patients should be asked about risk factors including sun exposure, history of sunburns, and especially family history, because up to 10% of melanoma cases report a first-degree or seconddegree relative with melanoma.21 Physical Examination
A meticulous and complete skin examination along with examination of typical and atypical lymphatic drainage basins should be performed, noting the number, type, and characteristics of moles or nevi. The American Cancer Society recommended ABCDEs (asymmetry, border, color, diameter, evolving) provide a simple guideline
Fig. 1. Distribution of HNMs. (Data from Refs.10–14)
Head and Neck Melanoma
to detect early warning signs of melanoma. Gachon and colleagues22 suggested the use of the “ugly duckling” warning sign, which focuses on the identification of pigmented or clinically amelanotic lesions that look different from the rest, to assist with the detection of lesions that do not fit the classic ABCDE criteria. Although all of these factors have been found to be predictors of a malignant lesion, an irregular border is the strongest predictor.23 In the head and neck, particular attention must be devoted to examining the scalp, including the hair-bearing areas, ears, nose, and eyelids in addition to the face. The hair-bearing scalp areas are best examined after taking off all hair bands and clips and then parting the dry loose hair in a systematic fashion using a comb. A complete examination of the ear includes the pinna, the external auditory canal with and without an otoscope, as well as behind the pinna. Both eyelids should be examined when open and closed. Examination of the lymph nodes should include both ipsilateral and contralateral submental, submandibular, jugular, anterior central, and posterior, as well as the supraclavicular and axillary basins. CLASSIFICATION AND STAGING Morphology
The morphologic types seen in HNM are similar to cutaneous melanoma. Superficial spreading melanoma is the most common subtype, accounting for 50% to 80% of cases, and appears flat because of the horizontal radial pattern of growth, which is followed by a subsequent vertical growth phase characterized by the presence of a dominant nest in the papillary dermis. Nodular melanoma, accounting for 20% to 30% of cases, is thick on palpation because of early vertical growth of the cancer cells. Lentigo maligna melanoma is commonly seen in later years within preexisting large freckles or Hutchinson freckles (lentigo maligna). Desmoplastic neurotropic melanoma is a variant that often lacks pigment and clinically has characteristics similar to hypertrophic scar, dermatofibroma, or fibrosarcoma with a propensity toward neural invasion. Although it is a rare form of melanoma, accounting for only around 1% of all cases, about half arise in the head and neck.24 Histology
The Clark Level and Breslow Thickness are the 2 histologic systems used for classification. Clark grading involves a qualitative system to determine the depth of the primary melanoma based on the level of invasion of the dermis, whereas the Breslow thickness system is based on the quantitative measurement of thickness in millimeters from the stratum granulosum to the deepest point of invasion.24 The Breslow thickness provides a powerful tool for prognostic staging of melanoma; consequently, emphasis on the Clark system has decreased. Clinical Staging
Based on current evidence, the American Joint Committee on Cancer has revised the staging for cutaneous melanoma.25 The latest revision includes ulceration in the scheme and replaces the Clark Level with mitotic rate in thin melanoma, highlighting their association with prognosis. Serum lactate dehydrogenase is included in M classification in addition to defining micrometastases and macrometastases. INVESTIGATIONS Biopsy
Excisional biopsy is the preferred technique for small, accessible lesions with a 1-mm to 2-mm margin because it is diagnostic, potentially therapeutic, and prognostic.
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Incisional or punch biopsy may be used for sampling larger lesions. Deep shave biopsies are frequently used when lesions are suggestive of both epidermoid carcinoma and melanoma.24 Needle biopsies are useful for assessing suspicious lymph nodes or metastasis. Careful planning of biopsy orientation is critical in HNM to avoid compromise if subsequent wide local excision and reconstruction becomes indicated. Imaging Recommendations
The role and extent of imaging for patients with HNM is controversial.26 Although sentinel lymph node biopsy (SLNB) is not 100% accurate, it is the most reliable means for regional staging and has better sensitivity and specificity than computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), elective lymph node dissection (ELND), and clinical examination.27 There are no recommended routine baseline or surveillance laboratory tests (lactate dehydrogenase, liver function test, chest radiography, CT, MRI, PET, bone scans, or gastrointestinal series) in patients with no signs or symptoms of metastasis. Fluorodeoxyglucose-PET has been shown to be effective for detecting metastatic melanoma, with sensitivity and specificity reported as high as 74% to 100% and 67% to 100%, respectively.28,29 PET is not recommended in early-stage node-negative HNM, but may be considered if symptoms warrant further imaging or to follow disease burden in stage IV disease.30 TREATMENT AND PATHOLOGIC STAGING
The oncologic management is best delivered by a multidisciplinary team, including surgeons, reconstructive surgeons, and medical and radiation oncologists. Treatment of Primary Lesion Wide local excision
Wide local excision (WLE) of the index lesion is the primary treatment of cutaneous melanoma. Malignant cells may extend microns to several millimeters beyond clinically visible margins, thus necessitating a wider and frequently deeper excision to ensure as complete a removal as possible. The recommendations for surgical margins for WLE for the head and neck are similar to other cutaneous melanomas, but this is not always possible because of the functional and cosmetic disability that may arise.31 Historically, a 5-cm margin excision was done until the 1970s, when Breslow and Macht32 reported successful treatment in thin melanoma patients with narrower margin excision. A prospective randomized control study by the World Health Organization33 on melanoma concluded that there was no significance in recurrence rates between 1-cm or 3-cm margin resection in cutaneous melanomas 2 mm or less. Surgical margin recommendations from the American Academy of Dermatology (AAD)34 published in 2011 are based on both evidence from prospective randomized control studies and consensus opinion when no prospective data were available (Table 1). The basis for these recommendations is as follows: Wide excision for melanoma is associated with reduced recurrence. For thin melanomas, currently there is no high-quality evidence to support excision of more than a 1-cm margin in improving survival or local recurrence rates. For primary melanomas of any thickness, there is no evidence to suggest that margin excision of more than 2 cm provides any additional benefit in terms of survival or local recurrence rates.
Head and Neck Melanoma
Table 1 American ADA surgical margin recommendations for primary cutaneous melanoma Breslow Thickness
Clinically Measured Surgical Margina
In situ
0.5–1.0 cm
1 mm
1 cm
1.01–2.0 mm
1–2 cm
>2 mm
2 cm
a
Wider margins might be necessary for lentigo maligna subtype. Adapted from Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol 2011;65:1032–47.
The AAD also recommends that the depth of excision be carried out to the level of muscle fascia, if possible, or at least to deep adipose tissue depending on location.34 A wider excision may be considered for lentigo maligna melanoma, given the potential for extensive subclinical extension, particularly in the head and neck. It is important to note that although the recommendations for surgical margin resection serve as guidelines, margins should be individualized. Adherence to these recommendations might be particularly challenging in HNM because of cosmetic and functional concerns associated with wide excision. Careful consideration of the risk of recurrence, defect size, and location should guide the extent of resection. Sentinel Node Biopsy and Lymphatic Drainage Patterns
SLNB was introduced by Morton and colleagues35 and modified by Robinson and colleagues36 to include preoperative lymphoscintigraphy. SLNB is used to identify the immediate draining lymph node from the primary tumor by injecting radioisotope and or blue dye with or without preoperative lymphoscintigraphy.37–39 The principle of SLNB is based on the rationale of the primary tumor having defined lymphatic drainage into specific nodal basins with the goal of identifying metastasis to regional lymph nodes. No evidence of metastasis in the sentinel lymph node (SLN) is highly indicative that the remaining nodes will not have metastatic spread.35 SLNB is the most sensitive and specific staging test for identification of micrometastatic melanoma in regional lymph nodes.40 As with melanoma of the trunk and extremities, SLNB status is the most important prognostic factor in HNM patients.31,41,42 SLNB is particularly useful in midline HNM, as lymphatic drainage in the head and neck is often aberrant and can result in identification of the sentinel node in more than one nodal basin or in an atypical, bilateral, or contralateral nodal basin. Some authors have noted a wide range in the false negative rates (3.4%–10.4%) for HNM SNLB as well as a decreased HNM SLN positive rate (10%–15%) compared with cutaneous melanoma elsewhere (16%–23%).43,44 Others have reported SLN positive rates in HNM that are not significantly different from other cutaneous melanomas, although the small patient numbers in these studies limit their interpretation. A worse survival in HNM with positive SLN compared with other anatomic locations has also been suggested.43 Indications for SLNB
Indications for consideration of SLNB for HNM are similar to those for other cutaneous melanomas and include all patients with lesions that have a Breslow thickness greater than 1.0 mm and a clinically negative nodal basin and all patients with ulceration or an
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increased mitotic rate (Fig. 2). SLNB may be considered for melanoma patients with less than 1.0-mm thickness with adverse features, including positive deep margins, lymphovascular invasion, young patients, or Clark Level IV or greater.42 Although some prefer not to perform SLNB after WLE due to disruption of natural lymphatic pathways, it may be acceptable even after WLE, if extensive reconstruction and lymphatic dissection have not been performed. One must also be prepared for drainage into atypical, contralateral, and deep cervical lymph node basins. SLNB technique
Patients are given intradermal injections of a radioactive colloid, usually Technectium99 sulfur colloid (0.5 mCi), around the primary lesion, after which a lymphoscintigraphy may be performed. If injection of the radiotracer into the subcutaneous tissue results in failure to detect the sentinel node, a repeat injection should be performed. Under anesthesia, intradermal isoflurane blue or methylene blue dye can be injected in addition to the radioactive colloid to map the lymph node. WLE of the melanoma may be performed first to reduce radioactivity from the primary injection, which may interfere with the ability to detect tracer uptake in the SLN; this is especially true in HNM, as the SLN may be in close proximity to the primary lesion. An intraoperative handheld gamma probe is used to localize the SNL and lymphatic channels.26 Cervical SLNB is performed using a 1-cm to 3-cm incision over the area of maximal radioactivity, while a periauricular incision is usually used for the parotid region. Identification and removal of the sentinel node are performed for all hot lymph nodes until the gamma counts in the basin are equal or less than 10% of the hottest lymph node removed.40 Histologic evaluation
Once the SLN is identified and excised, it is recommended that histologic evaluation be done using permanent paraffin section with hematoxylin and eosin staining and immunohistochemistry (IHC), as frozen sections have a high false negative rate ranging from 5% to 10%.45 Higher sensitivity of the IHC markers S-100 and MelanA make it the recommended stain compared with HMB-45, which is less sensitive. Permanent section allows for accurately discussing the prognosis and treatment of positive lymphatic nodes with the patient in an office setting before proceeding with definitive treatment.
Fig. 2. Algorithm for treatment of lymph node basin in HNMs. LN, lymph node; SLNB, sentinel lymph node biopsy.
Head and Neck Melanoma
ELND
ELND, with the aim of clearing all potential lymph nodes with metastatic melanoma, can have significant morbidity from lymphedema and injury to the major vascular and nervous structures. The survival benefit from ELND in HNM has not been proven, and with findings from the Multicenter Selective Lymphadenectomy trials-I,37 SLNB has become a more favored approach. A systematic review by Tanis and colleagues46 concluded that there was no conclusive evidence on the advantage of either elective neck dissection or SLNB in patients with clinically node-negative HNM of intermediate thickness. In a study of 46 patients with metastatic malignant melanoma, the authors concluded that involvement of more than 4 cervical or parotid nodes resulted in significant increase in distant metastases, but did not note an impact of location or metastases or method of neck dissection on survival.47 Bodem and colleagues48 suggested that in patients with proven lymph node metastases, complete neck dissection might be of benefit because the number of infiltrated nodes is often higher than expected. The role of neck dissection in HNM is not yet fully established. The number and levels should be determined based on tumor location and SLNB status. Prospective studies are necessary to provide convincing, reliable, and validated guidelines for cervical lymph node dissection in HNM. Parotid Management
Lymphatic drainage from the face, cheeks, lips, ears, and anterior scalp can include the parotid in addition to the neck. With a primary lesion in this location, the parotid could be a potential source of metastasis, with around 25% to 30% of HNM draining into the parotid lymph node basin.49,50 Although there is no consensus, the options when lymphoscintigraphy shows drainage to the parotid include parotid-sparing SLNB and superficial parotidectomy followed by cervical lymph node dissection in the event of confirmed metastasis to the SLN. The multiplicity, widespread distribution, and high frequency of parotid nodes have prompted some surgeons to advocate superficial parotidectomy over mapping.51 Suton and colleagues52 suggested that parotidectomy be considered for all HNM, except for posterior primaries and lower neck melanomas. Some authors also recommend parotidectomy for anterior melanoma.53,54 Because of the risk of neurovascular injury to the facial nerve and vessels, others have suggested a targeted, parotid-sparing approach for SLN in the parotid region. The targeted, parotid-sparing approach for SLN is technically more demanding and may place the facial nerve at a higher risk of injury.55 There are also concerns that fibrosis and inflammation after SLNB might result in an increased risk of facial nerve injury if reoperation of the parotid is necessary. Some studies have reported the low morbidity and accuracy of sentinel lymphadenectomy in the parotid gland.56,57 Proponents of the parotid lymph node biopsy highlight it as a less invasive operation compared with a superficial parotidectomy, with no increase in recurrence. Although there is a theoretic increased risk of injury to the facial nerve while doing a parotidectomy as a secondary procedure after the SLNB, some groups have noted no increase in facial nerve or bleeding complications.55 It would be prudent to prepare for a selective lymph node biopsy in the parotid region by an experienced surgeon, while also being prepared to perform a superficial parotidectomy if the SLN is not identified. A parotid lesion can also be investigated with a needle biopsy. Neck Dissection Technical aspects
In general, forehead and anterior scalp melanomas spread to the parotid, periparotid, and upper jugular lymph nodes, whereas those in the posterior scalp and occiput
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spread to the postauricular, suboccipital, and posterior triangle lymph nodes. Melanoma of the face and neck usually metastasize to the facial, submental, submandibular, and deep cervical nodes. The American Head and Neck Society (AHNS) classified the lymph nodes of the neck into 5 levels on each side, a central submental triangle, and a single central compartment (Fig. 3). The cheek and eyelid regions have 2 lymphatic drainage patterns, one to the parotid nodes and the other to level IB. The lymph drainage patterns in the lip region are to level IA or IB.58 Lymphatic drainage of the ear has no predictable pattern, but it most commonly drains to cervical level II and the preauricular and postauricular basins.59
Fig. 3. Level wise classification of neck nodes (Supported by the American Head and Neck Society). (From Harisinghani NG. Atlas of lymph node anatomy. New York: Springer; 2013. p. 2; with permission.)
Head and Neck Melanoma
Current guidelines for management of primary cutaneous melanoma do not specify recommendations for HNM.34 It is justifiable to perform regional lymphadenectomy alone in cases of primaries of the posterior scalp and posterior neck with no involvement of the submandibular and submental triangles.52 The AHNS and the American Academy of Otolaryngology-Head and Neck Surgery classified neck dissections into the following: 1. Radical neck dissection (RND)—removal of all ipsilateral cervical lymph node groups from levels I through V, together with spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle. 2. Modified radical neck dissection (MRND)—removal of all lymph node groups routinely removed in RND, but with preservation of one or more nonlymphatic structures (spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle). 3. Selective neck dissection (SND)—cervical lymphadenectomy with preservation of one or more lymph node groups and all nonlymphatic structures routinely removed in RND. 4. Extended neck dissection—removal of one or more additional lymph node groups or nonlymphatic structures, or both, not encompassed by RND. Indications
Neck dissections may be performed in the following clinical scenarios: clinically positive lymph nodes; positive SLNB in the neck; positive SLN in the parotid region; extensive invasive lymph node disease; and clinically negative lymph node disease. Clinically positive lymph nodes—therapeutic neck dissection Therapeutic lymph node dissection refers to the lymph node removal for clinically evident or palpable lymph nodes. The extent of neck dissection would depend on the number and location of the nodes as well as the primary lesion. Positive SLNB in the neck—therapeutic neck dissection Completion lymph node dissection is the lymphadenectomy done after a positive SLNB. The extent of neck dissection depends on the level of the SLN and the location of the primary lesion. Gyorki and colleagues60 reported that positive nonsentinel lymph nodes were mostly identified within or adjacent to the nodal level containing the SLN. Positive parotid SLN—therapeutic neck dissection and parotidectomy A parotidectomy is indicated with positive parotid SLN as well if clinically apparent disease is present in the parotid. A primary lesion involving the parietal or frontal scalp, face, cheeks, nose, or ear could potentially have drainage to the parotid in addition to the neck; therefore, a parotidectomy should be performed in conjunction with the neck dissection when the SLN is positive. Extensive invasive lymph node disease—therapeutic neck dissection including nonlymphatic structures RND should only be performed with extensive involvement
of the spinal accessory nerve, internal jugular vein, or sternocleidomastoid muscle. There are some data supporting MRND as having comparable efficacy to RND and advantageous efficacy over selective ND49,61; however, Shah and colleagues62 recommend complete RND for therapeutic conditions and limited neck dissection for elective procedures. No known lymph node disease—elective neck dissection ELND for clinically negative lymph node disease is no longer commonly performed since the advent of SLNB and
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involves lymph node dissection on patients without palpable lymph nodes or imaging studies suggesting lymph node disease. Proponents of ELND support this option, highlighting the challenges of SLN in the head and neck, especially the parotid region, due to possible atypical as well as multiple drainage patterns, SLN very close to the primary lesion, and the increased incidence of nodal recurrence in SLN negative patients. ADJUVANT THERAPY Radiotherapy
There is increased risk of recurrence in neck lymph nodes compared with other lymph node basins, with 24% and 14% recurrence rates in the neck and parotid, respectively.14 Furthermore, patients who have had recurrence are considered to be at increased risk of further recurrence.61,63 Current indications for adjuvant radiotherapy of primary site include64 HNM, especially mucosal melanomas, desmoplastic neurotropic melanoma, thick melanoma (>4 mm, especially if ulcerated or associated with satellite lesion), and inability to achieve negative resection margin. Lesions close to the eye or central and spinous nervous system can be excluded from radiotherapy.31 Although adjuvant radiotherapy has been shown to decrease the rate of local recurrence,65 even for patients with small tumors,66,67 there are conflicting reports on the effect of radiotherapy on survival.68,69 Chemotherapy
Interferon-a-2b (IFN-a-2b) has shown some benefit in patients at high risk of developing distant metastasis,70 but it has a limited benefit in patients with disseminated melanoma.71 In patients with nodal metastases, meta-analyses have shown a significant effect of IFN-a-2b on relapse-free survival and small improvements in survival.72,73 RECONSTRUCTION
WLE of melanomas of the head and neck can be especially challenging. The need for adequate margin excision is to be carefully balanced with both functional and cosmetic considerations, given the proximity of primary tumor to vital structures like eyes, nose, ears, and lips as well as to nerves and vessels. Also, due consideration should be given to the ease of follow-up examinations for recurrences, as areas at risk may no longer be anatomically oriented after reconstruction. Reconstruction Timing
Reconstruction can be performed immediately after WLE or may be delayed to ensure negative margins. Because of concerns about recurrence and need for surveillance, delayed reconstruction after WLE has been advised.74,75 Delayed skin grafting offers advantages of improved recipient bed vascularity, additional tissue bulk, reduced healing time, less contraction, and elimination of adjacent scarring to the defect.76 Bogle and colleagues77 found that immediate flap closure when primary closure is not possible can achieve acceptable functional and esthetic results, without compromising detection of recurrence. Immediate reconstruction may be considered in carefully selected patients. Sullivan and colleagues78,79 suggested that immediate reconstruction is safe for most HNM and did not find any difference in the incidence of positive margins between immediate and delayed reconstruction in 117 patients reviewed. Delayed reconstruction should be undertaken in patients with T4 HNM that is associated with an increased risk of positive margins after WLE, as well as in patients with perineural or bony invasion, or if postoperative radiotherapy is part of the management strategy.
Head and Neck Melanoma
Techniques
Reconstruction options include primary closure, skin graft, local skin flaps, regional muscle or fasciocutaneous flaps, free tissue flaps, tissue expansion, and a combination of one or more of these techniques (Table 2).80–82 Primary closure, although not always possible, may be performed if the defect is small and incisions are made along relaxing skin tension lines. Types of skin graft used can be full-thickness skin graft (FTSG) and split-thickness skin graft (STSG).
Table 2 Location-specific reconstruction options Scalp
MD
b,
*,
KEYWORDS Head and neck melanoma (HNM) Parotidectomy Sentinel lymph node Treatment of primary lesion Treatment of draining lymph node KEY POINTS Wide local excision is the mainstay in the treatment of the primary lesion with consideration given to specific anatomic constraints in head and neck melanoma (HNM). Sentinel lymph node biopsy (SLNB) is considered in all lesions with ulceration, mitoses greater than or equal to 1/mm2, stage1B or higher, and in all high-risk nonmetastatic melanoma. Lymphatic drainage patterns in the head and neck can be atypical and may involve the parotid gland. Higher rate of locoregional recurrence has been reported in SLN-negative patients in HNM compared with cutaneous melanoma elsewhere. Location of primary, SLNB status, node-positive disease, and the drainage pattern determines the extent of neck dissection and parotidectomy. Reconstructive strategy must be considered in multidisciplinary teams with reconstructive surgeons for large head and neck defects.
INTRODUCTION Epidemiology
It is estimated that melanoma of the head and neck comprises 6% to 25% of all cutaneous melanomas.1–3 Head and neck melanoma (HNM) is uncommon in patients under 30 years of age and is usually seen in adults older than 70 years.4 Men are at higher risk of developing HNM than women,5–7 and the incidence of melanoma of the face and neck is two times greater in men than in women, although the differences
Funding Support: None. Conflict of Interest: The authors have nothing to disclose. a Department of General Surgery, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA; b Department of General Surgery/Surgical Oncology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA; c Department of Otolaryngology/Head and Neck Surgery, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA * Corresponding author. E-mail address: [email protected] Surg Clin N Am 94 (2014) 1091–1113 http://dx.doi.org/10.1016/j.suc.2014.07.011 surgical.theclinics.com 0039-6109/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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are smaller in younger age groups.8 Sixty to 90% of HNMs occur on the face,3,9 with the scalp, neck, and ears less commonly involved (Fig. 1).10–14 The higher incidence of HNM in relation to total body surface area may be explained by the fact that the head and neck area is more affected by increased exposure to ultraviolet radiation and the higher density of melanocytes in the head and neck.3,15 Risk factors for HNM include the following: Continuous (occupational) sun exposure Higher levels of occupational sun exposure, whereas extremity melanoma was associated with a higher total sun exposure16,17 Lighter skin17,18 Increased number of sunburns Nevus count, although a positive association between nevus counts to HNM is weaker than that between nevus counts and trunk or extremity melanoma17 CLINICAL PRESENTATION History
As with cutaneous melanoma at any site on the body, early detection and diagnosis of HNM are vital for effective and timely therapeutic intervention. Approximately half of the time, melanoma is self-discovered, with 26% discovered by medical providers and the rest by family members or others.19 The most common presenting symptom is color change or growth of a preexisting lesion.20 Other presenting symptoms include itching, bleeding, ulceration, and pain, or paresthesias that would be a manifestation of late symptoms, occurring in thick melanomas.20 Patients should be asked about risk factors including sun exposure, history of sunburns, and especially family history, because up to 10% of melanoma cases report a first-degree or seconddegree relative with melanoma.21 Physical Examination
A meticulous and complete skin examination along with examination of typical and atypical lymphatic drainage basins should be performed, noting the number, type, and characteristics of moles or nevi. The American Cancer Society recommended ABCDEs (asymmetry, border, color, diameter, evolving) provide a simple guideline
Fig. 1. Distribution of HNMs. (Data from Refs.10–14)
Head and Neck Melanoma
to detect early warning signs of melanoma. Gachon and colleagues22 suggested the use of the “ugly duckling” warning sign, which focuses on the identification of pigmented or clinically amelanotic lesions that look different from the rest, to assist with the detection of lesions that do not fit the classic ABCDE criteria. Although all of these factors have been found to be predictors of a malignant lesion, an irregular border is the strongest predictor.23 In the head and neck, particular attention must be devoted to examining the scalp, including the hair-bearing areas, ears, nose, and eyelids in addition to the face. The hair-bearing scalp areas are best examined after taking off all hair bands and clips and then parting the dry loose hair in a systematic fashion using a comb. A complete examination of the ear includes the pinna, the external auditory canal with and without an otoscope, as well as behind the pinna. Both eyelids should be examined when open and closed. Examination of the lymph nodes should include both ipsilateral and contralateral submental, submandibular, jugular, anterior central, and posterior, as well as the supraclavicular and axillary basins. CLASSIFICATION AND STAGING Morphology
The morphologic types seen in HNM are similar to cutaneous melanoma. Superficial spreading melanoma is the most common subtype, accounting for 50% to 80% of cases, and appears flat because of the horizontal radial pattern of growth, which is followed by a subsequent vertical growth phase characterized by the presence of a dominant nest in the papillary dermis. Nodular melanoma, accounting for 20% to 30% of cases, is thick on palpation because of early vertical growth of the cancer cells. Lentigo maligna melanoma is commonly seen in later years within preexisting large freckles or Hutchinson freckles (lentigo maligna). Desmoplastic neurotropic melanoma is a variant that often lacks pigment and clinically has characteristics similar to hypertrophic scar, dermatofibroma, or fibrosarcoma with a propensity toward neural invasion. Although it is a rare form of melanoma, accounting for only around 1% of all cases, about half arise in the head and neck.24 Histology
The Clark Level and Breslow Thickness are the 2 histologic systems used for classification. Clark grading involves a qualitative system to determine the depth of the primary melanoma based on the level of invasion of the dermis, whereas the Breslow thickness system is based on the quantitative measurement of thickness in millimeters from the stratum granulosum to the deepest point of invasion.24 The Breslow thickness provides a powerful tool for prognostic staging of melanoma; consequently, emphasis on the Clark system has decreased. Clinical Staging
Based on current evidence, the American Joint Committee on Cancer has revised the staging for cutaneous melanoma.25 The latest revision includes ulceration in the scheme and replaces the Clark Level with mitotic rate in thin melanoma, highlighting their association with prognosis. Serum lactate dehydrogenase is included in M classification in addition to defining micrometastases and macrometastases. INVESTIGATIONS Biopsy
Excisional biopsy is the preferred technique for small, accessible lesions with a 1-mm to 2-mm margin because it is diagnostic, potentially therapeutic, and prognostic.
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Incisional or punch biopsy may be used for sampling larger lesions. Deep shave biopsies are frequently used when lesions are suggestive of both epidermoid carcinoma and melanoma.24 Needle biopsies are useful for assessing suspicious lymph nodes or metastasis. Careful planning of biopsy orientation is critical in HNM to avoid compromise if subsequent wide local excision and reconstruction becomes indicated. Imaging Recommendations
The role and extent of imaging for patients with HNM is controversial.26 Although sentinel lymph node biopsy (SLNB) is not 100% accurate, it is the most reliable means for regional staging and has better sensitivity and specificity than computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), elective lymph node dissection (ELND), and clinical examination.27 There are no recommended routine baseline or surveillance laboratory tests (lactate dehydrogenase, liver function test, chest radiography, CT, MRI, PET, bone scans, or gastrointestinal series) in patients with no signs or symptoms of metastasis. Fluorodeoxyglucose-PET has been shown to be effective for detecting metastatic melanoma, with sensitivity and specificity reported as high as 74% to 100% and 67% to 100%, respectively.28,29 PET is not recommended in early-stage node-negative HNM, but may be considered if symptoms warrant further imaging or to follow disease burden in stage IV disease.30 TREATMENT AND PATHOLOGIC STAGING
The oncologic management is best delivered by a multidisciplinary team, including surgeons, reconstructive surgeons, and medical and radiation oncologists. Treatment of Primary Lesion Wide local excision
Wide local excision (WLE) of the index lesion is the primary treatment of cutaneous melanoma. Malignant cells may extend microns to several millimeters beyond clinically visible margins, thus necessitating a wider and frequently deeper excision to ensure as complete a removal as possible. The recommendations for surgical margins for WLE for the head and neck are similar to other cutaneous melanomas, but this is not always possible because of the functional and cosmetic disability that may arise.31 Historically, a 5-cm margin excision was done until the 1970s, when Breslow and Macht32 reported successful treatment in thin melanoma patients with narrower margin excision. A prospective randomized control study by the World Health Organization33 on melanoma concluded that there was no significance in recurrence rates between 1-cm or 3-cm margin resection in cutaneous melanomas 2 mm or less. Surgical margin recommendations from the American Academy of Dermatology (AAD)34 published in 2011 are based on both evidence from prospective randomized control studies and consensus opinion when no prospective data were available (Table 1). The basis for these recommendations is as follows: Wide excision for melanoma is associated with reduced recurrence. For thin melanomas, currently there is no high-quality evidence to support excision of more than a 1-cm margin in improving survival or local recurrence rates. For primary melanomas of any thickness, there is no evidence to suggest that margin excision of more than 2 cm provides any additional benefit in terms of survival or local recurrence rates.
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Table 1 American ADA surgical margin recommendations for primary cutaneous melanoma Breslow Thickness
Clinically Measured Surgical Margina
In situ
0.5–1.0 cm
1 mm
1 cm
1.01–2.0 mm
1–2 cm
>2 mm
2 cm
a
Wider margins might be necessary for lentigo maligna subtype. Adapted from Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol 2011;65:1032–47.
The AAD also recommends that the depth of excision be carried out to the level of muscle fascia, if possible, or at least to deep adipose tissue depending on location.34 A wider excision may be considered for lentigo maligna melanoma, given the potential for extensive subclinical extension, particularly in the head and neck. It is important to note that although the recommendations for surgical margin resection serve as guidelines, margins should be individualized. Adherence to these recommendations might be particularly challenging in HNM because of cosmetic and functional concerns associated with wide excision. Careful consideration of the risk of recurrence, defect size, and location should guide the extent of resection. Sentinel Node Biopsy and Lymphatic Drainage Patterns
SLNB was introduced by Morton and colleagues35 and modified by Robinson and colleagues36 to include preoperative lymphoscintigraphy. SLNB is used to identify the immediate draining lymph node from the primary tumor by injecting radioisotope and or blue dye with or without preoperative lymphoscintigraphy.37–39 The principle of SLNB is based on the rationale of the primary tumor having defined lymphatic drainage into specific nodal basins with the goal of identifying metastasis to regional lymph nodes. No evidence of metastasis in the sentinel lymph node (SLN) is highly indicative that the remaining nodes will not have metastatic spread.35 SLNB is the most sensitive and specific staging test for identification of micrometastatic melanoma in regional lymph nodes.40 As with melanoma of the trunk and extremities, SLNB status is the most important prognostic factor in HNM patients.31,41,42 SLNB is particularly useful in midline HNM, as lymphatic drainage in the head and neck is often aberrant and can result in identification of the sentinel node in more than one nodal basin or in an atypical, bilateral, or contralateral nodal basin. Some authors have noted a wide range in the false negative rates (3.4%–10.4%) for HNM SNLB as well as a decreased HNM SLN positive rate (10%–15%) compared with cutaneous melanoma elsewhere (16%–23%).43,44 Others have reported SLN positive rates in HNM that are not significantly different from other cutaneous melanomas, although the small patient numbers in these studies limit their interpretation. A worse survival in HNM with positive SLN compared with other anatomic locations has also been suggested.43 Indications for SLNB
Indications for consideration of SLNB for HNM are similar to those for other cutaneous melanomas and include all patients with lesions that have a Breslow thickness greater than 1.0 mm and a clinically negative nodal basin and all patients with ulceration or an
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increased mitotic rate (Fig. 2). SLNB may be considered for melanoma patients with less than 1.0-mm thickness with adverse features, including positive deep margins, lymphovascular invasion, young patients, or Clark Level IV or greater.42 Although some prefer not to perform SLNB after WLE due to disruption of natural lymphatic pathways, it may be acceptable even after WLE, if extensive reconstruction and lymphatic dissection have not been performed. One must also be prepared for drainage into atypical, contralateral, and deep cervical lymph node basins. SLNB technique
Patients are given intradermal injections of a radioactive colloid, usually Technectium99 sulfur colloid (0.5 mCi), around the primary lesion, after which a lymphoscintigraphy may be performed. If injection of the radiotracer into the subcutaneous tissue results in failure to detect the sentinel node, a repeat injection should be performed. Under anesthesia, intradermal isoflurane blue or methylene blue dye can be injected in addition to the radioactive colloid to map the lymph node. WLE of the melanoma may be performed first to reduce radioactivity from the primary injection, which may interfere with the ability to detect tracer uptake in the SLN; this is especially true in HNM, as the SLN may be in close proximity to the primary lesion. An intraoperative handheld gamma probe is used to localize the SNL and lymphatic channels.26 Cervical SLNB is performed using a 1-cm to 3-cm incision over the area of maximal radioactivity, while a periauricular incision is usually used for the parotid region. Identification and removal of the sentinel node are performed for all hot lymph nodes until the gamma counts in the basin are equal or less than 10% of the hottest lymph node removed.40 Histologic evaluation
Once the SLN is identified and excised, it is recommended that histologic evaluation be done using permanent paraffin section with hematoxylin and eosin staining and immunohistochemistry (IHC), as frozen sections have a high false negative rate ranging from 5% to 10%.45 Higher sensitivity of the IHC markers S-100 and MelanA make it the recommended stain compared with HMB-45, which is less sensitive. Permanent section allows for accurately discussing the prognosis and treatment of positive lymphatic nodes with the patient in an office setting before proceeding with definitive treatment.
Fig. 2. Algorithm for treatment of lymph node basin in HNMs. LN, lymph node; SLNB, sentinel lymph node biopsy.
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ELND
ELND, with the aim of clearing all potential lymph nodes with metastatic melanoma, can have significant morbidity from lymphedema and injury to the major vascular and nervous structures. The survival benefit from ELND in HNM has not been proven, and with findings from the Multicenter Selective Lymphadenectomy trials-I,37 SLNB has become a more favored approach. A systematic review by Tanis and colleagues46 concluded that there was no conclusive evidence on the advantage of either elective neck dissection or SLNB in patients with clinically node-negative HNM of intermediate thickness. In a study of 46 patients with metastatic malignant melanoma, the authors concluded that involvement of more than 4 cervical or parotid nodes resulted in significant increase in distant metastases, but did not note an impact of location or metastases or method of neck dissection on survival.47 Bodem and colleagues48 suggested that in patients with proven lymph node metastases, complete neck dissection might be of benefit because the number of infiltrated nodes is often higher than expected. The role of neck dissection in HNM is not yet fully established. The number and levels should be determined based on tumor location and SLNB status. Prospective studies are necessary to provide convincing, reliable, and validated guidelines for cervical lymph node dissection in HNM. Parotid Management
Lymphatic drainage from the face, cheeks, lips, ears, and anterior scalp can include the parotid in addition to the neck. With a primary lesion in this location, the parotid could be a potential source of metastasis, with around 25% to 30% of HNM draining into the parotid lymph node basin.49,50 Although there is no consensus, the options when lymphoscintigraphy shows drainage to the parotid include parotid-sparing SLNB and superficial parotidectomy followed by cervical lymph node dissection in the event of confirmed metastasis to the SLN. The multiplicity, widespread distribution, and high frequency of parotid nodes have prompted some surgeons to advocate superficial parotidectomy over mapping.51 Suton and colleagues52 suggested that parotidectomy be considered for all HNM, except for posterior primaries and lower neck melanomas. Some authors also recommend parotidectomy for anterior melanoma.53,54 Because of the risk of neurovascular injury to the facial nerve and vessels, others have suggested a targeted, parotid-sparing approach for SLN in the parotid region. The targeted, parotid-sparing approach for SLN is technically more demanding and may place the facial nerve at a higher risk of injury.55 There are also concerns that fibrosis and inflammation after SLNB might result in an increased risk of facial nerve injury if reoperation of the parotid is necessary. Some studies have reported the low morbidity and accuracy of sentinel lymphadenectomy in the parotid gland.56,57 Proponents of the parotid lymph node biopsy highlight it as a less invasive operation compared with a superficial parotidectomy, with no increase in recurrence. Although there is a theoretic increased risk of injury to the facial nerve while doing a parotidectomy as a secondary procedure after the SLNB, some groups have noted no increase in facial nerve or bleeding complications.55 It would be prudent to prepare for a selective lymph node biopsy in the parotid region by an experienced surgeon, while also being prepared to perform a superficial parotidectomy if the SLN is not identified. A parotid lesion can also be investigated with a needle biopsy. Neck Dissection Technical aspects
In general, forehead and anterior scalp melanomas spread to the parotid, periparotid, and upper jugular lymph nodes, whereas those in the posterior scalp and occiput
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spread to the postauricular, suboccipital, and posterior triangle lymph nodes. Melanoma of the face and neck usually metastasize to the facial, submental, submandibular, and deep cervical nodes. The American Head and Neck Society (AHNS) classified the lymph nodes of the neck into 5 levels on each side, a central submental triangle, and a single central compartment (Fig. 3). The cheek and eyelid regions have 2 lymphatic drainage patterns, one to the parotid nodes and the other to level IB. The lymph drainage patterns in the lip region are to level IA or IB.58 Lymphatic drainage of the ear has no predictable pattern, but it most commonly drains to cervical level II and the preauricular and postauricular basins.59
Fig. 3. Level wise classification of neck nodes (Supported by the American Head and Neck Society). (From Harisinghani NG. Atlas of lymph node anatomy. New York: Springer; 2013. p. 2; with permission.)
Head and Neck Melanoma
Current guidelines for management of primary cutaneous melanoma do not specify recommendations for HNM.34 It is justifiable to perform regional lymphadenectomy alone in cases of primaries of the posterior scalp and posterior neck with no involvement of the submandibular and submental triangles.52 The AHNS and the American Academy of Otolaryngology-Head and Neck Surgery classified neck dissections into the following: 1. Radical neck dissection (RND)—removal of all ipsilateral cervical lymph node groups from levels I through V, together with spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle. 2. Modified radical neck dissection (MRND)—removal of all lymph node groups routinely removed in RND, but with preservation of one or more nonlymphatic structures (spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle). 3. Selective neck dissection (SND)—cervical lymphadenectomy with preservation of one or more lymph node groups and all nonlymphatic structures routinely removed in RND. 4. Extended neck dissection—removal of one or more additional lymph node groups or nonlymphatic structures, or both, not encompassed by RND. Indications
Neck dissections may be performed in the following clinical scenarios: clinically positive lymph nodes; positive SLNB in the neck; positive SLN in the parotid region; extensive invasive lymph node disease; and clinically negative lymph node disease. Clinically positive lymph nodes—therapeutic neck dissection Therapeutic lymph node dissection refers to the lymph node removal for clinically evident or palpable lymph nodes. The extent of neck dissection would depend on the number and location of the nodes as well as the primary lesion. Positive SLNB in the neck—therapeutic neck dissection Completion lymph node dissection is the lymphadenectomy done after a positive SLNB. The extent of neck dissection depends on the level of the SLN and the location of the primary lesion. Gyorki and colleagues60 reported that positive nonsentinel lymph nodes were mostly identified within or adjacent to the nodal level containing the SLN. Positive parotid SLN—therapeutic neck dissection and parotidectomy A parotidectomy is indicated with positive parotid SLN as well if clinically apparent disease is present in the parotid. A primary lesion involving the parietal or frontal scalp, face, cheeks, nose, or ear could potentially have drainage to the parotid in addition to the neck; therefore, a parotidectomy should be performed in conjunction with the neck dissection when the SLN is positive. Extensive invasive lymph node disease—therapeutic neck dissection including nonlymphatic structures RND should only be performed with extensive involvement
of the spinal accessory nerve, internal jugular vein, or sternocleidomastoid muscle. There are some data supporting MRND as having comparable efficacy to RND and advantageous efficacy over selective ND49,61; however, Shah and colleagues62 recommend complete RND for therapeutic conditions and limited neck dissection for elective procedures. No known lymph node disease—elective neck dissection ELND for clinically negative lymph node disease is no longer commonly performed since the advent of SLNB and
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involves lymph node dissection on patients without palpable lymph nodes or imaging studies suggesting lymph node disease. Proponents of ELND support this option, highlighting the challenges of SLN in the head and neck, especially the parotid region, due to possible atypical as well as multiple drainage patterns, SLN very close to the primary lesion, and the increased incidence of nodal recurrence in SLN negative patients. ADJUVANT THERAPY Radiotherapy
There is increased risk of recurrence in neck lymph nodes compared with other lymph node basins, with 24% and 14% recurrence rates in the neck and parotid, respectively.14 Furthermore, patients who have had recurrence are considered to be at increased risk of further recurrence.61,63 Current indications for adjuvant radiotherapy of primary site include64 HNM, especially mucosal melanomas, desmoplastic neurotropic melanoma, thick melanoma (>4 mm, especially if ulcerated or associated with satellite lesion), and inability to achieve negative resection margin. Lesions close to the eye or central and spinous nervous system can be excluded from radiotherapy.31 Although adjuvant radiotherapy has been shown to decrease the rate of local recurrence,65 even for patients with small tumors,66,67 there are conflicting reports on the effect of radiotherapy on survival.68,69 Chemotherapy
Interferon-a-2b (IFN-a-2b) has shown some benefit in patients at high risk of developing distant metastasis,70 but it has a limited benefit in patients with disseminated melanoma.71 In patients with nodal metastases, meta-analyses have shown a significant effect of IFN-a-2b on relapse-free survival and small improvements in survival.72,73 RECONSTRUCTION
WLE of melanomas of the head and neck can be especially challenging. The need for adequate margin excision is to be carefully balanced with both functional and cosmetic considerations, given the proximity of primary tumor to vital structures like eyes, nose, ears, and lips as well as to nerves and vessels. Also, due consideration should be given to the ease of follow-up examinations for recurrences, as areas at risk may no longer be anatomically oriented after reconstruction. Reconstruction Timing
Reconstruction can be performed immediately after WLE or may be delayed to ensure negative margins. Because of concerns about recurrence and need for surveillance, delayed reconstruction after WLE has been advised.74,75 Delayed skin grafting offers advantages of improved recipient bed vascularity, additional tissue bulk, reduced healing time, less contraction, and elimination of adjacent scarring to the defect.76 Bogle and colleagues77 found that immediate flap closure when primary closure is not possible can achieve acceptable functional and esthetic results, without compromising detection of recurrence. Immediate reconstruction may be considered in carefully selected patients. Sullivan and colleagues78,79 suggested that immediate reconstruction is safe for most HNM and did not find any difference in the incidence of positive margins between immediate and delayed reconstruction in 117 patients reviewed. Delayed reconstruction should be undertaken in patients with T4 HNM that is associated with an increased risk of positive margins after WLE, as well as in patients with perineural or bony invasion, or if postoperative radiotherapy is part of the management strategy.
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Techniques
Reconstruction options include primary closure, skin graft, local skin flaps, regional muscle or fasciocutaneous flaps, free tissue flaps, tissue expansion, and a combination of one or more of these techniques (Table 2).80–82 Primary closure, although not always possible, may be performed if the defect is small and incisions are made along relaxing skin tension lines. Types of skin graft used can be full-thickness skin graft (FTSG) and split-thickness skin graft (STSG).
Table 2 Location-specific reconstruction options Scalp
