Clin Plastic Surg

Melanoma

Maurice Y. Nahabedian, MD, FACS

Division of Plastic and Reconstructive Surgery, Johns Hopkins University, 601 North Caroline Street 8152C,

Baltimore, MD 21287, USA

The incidence of cutaneous melanoma continues

to increase worldwide. According to current figures

from the American Cancer Society, invasive mela-

noma ranks fifth in men and seventh in women

among the most common cancers in the United States

[1,2]. Approximately 95,000 people will be diag-

nosed with melanoma in the United States in 2004.

Of these, approximately 40,000 cases will be in situ

and 55,000 will be invasive. This figure represents a

4% increase in incidence compared with the 2003

statistics. It is estimated that invasive melanoma will

be diagnosed in nearly 30,000 men and 25,000

women and that nearly 8000 deaths will be attributed

to melanoma this year. This figure represents 80% of

all deaths due to skin cancer. Survival is directly

related to staging, with 5-year survival rates that

range from 95% for stage I melanoma to 2% for

stage IV melanoma.

Evaluation of the suspected melanoma

In light of the increasing incidence of melanoma,

public awareness has improved. Patients with pig-

mented skin lesions are seeking attention with

increased frequency. The vast majority of these pig-

mented skin lesions are benign and normally would

not require treatment. The decision about which skin

lesions require biopsy is clinically challenging and

can sometimes be difficult because of the wide range

0094-1298/05/$ – see front matter D 2005 Elsevier Inc. All rights

doi:10.1016/j.cps.2004.11.003

E-mail address: mnahabed@jhmi.edu

and variety. The clinical criterion that is currently

used in the evaluation of a suspected melanoma is the

‘‘ABCD’’ algorithm (Table 1). The differential diag-

nosis for the pigmented lesion is extensive and

includes—but is not limited to—compound nevi,

junctional nevi, pigmented basal cell carcinoma, and

an array of keratoses. Melanoma can present in an

amelanotic form and can be mistaken for a benign

lesion. Therefore, it has become customary practice

to perform a biopsy on any lesion in which there has

been a change in appearance or behavior. Changes in

appearance may include changes in border irregu-

larity, tone, color, and size. Changes in behavior may

include bleeding, itching, and altered texture.

Biopsy of the suspected melanoma

Various biopsy techniques are used, including

incisional, punch, excisional, and shave. The indica-

tions for each are based on the clinical characteristics

and location of the lesion. For suspicious lesions

measuring less than 1 cm in diameter and located on

most skin surfaces on the body, an excisional biopsy

with a 1- to 2-mm margin is recommended, because a

re-excision can be performed, if necessary, with ap-

propriate margins of excision. For suspicious lesions

measuring greater than 1 cm in diameter, an inci-

sional or punch biopsy is usually performed to avoid

disruption of the lymphatic channels around the

lesion in the event of a future sentinel lymph node

biopsy. Re-excision of a pathologically confirmed

melanoma can then be planned with appropriate mar-

gins. A shave biopsy has no role in a lesion that is

suspicious for melanoma.

32 (2005) 249 – 259

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plasticsurgery.theclinics.com

Table 1

The ‘‘ABCD’’ criteria for evaluation of a lesion with char-

acteristics of melanoma

Criterion Characteristic

A Asymmetry Uneven growth rate

B Border Irregular

C Color Variation and shading

D Diameter Large (> 6 mm)

Table 2

Current recommended margins of excision for melanoma

Thickness of melanoma Margin of excision

Melanoma in situ 5 mm

< 1 mm 1 cm

1–2 mm 1–2 cm

2–4 mm 2 cm

> 4 mm � 2 cm

nahabedian250

Occasionally, following biopsy of a pigmented

skin section, the final pathology report will return as

atypical nevi. The pathologic interpretation and

clinical significance of these lesions is controversial.

Common descriptive phrases include cytologic atypia

and architectural disorder [3]. Cytologic atypia re-

fers to the variability in the size and shape of the

melanocytic nuclei and is graded as mild, moderate,

or severe. Architectural disorder refers to the lentigi-

nous growth pattern of the melanocytes along the

rete ridges. Although these lesions are not referred

to as melanoma, they are considered premalignant,

and re-excision is often recommended. Complete

excision with a 5-mm margin is recommended for

lesions demonstrating severe cytologic atypia with

architectural disorder. Lesions demonstrating mild to

moderate cytologic atypia do not usually require re-

excision as long as the margins of excision are clear.

Although there is no conclusive proof that these

lesions will eventually become melanoma, the pres-

ence of similar cells has been demonstrated in true

melanomas; hence, complete excision is usually

recommended [4].

The pathologic interpretation of melanoma has

various components. These include radial growth

phase, vertical growth phase, Breslow thickness, and

Clark level of invasion. Radial growth is demon-

strated when the nest of melanoma cells within the

epidermis exceeds that in the dermis. Vertical growth

is demonstrated when the nests of melanoma cells in

the papillary dermis exceed that in the epidermis.

This pattern is commonly demonstrated with nodular

melanoma and is significant for an increased propen-

sity for metastases. ‘‘Breslow level’’ refers to the

thickness of the melanoma in millimeters and is

measured from the granular layer of the epidermis to

the base of the tumor. ‘‘Clark level’’ refers to the layer

of invasion and includes the epidermis, papillary

dermis, papillary–reticular junction, reticular dermis,

and subcutaneous fat. The current American Joint

Committee on Cancer classification incorporates this

criterion only for the thin and invasive melanoma

measuring less than 1 mm in thickness [5].

Excision of the melanoma

The appropriate margin of excision for a con-

firmed melanoma has a long history of controversy

but is currently well defined (Table 2). The margin of

excision is based on the thickness of the melanoma.

Excision margins greater than 2 cm are currently

deemed unnecessary in most cases. This recommen-

dation is based on several well-designed prospective

studies that have demonstrated that margins of 3 cm,

4 cm, and 5 cm for melanomas that exceed 1 mm in

thickness do not result in improved local control or

survival compared with a 2-cm margin [6–8]. Lens

et al [9] reviewed four randomized controlled trials

comparing narrow with wide excision and found no

difference with regard to recurrence or survival.

However, in a recent prospective study that compared

excision margins of 1 cm and 3 cm in patients with

invasive melanoma of at least 2 mm in thickness, an

excision margin of 1 cm was associated with a

significantly greater risk (P = 0.05) of locoregional

recurrence [10]. No statistically significant difference

was seen in overall survival. The number of patients,

median age, and median thickness were similar in

the two groups (447 versus 453 patients; 57 versus

58 years of age; tumor thickness of 3.0 mm versus

3.1 mm).

The role of Mohs micrographic surgery in the

surgical management of melanoma has generated

controversy. Advocates of the Mohs technique argue

that it has the benefit of limiting the margin of

excision. This limitation is especially important in

critical areas with aesthetic importance, such as the

face [11]. However, the current recommendations for

margins of excision, based on years of investigation

and prospective studies, do not support the concept of

minimal margins. For less aggressive forms of mela-

noma, such as lentigo maligna on the face, Mohs may

be useful and appropriate in some circumstances;

however, its use for invasive melanoma is not

recommended. The risks of tumor implantation, false

negative margins due to suboptimal melanocytic

staining, and inadequate margins limit the use and

benefit of this technique.

Fig. 2. Outline of the wedge excision.

melanoma 251

Melanoma excision and closure based on anatomic

location

Most melanomas are excised in an elliptic fashion

and closed primarily. This pattern holds especially

true for the melanoma located on the trunk or ex-

tremities. Occasionally, larger defects that are not

amenable to primary closure will require more ad-

vanced reconstructive techniques, such as adjacent

tissue rearrangement, skin graft, or free tissue trans-

fer. These procedures are not commonly needed for

most melanoma defects that are located on the trunk

or extremity. However, there are certain anatomic

sites where the excision and reconstruction are more

complicated because of skin thickness, complex

anatomy, and proximity to important structures [12].

These areas are discussed separately.

Ear

Melanoma arising on the ear can be difficult to

manage because of proximity of the skin to the

underlying cartilage and contour issues. Options for

surgical management of the primary tumor have in-

cluded wedge resection, Mohs resection, partial

amputation, skin and subcutaneous resection with

preservation of the perichondrium, and total amputa-

tion [13]. In general, for a melanoma in situ, the skin

is excised with a 5-mm margin, and cartilage excision

is usually not necessary. The defect is repaired by

Fig. 1. A melanoma involving the posterior helical rim of

the ear.

primary closure (when possible) or by using a full-

thickness skin graft. Management of the invasive

melanoma is more complicated. For melanoma lo-

cated on the helical rim, a wedge excision, including

skin and cartilage, is usually necessary (Figs. 1–4).

The acquired defect is repaired by primary closure,

when possible, or by local advancement flaps, such

as the Antia-Buch procedure or the chonchal trans-

Fig. 3. Immediate closure of the helical rim defect.

Fig. 4. Six-month follow-up demonstrating natural contour

with minimal distortion of the ear.

Fig. 5. Melanoma in situ involving the dorsal aspect of

the nose.

nahabedian252

position flap [14]. For melanoma located in the

chonchal region, the lesion is excised; it usually

includes the underlying cartilage but not the posterior

skin. These defects are repaired using a full-thickness

skin graft.

Eyelid

The eyelid is a challenging structure, primarily

because of its complex anatomy and function. The

dermal component of eyelid skin is much thinner than

other cutaneous regions of the body; hence, melano-

mas involving the eyelid tend to be more invasive. The

excision usually includes the anterior lamellar struc-

tures (skin, orbicularis oculi) and may also include the

posterior lamellar structures (tarsal plate, orbital fat,

conjunctiva). The width and extent of the excision

depends on the thickness of the melanoma. Esmaeli

et al [15] recently demonstrated that a 5-mm margin

of excision is adequate for thin melanomas involving

the eyelid. The margin of excision did not have a

statistically significant effect on local, regional, or

distant recurrence, whereas the Breslow thickness did.

Reconstruction of the acquired eyelid defect is

based on its size and location [14]. In general, for

defects that are less than 25% of the lid margin,

primary closure of the skin and tarsus is possible. For

defects that exceed 25% of the lid margin, more

sophisticated techniques tend to be necessary. These

techniques can include cartilage grafts from the ear or

nose to reconstruct the tarsus, transposition skin and

muscle flaps from the opposing eyelid, and complex

adjacent tissue rearrangements using Mustarde flaps.

Nose

Melanoma arising on the nose can pose a surgical

challenge. The nose is a highly complex structure

composed of skin of variable thickness, subcutaneous

fat, cartilage, bone, and nasal lining. The cutaneous

surface of the upper two thirds of the nose is thin,

nonsebaceous, and mobile, whereas the lower third of

the nose is thick, sebaceous, and relatively nonmobile.

The supportive structure of the upper two thirds of the

nose is primarily nasal bone, whereas the lower third

is cartilage. Excision of melanoma involving the nose

can result in a substantial defect that is difficult to

close. Given the complexity of the reconstruction,

delayed reconstruction is usually recommended for

defects that will require techniques more extensive

than primary closure. This measure is taken to ensure

pathologic confirmation of clear margins. The tem-

porary management of the open defect can include

local wound care using Xeroform gauze (Tyco

Healthcare Group, LP, Mansfield, MA) or Allograft.

The reconstructive technique is usually based on

the size of the acquired defect [14]. Small defects

measuring less than 5 mm are usually closed

primarily with minimal distortion. However, larger

defects may require more complex reconstructive

techniques to maintain the natural nasal contour. Full-

thickness skin grafts may be used; however, they may

result in a patch-like appearance with some contour

irregularity. Adjacent tissue rearrangement in the

form of a unilobe or bilobe flap is useful for defects

ranging in diameter from 5 mm to 2 cm (Figs. 5–8).

These flaps are commonly based in the upper two

thirds of the nose, where the skin is mobile and easily

Fig. 8. Six-month follow-up demonstrating an acceptable

aesthetic outcome.

Fig. 6. The acquired defect and outline of a unilobe trans-

position flap.

melanoma 253

rearranged. The thick and sebaceous nature of the

lower nasal skin makes it difficult to mobilize. These

flaps are usually performed in a single stage. Defects

exceeding 2 cm usually require remote flaps, such as

the midline forehead flap or the Bishop-Meider flap.

These procedures are usually completed in two to

three stages. Total nasal reconstruction is a highly

specialized operation that often includes free-tissue

transfer for bulk and lining, cartilage support grafts,

and local flaps for skin resurfacing. These procedures

often require five to six operations to complete.

Hands and feet

Acral lentiginous melanoma commonly affects the

plantar surface of the foot and the dorsum of the hand

and foot. Plantar melanoma can occur in individuals

with all degrees of skin pigmentation. These mela-

nomas are less common than those that occur on the

trunk and extremities and are often associated with a

poor prognosis because of delayed diagnosis. The

surgical management of these melanomas includes

excisional biopsy followed by definitive resection

[16]. Closure of the acquired defect is obtained by

Fig. 7. The flap is inset with minimal distortion.

primary closure when possible, skin graft, local

rotation flap, or free tissue transfer (Figs. 9 and 10)

[14]. Local control is usually obtained for lesions

measuring less than 1.5 mm with a 1-cm margin of

resection. For lesions exceeding 1.5 mm in thickness,

regional or systemic disease has been demonstrated in

greater than 50%.

Subungual melanoma

The subungual melanoma will usually present as a

narrow, pigmented streak that extends vertically from

the proximal nail fold to the distal edge of the nail.

The differential diagnosis includes trauma, as well as

hematopoetic and vascular disorders. The initial

Fig. 9. Acral lentiginous melanoma involving the plantar

surface in an African American man.

Fig. 10. One-year follow-up following excision and

skin graft.

nahabedian254

evaluation includes a thorough history and physical

examination, followed by a biopsy. The biopsy

technique first involves a digital nerve block, using

1% lidocaine with or without bupivacaine (Mar-

caine), followed by total or partial removal of the nail

plate. The sterile and germinal matrix are thoroughly

inspected for areas of abnormal pigmentation. A

biopsy is performed on any area of abnormal pig-

mentation using a 3-mm punch; however, other

techniques may be used. If no abnormal pigmentation

is observed, then a 3-mm, full-thickness punch bi-

opsy of the germinal matrix is completed. It is

important to perform a biopsy on that portion of the

matrix that is in line with the pigmented streak. On

completion, the nail plate is reapplied to prevent

desiccation of the matrix.

The confirmation of subungual melanoma calls

for aggressive treatment. Amputation of the distal

digit is usually required [16]. The level of amputation

(proximal or distal interphalangeal joint) is deter-

mined by the thickness of the melanoma. In general,

melanomas that are less than 2 mm in thickness

require amputation at the level of the distal inter-

phalangeal joint, and thicker melanomas require

amputation at the level of the proximal interphalan-

geal joint. Evaluation of the regional lymph node

basin is often required for these tumors. Despite this

treatment, nodal metastases have been demonstrated

in 46% of patients within 1 year [16].

Sentinel lymph node biopsy

The sentinel lymph node biopsy (SLNB) repre-

sents a significant advance in the management of

melanoma [17]. The sentinel lymph node is defined

as the first lymph node in a lymphatic basin that

receives afferent lymph flow from the primary tumor

site. The likelihood that the sentinel lymph node is

negative while another lymph node in the same basin

is positive is low. Successful identification and

removal of the sentinel lymph node provides accurate

staging of the entire nodal basin. The sentinel lymph

node will occasionally demonstrate some degree of

pigmentation; however, it is important to recognize

that the lymph node pigmentation may not be due to

melanoma [18].

SLNB is currently recommended for patients with

invasive melanoma with a thickness that ranges from

1 to 4 mm [19,20]. The use of SLNB in patients with

melanoma that is less than 1 mm or greater than

4 mm in thickness is controversial and is reviewed

later in this article. It is important to remember that

SLNB is a diagnostic and not a therapeutic tool. The

principal advantage of SLNB is that it significantly

reduces the incidence of lymphedema, because a total

lymphadenectomy is usually not necessary.

Technique of sentinel lymph node biopsy

Two methods of SLNB are in current use, one

using the blue dye and the other the radiolabeled

isotope Technetium 99 [21]. Both are sensitive tech-

niques that can successfully identify a sentinel lymph

node in most cases. Both the blue dye and the radio-

isotope techniques involve an intradermal injection of

the material at the peripheral margin of the mela-

noma. The agents enter the dermal lymphatic and

migrate to the regional lymph node basin. This

process usually takes at least 20 minutes and can last

as long as 24 hours. The excision of the melanoma

and the SLNB should preferably be completed during

the same operation. With the blue dye technique,

temporary staining of the dermal lymphatic is ob-

served, leading to the sentinel lymph node. This

lymph node is then surgically excised. With the

radioisotope technique, a gamma probe is positioned

over the regional lymph node, and the radioactivity is

quantitated. A count of at least 6000 units over base-

line is usually necessary to qualify a lymph node as

sentinel. Occasionally, more than one lymph node is

detected using these techniques. All suspicious lymph

nodes should be removed (Figs. 11–13).

The anatomic location of the melanoma should be

considered in preparation for an SLNB, because of

Fig. 11. Subungual melanoma of the thumb.

Fig. 13. The sentinel lymph node is excised. Note the areas

of pigmentation secondary to nodal metastases.

melanoma 255

the anatomy and distribution of the lymphatic path-

ways [22]. For melanoma located on the upper or

lower extremity, SLNB is straightforward, because

the lymphatic pathways are constant and drain

proximally into the inguinal and axillary lymph node

basin. Generally, the excision and the SLNB are

performed simultaneously. However, in some cases a

pigmented lesion is completely excised that on

histologic analysis demonstrates an invasive mela-

noma with a thickness between 1 and 4 mm. In these

situations, a delayed SLNB is possible, despite the

disrupted lymphatics and scar. The blue dye or

radioisotope is injected proximal to the incision in

the direction of the regional lymph node basin.

Fig. 12. Localization of an axillary lymph node follow-

ing lymphoscintigraphy.

The SLNB procedure has simplified the operative

management for melanomas located on the trunk

and head and neck region [19–21]. In the past, for

patients without palpable adenopathy, it was diffi-

cult to determine which nodal basin was at risk for

regional metastases. For truncal melanoma, the lym-

phatic channels can drain into the axillary or inguinal

lymph node basins. For head and neck melanoma, the

lymphatics can drain into the cervical, supraclavicu-

lar, submandibular, parotid, and retroauricular lymph

node basins. The SLNB technique has facilitated

management by accurately assessing the lymphatic

pathway [23]. However, the sensitivity and specificity

of a delayed SLNB for previously excised melanomas

located in the trunk, head, and neck region are

compromised by the circumferentially disrupted lym-

phatic pathways.

Sentinel lymph node biopsy for the invasive

melanoma less than 1 mm

The use of SLNB for the thin invasive melanoma

is controversial [24]. This debate stems from studies

demonstrating a low risk for regional metastases in

these cases, a minimal survival or therapeutic ad-

vantage from SLNB, and potential morbidity [25,26].

The 5-year survival for patients with stage I

melanoma ranges from 91% to 95%. However, re-

cent evidence supports the use of SLNB in patients

with invasive melanoma measuring less than 1 mm.

Corsetti et al [27] have demonstrated a recurrence rate

of 18.4% in patients with melanoma less than or

equal to 1 mm at 3-year follow-up. Bedrosian et al

[28] have demonstrated sentinel lymph node meta-

stases in 5.6% of patients with melanoma less than

1 mm in thickness. These studies demonstrate the

existence of a subset of patients with thin invasive

melanoma that displays a more aggressive and po-

nahabedian256

tentially lethal behavior. Current indications for

identifying patients at high risk for regional metas-

tases include any T-1 melanoma (<1 mm) associated

with ulceration, regression on histologic evaluation, a

positive deep margin on initial biopsy, a Clark level

of invasion that extends to the reticular dermis or

subcutaneous fat (IV or V), and a previous history of

melanoma [24]. Exceptions to these criteria include

the indication of SLNB for Clark level III invasion in

patients with acral lentiginous melanoma and for a

thickness of 0.9 mm in patients with superficial

spreading or nodular melanoma, because these

lesions are associated with an increased propensity

for metastases.

Sentinel lymph node biopsy for the invasive

melanoma greater than 4 mm

The benefit of SLNB for invasive melanoma

greater than 4 mm in thickness is controversial

[29,30], because the long-term survival is generally

poor and the local recurrence is higher than in mela-

noma of less than 4 mm. Carlson et al [29] state that

the pathologic status of the sentinel lymph node is a

strong independent prognostic factor for survival and

that SLNB should routinely be performed. Caraco

et al [30], however, have demonstrated no significant

difference in the 3-year survival curves between

patients with thick melanomas who were node-

positive and node-negative following SLNB.

Although SLNB is not routinely performed for

melanomas greater than 4 mm in thickness, further

studies appear warranted.

Lymphadenectomy

With the increasing use of the SLNB technique,

lymphadenectomy for stages II, III, and IV melanoma

has become less frequent. In patients with a negative

sentinel lymph node, total lymphadenectomy is

usually not necessary. However, in patients in whom

the sentinel lymph node is positive, a lymphadenec-

tomy is usually performed. In patients in whom a

lymph node is palpable, a fine needle aspiration of the

lymph node is performed. Histologic confirmation of

melanoma is followed by a lymphadenectomy.

The need for an elective lymph node dissection

(ELND) is controversial [31,32]. Recently, the num-

ber of these procedures performed has significantly

declined, after it was demonstrated in four large,

prospective, randomized clinical trials that ELND

failed to show any survival advantage in patients with

intermediate-thickness melanoma (1–4 mm). ELND

is currently not recommended in patients with thick

melanoma (>4 mm), because of the high risk for

regional and distant metastatic disease (60%–70%).

In addition, ELND without lymphoscintigraphy in the

head and neck region may be misdirected in up to

50% of cases, because of the variability in lym-

phatic pathways.

The technique of lymphadenectomy varies based

on the anatomic location. The principal lymphatic

basins are located in the cervical neck, axillary, and

inguinal territories. The number of lymph nodes re-

moved ranges from 10 to 50 and is dependent on the

anatomic location. The details of the operative proce-

dures are beyond the scope of this article, and the

reader is referred elsewhere [33–35]. However, the

salient features will be discussed.

Neck

The lymph nodes in the cervical region have five

distinct locations based on the sternomastoid muscle.

They are recognized as level I through level V lymph

node basins. Within the neck, four types of lymph-

adenectomy can be performed. These include the ra-

dical neck dissection (RND), modified (functional)

radical neck dissection (MRND), extended radical

neck dissection (ERND), and selective neck dissec-

tion (SND). The difference between the RND and the

MRND is that the sternomastoid muscle, internal

jugular vein, spinal accessory nerve, and nerves of the

cervical plexus are preserved with the latter. Candi-

dates for RND include patients with multiple or large

(>3-cm) lymph nodes, soft tissue involvement, or

tumor in the posterior triangle and those who have

undergone failed radiation therapy. Functional neck

dissection is recommended for patients with a

positive sentinel lymph node and those with a

palpable lymph node less than 3 cm. The ERND is

considered when there is involvement of the sub-

occipital or retroauricular lymph nodes. The SND,

also called the supraomohyoid neck dissection, re-

moves lymph nodes located above the omohyoid

muscle and primarily in the submental and subman-

dibular triangles.

Axilla

The indications for axillary lymphadenectomy

have changed over the years. The most common in-

dication today is for patients with a positive lymph

node biopsy, usually using the sentinel technique. The

dissection preserves the long thoracic and thoraco-

melanoma 257

dorsal nerves and generally includes 10 to 20 lymph

nodes. Lymphedema of the upper extremity has been

demonstrated in 15% to 20% of patients who have a

complete axillary lymphadenectomy and in approxi-

mately 1% following sentinel lymphadenectomy.

Inguinal

Indications for inguinal lymphadenectomy include

the histologic demonstration of melanoma in a

sentinel or palpable lymph node. The dissection can

include the superficial or deep lymph nodes. The

lymph node chain is generally located along the path

of the femoral vessels. Complications of inguinal

lymphadenectomy include infection in 10% to 15%

and lower-extremity lymphedema in 20%.

Management of recurrent melanoma

Recurrent melanoma is associated with a

decreased survival. The site of recurrence may be

the primary location, in transit, regional lymph node

basin, or a distant organ. The recurrence risk is based

on stage at presentation, presence of ulceration, mar-

gin of excision, and extent of operation [36]. Prog-

nostic factors associated with a poor survival include

tumor vascularity, tumor thickness, mitotic index,

ulceration, and microsatellites [37,38]. Karakousis

et al [39] have demonstrated a 3.8% overall rate of

local recurrence with a progressive increase based on

the thickness of the melanoma. This increase was

2.3% for the 1- to 2- mm melanoma, 4.2% for the

2- to 3-mm melanoma, and 11.7% for the 3- to 4-mm

melanoma. Balch [35] has demonstrated that the risk

for regional nodal recurrence is 25% for patients with

a primary melanoma that measures between 0.76 mm

and 1.5 mm and 60% for patients with a primary

melanoma that measures between 1.5 mm and 4 mm.

Recent studies have evaluated the role of the im-

mune system in the prediction of recurrence. Cur-

rently, there is no method of identifying patients with

occult melanoma who are at higher risk for recur-

rence. Kelly et al [40] have studied tumor-associated

antigen (TA90) and immune complexes (IC) that

circulate in the sera of patients with melanoma. Gupta

[41] had previously demonstrated that, in patients

with stage IV melanoma, the levels of TA90 are high

and the levels of TA90-IC are low, whereas, in pa-

tients with stage I melanoma, the levels of TA90 are

low and the levels of TA90-IC are high. Using

ELISA, it was demonstrated that TA90-IC was ele-

vated in 77% of patients who developed recurrent

melanoma. The 5-year survival was 84% for pa-

tients without detectable levels of TA90-IC and

36% for patient with detectable levels of TA90-IC

(P = 0.0001). This technique detected recurrence

an average of 19 months sooner than routine clinical

and radiologic examination.

In the case of a patient with recurrent melanoma,

management decisions can be difficult. Options for

surgical management include complete resection,

lymphadenectomy, and isolated limb perfusion. How-

ever, in deciding on the appropriate treatment, one

should consider the tumor biology, patient expec-

tations, and whether the procedure is curative or

palliative [42]. Predictors of survival following

metastatic resection include the site of metastasis,

the number of metastases, and the disease-free in-

terval [42].

The most common sites of recurrence of mela-

noma include the skin, the subcutaneous tissue, and

the lymph node basin. Resection of the recurrence

that is confined to these areas is usually performed

without morbidity and results in a 5-year survival rate

of 5% to 38% [42]. Other, less common sites of

recurrence include the lung (15%–36%), the brain

(8%–15%), the gastrointestinal tract (2%–4%), and

the adrenal gland. Although surgical resection is

possible and is sometimes indicated for these loca-

tions, other therapies are also considered, such as

radiation, chemotherapy, and isolated limb perfusion.

Isolated limb perfusion (ILP) has been a thera-

peutic option for nearly 50 years [43]. It has tra-

ditionally been used for in-transit melanoma, bulky

recurrent disease, or melanoma that is confined to an

extremity [44]. The technique involves isolation of

the vascular compartment of the extremity, cannula-

tion of the artery and vein, and perfusion of the ex-

tremity with high concentrations of chemotherapeutic

agents, such as melphalan, tumor necrosis factor, or

cis-platinum. The perfusate can be heated to take

advantage of the tumoricidal effect of regional hyper-

thermia [45].

Isolated limb perfusion has traditionally been

recommended to patients as a last resort to avoid

amputation. Various centers worldwide have used

ILP with reasonable success. The median complete

response (CR) is approximately 50% using melpha-

lan, and the overall response (OR) rate is approxi-

mately 85% [46,47]. When tumor necrosis factor is

added to the treatment, the median CR and OR

increase to 75% and 95%, respectively. Based on

these studies, it appears that ILP is useful in certain

situations. Complications include skin erythema,

myopathy, peripheral neuropathy, and lymphedema.

For additional information about ILP, the reader is

referred elsewhere [46,47].

nahabedian258

Summary

The surgical management of melanoma continues

to evolve. A large body of information serves as a

foundation for the oncologic principles, surgical

excisions, and reconstructive methodologies that are

currently in use. This article serves as a guide for the

physician considering surgical management of the

melanoma patient.

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