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Acs0304 Surgical Management Of Melanoma And Other Skin Cancers
- 1. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 1
4 MALIGNANT SKIN LESIONS
Jennifer A.Wargo, M.D., and Kenneth Tanabe, M.D., F.A.C.S.
Physical Examination
Given the variable natural history and prognosis of skin malignan-
cies, clinical assessment and management of these lesions can be Physical examination should include a complete skin examina-
challenging. Malignant skin lesions have become increasingly preva- tion, as well as examination of mucosal membranes. In the case of a
lent over the past several years. In the United States, approximately possible melanoma, particular attention should be paid to the pres-
1.2 million cases of nonmelanoma skin cancer are diagnosed annu- ence or absence of surrounding nodules or nodules between the
ally.1 More alarming is the observation that approximately 80,000 skin lesion and the closest nodal basins that may represent in-transit
cases of melanoma are now diagnosed each year2—a figure that that metastases. Attention should be paid to the draining nodal basins
has been steadily rising,3 to the point where the current lifetime risk because lymph node metastases are known to occur in both squa-
for the development of melanoma is 1 in 75.2 This disturbing in- mous cell carcinoma (SCC) and melanoma.
crease in the incidence of both nonmelanoma skin cancer and If the lesion is not clinically suspicious, conservative monitoring
melanoma can largely be attributed to prevailing social attitudes to- through patient self-examination and regular follow-up with a
ward sun exposure.4 healthcare provider is appropriate.
Given the increasing prevalence of skin cancers and the pivotal
INVESTIGATIVE STUDIES
role surgeons play in their treatment, it is critical that surgeons
be well informed about the recognition, workup, and manage-
ment of these conditions. Accordingly, in what follows, we address Biopsy
evaluation and management of malignant skin lesions in detail; Any clinically suspicious lesion should undergo either excisional
management of benign skin lesions is beyond the scope of this biopsy (if the lesion is small) or incisional biopsy (if the lesion is
chapter. large). Excisional biopsy typically incorporates a 1 to 4 mm margin
of normal skin, depending on the clinical characteristics of the le-
sion.With some types of lesions (e.g., a dysplastic nevus), the use of
Assessment of Potentially Malignant Skin Lesions this margin may eliminate the need for subsequent reexcision if the
lesion proves to contain high-grade cytologic atypia. In any case, no
CLINICAL EVALUATION
attempt should be made to perform a definitive radical excision un-
til a diagnosis is established by means of biopsy.
History A full-thickness excision that extends into the subcutaneous fat
A careful history should be obtained, with particular attention should be performed, and the specimen should be marked for
paid to the extent of previous sun exposure. A history of blistering orientation to help the pathologist evaluate the margins for possi-
sunburn in childhood or adolescence is a significant risk factor and ble microscopic involvement with tumor cells. As a rule, electro-
is reported by virtually all white persons with melanomas.5 A per- cauterization should not be employed to remove the specimen, be-
sonal or family history of skin cancer is also a risk factor: the likeli- cause it creates artifacts that can substantially distort cells at the
hood that melanoma will develop is increased eight- to 12-fold margins. Shave biopsy is discouraged for evaluation of pigmented
when a first-degree relative has a history of melanoma.6 Previous lesions because it may create a positive deep margin, thereby com-
immunosuppression or transplantation should be inquired about as promising determination of the true depth of penetration of a
well; both place the patient at higher risk for the development of skin melanoma. In the case of an elliptically shaped excisional biopsy
cancer. on an extremity, the long axis of the specimen should be oriented
A detailed history of the lesion’s development, starting with the along the long axis of the extremity to facilitate subsequent reexci-
time when it was first noted and including any changes in its size or sion if necessary.
appearance, should be elicited. Such a history will help the clinician
EXCISION OF MALIGNANCY
make the initial judgment regarding whether the lesion is suspicious
or nonsuspicious. Generally speaking, lesions are considered non- If the lesion proves to be benign, no further treatment is usually
suspicious if they remain stable and uniform in terms of their physi- required. If it proves to be malignant, further excision with appropri-
cal characteristics (e.g., size, shape, color, profile, and texture). An ate margins is usually necessary, and tumor staging becomes an im-
example of a nonsuspicious lesion is a simple nevus, which typically portant concern. Appropriate excision margins for different skin
becomes apparent at 4 to 5 years of age, darkens with puberty, and cancers are discussed in more detail elsewhere [see Management of
fades in the seventh to eighth decades of life. Pigmented lesions that Specific Types of Skin Cancer, below].
have an irregular border or demonstrate a change in size, color, or For lesions excised in an ellipse of skin and fat, the length of the
texture are considered suspicious. Careful attention should also be ellipse should be approximately 3.5 to 4 times the width to allow
paid to constitutional symptoms. Patients who present with tension-free closure without dog-ears. If an area cannot be closed
metastatic disease may have systemic or focal complaints, such as primarily, skin grafting may be necessary [see 3:7 Surface Reconstruc-
headaches or, in the case of melanoma that has metastasized to the tion Procedures]. For very large lesions or lesions in difficult areas
brain, visual changes. (e.g., the face), specialized flaps may be required.
- 2. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 2
Management of Specific Types of Skin Cancer often turn out to be larger than they appear clinically, and they gen-
erally have a more aggressive natural history than other BCCs; as a
BASAL CELL CARCINOMA
result, complete excision can be highly challenging.
Incidence and Epidemiology Treatment
Basal cell carcinoma (BCC) is the most common malignancy in Surgical excision remains the mainstay of treatment for primary
white persons7 and the most prevalent type of skin cancer overall. BCCs.Typically, a surgical margin of 4 mm is recommended when
The incidence varies widely across the globe (e.g., 146/100,000 in possible.11 With small defects, primary closure is generally feasible;
the United States, compared with 726/100,000 in Australia).8 The with larger defects, rotation flaps or skin grafting may be necessary.
lifetime risk of BCC for a white person in the United States is ap- Lymphatic spread identified in the primary tumor, though present
proximately 30%.1 Although BCCs have a very low metastatic po- only in extraordinarily rare cases, may be an indication for lymphat-
tential, they impose heavy economic and social burdens on patients ic mapping.12
and society. Other surgical techniques used to treat BCC include cryo-
The vast majority of BCCs are found on the head and neck. surgery, curettage and cauterization, and Mohs’ micrographic
There is no known precursor lesion. The risk of development of surgery. Cryosurgery and curettage are generally contraindicated
BCC seems to be most closely related to exposure to ultraviolet ra- for large or morpheaform BCCs or tumors in high-risk areas (e.g.,
diation. Whereas substantial sun exposure during childhood and the central face), because surgical margins cannot be assessed.
adolescence increases the risk of BCC, no studies have demonstrat- Mohs’ micrographic surgery involves excision of serial sections with
ed any significant correlation between the development of BCC intraoperative histologic examination of frozen sections to control
and cumulative exposure to ultraviolet light in adulthood.9 Several surgical margins. It is particularly useful in treating morpheaform
heritable conditions are associated with an increased risk of BCC, BCCs, recurrent BCCs, and BCCs in high-risk sites (with 5-year
including albinism, xeroderma pigmentosum, and Gorlin syn- cure rates approaching 95%).13
drome. Patients with Gorlin syndrome typically have multiple Nonsurgical modalities available for treatment of BCC include
BCCs, as well as anomalies of the spine and the ribs, jaw cysts, radiotherapy, photodynamic therapy, and the application of topical
pitting of the palms and the soles, and calcification of the falx cere- agents (e.g., 5-fluorouracil [5-FU], imiquimod, and intralesional
bri. This syndrome is inherited in an autosomal-dominant interferon alfa [IFN-α]). Radiation therapy is generally reserved for
fashion.10 elderly patients with extensive lesions that preclude excision; 5-year
cure rates in this population approach 90%.14 Photodynamic ther-
Histologic Subtypes apy involves the application of a 20% emulsion of δ-aminolevulinic
Several subtypes of BCC have been identified. Typical patterns acid to the lesion, followed by exposure to light in the wavelength
seen in more mature lesions include nodular or cystic BCC, superfi- range of 620 to 640 nm.This therapy is based on the uptake of the
cial BCC, morpheaform BCC, and pigmented BCC. Nodular porphyrin metabolite by the tumor with subsequent conversion to
BCC, also known as rodent ulcer, is the classic type. Nodular BCCs protoporphyrin IX, which results in destruction of the tumor in the
typically present as solitary lesions, often on the face, and are usually presence of light.10 The response rates observed with photodynam-
shiny and red with central telangectasias [see Figure 1a], an indurat- ic therapy are somewhat lower than those observed with other ther-
ed edge, and an ulcerated center. If the contents of the lesion are soft apies: the overall clearance rate is 87%, but the clearance rate for
and can be expressed, the condition is referred to as cystic BCC. Su- nodular BCC is only 53%.15 5-FU, in the form of a 5% cream,
perficial BCC is typically found on the trunk and appears as a slow- may be used in the management of multiple BCCs of the trunk
growing erythematous patch that is often mistaken for eczema or and limbs. Imiquimod is also given in a 5% cream to treat BCCs,
psoriasis.10 Morpheaform BCC [see Figure 1b] accounts for only a with clearance rates ranging from 70% to 100%.16 INF-α may be
minority of these lesions, but it exhibits clinical features that are es- administered directly into the lesion; in a series of 140 patients
pecially noteworthy for surgeons. In particular, morpheaform BCCs treated in this manner, a 67% cure rate was reported.17
a b
Figure 1 Shown are (a) a typical basal cell carcinoma and (b) a morpheaform basal
cell carcinoma.
- 3. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 3
a b
Figure 2 Shown are squamous cell carcinomas related to (a) radiation exposure and
(b) sun exposure.
Patients who have been treated for any skin cancer, including keratosis to invasive SCC.The lesions are typically located on sun-
BCC, are at higher risk for the development of additional skin can- exposed areas of the head, neck, trunk, or legs; when they are locat-
cers and should therefore perform self-examinations at frequent in- ed on the genitalia, the condition is referred to as erythroplasia of
tervals to check for suspicious lesions. Such patients should also re- Queyrat. Lesions that develop on non–sun-exposed areas may be as-
ceive counselling to reduce sun exposure, with the aim of limiting sociated with internal malignancy.22 Intraepithelial SCCs typically
further damage from ultraviolet irradiation. High-risk patients (e.g., appear as erythematous, slightly keratotic plaques and are usually
those with Gorlin syndrome and those who are receiving immuno- larger than the lesions of actinic keratosis. They should be excised
suppressive therapy after renal transplantation) should be offered with a 5 mm to 1 cm margin.
oral retinoid therapy in an effort to prevent the development of oth-
er nonmelanoma skin cancers.17 Diagnosis
As noted (see above), SCCs are most often associated with sun
SQUAMOUS CELL CARCINOMA
exposure, though they may also be seen in patients with old scars,
radiation-damaged skin [see Figure 2a], or chronic open wounds.23
Incidence and Epidemiology Chronic inflammation and irritation appear to be the common de-
SCC of the skin is the second most common form of non- nominators. SCC that arises in a burn scar or a chronic, open
melanoma skin cancer overall. It is the most common tumor in el- wound overlying osteomyelitis is often referred to as a Marjolin ul-
derly patients, probably as a consequence of cumulative doses of sun cer. SCCs that develop from Marjolin ulcers are characterized by
exposure over the course of their lifetimes. In white persons, the life- aggressive regrowth after incomplete biopsy.
time risk for the development of SCC is nearly 10%. SCCs typically appear as reddish-brown, pink, or flesh-colored
The majority (50% to 60%) of cutaneous SCCs are found on the keratotic papules [see Figure 2b]; ulceration is sometimes, though not
head and neck. In one series, nearly 50% of fatal cases of SCC oc- always, present. If there is extensive hyperkeratosis, a cutaneous
curred in patients in whom the lesion arose on the ear.18 The mor- “horn” may be evident.18 Symptoms that may suggest malignant
tality associated with SCC is estimated to be approximately transformation of actinic keratosis into SCC include pain, erythema,
1/100,000.19 ulceration, and induration. Histologically, SCCs are characterized
by nests of atypical keratinocytes that have invaded into the dermis,
Precursor Lesions which may be either well or poorly differentiated.
Unlike BCCs, SCCs often arise in precursor lesions, such as ac- Once the diagnosis of SCC is suspected, careful attention should
tinic keratoses.20 Actinic keratoses, sometimes referred to as solar be paid to the draining nodal basins with the aim of detecting possi-
keratoses, develop in chronically sun-damaged areas of the body. ble lymph node metastasis. The risk of such metastasis is between
These lesions are often multiple, are generally ill-defined and irregu- 2% and 4% overall but is somewhat higher in patients with relative-
lar, and may range in size from about 1 mm to a few centimeters. ly large and poorly differentiated lesions and in patients with lesions
They have a scaly appearance and exhibit a wide variety of colors, located on the scalp, the nose, the ears, the lips, or the extremities.
from dark brown to flesh-pink. Biopsy may be necessary to rule out The most common sites of metastasis are regional lymph nodes, the
the presence of a SCC. Although the rate at which actinic keratosis lungs, and the liver. When metastasis or recurrence develops, it is
undergoes malignant transformation to SCC is less than 0.1% per typically within 3 years after treatment of the index lesion.
year,21 lesions should nevertheless be treated to reduce the chances
of progression. Treatment options include cryotherapy, curettage, Treatment
and topical therapy. Surgical excision of actinic keratoses is rarely For primary SCC, as for BCC, surgical excision remains the
necessary but may be indicated if there is a high level of suspicion for mainstay of treatment; however, the recommended margin of
concurrent SCC. excision for SCCs is generally larger than that for BCCs, rang-
Intraepithelial SCC (carcinoma in situ), also known as Bowen ing from 0.5 to 2 cm. Smaller lesions can often be closed pri-
disease, is thought to be the next step in the progression from actinic marily; larger lesions may require rotation flaps or skin grafting.
- 4. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 4
Nonexcisional therapeutic options for SCC are similar to those Table 1—ABCD Guidelines for Pigmented Lesions
for BCC. Surgical choices include cryosurgery, curettage and cau-
terization, and Mohs’ micrographic surgery. Nonsurgical choices in- Characteristic Comments
clude radiotherapy, photodynamic therapy, and topical therapy with
agents such as 5-FU, imiquimod, and intralesional IFN-α. Most early lesions grow at uneven rate, resulting in an
Asymmetry
asymmetrical appearance
Posttreatment recommendations for SCC patients are essentially
the same as for BCC patients [see Basal Cell Carcinoma,Treatment, Border irregularity Uneven growth rate also results in irregular border
above]: frequent self-examination to look for suspicious lesions,
Irregular growth also causes new shades of black and
counseling to reduce sun exposure, and the offer of oral retinoid Color variegation
of light and dark brown
therapy for high-risk patients.17
Lesions with ABC features and diameter > 6 mm
Diameter
MELANOMA should be considered suspicious for melanoma
Incidence and Epidemiology 5. A history of 3 or more years of an outdoor summer job as a
Although melanoma is less common than BCC or SCC, it is teenager; and
clearly more deadly than either. It is currently the sixth leading cause 6. Marked freckling on the upper part of the back.
of cancer-related death in the United States, and its incidence is in-
For a person with one or two of these factors, the risk of melanoma
creasing faster than the incidence of any other malignancy.
is increased 3.5-fold; for a person with three or more, the risk is in-
Melanoma is slightly more common in men than in women, and the
creased 20-fold.
median age at diagnosis is 57 years.6 An average of 18.8 life-years
The recommended frequency for melanoma screening should be
are lost for each melanoma death,24 and it is estimated that one
based on these six risk factors. Routine screening of low-risk patients
United States citizen dies of melanoma every hour.25
through total body skin examinations performed by healthcare
Melanoma results from the malignant transformation of
providers is not a supported practice. Self-screening, however, is
melanocytes, which are responsible for pigment production.The ge-
clearly recommended, and excellent educational materials on this
netic factors implicated in this transformation have not been well
subject are available from the American Academy of Dermatology
characterized. As noted [see Assessment of Potentially Malignant
and the American Cancer Society. Nevertheless, physicians should
Skin Lesions, Clinical Evaluation, History, above], patients with a
take every opportunity to screen patients as the occasion arises; in
family history of melanoma are at substantially higher risk for the
general, the lesions found by physicians are significantly thinner than
development of melanoma.6 Somatic mutations in the p16 tumor
those detected by patients or their spouses.28
suppressor gene have been identified in both familial and sporadic
For effective treatment of melanomas, early recognition is critical.
cases of melanoma.26 Environmental factors—specifically, exposure
The ABCD (Asymmetry, Border irregularity, Color variegation, Di-
to ultraviolet radiation—are also implicated in the maligant transfor-
ameter) guidelines for pigmented lesions are frequently used as aids
mation of melanocytes. Increased risk of melanoma is associated
to melanoma identification [see Table 1].29 Melanomas often occur
with intermittent intense sun exposure rather than with the cumula-
on sun-exposed areas of the upper trunk and the extremities, and
tive effect of long-term mild exposure, though the exact mechanism
they are typically asymmetric, with irregular borders and variegated
behind the pathogenesis remains unknown.
pigmentation [see Figure 3a]. Occasionally, they lack pigmentation or
Screening and Diagnosis are associated with significant gross ulceration. Any lesion that ap-
pears suspicious for melanoma should undergo biopsy. Histological-
In one study, multivariate analysis identified the following six risk
ly, melanomas are characterized by atypical melanocytes with mitot-
factors as important in the development of malignant melanoma27:
ic figures. Special staining, most commonly with HMB-45 or S100,
1. A family history of melanoma; may also be performed.
2. A history of three or more blistering sunburns before the age of
20; Histologic Subtypes
3. Blonde or red hair; Melanoma may be classified into histologic subtypes on the basis
4. The presence of actinic keratosis; of growth pattern and anatomic location. It should be kept in mind,
a b
Figure 3 Shown are (a) a typical melanoma and (b) an acral lentiginous melanoma.
- 5. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 5
Table 2—Clark System for Staging Melanoma low system or the Clark system [see Table 2]. In the Breslow system, a
calibrated ocular micrometer is employed to measure tumor thick-
Clark Level Degree of Tumor Invasion 5-Year Survival (%) ness from the epidermal surface to the deepest point of the tumor’s
extension into tissue.31 In the Clark system, the levels are defined by
Level I Malignant melanocytes are confined to 99 the presence or absence of malignant melanocytes in each of the fol-
epidermis
lowing layers: epidermis, papillary dermis, reticular dermis, and sub-
Malignant melanocytes infiltrate papillary cutaneous fat [see Figure 4].32
Level II 95
dermis singly or in small nests
Over the past several years, extensive research has been conduct-
Malignant melanocytes fill and expand pap- ed on factors that affect prognosis in both early-stage and late-stage
illary dermis, with extension of tumor to melanoma. Clinical factors that have been shown to possess signifi-
Level III 82
papillary-reticular dermal interface (usually
signifying vertical growth phase) cant prognostic value include age, sex, the location of the
melanoma, the number of lymph nodes involved, the presence of
Malignant melanocytes infiltrate reticular distant metastasis, and the serum lactate dehydrogenase (LDH)
Level IV 71
dermis in significant fashion
level.33 In general, the prognosis is better when the patient is
Malignant melanocytes infiltrate subcuta- younger than 65 years of age, when the patient is female, when the
Level V 49
neous fat
tumor is located on an extremity, when no lymph nodes are in-
volved, when there is no evidence of distant metastasis, and when
however, that the specific subtype a tumor falls into, in itself, is not the serum LDH level is normal.
as important as the pattern of growth (i.e., radial versus vertical) and Melanomas are usually staged according to the system developed
the depth of penetration.30 The main subtypes are lentigo maligna by the American Joint Committee on Cancer (AJCC), the latest ver-
melanoma, superficial spreading melanoma, acral lentiginous sion of which was approved in 2002 [see Tables 3 and 4].34 The AJCC
melanoma, and nodular melanoma. Of these, superficial spreading stage correlates well with the 5-year survival rate [see Table 5].34
melanoma is the most common, accounting for more than 70% of
melanomas. These lesions occur most frequently in white adults, Stage I and II melanoma The vast majority of melanoma pa-
typically on the back or the legs. Nodular melanoma is the second tients have a clinically localized form of the disease (i.e., stage I or II).
most common subtype, accounting for between 15% and 30% of all Several clinical factors have been identified and employed for risk
melanomas.These lesions often appear dome-shaped and may oc- stratification and prognosis in this heterogeneous group. The most
cur anywhere on the body.They typically manifest an early vertical important prognostic factors in early-stage melanoma are tumor
growth phase and thus tend to invade the dermis early in their nat- thickness (T1 through T4) and the presence or absence of ulceration:
ural history. Lentigo maligna melanoma accounts for approximately 5-year survival in patients with stage I and II melanomas falls signifi-
5% of all melanomas and is believed to arise in a focus of lentigo cantly as tumor thickness increases and is substantially reduced (from
maligna (Hutchinson freckle). These lesions demonstrate a pro- 80% to 55%) in the presence of ulceration.30 In the past few years, the
longed radial growth phase before exhibiting an invasive compo- mitotic rate in the primary tumor has also been identified as an im-
nent. Acral lentiginous melanoma occurs on the hands or the feet portant prognostic factor, one that may eventually prove more impor-
[see Figure 3b], often under the nailbed, where the dermis is thinner tant than the presence or absence of ulceration in this population.35
(subungual melanoma).There also exists a relatively rare histologic Accordingly, it is likely that tumor mitotic rate will be incorporated
subtype known as desmoplastic melanoma, which typically occurs into the next iteration of the AJCC’s melanoma staging system.
in areas of sun damage and tends to recur locally more often than Study of thin (< 1 mm) melanomas, in particular, has led to fur-
other subtypes do. ther refinement of risk stratification.The Clark level has prognostic
implications for these lesions, in that tumors extending to Clark lev-
Staging and Prognosis el IV are considered T1b regardless of their actual thickness and are
An important variable in the prognosis of melanoma is the thick- associated with a worse prognosis. A 2004 report from the Universi-
ness of the primary tumor, as assessed by means of either the Bres- ty of Pennsylvania described a prognostic model that made use of a
I II III IV V
Epidermis
Figure 4 The Clark system classifies
skin tumors according to the level of
Papillary Dermis invasion, determined by the presence or
absence of malignant melanocytes in the
epidermis, papillary dermis, reticular
Reticular Dermis dermis, and subcutaneous fat.
Subcutaneous Fat
- 6. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 6
Table 3—American Joint Committee on Cancer TNM tases), with or without in-transit or satellite lesions.The presence of
Clinical Classification of Melanoma85 lymph node metastases is associated with a substantially worse prog-
nosis, with fewer than 50% of node-positive patients surviving for 5
years.34 The number of involved nodes is also a significant prognos-
TX Primary tumor cannot be assessed (e.g., shave
biopsy or regressed melanoma) tic factor and is included as such in the current version of the AJCC
Tis Melanoma in situ melanoma staging system.
T0 No evidence of primary tumor Four prognostic factors have been identified that influence sur-
T1 Lesion thickness ≤ 1.0 mm vival in patients with stage III melanoma: (1) the number of lymph
T1a: ulceration absent and Clark level II or III nodes with metastases; (2) the presence of microscopic tumor de-
T1b: ulceration present or Clark level IV or V posits in lymph nodes, as opposed to macroscopic deposits; (3) the
T2 Lesion thickness 1.01–2.0 mm presence of in-transit or satellite metastases; and (4) the presence of
Primary tumor (T) ulceration in the primary lesion.34 At one time, the size of the in-
T2a: ulceration absent
T2b: ulceration present volved lymph node was believed to be a significant prognostic factor,
T3 Lesion thickness 2.01–4.0 mm and it was included in earlier staging systems; currently, it is under-
T3a: ulceration absent stood that this variable does not in fact exhibit a significant correla-
T3b: ulceration present tion with survival.37 However, macroscopic disease (i.e., disease that
T4 Lesion thickness > 4.0 mm is identified clinically and confirmed histologically) does have a sig-
T4a: ulceration absent nificant impact: the survival rate is much poorer in patients with
T4b: ulceration present macroscopic disease than in those with microscopic disease.34
In-transit and satellite metastases represent dissemination of tu-
NX Regional lymph nodes cannot be assessed mor via lymphatic channels. The 5-year survival rates observed in
N0 No regional lymph node metastasis patients with these findings are similar to those observed in patients
N1 1 metastatic lymph node with lymph node metastases. If in-transit or satellite metastases are
N1a: micrometastases present present in association with lymph node metastases (N3), the sur-
N1b: macrometastases present vival rate is markedly reduced.34
N2 2 or 3 metastatic lymph nodes
Regional lymph N2a: micrometastases present
nodes (N) Stage IV melanoma For stage IV melanoma, the most im-
N2b: macrometastases present portant prognostic factors appear to be (1) the site at which a dis-
N2c: in-transit metastases or satellite metas- tant metastasis occurs and (2) the serum LDH level. Within this
tases present without metastatic lymph nodes
group, patients with cutaneous metastases and normal serum
N3 ≥ 4 metastatic lymph nodes; matted lymph
LDH levels have by far the most favorable prognosis.There are sig-
nodes; or combinations of in-transit metastases,
satellite metastases, or ulcerated melanoma and nificant differences in 1-year survival between patients who have
metastatic lymph nodes cutaneous, subcutaneous, or distant nodal metastases (M1), those
who have lung metastases (M2), and those who have any other
MX Distant metastases cannot be assessed
visceral metastases or who have any metastases in association with
M0 No distant metastasis
an elevated serum LDH level (M3).The predicted 1-year survival
M1 Distant metastases
rates for M1, M2, and M3 patients are 59%, 57%, and 41%,
M1a: metastases to skin, subcutaneous tissues,
Distant metastases respectively.34
(M) or distant lymph nodes
M1b: metastases to lung
M1c: metastases to all other visceral sites or dis-
tant metastases at any site associated with ele-
vated serum LDH Table 4—American Joint Committee on Cancer
Staging System for Melanoma
LDH—lactic dehydrogenase
Stage T N M
risk-stratification algorithm based on four factors: (1) mitotic rate
(0% versus ≥ 1%), (2) growth pattern (radial or vertical), (3) gender, 0 Tis N0 M0
and (4) tumor-infiltrating lymphocyte (TIL) activity (brisk, non- IA T1a N0 M0
brisk, or absent).36 For minimal-risk and low-risk patients, the pre-
IB T1b, T2a N0 M0
dicted risk for metastasis was less than 4%, whereas for moderate-
risk and high-risk patients, the predicted risk for metastasis was 12% IIA T2b, T3a N0 M0
and 30%, respectively.36
IIB T3b, T4a N0 M0
Intermediate-thickness (1 to 4 mm) melanomas are clearly asso-
ciated with a worse prognosis than thin melanomas: the 5-year sur- IIC T4b N0 M0
vival rate is 89% for patients with nonulcerated T2 lesions and IIIA T1–4a N1a, N2a M0
77.4% for those with ulcerated lesions. For patients with ulcerated
T3 lesions, the predicted 5-year survival rate is 63%. IIIB T1–4b N1a, N2a M0
For node-negative patients with thick (> 4 mm) lesions, the 5- T1–4a N1b, N2b M0
year survival rate is 67.4%; this figure drops to 45.1% if the lesion is Any T N2c M0
ulcerated.34 IIIC T1–4b N1b, N2b M0
Any T N3 M0
Stage III melanoma Stage III melanoma is characterized by
IV Any T Any N M1
the presence of nodal metastases (micrometastases or macrometas-
- 7. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 7
Table 5—5-Year Melanoma Survival Correlated Sentinel lymph node biopsy. An important issue in the surgical
with AJCC Stage management of melanoma is the use of sentinel lymph node biopsy
(SLNB) [see 3:6 Lymphatic Mapping and Sentinel Lymph Node Biop-
Stage TNM 5-Year Survival (%) sy], which has essentially replaced elective lymph node dissection.
Sentinel lymph node (SLN) status is the single most important pre-
IA T1a N0 M0 95.3 dictor of survival in patients with melanoma40 and is now considered
T1b N0 M0 90.9
a standard approach in the United States. A positive result is defined
IB as the presence of identifiable melanoma cells on routine hema-
T2a N0 M0 89.0 toxylin-eosin staining, immunohistochemical staining with S100 or
T2b N0 M0 77.4 HMB-45, or both. Preoperative lymphatic mapping via lympho-
IIA scintigraphy is often quite helpful, in that many lesions have variable
T3a N0 M0 78.7 drainage basins that cannot be predicted clinically, and some lesions
T3b N0 M0 63.0 even drain to contralateral nodes.41 The greatest accuracy is
IIB achieved with SLNB when both radioactive colloid and blue dye are
T4a N0 M0 67.4 used.42
IIC T4b N0 M0 45.1 SLNB should not be performed in patients with clinically positive
nodes or in those who would otherwise not be considered for lymph-
T1–4a N1a M0 69.5
IIIA adenectomy. It is generally recommended for patients who are at
T1–4a N2a M0 63.3 moderate or high risk for harboring occult regional node metastases.
In patients with T1 primary tumors, SLNB may be considered in
T1–4b N1a M0 52.8
selected scenarios (i.e., primary tumor ulceration or extensive re-
T1–4b N2a M0 49.6 gression, a high mitotic rate, a Clark level IV lesion, or a positive
IIIB
T1–4a N1b M0 59.0
deep margin).38
The impact of SLNB on the management of melanoma has been
T1–4a N2b M0 46.3 impressive.The results greatly facilitate accurate staging and play an
T1–4b N1b M0 29.0 important role in helping the clinician decide whether to perform
completion lymph node dissection (CLND) or to offer adjuvant
IIIC T1–4b N2b M0 24.0 therapy. Several studies have demonstrated significant differences in
Any T N3 M0 26.7 survival and disease-free interval between SLN-negative patients
and SLN-positive patients.43,44 One such study reported a 3-year
Any T any N M1a 18.8
disease-free survival rate of 88.5% in SLN-negative patients, com-
IV Any T any N M1b 6.7 pared with 55.8% in SLN-positive patients.43
Any T any N M1c 9.5
Surgical treatment of stage III melanoma Completion
lymph node dissection. At present, CLND is recommended for
management of the regional lymph node drainage basin in the pres-
Initial Evaluation ence of a positive SLN. Some clinical trial results do not appear to
For initial evaluation of patients with thin melanomas (< 1 mm), support this recommendation. For example, four randomized trials
no routine laboratory or radiologic tests are recommended. For pa- failed to demonstrate any overall survival benefit for patients ran-
tients with thicker melanomas (≥ 1 mm), some clinicians recom- domly assigned to undergo elective lymph node dissection.45-48 It
mend a chest x-ray. For patients with stage III disease, chest radio- should be noted, however, that most of the patients in these studies
graphy or computed tomography of the chest, the abdomen, and the did not have lymph node metastases, and thus, the trials did not
pelvis may be performed and are indicated for any signs or symp- have sufficient statistical power to detect a small survival benefit.49
toms of metastases. If inguinal lymphadenopathy is apparent, pelvic Other trial results, however, do support the recommendation for
CT should be performed to assess the iliac lymph nodes.38 For pa- CLND in node-positive patients, including those of the World
tients with stage IV disease, chest radiography should be performed Health Organization Program Trial No. 14, which demonstrated
and serum LDH levels obtained. Magnetic resonance imaging of that the 5-year survival rate in patients with occult nodal metastases
the brain and CT of the chest, the abdomen, and the pelvis should detected at elective lymph node dissection was significantly better
be performed to address any signs or symptoms of metastases and than that in patients who underwent delayed lymphadenectomy at
before any therapy is initiated. Any other imaging done will be guid- the time when palpable nodal metastases developed (48% versus
ed by protocol if the patient is enrolled in a clinical trial.38 27%).47
Nonetheless, the impact of CLND on overall survival is still a
Treatment matter for debate. The results of the first Multicenter Selective
Surgical treatment of stage I and II melanoma Margins of Lymphadenectomy Trial (MSLT suggest that SLNB with imme-
-I)
excision. Surgical excision remains the mainstay of treatment for diate CLND if the SLN is positive improves disease-free survival
melanoma. The width of the recommended surgical margin de- but not overall survival.50 In this trial, 1,973 patients were randomly
pends on the thickness of the lesion and has been well defined by a assigned in a 4:6 ratio to undergo either (1) wide excision (WE) fol-
series of prospective randomized clinical trials.39 According to most lowed by nodal observation or (2) WE plus lymphatic mapping and
current recommendations, a 0.5 cm margin is adequate for melano- sentinel lymph node biopsy (LM/SLNB) with immediate CLND if
ma in situ, a 1 cm margin is suggested for melanomas thinner than the SLN was positive.The two groups were comparable in regard to
1.0 mm, a 1 or 2 cm margin should be obtained for melanomas be- both patient variables (i.e., age and gender distribution) and lesion
tween 1 and 2 mm thick, and a 2 cm margin is required for melano- variables (i.e., location, thickness, and ulceration status). SLNs were
mas thicker than 2 mm.39 analyzed by means of hematoxylin-eosin staining and immunohisto-
- 8. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 8
chemical staining.The incidence of wound complications at the pri- is 54%.60 Unfortunately, the beneficial effect is often short-lived,
mary site was comparable in the two groups, though surgical mor- with recurrence rates reaching 50% within 1 to 1.5 years after ILP.61
bidity was significantly greater when SLNB was followed by In a 2004 series, the overall 5-year survival rate after ILP was 32%.61
CLND.50 A planned interim analysis presented at the American So- Recurrence after ILP may be treated with surgical excision, though it
ciety of Clinical Oncology in 2005 demonstrated a significant differ- has also been successfully treated with repeat ILP in patients with
ence in disease-free survival between the two groups (73% for WE extensive disease.62
followed by nodal observation versus 78% for WE plus LM/SLNB);
however, the difference in overall survival was not statistically signifi- Adjuvant therapy for stage IIB and III melanoma Radio-
cant (86% for WE followed by nodal observation versus 87% for therapy. Radiotherapy has been used with some success after ther-
WE plus LM/SLNB).51 These data led some to suggest that a sur- apeutic lymph node dissection in patients with high-risk lesions, re-
vival benefit might be gained by performing LM/SLNB followed by sulting in a decreased local recurrence rate63 and a modest survival
CLND in the event of a positive SLN, but this suggestion has not benefit64 in comparison with historic controls.This modality is typi-
been widely accepted.52 A study now under way, the second Multi- cally employed in stage III patients who have poor prognostic patho-
center Selective Lymphadenectomy Trial (MSLT -II), will assess the logic factors (e.g., positive surgical margins, multiple positive nodes,
therapeutic value of CLND against that of SLNB alone in patients extracapsular spread, or vascular or perineural involvement).65
who have a positive SLN.51
An important factor in considering whether to perform CLND Interferon therapy. Perhaps the most efficacious adjuvant agent
after a positive SLNB is the likelihood of finding metastases in the tested to date is IFN-α2b, which is currently approved by the United
remaining non-SLNs. In one series, 90 (14%) of 658 patients had a States Food and Drug Administration for adjuvant treatment of stage
positive SLN, and only 18 (20%) of the 90 showed evidence of IIB and stage III melanoma. Although a trial reported in 1996 found
metastases in additional non-SLNs removed during CLND.53 The that 1 year of high-dose IFN-α2b therapy led to a prolonged relapse-
number of positive nodes clearly has an impact on prognosis (as re- free interval and improved overall survival,66 subsequent trials and a
flected by its inclusion in the current version of the AJCC’s meta-analysis did not confirm this overall survival benefit.67 Further-
melanoma staging system34), and this fact lends support to the argu- more, nearly all patients experience adverse effects (e.g., fatigue, neu-
ment for performing a CLND after a positive SLNB. tropenia, headache, fever, and chills) with interferon therapy.66
Another issue that has not yet been resolved is the extent of lymph
node dissection required. One group, reviewing their experience Treatment of stage IV melanoma Metastasectomy. There is
with lymph node dissection before the use of SLNB, concluded that a large body of literature supporting resection of metastases from
the extent of lymph node dissection was a more important concern melanoma.The following five factors are commonly cited as predic-
with higher tumor burdens and a less important one with lower tu- tive of survival after metastasectomy: (1) the initial disease stage, (2)
mor burdens.54 Patients with micrometastatic disease in an SLN are the disease-free interval after treatment of the primary melanoma,
clearly different from patients with bulky nodal disease, and the po- (3) the initial site of metastasis, (4) the extent of metastatic disease
tential benefits of aggressive lymph node dissection in either group (single versus multiple sites), and (5) the ability to achieve complete
must be carefully weighed against the morbidity of the procedure. resection.57 In well-selected patients, this procedure can yield a rea-
Several studies are under way that should help address this issue, in- sonable likelihood of survival: a 1995 series reported a 5-year sur-
cluding MSLT 55 The roles of lymphadenectomy and adjuvant in-
-II. vival rate of 27% in all patients after pulmonary metastasectomy and
terferon alfa-2b (IFN-α2b) may be addressed by results from the a rate of 39% in patients with a single metastatic lesion.68 More
Sunbelt Melanoma Trial.56 modest benefits have been observed after resection of metastases to
the GI tract: a 1996 series reported a median survival of 44.5
Therapeutic lymph node dissection. Therapeutic lymph node dis- months in patients in whom a complete resection was achieved,
section is performed in patients who show evidence of lymph node compared with a median survival of 4 weeks in those in whom com-
metastases on physical examination. Some of these patients will sur- plete resection could not be achieved.69
vive for extended periods; most will at least be rendered free of the The five aforementioned factors are of critical importance in pa-
signs and symptoms of nodal metastases.57 tient selection for metastasectomy.To improve patient selection for
curative procedures, surgeons often treat patients with a single-site
Isolated limb perfusion. Most patients with in-transit metastases asymptomatic metastasis by administering chemotherapy for 2 to 3
experience unfavorable outcomes, with 5-year survival rates ranging months before considering resection, the aim being to see whether
from 25% to 30%. Surgical excision to clear margins is the mainstay the disease stabilizes or additional metastases develop.57 If there is a
of therapy when the size and number of the lesions permit. Amputa- response to treatment or the disease stabilizes with no evidence of
tion is rarely necessary. further metastases, they proceed with resection.57
A therapeutic alternative to surgical excision for patients who have It is extremely important to perform high-quality imaging before
extensive in-transit metastases in an extremity is the technique considering resection of metastases.The use of 18-fluorodeoxyglu-
known as isolated limb perfusion (ILP).The prime advantage of ILP cose positron emission tomography (FDG-PET) may help detect
is that it can achieve high regional concentrations of therapeutic occult metastatic disease more accurately. A 2004 comparison of
agents while minimizing systemic side effects.58 The arterial supply FDG-PET with conventional imaging in patients with stage IV
and the venous drainage are isolated, and a tourniquet may also be melanoma reported a sensitivity and specificity of 76% and 87% for
used to occlude superficial collateral veins. An oxygenated extracor- conventional imaging, 79% and 87% for FDG-PET, and 88% and
poreal circuit is employed to circulate a chemotherapeutic agent 91% for conventional imaging combined with FDG-PET.70 With
(typically melphalan) for 1 to 1.5 hours.The temperature of the limb FDG-PET, as with any other imaging modality, appropriate use de-
is usually elevated to 39° to 40° C.59 In patients who have clinically pends on a clear understanding of its capabilities and limitations.
positive nodes, therapeutic lymph node dissection is performed in Another important indication for metastasectomy is palliation; the
the same setting, just before limb perfusion.The effect of ILP can be vast majority of patients with stage IV melanoma will not be candi-
dramatic; for example, the rate of complete response with melphalan dates for curative-intent metastasectomy.The goal of a palliative pro-
- 9. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 9
cedure is to control identifiable symptoms (e.g., GI bleeding or patient with a significant antitumor response conferred impressive T
pain) caused by an advanced malignancy while minimizing morbid- cell responses.83
ity.57 A thorough discussion should be held among the surgeon, the Despite some advances in therapy, overall survival for patients
patient, and the family to address the goals and expected outcomes with stage IV melanoma has not improved over the past 20 years.
of the procedure, as well as its potential morbidity.71 Overall 5-year survival remains lower than 5%, with a median sur-
vival of only 7.5 months.84 The best hope for future improvements
Chemotherapy. To date, the rates of objective response to probably lies in the treatment of micrometastatic disease by means
chemotherapy for melanoma have been somewhat disappointing. of targeted chemotherapy and immunotherapy.
Darcarbazine (DTIC) is the only currently approved chemothera-
peutic agent for melanoma, and it offers no more than marginal
therapeutic benefit, with moderate side effects.72 Various combina- Operative Technique
tion regimens—including BOLD (bleomycin, vincristine, lomustine The inguinal nodes drain the anterior and inferior abdominal wall,
[CCNU], DTIC), CVT (cisplatin, vincristine, DTIC), and CBDT the perineum, the genitalia, the hips, the buttocks, and the thighs. A
(cisplatin, carmustine [BCNU], DTIC, tamoxifen)—have been em- superficial groin dissection removes the inguinal nodes, whereas a
ployed, with response rates ranging from 9% to 55%.72 The oral deep groin dissection incorporates the iliac and obturator nodes. Pal-
alkylating agent temozolamide has been studied in stage IV pable nodes can be marked on the patient before operation.
melanoma patients; compared with DTIC, it yields a modest pro-
SUPERFICIAL GROIN DISSECTION
longation of survival, with an acceptable side-effect profile.73
The patient is placed in a supine position on the operating table,
Melanoma vaccines. Several experimental melanoma vaccines with the hip slightly abducted and with the hip and knee slightly
are being investigated for possible use in advanced-stage melanoma. flexed and supported by a pillow. A Foley catheter is inserted, and
These agents use a variety of modalities to present melanoma anti- the skin is prepared and draped.
gens to host immune cells in an immunostimulatory context.74-76 The femoral artery, the anterior superior iliac spine, the pubic tu-
There was considerable initial optimism regarding this approach, bercle, and the apex of the femoral triangle are marked. A diagonally
but a 2004 review of the experience at the National Cancer Institute oriented skin incision is made that extends from a point medial to
found that the response rate for cancer vaccines was only 2.6%77 (a
figure comparable to the results obtained by others). The authors
concluded that the use of cancer vaccines may still prove to be a vi- MEDIAL DISSECTION Spermatic
able strategy, but profound changes will be required to enhance the Cord
Inguinal
efficacy of these agents. Ligament
Immunotherapy. At present, immunotherapy is perhaps the most
promising area of investigation with respect to the treatment of ad- Pectineal Muscle
vanced melanoma. Immunotherapy has been defined in various
ways, but in general, it can be thought of as a form of treatment Long Adductor
based on the concept of modulating the immune system to achieve a Lymphatics Muscle
therapeutic goal.78 There are several different modalities that can be
considered immunotherapy, including monoclonal antibody therapy Skin
Fascia
and interferon-based therapy. For present purposes, we will focus on Specimen
two modalities that are currently under active investigation: high-
dose interleukin-2 (IL-2) therapy and adoptive cell transfer.
In initial studies, the response rates after high-dose IL-2 therapy
for melanoma have ranged from 15% to 20%, with about half of the
responding patients experiencing complete regression.79 In those pa-
tients who do achieve a complete response, the effect is often
durable.80 Unfortunately, IL-2 immunotherapy is associated with se-
vere side effects.
Adoptive cell transfer involves the administration of activated cy-
totoxic T lymphocytes (CTLs) that are generated against specific tu-
mor types.These CTLs can be generated either by using specific tu-
mor-associated antigens or by culturing lymphocytes with tumor
cells.The objective is to encourage the selection of tumor-specific T
lymphocytes that are capable of generating a strong immunologic
response and thereby help break the body’s immunologic tolerance
of the tumor. Unfortunately, initial clinical trials of activated T cell Distal Portion of
Great Saphenous
transfer for other types of malignancy found that the transferred cells Vein Ligated
did not remain present in sufficient concentrations to yield a signifi-
cant clinical effect.81 However, the addition of nonmyeloablative
lymphodepleting chemotherapy, followed by autologous transfer of
tumor-specific CTLs in conjunction with IL-2 administration, was
shown to result in rapid clonal expansion of tumor-specific T lym-
phocytes in vivo, which was associated with a significant clinical re- Figure 5 Superficial groin dissection. The incision is deepened to
sponse.82 In a 2005 study, transfer of a T cell receptor gene from a include the deep muscular fascia.
- 10. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 10
Inguinal
Ligament Lymphatics Continue under
Inguinal Ligament Medial to
Specimen Femoral Vein
Retracted
Great Saphenous
Vein Stump
LATERAL DISSECTION
Pectineal
Muscle Nodal Tissue
Fascia
Femoral Sheath
Being Entered
Fascia
Branch of
Femoral
Nerve
Figure 6 Superficial groin dissection. The investing fascia overly- Sartorius Muscle
ing the femoral nerve and vessels is removed.
Figure 7 Superficial groin dissection. The groin dissection is
the anterior superior iliac spine down to the apex of the femoral tri- continued on the lateral side.
angle; the incision is formed in the shape of an S so as not to cross
the thigh flexion crease at a right angle. An incision oriented and
shaped in this manner will cause the least possible interference with
the musculocutaneous and cutaneous vascular territories of the skin, Fat and
will minimize ischemia to the skin flaps, and will avoid a flexion con- Lymphatics
tracture. Flaps are raised to allow identification of the medial border
of the sartorius, the lateral border of the adductor longus, and the ex-
ternal oblique fascia on the lower abdominal wall.
Fat and nodal tissue are swept inferiorly off the external oblique
aponeurosis, the spermatic cord, and the inguinal ligament [see Fig-
ure 5] and are reflected inferiorly.The fat and lymph nodes are then Great
dissected from the femoral triangle, starting medially at the lateral Saphenous
edge of the adductor longus and proceeding laterally [see Figures 6 Vein
Femoral
and 7].The femoral vessels are left undisturbed.The saphenous vein Sheath
is ligated and divided at the fossa ovalis [see Figure 8]; it is also ligated
and divided as it exits the femoral triangle distally.The specimen is Femoral
then dissected free from the femoral nerve.This step usually entails Vein
sacrificing branches of the lateral femoral cutaneous nerve, thereby Femoral
Artery
resulting in numbness of the anterolateral thigh.
Cloquet’s lymph nodes are located medial to the femoral vein un-
der the inguinal ligament.These nodes are dissected out and submit-
ted as a separate specimen. If Cloquet’s nodes contain melanoma,
the risk that iliac nodes will harbor melanoma is high, and a deep Figure 8 Superficial groin dissection. The great saphenous
groin dissection should be performed (see below). vein is ligated and divided.
- 11. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 11
DEEP GROIN DISSECTION
external iliac vessels is dissected; the dissection proceeds proximally
The inguinal ligament is divided, and the inguinal canal is further to the origins of the internal iliac vessels (avoiding the ureter) and in-
exposed by releasing the internal oblique abdominal muscle, the corporates the nodes overlying the obturator foramen while carefully
transversus abdominis, and the fascia transversalis and dissecting avoiding injury to the obturator nerve.The deep epigastric vessels are
into the retroperitoneal space.The deep circumflex iliac vessels are usually ligated at their origins from the external iliac artery and vein.
ligated, and the peritoneum is separated from the preperitoneal fat The lymph node–bearing specimen is then removed as a unit, ori-
and nodes by means of blunt finger dissection. Alternatively, rather ented, and marked with sutures for orientation and identification.
than dividing the inguinal ligament, one may make a separate inci- The inguinal canal is reconstructed to prevent a hernia. Any defect
sion in the external oblique fascia parallel to and above the inguinal medial to the femoral vessels under the ligament is sutured closed
ligament. with Cooper’s ligament.The sartorius is detached from the anterior
Retractors are inserted to widen the retroperitoneal space, and the superior iliac spine and is sutured to the midportion of the inguinal
peritoneum and the abdominal viscera are retracted medially. The ligament to cover the femoral vessels.The skin and the subcutaneous
chain of lymph nodes, areolar tissue, and adventitial tissues along the tissues are then closed in layers over a soft suction drain.
References
1. Miller DL, Weinstock MA: Nonmelanoma skin medical provider. Mt Sinai J Med 68:243, 2001 patients: validation of the American Joint
cancer in the United States: incidence. J Am Acad 19. Weinstock MA, Bogaars HA, Ashley M, et al: Committee on cancer staging system for cuta-
Dermatol 30:774. 1994 Nonmelanoma skin cancer mortality: a popula- neous melanoma. J Clin Oncol 19:3622, 2001
2. Rigel DS, Friedman RJ, Kopf AW: The incidence tion-based study. Arch Dermatol 127:1194, 1991 35. Francken AB, Shaw HM, Thompson JF, et al: The
of malignant melanoma in the United States: 20. Goldman GD: Squamous cell cancer; a practical prognostic importance of tumor mitotic rate con-
issues as we approach the 21st century. J Am Acad approach. Semin Cutan Med Surg 17:80, 1998 firmed in 1317 patients with primary cutaneous
Dermatol 34:839, 1996 melanoma and long follow-up. Ann Surg Oncol
21. Marks R: Squamous cell carcinoma. Lancet 347: 11:426, 2004
3. Hall HI, Miller DR, Rogers JD, et al: Update on 735, 1996
the incidence and mortality from melanoma in the 36. Gimotty PA, Guerry D, Ming ME, et al: Thin pri-
United States. J Am Acad Dermatol 40:35, 1999 22. Miki Y, Kawatsu T, Matsuda K, et al: Cutaneous mary cutaneous malignant melanoma: a prognos-
and pulmonary cancers associated with Bowen’s tic tree for 10-year metastasis is more accurate
4. Urbach F: Incidence of nonmelanoma skin cancer.
disease. J Am Acad Dermatol 6:26, 1982 than American Joint Committee on Cancer stag-
Dermatol Clin 9:751, 1991
23. Brownstein MH, Rabinowitz AD: The precursors ing. J Clin Oncol 22:3668, 2004
5. English DR, Armstrong BK, Kricker A: How
of cutaneous squamous cell carinoma. Int J Derm- 37. Buzaid AC, Tinoco LA, Jendiroba D, et al:
much melanoma is caused by sun exposure?
atol 18:1, 1979 Prognostic value of size of lymph node metastases
Melanoma Res 3:395, 1993
24. SEER cancer statistics review, 1973–1999. Ries in patients with cutaneous melanoma. J Clin Oncol
6. Rager EL, Bridgeford EP, Ollila DW: Cutaneous 13:2361, 1995
LA, Eisner MP, Kosary CL, et al, Eds. National
melanoma: update on prevention, screening, diag-
Cancer Institute, Bethesda, Maryland, 2002. 38. Johnson TM, Bradford CR, Gruber SB, et al:
nosis, and treatment. Am Fam Physician 72:269,
http://seer.cancer.gov/csr/1973_1999, accessed Staging workup, sentinel node biopsy, and follow-
2005
June 2006 up tests for melanoma. Arch Dermatol 140:107,
7. Miller SJ: Aetiology and pathogenesis of basal cell 2004
25. Greenlee RT, Hill-Harmon MB, Murray T, et al:
carcinoma. Clin Dermatol 13:527, 1995
Cancer statistics 2001. CA Cancer J Clin 51:15, 39. Riker AI, Glass F, Perez I, et al: Cutaneous
8. Marks R, Staples M, Giles G: Trends in non- 2001 melanoma: methods of biopsy and definitive surgi-
melanoma skin cancer treated in Australia: the sec-
26. Hashemi J, Linder S, Platz A, et al: Melanoma cal excision. Dermatol Ther 18:387, 2005
ond national survey. Int J Cancer 53:585, 1993
development in relation to non-functional 40. Gershenwald JE, Colome MI, Lee JE, et al:
9. Vitasa BC, Taylor HR, Strickland PT, et al: p16/INK4A protein and dysplastic nevus syn- Patterns of recurrence following a negative sentinel
Association of nonmelanoma skin cancer and drome in Swedish melanoma kindred. Melanoma lymph node biopsy in 243 patients with stage I or
actinic keratosis with cumulative solar ultraviolet Res 9:21, 1999 II melanoma. J Clin Oncol 16:2253, 1998
exposure in Maryland watermen. Cancer 65:2811,
27. American Academy of Dermatology: Melanoma 41. Thompson JF, Uren RF: Lymphatic mapping in
1990
Net. management of patients with primary cutaneous
10. Wong CSM, Strange RC, Lear JT: Basal cell carci- http://www.skincarephysicians.com/melanomanet, melanoma. Lancet Oncol 6:877, 2005
noma. BMJ 327:794, 2003 accessed June 2006
42. Morton DL, Thompson JF, Nieweg OE: The sen-
11. Telfer NR, Colver GB, Bowers PW: Guidelines for 28. Schwartz JL, Wang TS, Hamilton TA, et al: Thin tinel lymph node biopsy procedure: identification
the management of basal cell carcinoma. Br J primary cutaneous melanomas: associated detec- with blue dye and a gamma probe. Textbook of
Dermatol 141:415, 1999 tion patterns, lesion characteristics, and patient Melanoma. Thompson JF, Morton DL, Kroon
12. Harwood M, Wu H, Tanabe K, et al: Metastatic characteristics. Cancer 95:1562, 2002 BB, Eds. Martin Dunitz, London, 2004, p 323
basal cell carcinoma diagnosed by sentinel lymph 29. Friedman RJ, Rigel DS, Silverman MK, et al:
node biopsy. J Am Acad Dermatol 53:475, 2005 43. Gershenwald JE, Mansfield PF, Lee JE, et al: Role
Malignant melanoma in the 1990s: the continued of lymphatic mapping and sentinel lymph node
13. Rowe DE, Carroll RJ, Day CL Jr: Mohs surgery is importance of early detection and the role of the biopsy in patients with thick (> 4 mm) primary
the treatment of choice for recurrent (previously physician examination and self-examination of the melanoma. Ann Surg Oncol 7:160, 2000
treated) basal cell carcinoma. J Dermatol Surg skin. CA Cancer J Clin 41:201, 1991
Oncol 15:424. 1989 44. Gershenwald JE, Thompson W, Mansfield PF, et
30. Crowson AN, Magro CM, Mihm MC Jr: al: Multi-institutional melanoma lymphatic map-
14. Silverman MK, Kopf AW, Gladstein AH, et al: Prognosticators of melanoma, the melanoma ping experience: the prognostic value of sentinel
Recurrence rates of treated basal cell carcinomas. report, and the sentinel lymph node. Mod Pathol lymph node status in 612 stage I or II melanoma
Part 4: x-ray therapy. J Dermatol Surg Oncol 19:S71, 2006 patients. J Clin Oncol 17:976, 1999
18:549, 1992 31. Breslow A: Thickness, cross-sectional areas and 45. Sim FH, Taylor WF, Pritchard DJ, et al:
15. Peng Q, Warloe T, Berg K, et al: 5-Aminolevulinic depth of invasion in the prognosis of cutaneous Lymphadenectomy in the management of stage I
acid-based photodynamic therapy. Cancer 79: melanoma. Ann Surg 172:902, 1970 malignant melanoma: a prospective randomized
2282, 1997 32. Clark WH Jr, From L, Bernardino EA, et al: study. Mayo Clin Proc 61:697, 1986
16. Chimenti S, Peris K, Cristofaro S, et al: Use of Histogenesis and biologic behavior of primary 46. Veronesi U, Adamus J, Bandiera DC, et al: Delayed
recombinant interferon alpha-2b in the treatment human malignant melanomas of the skin. Cancer regional lymph node dissection in stage I
of basal cell carcinoma. Dermatology 190:214, Res 29:705, 1969 melanoma of the skin of the lower extremities.
1995 33. Homsi J, Kashani-Sabet M, Messina JL, et al: Cancer 49:2420, 1982
17. Hodak E, Ginzburg A, David M, et al: Etretinate Cutaneous melanoma: prognostic factors. Cancer 47. Cascinelli N, Morabito A, Santinami M, et al:
treatment of the naevoid basal cell cancinoma syn- Control 12:223, 2005 Immediate or delayed dissection of regional nodes
drome. Int J Dermatol 26:606, 1987 34. Balch CM, Soong SJ, Gershenwald JE, et al: in patients with melanoma of the trunk: a random-
18. Shelton RM: Skin cancer: a review and atlas for the Prognostic factors analysis of 17,600 melanoma ized trial. WHO Melanoma Programme. Lancet
- 12. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 4 Malignant Skin Lesions — 12
351:793, 1998 patients with multiple in-transit metastases. Ann Prolongation of survival in metastatic melanoma
48. Balch DM, Soong S, Ross MI, et al: Long-term Surg 240:939, 2004 after active specific immunotherapy with a new
results of a multi-institutional randomized trial 62. Feldman AL, Alexander HR Jr, Bartlett DL, et al: polyvalent melanoma vaccine. Ann Surg 216:463,
comparing prognostic factors and surgical results Management of extremity recurrences after com- 1992
for intermediate thickness melanomas (1.0 to 4.0 plete responses to isolated limb perfusion in 75. Butterfield LH, Ribas A, Dissette VB, et al:
mm). Intergroup Melanoma Surgical Trial. Ann patients with melanoma. Ann Surg Oncol 6:562, Determinant spreading associated with clinical
Surg Oncol 7:87, 2000 1999 response in dendritic cell-based immunotherapy
49. McMasters KM, Reintgen DS, Ross MI, et al: 63. Stevens G, Thompson JF, Firth I, et al: Locally for malignant melanoma. Clin Cancer Res 9:998,
Sentinel lymph node biopsy for melanoma: con- advanced melanoma: results of postoperative 2003
troversy despite widespread agreement. J Clin hypofractionated radiation therapy. Cancer 88:88, 76. Soiffer R, Hodi FS, Haluska F, et al: Vaccination
Oncol 19:2851, 2001 2000 with irradiated, autologous melanoma cells engi-
50. Morton D, Thompson JF, Cochran AJ: Sentinel 64. Ang KK, Byers RM, Peters LJ, et al: Regional neered to secrete granulocyte-macrophage colony-
node biopsy for early-stage melanoma: accuracy radiotherapy as adjuvant treatment for head and stimulating factor by adenoviral-mediated gene
and morbidity in MSLT-I: an international multi- neck malignant melanoma. Arch Otolaryngol transfer augments antitumor immunity in patients
center trial. Ann Surg 242:302, 2005 Head Neck Surg 116:169, 1990 with metastatic melanoma. J Clin Oncol 21:3343,
51. Morton DL: Interim results of the Multicenter 2003
65. Morris KT, Marquez CM, Holland JM, et al:
Selective Lymphadenectomy Trial (MSLT-I) in Prevention of local recurrence after surgical 77. Rosenberg SA, Yang JC, Restifo NP: Cancer
clinical stage I melanoma. debulking of nodal and subcutaneous melanoma immunotherapy: moving beyond current vaccines.
http://www.asco.org/ac/1,1003,_12-002511- deposits by hypofractionated radiation. Ann Surg Nature Med 10:909, 2004
00_18-0034-00_19-003013,00.asp, accessed July Oncol 7:680, 2000 78. Immunotherapy.Wikipedia,The Free Encyclopedia.
31, 2006
66. Kirkwood JM, Strawderman MH, Ernstoff MS, et http://en.wikipedia.org/wiki/Immunotherapy,
52. Thomas JM: Time for comprehensive reporting of al: Interferon alfa-2b adjuvant therapy of high risk accessed August 2, 2006
MSLT-1. Lancet Oncol 7:9, 2006 resected cutaneous melanoma: The Eastern 79. Rosenberg SA, Yang JC, Topalian SL, et al:
53. Clinical Practice Guidelines for the Management Cooperative Oncology Group Trial EST 1684. J Treatment of 283 consecutive patients with
of Cutaneous Melanoma. National Health and Clin Oncol 14:7, 1996 metastatic melanoma or renal cell cancer using
Medical Research Council, Canberra, 1999 67. Wheatley K, Ives N, Hancock B, et al: Does adju- high-dose bolus interleukin-2. JAMA 271:907,
54. Chan AD, Essner R, Wanek LA, et al: Judging the vant interferon-alpha for high-risk melanoma pro- 1994
therapeutic value of lymph node dissections for vide a worthwhile benefit? A meta-analysis of the
80. Atkins MB, Kunzel L, Sznol M, et al: High-dose
melanoma. J Am Coll Surg 191:16, 2000 randomised trials. Cancer Treat Rev 29:241, 2003
recombinant IL-2 therapy in patients with
55. Morton DL, Thompson JF, Essner R, et al: 68. Tafra L, Dale PS, Wanek LA, et al: Resection and metastatic melanoma: long-term survival update.
Validation of the accuracy of intraoperative lym- adjuvant immunotherapy for melanoma metastat- Cancer J Sci Am 6S:11, 2000
phatic mapping and sentinel lymphadenectomy for ic to the lung and thorax. J Thorac Cardiovasc Surg
81. Dudley ME, Wunderlich J, Nishimura MI, et al:
early-stage melanoma: a multicenter trial. 110:119, 1995
Adoptive transfer of cloned melanoma-reactive T
Multicenter Selective Lymphadenectomy Trial 69. Ollila DW, Essner R, Wanek LA, et al: Surgical lymphocytes for the treatment of patients with
Group. Ann Surg 230:453, 1999 resection for melanoma metastatic to the gastroin- metastatic melanoma. J Immunother 24:363, 2001
56. McMasters KM: The Sunbelt Melanoma Trial. testinal tract. Arch Surg 131:975, 1996
82. Dudley ME, Wunderlich JR, Robbins PF, et al:
Ann Surg Oncol 8:41S, 2001 70. Finkelstein SE, Carrasquillo JA, Hoffman JM, et Cancer regression and autoimmunity in patients
57. Wong SL, Coit DG: Role of surgery in patients al: A prospective analysis of positron emission after clonal repopulation with antitumor lympho-
with stage IV melanoma. Curr Opin Oncol tomography and conventional imaging for detec- cytes. Science 298:850, 2002
16:155, 2004 tion of stage IV metastatic melanoma in patients
undergoing metastasectomy. Ann Surg Oncol 83. Hughes MS,Yu YY, Dudley ME, et al: Transfer of
58. Benckhuijsen C, Kroon BB, van Geel AN, et al: a TCR gene derived from a patient with marked
11:731, 2004
Regional perfusion treatment with melphalan for antitumor response conveys highly active T cell
melanoma in a limb: an evaluation of drug kinet- 71. Miner TJ, Jaques DP, Shriver CD: A prospective effector functions. Hum Gene Ther 16:457, 2005
ics. Eur J Surg Oncol 14:157, 1988 evaluation of patients undergoing surgery for the
palliation of an advanced malignancy. Ann Surg 84. Barth A, Wanek LA, Morton DL: Prognostic fac-
59. Lingam MK, Byrne DS, Aitchison T, et al: A single tors in 1,521 melanoma patients with distant
center’s 10-year experience with isolated limb per- Oncol 9:696, 2002
metastases. J Am Coll Surg 181:193, 1995
fusion in the treatment of recurrent malignant 72. Cohen GL, Falkson CI: Current treatment options
melanoma of the limb. Eur J Cancer 32A:1668, for malignant melanoma. Drugs 55:791, 1998 85. Balch CM, Buzaid AC, Soong SJ, et al: Final ver-
1996 sion of the American Joint Committee on Cancer
73. Middleton MR, Grob JJ, Aaronson N, et al: staging system for cutaneous melanoma. J Clin
60. Vrouenraets BC, Nieweg OE, Kroon BB: Thirty- Randomized phase III study of temozolamide ver- Oncol 19:3635, 2001
five years of isolated limb perfusion for melanoma: sus dacarbazine in the treatment of patients with
indications and results. Br J Surg 83:1319, 1996 advanced metastatic malignant melanoma. J Clin
Oncol 18:158, 2000 [erratum, J Clin Oncol
61. Grunhagen DJ, Brunstein F, Graveland WJ, et al:
18:2351, 2000] Acknowledgment
One hundred consecutive isolated limb perfusions
with TNF-alpha and Melphalan in melanoma 74. Morton DL, Foshag IJ, Hoon DS, et al: Figures 5 through 8 Susan E. Brust, C.M.I.