AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

Epidemiology

Despite recent declines in the incidence and mortality of cancer overall, the incidence of cutaneous melanoma continues to escalate. As a result, 56,940 new cases of melanoma will be diagnosed in the United States in 2007. From these statistics, we can extrapolate that roughly 1 in every 76 American males and 1 in every 163 American females will develop malignant melanoma by the age of 70.  Since approximately 10-20% of all cutaneous melanomas arise in the head and neck region, the incidence in this area has similarly increased, from 2 per 100,000 in 1996 to 2.7 per 100,000 in 2001.

The mortality associated with cutaneous melanoma is also growing at a rate second only to that of lung cancer. In 2007, greater than 8,100 patients are expected to succumb to the disease in the United States alone. Although the 5-year relative survival rates for cutaneous melanoma have demonstrated a 10% improvement over the past 3 decades, 10-year survival rates remain essentially unchanged at 54%.

Of the lesions that develop in the head and neck region, most melanomas arise in the face (47%). The remainder are found on the neck, which accounts for 29%, the scalp (14%), and the ear (10%). In addition, approximately 55% of mucosal melanomas are found in the head and neck.

Risk factors

Many risk factors for melanoma have been identified. The most important risk factor is exposure to sunlight, particularly UV-B radiation. Recent studies suggest that cutaneous melanomas of the head and neck are significantly more likely to occur in people with high levels of total sun exposure. Conversely, melanomas on the trunk tend to develop on people with lower levels of ambient sunlight exposure, but who also experience higher levels of recreational exposure on the chest and back. Sunburns early in life and exposure to UV radiation from tanning beds are other factors in the development of melanoma. 

People who burn easily, such as those with fair or red hair, blue eyes, and light-colored skin, are most prone to develop melanoma. The presence of freckling and benign nevi also indicates an increased risk for melanoma development. The number of nevi appears to be more important than the size. The presence of more than 100 benign-appearing nevi in adults or greater than 50 clinically normal nevi in children increases risk.

Additionally, a patient with any atypical or dysplastic nevi is at a heightened risk. Patients with a previously diagnosed melanoma are also at increased risk, and 5-10% eventually develop a second primary.

Finally, genetics may play a role. Patients having at least one affected first-degree relative possess a higher likelihood of developing malignant melanoma. The CDKN2A (p16) chromosomal mutation is the most commonly isolated genetic culprit. 

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Skin Cancer and Skin Biopsy.

DIAGNOSIS

Section 3 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

Despite great advances in the treatment of melanoma, the best hope for patients remains early diagnosis. Most melanomas are initially discovered by the patient or his/her partner. Classic warning signs and symptoms include any cutaneous lesion that changes color, size, or shape. Persistent pruritus is also a common early symptom. More advanced lesions frequently become friable, tender, painful, crusted, or ulcerated.

The American Cancer Society developed the ABCDEs to serve as a simple guideline of early melanoma warning signs. Melanoma should be suspected in any skin lesion that is Asymmetric, that has an irregular Border, that is variegated or dark in Color, that is larger than 6 mm in Diameter, or that is Elevated. Experienced visual inspection is often the key to distinguishing a melanoma from other common benign pigmented skin lesions, such as: lentigo simplex, junctional nevus, compound nevus, intradermal nevus, blue nevus, solar lentigo, seborrheic keratosis.

Although less than 25% of melanomas are initially diagnosed during routine office examinations, those that are found by physicians tend to be thinner. Thus, a regular full-body cutaneous examination by the primary care provider is crucial to diagnosis at an early stage. The entire cutaneous surface of the head and neck should be examined, paying particular attention to sun-exposed areas. Certain areas are often overlooked: the scalp, the oral cavity, and the neck. The scalp can easily be examined by using a comb to separate the hair. The oral cavity is often forgotten in the search for melanoma; however, its importance cannot be understated. To achieve any hope of curing a mucosal melanoma, oral pigmented lesions must be found and a biopsy sample obtained early. The neck is important in the search for regional metastases.

Types of Cutaneous Malignant Melanoma

Mucosal melanoma is a rare form of melanoma that accounts for approximately 1-4% of cases of head and neck melanoma. Most of these tumors (55%) arise in the nasal cavity, followed by the oral cavity (40%). Although the growth patterns of mucosal melanoma tend to mirror the nodular pattern of their cutaneous counterparts, they differ in that tumoral thickness is not well correlated with the prognosis. Although most patients present with clinically localized disease, over 50% experience local recurrence after treatment. Prognosis is dismal, regardless of the thickness of the primary lesion. In the literature, mean 5-year survival rates range from 0-44%.

Staging

• Stage I and II - Localized primary melanoma
• Stage III - Metastasis to single regional lymph node basin (with or without in-transit metastases)
• Stage IV – Distant metastatic disease

Clark levels

Two popular microstaging systems for melanoma are the Clark levels and the Breslow thickness classifications. The Clark method is used to stage the melanoma according to its depth of penetration into the deep levels of skin, as follows:

• Level I - Confined to the epidermis
• Level II - Spread into the papillary dermis
• Level III - Spread into the papillary dermis–reticular dermis junction
• Level IV - Spread into the reticular dermis
• Level V - Spread into the subcutaneous fat

In the Clark system, level I or II lesions are typically tumors growing in the radial phase. Level III and higher tumors have reached the vertical growth phase. In their study, the AJCC Melanoma Task Force determined that the Clark level is an independent predictive feature for thin melanomas (T1) but not for thicker lesions.  Therefore, the level of invasion is currently only considered for thin melanomas.

Breslow thickness

The Breslow thickness classification is used to stage melanoma according to the thickness of the lesion, as measured from the granular layer of the epidermis to the deepest point of tumor infiltration in the vertical dimension. The system is as follows:

• Less than 0.76 mm - Thin lesion (T1)
• 0.76-1.50 mm - Intermediate thickness (T2)
• 1.51-4.00 mm - Intermediate thickness (T3)
• More than 4 mm - Thick lesion (T4)

The Breslow thickness classification is generally the most widely accepted method because its results are most consistently reproducible. Based on the results of the Melanoma Task Force study, the revised AJCC staging system modified this classification system to use even-integer cut points of 1, 2, and 4 mm.

Prognostic Factors

• The thickness of the tumor
• The status of the regional lymph-node basin.

Prognostic indicators can be further subdivided based on TNM staging. When considering localized disease (T classification), tumor thickness is the most significant prognostic indicator; however, the presence of ulceration has also been found to be an important predictor of outcome.

Three statistically significant prognostic factors have been identified in regional disease (N classification). The most important indicator for patients with nodal metastasis is the number of positive lymph nodes. Tumor burden within the lymph nodes (microscopic vs macroscopic disease) and ulceration of the primary tumor are also important factors.

Finally, in patients with distant metastases (M classification), the anatomic site of spread is the most important indicator of prognosis.  Patients with involvement of the skin, subcutaneous tissues, or distant lymph nodes have a better prognosis than those with metastases to the lungs or visceral organs.

Although not included in formal staging systems, the anatomic location of primary lesions has also been found to correlate with prognosis. In their review of 5093 patients, Garbe et al discovered significantly lower 10-year survival rates for cutaneous melanoma on the head and neck (54%) than for those on the trunk (61%), the upper extremities (76%), or lower extremities (71%).¹ Furthermore, the prognosis for patients with lesions on the face appears to be more favorable than for those with cutaneous melanoma of the scalp or neck.

TREATMENT

Section 4 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

Biopsy

The prognosis and treatment of cutaneous melanoma depends greatly on the thickness of the lesion. Thus, the key to evaluation of suspected lesions focuses on obtaining a full-thickness biopsy. Excisional biopsy is the best choice for small lesions or for large lesions in cosmetically favorable locations. Excisional biopsy should extend down to the subcutaneous fat, with a small (2-3 mm) peripheral margin. Punch biopsy can be performed for large lesions or for lesions with a low suspicion of melanoma in a cosmetically unfavorable location. The biopsy should be performed at the highest or thickest point of the lesion.

Incisional biopsy is not recommended. Likewise, techniques that do not permit a full-thickness sample, such as shave or curette biopsy, are discouraged. Furthermore, pigmented lesions should not be definitively treated with laser therapy, electrocautery, or cryotherapy unless biopsy analysis proves them to be noncancerous.

Excision

To date, 4 prospective, randomized trials have been conducted to determine adequate margins of resection. Veronesi et al in 1988, Balch et al in 1993, Banzet et al in 1993, and Cohn-Cedermark et al in 2000 each examined the local recurrence rates for melanomas of varying thickness.^{2, 3, 4, 5} On the basis of their results, margins of 0.5 cm are recommended for melanoma in situ, margins of 1 cm are proposed for lesions smaller than 1 mm, margins of 1-2 cm are proposed for lesions of 1.01-2.0 mm thickness, and margins of 2 cm are proposed for lesions larger than 2 mm. In general, the margin of excision should be approximately 10 times as wide as the deepest penetration of tumor; therefore, a 2-cm margin is recommended for a lesion that is 2 mm thick.

Surgeons operating in the head and neck face the difficult dilemma of removing enough tissue to obtain adequate tumor-free margins yet retaining normal tissue in a cosmetically sensitive area. The desire to retain tissue may contribute to the generally increased recurrence rate of head and neck melanoma.

Mohs surgery

The indications for Mohs micrographic surgery (MMS) have been widely expanded in recent years. The American Academy of Dermatology has now recognized Mohs micrographic surgery as a useful technique for the treatment of melanoma, particularly of the face. The National Institutes of Health also recognizes Mohs surgery as a potentially useful technique for melanoma. However, in its 1997 Melanoma Surgical Practice Guidelines, the Society of Surgical Oncology maintains that Mohs surgery is inappropriate for the treatment of melanoma.

In 1997, Zitelli et al showed that the 5-year survival and metastatic control rates for Mohs surgery were equivalent to or better than rates in matched historical controls treated with wide local excision.⁶ Using the Mohs technique, the authors were able to spare normal tissue because 83% of the tumors were excised with a 6-mm margin. These results were confirmed by Bricca et al in their review of 625 patients who underwent MMS for primary cutaneous melanoma.⁷ MMS demonstrated lower overall recurrence rates (0.2% versus 9%) and lower metastasis rates (across all Breslow thickness groups) when compared with treatment with conventional surgery.

Despite these promising results, MMS is not currently considered the standard of care for cutaneous melanoma of the head and neck. More study is required before any recommendations can be made regarding its use.

MANAGEMENT OF THE LYMPHATIC BASIN

Section 5 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

Elective dissection of the lymph nodes

For most solid tumors, including cutaneous malignant melanoma, the most powerful predictor of survival is the status of the regional lymph nodes. As the understanding of the tumor biology of malignant melanoma continues to evolve, the traditional role for lymphadenectomy in the evaluation of at-risk regional nodes has been challenged.

For a patient with clinical evidence of regional nodal metastases at presentation, lymph node dissection with treatment of the primary lesion is appropriate. The procedure can often be selective neck dissection to remove the specific lymphatic sites involved with disease because of the tendency of regional melanoma metastases to grow in a pushing rather than an invasive fashion. For clinically evident, extensive regional metastases in the neck, comprehensive neck dissection is appropriate.

The site of the primary lesion must be considered when neck dissection is planned in order to remove all intervening lymphatic drainage to the suspicious or positive node. The primary site must also be considered when one plans elective lymph node dissection (ELND) for clinically negative necks. For primary lesions involving the parietal or frontal scalp, temple, lateral forehead, lateral cheek, or ear, superficial parotidectomy in conjunction with neck dissection is appropriate because the parotid may harbor the primary echelon nodes. For a primary lesion on the scalp posterior to a line drawn from the tragus to the vertex of the scalp, posterior-lateral neck dissection, which includes the postauricular, suboccipital, external jugular, and posterior triangle nodal groups, is appropriate. For the patient with an unknown primary lesion with evidence of neck nodal disease, a level I-V comprehensive neck dissection is appropriate.

Notable controversy arises in the treatment of the clinically negative nodal basin. For thin (1.0 mm) melanomas, the risk of occult lymphatic metastases is sufficiently low that prophylactic neck dissection is unwarranted. Patients with thick (>4.0 mm) melanomas have a poor prognosis, and prophylactic neck dissection does nothing to alter that prognosis. The strongest support for elective treatment of the clinically negative nodal basin is for melanomas of intermediate thickness (1.01-4.00 mm).

Several retrospective studies have demonstrated a possible survival benefit for elective treatment of the clinically negative nodal basin; however, data from 2 large prospective multicenter trials failed to show such an advantage. The Intergroup Melanoma Surgical Trial (IMST) was the first prospective, randomized trial to show a survival benefit in patients with melanoma treated with elective node dissection. However, this benefit was limited to a subset of patients 60 years of age and younger, as well as those whose tumor was nonulcerated or measured 1-2 mm in thickness.

Thus, until recently, a strong argument could be made for the “wait-and-see approach” to the clinically negative nodal basin because of the morbidity of dissection without evidence of a clear survival benefit. That is, until results of the Eastern Cooperative Oncology Group trial of high-dose interferon (IFN) alfa-2b as adjuvant treatment for high-risk melanomas indicated that elective nodal dissection should not be delayed until disease is clinically detectable.⁸ In this randomized prospective trial, the relapse-free survival and overall survival rates improved in patients treated with IFN alfa-2b versus controls subjects. Striking differences were noted in a small subset of patients who had occult nodal metastases treated with IFN versus control. Data from this trial strongly support an elective nodal staging procedure in all patients with intermediate-thickness malignant melanoma.

Biopsy of sentinel lymph nodes

The concept of the sentinel lymph node (SLN), as Morton first described it, has emerged as a potential solution to the debate over elective node dissection.⁹ The SLN is the first node in the drainage pattern of a tumor. In theory, malignant cells must pass through the SLN before continuing on to second-echelon nodes. Therefore, by sampling the SLN, the surgeon can detect the earliest evidence of regional disease in the clinically negative nodal basin.

The techniques of biopsy and examination of the SLN have evolved rapidly over the past few years. In the current technique, radioactive material and/or blue dye is injected at the periphery of the tumor.  Preoperative lymphoscintigraphy, in addition to an intraoperative, handheld gamma probe, is then used to locate the first lymph node(s) draining the tumor. These nodes are excised and sent for pathologic evaluation. Patients with pathologically positive SLNs receive therapeutic nodal dissection.
 
Over a decade of experience has consistently demonstrated that intraoperative lymphatic mapping and SLN biopsy function is a highly sensitive surrogate to elective lymph node dissection, accurately reflecting the histologic status of the entire nodal basin. With the combination of blue dye and gamma probe lymphoscintigraphy, SLN biopsy has a success rate of over 90% with a false-negative rate of 2% or less.

The technique of SLN biopsy has many potential advantages over ELND. First, preoperative lymphoscintigraphy has the ability to identify all nodal basins involved in the drainage of the primary tumor. Conversely, ELND has traditionally been directed at the most likely site of nodal drainage. Several lymphoscintigraphy studies have revealed that a significant number of tumors drain to either multiple or unpredictable nodal basins. This is particularly true for lesions developing in areas with rich lymphatics, such as the head and neck.

This was confirmed by O’Brien et al, who reported a 34% rate of discordance between clinically predicted lymphatic drainage pathways and the pathways found during lymphoscintigraphy of 97 patients with cutaneous head and neck melanoma.¹⁰ Thus, elective nodal dissection can be misdirected in up to one third of cases. By contrast, SLN biopsy targets the most likely node basins to present with metastatic disease, thereby providing surgeons with more accurate information for prognosis and staging.

A second advantage of SLN biopsy over ELND stems from the fact that an average of 1-3 nodes are excised, rather than an entire nodal basin. This feature allows more thorough examination of the sampled nodes for evidence of metastatic disease. Typical examination of a lymph node involves the staining of 1 or 2 sections through the middle of the node with routine hematoxylin and eosin. Using this technique, less than 1% of the submitted material is scrutinized. This technique is accurate for detecting 1 tumor cell in the background of 1,000 healthy cells.

Newer techniques have been developed to increase the sensitivity of tumor cell detection. These include immunohistochemical techniques, cell culture, and polymerase chain reaction (PCR)–based techniques, which can augment sensitivity up to 1 tumor cell in 100,000 healthy cells, an increase of 2 magnitudes. Nevertheless, these sophisticated methods are too costly and labor intensive to be routinely applied to the entire contents of a lymphatic basin.

The SLN biopsy technique also produces less morbidity than ELND.  When lymphoscintigraphy and intraoperative gamma-probe localization is combined with a blue dye technique, the precise location of sentinel lymph nodes can usually be identified in 3 dimensions to within 1 cm. The SLN can then be removed through a skin incision that is often shorter than 1 cm, typically on an outpatient basis.

Sentinel lymph node biopsy in the head and neck

The widespread use of sentinel lymph node (SLN) biopsy in the management of head and neck melanoma has been limited by several concerns. As previously stated, lymphatic drainage in the head and neck region is complex, with multiple primary channels and the potential for multiple SLN sites. Excision of these nodes can also be technically challenging secondary to the small distances between sentinel nodes, making detection and isolation difficult. Furthermore, approximately 25-30% of the sentinel nodes are found within the parotid gland, and concerns of facial nerve injury have led many surgeons to advocate superficial parotidectomy over SLN biopsy. Furthermore, the cooperation of experienced pathologists and nuclear medicine staff are essential to the success of the procedure.

Although several articles have examined the utility of SLN biopsy for malignant melanoma of the head and neck, no clear consensus has been established. A number of papers (including those by Alex et al in 1998, Bostick et al in 1997, Schmalbach et al in 2003, Wagner et al in 2000, and Wells et al in 1997) present convincing evidence that SLN biopsy is a reliable and safe technique for detecting melanoma metastases in the head and neck.^{11, 12, 13, 14, 15}

SLNs were successfully localized in greater than 90% of cases. In fact, with the combined use of blue dye mapping and gamma probe lymphoscintigraphy, 5 studies demonstrated success rates of 95% or better. The rate of tumor-containing SLNs ranged from 11-17%, with a 0-4.5% false-negative rate. Additionally, reviews by Schmalbach et al and Loree et al describe accurately localizing intraparotid SLNs in at least 93% of cases.^{16, 17} These nodes were subsequently excised without any permanent facial nerve injury. Superficial parotidectomy served as a safe alternative for nodal harvest when the SLN could not be isolated.

Other studies, such as the prospective review by Jansen et al, demonstrate the difficulties of SLN biopsy in the head and neck region.¹⁸ In their series of 30 patients, SLNs were found in 90% of the cases, but 15% of these nodes could not be identified surgically. Furthermore, intraparotid SLNs in 4 of 10 patients were left untouched secondary to concerns of injuring facial nerve branches during dissection. Finally, 2 false-negative SLN specimens were found in the series of 10 patients with lymph node metastases. The sensitivity rate of 80% in this study compares unfavorable with those of previously mentioned articles.

Thus, more long-term studies are clearly required to evaluate whether SLN biopsy will provide any prognostic importance or significant survival benefit in patients with cutaneous melanoma of the head and neck. However, most data suggest that SLN theory applies to the head and neck region and that the technique may be a promising adjunct to management of this devastating disease.

MEDICAL TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

In the treatment of cutaneous melanoma, adjuvant systemic therapy is primarily reserved for 2 subpopulations of patients. The first group of patients is those with Stage IIB or Stage III disease, who are at high risk of recurrence after definitive surgery. This includes individuals with ulcerated lesions, with thick tumors (greater than 4 mm deep), or with nodal metastases. The second subgroup of patients includes those with distant metastases.

Malignant melanoma is known to be a relatively chemoresistant tumor. As such, chemotherapy has yielded poor results and no regimen has been found to definitively impact survival. Dacarbazine (DTIC) has been the only chemotherapeutic agent to demonstrate significant activity against melanoma. Nevertheless, response rates to single-agent therapy with DTIC have been disappointing, averaging 10-20%. Furthermore, even multiagent chemotherapy rarely yields a response rate greater than 40%.

Interferons function as biologic response modifiers, enhancing phagocytosis and free radical production in macrophages, as well as increasing the activity of natural killer cells. Since 1984, a series of 4 Eastern Cooperative Oncology Group (ECOG) and Intergroup trials have evaluated the efficacy of high-dose interferon alfa-2b (IFN alfa-2b) in approximately 2,000 patients with Stage IIB and Stage III melanoma.

The ECOG Trial E1684, the Intergroup Trial E1690, the Intergroup Trial E1694, and the ECOG Trial E2696 collectively confirmed a statistically significant benefit in relapse-free survival (RFS) with high-dose IFN alfa-2b (HDI) therapy versus observation alone.^{19, 20, 21} Although the impact on overall survival (OS) varied among the studies, the E1684 trial demonstrated a significant survival benefit associated with HDI versus observation alone, and the E1694 trial illustrated a similar benefit over the ganglioside GM2/keyhole limpet hemocyanin (GMK) vaccine. Based on the results of these trials, the FDA has approved a 52-week adjuvant therapy regimen consisting of HDI administered intravenously 5 days a week for 4 weeks, followed by a maintenance dose of subcutaneous INF alfa-2b given 3 times a week for 48 weeks.

Despite the promise of HDI therapy, the associated side effects and toxicities are not insignificant. Most patients experience flu-like symptoms, and many (20-30%) suffer from severe, intolerable fatigue. Neurologic and psychiatric side effects are also common. As a result, a variety of alternative regimens have been investigated.

Vaccines are one such alternative, and the various strategies may be divided into 2 categories. Polyvalent tumor-cell vaccines present melanoma-specific antigenic targets to the immune system, thus stimulating antibody and T-cell responses. One such vaccine is currently undergoing Phase III trials at the John Wayne Cancer Center. A second category of vaccines include gangliosides and peptides, which elicit antibody and/or T-cell responses in a more focused and reproducible manner than their polyvalent counterparts. A study conducted at Memorial Sloan-Kettering Cancer Center demonstrated that ganglioside GM2 administered in combination with bacille Calmette-Guérin (BCG) improved RFS and OS in Stage III melanoma patients.

CONCLUSION

Section 7 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

The incidence of melanoma of the head and neck has been increasing dramatically in the last several decades. Much of this change is related to increased sun exposure in the general population. For melanoma, like other cancers, the best opportunity for cure is with early and aggressive treatment. The primary treatment of melanoma is wide surgical excision, with most surgeons performing SLND or elective lymphadenectomy for intermediate-thickness lesions. Primary radiation therapy and chemotherapy are usually reserved for palliative treatment in far-advanced lesions. IFN alfa-2b has shown promise as adjuvant therapy of melanoma. Many other adjuvant therapies are under investigation. The greatest hope for controlling this disease lies in careful surveillance and early detection of atypical pigmented lesions.

MULTIMEDIA

Section 8 of 9  

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

Media file 1:  Malignant melanoma of the face and neck. Photo shows the characteristic appearance of a benign compound nevus. This lesion was not suspected to be a melanoma because it is lightly and uniformly pigmented and round and because it has regular borders.
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Media file 2:  Malignant melanoma of the face and neck. Slightly elevated pigmented lesion is a benign compound nevus. Although pigmented, the pigment is uniform. This photograph can be compared with those of melanomas to see the striking differences in the pigmentation and borders of this benign lesion.
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Media file 3:  Malignant melanoma of the face and neck. Atypical mole syndrome (dysplastic nevus syndrome). Typical example in a patient with multiple atypical moles. Such patients are at increased risk of melanoma, particularly if they have family members with a history of melanoma.
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Media file 4:  Malignant melanoma of the face and neck. Giant congenital nevus. Patients with this lesion are at increased risk of melanoma, particularly if it covers more than 5% of the body surface area.
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Media file 5:  Malignant melanoma of the face and neck. Typical basal cell carcinoma with raised border, central ulceration, and surface telangiectasias.
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Media file 6:  Malignant melanoma of the face and neck. Typical melanoma with asymmetry, irregular borders, irregular coloration, large diameter, and elevated appearance (ABCDEs).
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Media file 7:  Malignant melanoma of the face and neck. Typical melanoma with asymmetry, irregular borders, irregular coloration, large diameter, and elevated appearance (ABCDEs). A biopsy sample should be obtained in lesions such as this.
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Media file 8:  Malignant melanoma of the face and neck.
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Media file 9:  Malignant melanoma of the face and neck.
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Media file 10:  Malignant melanoma of the face and neck.
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Media file 11:  Malignant melanoma of the face and neck. Image courtesy of Hon Pak, MD.
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Media file 12:  Malignant melanoma of the face and neck. A 1.5-cm melanoma with characteristic asymmetry, irregular borders, and color variation. Image courtesy of Wendy Brick, MD.
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Media file 13:  Malignant melanoma of the face and neck. Lentigo maligna melanoma, right lower cheek. Central erythematous papule represents invasive melanoma with surrounding macular lentigo maligna (melanoma in situ). Image courtesy of Susan M. Swetter, MD.
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REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Diagnosis
• Treatment
• Management of the Lymphatic Basin
• Medical Treatment
• Conclusion
• Multimedia
• References

1. Garbe C, Büttner P, Bertz J, Burg G, d'Hoedt B, Drepper H. Primary cutaneous melanoma. Prognostic classification of anatomic location. Cancer. May 15 1995;75(10):2492-8. [Medline].
2. Veronesi U, Cascinelli N, Adamus J, et al. Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm. N Engl J Med. May 5 1988;318(18):1159-62. [Medline].
3. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial. Ann Surg. Sep 1993;218(3):262-7; discussion 267-9. [Medline].
4. Banzet P, Thomas A, Vuillemin E, et al. Wide versus narrow surgical excision in thin (<2 mm) stage I primary cutaneous malignant melanoma: long-term results of French multicentric prospective randomized trial on 319 patients. Proc Am Assoc Clin Oncol. 1993;12:387.
5. Cohn-Cedermark G, Rutqvist LE, Andersson R, Breivald M, Ingvar C, Johansson H. 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 0.8-2.0 mm. Cancer. Oct 1 2000;89(7):1495-501. [Medline].
6. Zitelli JA, Brown C, Hanusa BH. Mohs micrographic surgery for the treatment of primary cutaneous melanoma. J Am Acad Dermatol. Aug 1997;37(2 Pt 1):236-45. [Medline].
7. Bricca GM, Brodland DG, Ren D, Zitelli JA. Cutaneous head and neck melanoma treated with Mohs micrographic surgery. J Am Acad Dermatol. Jan 2005;52(1):92-100.
8. Kirkwood JM, Manola J, Ibrahim J, Sondak V, Ernstoff MS, Rao U. A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res. Mar 1 2004;10(5):1670-7. [Medline].
9. Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. Apr 1992;127(4):392-9. [Medline].
10. O'Brien CJ, Uren RF, Thompson JF, Howman-Giles RB, Petersen-Schaefer K, Shaw HM. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg. Nov 1995;170(5):461-6. [Medline].
11. Alex JC, Krag DN, Harlow SP, et al. Localization of regional lymph nodes in melanomas of the head and neck. Arch Otolaryngol Head Neck Surg. Feb 1998;124(2):135-40. [Medline].
12. Bostick P, Essner R, Sarantou T, et al. Intraoperative lymphatic mapping for early-stage melanoma of the head and neck. Am J Surg. Nov 1997;174(5):536-9. [Medline].
13. Schmalbach CE, Nussenbaum B, Rees RS, Schwartz J, Johnson TM, Bradford CR. Reliability of sentinel lymph node mapping with biopsy for head and neck cutaneous melanoma. Arch Otolaryngol Head Neck Surg. Jan 2003;129(1):61-5. [Medline].
14. Wagner JD, Park HM, Coleman JJ 3rd, Love C, Hayes JT. Cervical sentinel lymph node biopsy for melanomas of the head and neck and upper thorax. Arch Otolaryngol Head Neck Surg. Mar 2000;126(3):313-21. [Medline].
15. Wells KE, Rapaport DP, Cruse CW, et al. Sentinel lymph node biopsy in melanoma of the head and neck. Plast Reconstr Surg. Sep 1997;100(3):591-4. [Medline].
16. Schmalbach CE, Johnson TM, Bradford CR. The management of head and neck melanoma. Curr Probl Surg. Nov 2006;43(11):781-835. [Medline].
17. Loree TR, Tomljanovich PI, Cheney RT, Hicks WL Jr, Rigual NR. Intraparotid sentinel lymph node biopsy for head and neck melanoma. Laryngoscope. Aug 2006;116(8):1461-4. [Medline].
18. Jansen L, Koops HS, Nieweg OE, Doting MH, Kapteijn BA, Balm AJ. Sentinel node biopsy for melanoma in the head and neck region. Head Neck. Jan 2000;22(1):27-33. [Medline].
19. 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. Sep 1996;3(5):446-52. [Medline].
20. Kirkwood JM, Ibrahim JG, Sondak VK, Richards J, Flaherty LE, Ernstoff MS. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. Jun 2000;18(12):2444-58. [Medline].
21. Kirkwood JM, Ibrahim J, Lawson DH, Atkins MB, Agarwala SS, Collins K. High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696. J Clin Oncol. Mar 1 2001;19(5):1430-6. [Medline].
22. Agarwala SS, Kirkwood JM. Adjuvant interferon treatment for melanoma. Hematol Oncol Clin North Am. Aug 1998;12(4):823-33. [Medline].
23. Alex JC, Weaver DL, Fairbank JT, et al. Gamma-probe-guided lymph node localization in malignant melanoma. Surg Oncol. Oct 1993;2(5):303-8. [Medline].
24. Atkins MB. Immunotherapy and experimental approaches for metastatic melanoma. Hematol Oncol Clin North Am. Aug 1998;12(4):877-902, viii. [Medline].
25. 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. Aug 15 2001;19(16):3635-48. [Medline].
26. Balch CM, Soong SJ, Atkins MB, et al. An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin. May-Jun 2004;54(3):131-49; quiz 182-4. [Medline]. [Full Text].
27. Balch CM, Soong SJ, Bartolucci AA, et al. Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg. Sep 1996;224(3):255-63; discussion 263-6. [Medline].
28. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. Aug 15 2001;19(16):3622-34. [Medline].
29. Byers RM. Treatment of the neck in melanoma. Otolaryngol Clin North Am. Oct 1998;31(5):833-9. [Medline].
30. Carlson GW, Murray DR, Lyles RH, Hestley A, Cohen C. Sentinel lymph node biopsy in the management of cutaneous head and neck melanoma. Plast Reconstr Surg. Mar 2005;115(3):721-8. [Medline].
31. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. Oct 15 1998;83(8):1664-78. [Medline].
32. Coit D, Wallack M, Balch C. Society of Surgical Oncology practice guidelines. Melanoma surgical practice guidelines. Oncology (Huntingt). Sep 1997;11(9):1317-23. [Medline].
33. Essner R. Surgical treatment of malignant melanoma. Surg Clin North Am. Feb 2003;83(1):109-56. [Medline].
34. Geara FB, Ang KK. Radiation therapy for malignant melanoma. Surg Clin North Am. Dec 1996;76(6):1383-98. [Medline].
35. Gershenwald JE, Buzaid AC, Ross MI. Classification and staging of melanoma. Hematol Oncol Clin North Am. Aug 1998;12(4):737-65. [Medline].
36. Golger A, Young DS, Ghazarian D, Neligan PC. Epidemiological features and prognostic factors of cutaneous head and neck melanoma: a population-based study. Arch Otolaryngol Head Neck Surg. May 2007;133(5):442-7. [Medline].
37. Green RJ, Schuchter LM. Systemic treatment of metastatic melanoma with chemotherapy. Hematol Oncol Clin North Am. Aug 1998;12(4):863-75, viii. [Medline].
38. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. Jan-Feb 2007;57(1):43-66. [Medline].
39. Karakousis CP. Surgical treatment of malignant melanoma. Surg Clin North Am. Dec 1996;76(6):1299-312. [Medline].
40. Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. May 1 2001;19(9):2370-80. [Medline].
41. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. Jan 1996;14(1):7-17. [Medline].
42. McCarthy WH, Shaw HM. The surgical treatment of primary melanoma. Hematol Oncol Clin North Am. Aug 1998;12(4):797-805, vi. [Medline].
43. Morton DL, Wen DR, Foshag LJ, et al. Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck. J Clin Oncol. Sep 1993;11(9):1751-6. [Medline].
44. NIH Consensus conference. Diagnosis and treatment of early melanoma. JAMA. Sep 9 1992;268(10):1314-9. [Medline].
45. Patrick RJ, Fenske NA, Messina JL. Primary mucosal melanoma. J Am Acad Dermatol. May 2007;56(5):828-34. [Medline].
46. Penel N, Mallet Y, Mirabel X, Van JT, Lefebvre JL. Primary mucosal melanoma of head and neck: prognostic value of clear margins. Laryngoscope. Jun 2006;116(6):993-5. [Medline].
47. Reintgen D, Balch CM, Kirkwood J, Ross M. Recent advances in the care of the patient with malignant melanoma. Ann Surg. Jan 1997;225(1):1-14. [Medline].
48. Whiteman DC, Stickley M, Watt P, Hughes MC, Davis MB, Green AC. Anatomic site, sun exposure, and risk of cutaneous melanoma. J Clin Oncol. Jul 1 2006;24(19):3172-7. [Medline].
49. Zitsch RP, Renner JG. Cutaneous Melanoma of the Head and Neck: A Self-Instructional Package. Alexandria, Va:. American Academy of Otolaryngology, Head and Neck Surgery Foundation;1996.

Article Last Updated: Jul 3, 2008