Skin Cancer of the Head and Neck

Yun-Hsuan Ouyang, M.D.1

ABSTRACT

The majority of skin cancers of the head and neck are nonmelanoma skin cancers
(NMSC). Basal cell carcinoma and squamous cell carcinoma are the most frequent types of
NMSC. Malignant melanoma is an aggressive neoplasm of skin, and the ideal adjuvant
therapy has not yet been found, although various options for treatment of skin cancer are
available to the patient and physician, allowing high cure rate and excellent functional and
cosmetic outcomes. Sunscreen protection and early evaluation of suspicious areas remain
the first line of defense against skin cancers.

KEYWORDS: Basal cell carcinoma, melanoma, Mohs’ micrographic surgery,

nonmelanoma skin cancer, squamous cell carcinoma

S kin cancer is the most common malignancy in burn easily. In addition, NMSC may arise from preex-
the United States and makes up about one third of all isting conditions such as scars, chronic ulcers (Marjolin’s
cancers diagnosed. The common skin cancers include ulcer), and sinuses.3
nonmelanoma skin cancers (NMSCs) and melanoma. There are two types of people with rare genetic
The majority of skin cancers of the head and neck are syndromes—xeroderma pigmentosa and nevoid basal
NMSCs.1 This article reviews NMSC and malignant cell carcinoma syndrome—who have an increased risk
melanoma separately. of developing NMSC. Xeroderma pigmentosa is an
autosomal-recessive genetic disorder with reduced cell
capacity to repair DNA damaged by UVR. It is asso-
NONMELANOMA SKIN CANCERS ciated with the development of many skin tumors,
Squamous cell carcinoma (SCC) and basal cell carci- particularly SCC, but also BCC and melanoma, at a
noma (BCC) are by far the most frequent pathologic young age. Nevoid basal cell carcinoma syndrome is an
types of NMSC; the ratio of BCC to SCC is
3 to 4:1.1 autosomal-dominant genetic syndrome characterized
by the presence or occurrence of multiple BCCs, cysts
of the jaws, rib abnormalities, palmar and plantar pits,
Etiology and Risk Factors and calcification of the falx cerebri. The major treat-
The most important factor involved in the pathogenesis ment is early recognition, then ultraviolet shielding,
of NMSC is the cumulative amount of exposure to and lifelong monitoring of the skin for development of
ultraviolet radiation (UVR). UVR in the wavelength malignancies.4
range 290 to 320 nm is the most carcinogenic.1,2 Other An increased incidence of NMSC, especially
risk factors may contribute to the development of SCC, of the head and neck has also been found in
NMSC, including radiation exposure, long-term intake transplant recipients.5 These SCCs are more likely to
of arsenic, and fair-skinned people who tan poorly and behave aggressively and have a high rate of metastasis.6

1
E-Da Hospital, Kaohsiung County, Taiwan. Semin Plast Surg 2010;24:117–126. Copyright # 2010 by Thieme
Address for correspondence and reprint requests: Yun-Hsuan Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001,
Ouyang, M.D., No. 1, E-Da Road, Yon-Chau Township, Kaohsiung USA. Tel: +1(212) 584-4662.
County 824, Taiwan (R.O.C) (e-mail: [email protected]). DOI: http://dx.doi.org/10.1055/s-0030-1255329.
Advances in Head and Neck Reconstruction, Part I; Guest Editors, ISSN 1535-2188.
Samir Mardini, M.D., Christopher J. Salgado, M.D., and Hung-Chi
Chen, M.D., F.A.C.S.
117
118 SEMINARS IN PLASTIC SURGERY/VOLUME 24, NUMBER 2 2010

Epithelial Skin Cancers cells that proliferate downward into the dermis are
noted. The tumor masses are composed in varying
BASAL CELL CARCINOMA proportions of normal squamous cells and atypical squ-
The most common skin cancer is BCC, accounting for amous cells. According to the degree of keratinous
70 to 75% of skin cancers. There are five clinical types of differentiation, SCC can be subdivided into well differ-
BCC: entiated, moderately differentiated, or poorly differenti-
ated types. In general, with the more poorly
1. noduloulcerative BCC, including rodent ulcer differentiated change of the tumor, the fewer keratin
2. superficial BCC pearls formed, the higher the nuclear/cytoplasmic ratio,
3. morpheaform BCC and the more severe the nuclear atypia.7
4. pigmented BCC There are certain clinical factors that correlate
5. fibroadenoma. SCC with increased risk of local recurrence and meta-
stasis. These include:
The first three of these are mentioned with the
greatest frequency. The noduloulcerative lesions are the  size greater than 2 cm
most common type, accounting for 75% of cases of BCC.  poor histologic differentiation
The typical clinical appearance is a well-circumscribed  involvement of sites such as the external ear or lip
nodule or plaque with pearly border and overlying  tumor arising from a previous scar
telangiectasia and may be combined with rodent ulcer.  perineural invasion
Superficial BCC represents
10% of BCC. The clinical  occurrence in immunosuppressed patients.11
presentation is discrete erythematous macules or plaques
with scaly change and a thin rolled border.6,7
BCC tends to share the common histopathologic Nonepithelial Skin Cancers
features of a predominant basal cell type, peripheral Apart from BCC or SCC, the remaining 5% of NMSCs
palisading of lesional cell nuclei, and a mucinous stroma develop from skin appendages, neuroendocrine cells,
with artificial cleft between the epithelial island and the mesenchymal cells, or vascular structures.
stroma. In addition, there are variable degrees of cyto- Merkel cell carcinoma is a rare and aggressive
logic atypia and mitotic activity.7 neuroendocrine dermal neoplasm. The classic appear-
The incidence of metastasis in BCC is very rare, ance is a solitary red to violaceous nodule. Most of these
occurring in 0.0028 to 0.1% of patients. Review of the tumors are typically less than 2 cm in size but can reach
literature shows that morpheaform, adenocystic, meta- sizes as large as 10 cm. The majority of cases affect the
typical, and basosquamous types of BCC have a rela- head and neck and are thought to be caused by the
tively high local recurrence rate. The affinity of actinic damage associated with sun exposure. The
aggressive BCCs for perineural invasion has also been histopathology shows dense, small, blue round cells
reported.7,8 closely spaced in a trabecular pattern and sheets. Chro-
matin is delicate and uniformly distributed. Mitosis and
SQUAMOUS CELL CARCINOMA nuclear fragments are regular features.12 Treatment for
Review of several studies has shown that SCC may arise Merkel cell carcinoma must be aggressive. Local re-
from precancerous lesions such as actinic keratosis (AK). currence after resection has been reported in as many as
The prevalence of AK in fair-skinned people ranges from 44% of patients. Tumor resection with a 2- to 3-cm
11 to 26%, and it was estimated that the risk of develop- tumor-free margin is recommended in most studies, but
ment of SCC from AK ranges between 6% and 10%.9 this is often difficult to achieve in the head and neck.
Bowen’s disease is another pathologic entity that is Adjuvant radiotherapy and chemotherapy are advo-
thought to represent in situ SCC of the skin; it is cated for treatment of advanced disease, but their role
commonly misdiagnosed as eczema or psoriasis. Accord- remains unproven.13
ing to the literature, it becomes invasive SCC in 3 to 5% of Dermatofibrosarcoma protuberans (DFSP) is an
patients, of whom
13% will go on to develop metastases. intermediate malignancy that derives from dermal fibro-
Microscopically, Bowen’s disease is characterized by full- blasts. It usually forms an indurated plaque with multiple
thickness involvement of the epidermis and the piloseba- reddish to purple nodules. It usually occurs on the trunk
ceous epithelium by atypical keratinocytes.10 or the proximal extremities of young adults; only
10 to
SCC is the second most common skin cancer. 15% develop on the head and neck. The histopathology
Clinically, SCC of the skin most commonly consists of a of DFSP shows compact, monomorphous spindle cells
shallow ulcer surrounded by a wide, elevated, indurated arranged in a storiform pattern from dermis to subcuta-
border on a sun-exposed area of the body. The ulcer is neous fat, and it usually shows a characteristic honey-
often covered by a crust with a granulated base. On comb pattern in the subcutis. Local recurrence is
44%,
histologic examination, irregular masses of epidermal but metastases occur in only 1 to 4% of patients. Several
 SKIN CANCER OF THE HEAD AND NECK/OUYANG 119

studies have concluded that wide excision with a 2-cm Staging

tumor-free margin is necessary for adequate treatment. The tumor, node, metastasis (TNM) staging system for
Because of functional and cosmetic concerns, Mohs’ NMSC recommended by the American Joint Committee
microsurgery (described later) is an alternative treatment on Cancer Staging is based on retrospective data and uses
of choice.14 the end points of recurrence and survival. For example, a
Atypical fibroxanthoma (AFX) is a neoplasm of T1 tumor is 2 cm or smaller, T2 lesions are larger than
low-grade malignancy related to malignant fibrous his- 2 cm but not larger than 5 cm, and T3 tumors are those
tiocytoma. It usually presents as a solitary nodule less that are larger than 5 cm. T4 tumors are characterized by
than 2 cm in diameter on the exposed skin of the head invasion of adjacent structures such as cartilage, nerve,
and neck or dorsum of the hand of elderly patients, often muscle, or bone. Only two categories are used to classify
with a short history of rapid growth. The histopatho- regional lymph node metastasis: N0 for no metastasis,
logic finding usually shows an exophytic, dense cellular and N1 for any positive lymph node regardless of size. If
neoplasm with ulcerated surface. The classic tumor is upon pathology evaluation the stage changes, the new
composed of pleomorphic histiocyte-like cells and atyp- stage is denoted with a ‘‘p’’ as a prefix (e.g., ‘‘pT4’’).17
ical giant cells, often with bizarre nuclei and numerous
mitotic figures. Despite its apparently malignant histo-
logic features—a small number of metastases have been Treatment
reported—AFX usually follows an indolent or locally
aggressive course. The recommended surgical treatment CURETTAGE AND ELECTRODESICCATION
should include complete excision and margin control. In The principle of curettage and electrodesiccation (C&D)
most instances, it seems unnecessary to use excisional is to use heat to kill residual tumor cells left after sharp
margins greater than 1 cm to achieve a tumor-free curettage. This is the most widely used treatment for
margin.12 NMSC, in particular BCC. The indications for C&D
Sebaceous carcinoma is a malignant tumor derived include:
from the adnexal epithelium of sebaceous glands. It may
arise in ocular or extraocular sites and exhibit diverse  primary BCC smaller than 1 cm
clinical presentations. The most common presentation is  well-demarcated and well-differentiated SCC
a small, slowly enlarging, deep-seated nodule on the  anatomic sites at low risk for recurrence such as trunk,
upper eyelid that clinically is indistinguishable from a neck, and extremities.
chalazion. About 25% of all reported cases of sebaceous
carcinoma are extraocular. Because it can occur in any The contraindications for C&D include:
site containing sebaceous glands, its incidence is highest
in the head and neck region where sebaceous glands are  neoplasm located in areas at high risk for recurrence,
most plentiful. Histologically, there are variable-sized, such as nose, ear, and periocular and perioral areas
irregular lobules with undifferentiated cells and distinct  pathology reported as melanoma.
sebaceous cells containing foamy cytoplasm. Many un-
differentiated cells and sebaceous cells appear atypical; The advantages of C&D include rapidity of treat-
changes includes nuclear pleomorphism or atypical mi- ment, low cost, ease of treatment, and cure rates in excess
tosis. The clinical appearance of sebaceous carcinoma is of 90%. The disadvantage is that this method may
not pathognomic, so the diagnosis is often delayed for induce hypopigmented or hypertrophic scars. Also, no
months or years. Ocular sebaceous carcinoma quite specimen is available for histologic review of the margins
frequently causes regional metastases, and the mortality after treatment.6,18
rate is
22%. In general, excision with wide (5 to 6 mm)
surgical margins with frozen sections is the basis for CRYOSURGERY
treatment. Metastatic disease may be treated by excision Cryosurgery is performed with freezing temperatures to
and/or radiation and/or chemotherapy.15 selectively destroy skin cancers. The most common
Adnexal carcinoma may derive from eccrine glands, method is to use liquid nitrogen via spray or metal probe.
apocrine glands, and hair follicles. Most of these tumors In general, a double freeze-thaw cycle with a tissue
are highly malignant. It is estimated that they account temperature of –508C is required to ensure the destruc-
for 0.005% of all skin lesions and less than 1% of all head tion of most neoplastic tissue. This method has similar
and neck skin cancers. Currently, many lesions are indications and limitations to those of C&D. Compared
excised initially for diagnostic purposes. Because of the with procedures such as C&D, the major disadvantage
rare occurrence of these tumors, it is difficult to obtain a of cryosurgery is that effective treatment requires more
sufficient number of cases from a single institution to skill and experience; also, it may be associated with more
perform meaningful clinical trials of other therapeutic morbidity such as swelling, blistering, weeping, and
modalities.16 oozing over the treated area. Caution should be used
120 SEMINARS IN PLASTIC SURGERY/VOLUME 24, NUMBER 2 2010

when treating lesions on the lip, nasal ala, or eyelid, resection and pathologic examination is repeated until
because wound contraction can lead to retraction of free the margins are tumor-free.
margins and asymmetry. The cure rates for neoplasms Compared with other treatment modalities,
treated with cryosurgery range from 94 to 99%.6 MMS offers a high cure rate of skin cancer in selected
settings. Overall 5-year cure rates of greater than 99% are
SURGICAL EXCISION achieved in the excision of primary BCC, and 96% are
Surgical resection is the most common method of treat- attained for recurrent BCC. On the other hand, for SCC
ment for skin cancer of the head and neck. The physician treated with MMS, the 5-year cure rate of patients with
should keep four goals in mind: metastases was 16% compared with the 5-year cure rate
of 98% in those without metastases. The major disad-
1. total removal or destruction of the tumor vantages of MMS are prolonged procedure, special
2. maximal preservation of normal tissue equipment (cryostat), and a highly trained surgical
team (histotechnologist, Mohs’ surgeon, and dedicated
3. preservation of function pathologist).20
4. optimal cosmesis.
RADIOTHERAPY
The most important principle of treatment is Although radiation therapy is now used much less than
complete tumor excision because if this goal is not previously for the primary management of NMSC, it is
achieved, the other goals cannot be achieved. estimated that 90% of lesions smaller than 3 cm can be
Adequate margins of resection are necessary to controlled using radiotherapy. Surgical excision may
achieve clear margins. For the majority of BCC and cause severe functional or cosmetic deficits, thus primary
SCC cases, 4-mm margins are sufficient for lesions radiotherapy is an important option. Indications for
smaller than 2 cm in diameter. However, if the tumor postoperative radiotherapy include large or recurrent
is 2 cm or greater, is in high-risk areas, is invading fat, or primary lesions, close or positive tumor margins and/or
is not well differentiated, 6-mm margins of excision are perineural invasion, or radiosensitive neoplasms such as
required.19 In addition, care must be taken to take Merkel cell carcinoma.21,22
appropriate deep margins. Although sentinel node ex- There are several points of caution. Dosages are
cision is not routinely practiced for NMSC, local and carefully calculated to minimize damage to surrounding
regional metastasis must be evaluated when present. tissue, and any radiosensitive organ should be shielded if
Reconstruction of the defect depends on the size the tumor is near it. The contraindication of radio-
of the defect and the nature of the tumor excised. For therapy is nevoid basal cell carcinoma syndrome.6
smaller lesions, primary closure and healing by secondary
intention are appropriate options. Intermediate defects TOPICAL 5-FLUOROURACIL TREATMENT
may need a skin graft or local advancement of a rota- 5-Fluorouracil (5-FU) is a structural analogue of thymine
tional flap for adequate closure. For large defects, re- that inhibits thymidylate synthetase, thereby interfering
gional or distant pedicled flaps or free flaps are used. with DNA synthesis in dividing cells and causing cell
Therefore, careful preoperative assessment, including death. Topical 5-FU therapy can result in cure rates of
diagnostic imaging and consultation with an experienced 92% for SCC in situ and 95% for superficial BCC. The
reconstructive surgeon, is essential if use of rotational disadvantage of topical 5-FU treatment is significant
flaps or free flaps is needed. inflammation and irritation during treatment.6

MOHS’ MICROGRAPHIC SURGERY LASERS

Mohs’ micrographic surgery (MMS) is a specialized type Lasers play a limited role in the management of NMSC.
of surgical technique that maximally preserves healthy The carbon dioxide laser can be used in the focus mode
tissue. Frederic E. Mohs developed the procedure in the to excise lesions or in the defocused mode to vaporize
1930s. After modification of the method in the follow- lesions. It may be a choice of treatment for precancerous
ing years, the current procedure is first to use local lesions.
anesthesia to outline the tumor with a 1- to 3-mm
margin. Then a curette is used to debulk the tumor PHOTODYNAMIC THERAPY
with excision begun at a 45-degree angle to the skin. Photodynamic therapy (PDT) is a treatment modality
Before complete excision of the tumor, the initial etch- involving the administration of a photosensitizing com-
ing incision should include asymmetric marks to enable pound and the accumulation of the sensitizer molecules
accurate marginal tumor mapping. The tissue specimen in the target cells, followed by selective irradiation of the
is oriented and divided into four sections to permit lesion with visible light. The procedure results in tumor
processing of horizontal frozen sections and histologic necrosis. Hematoporphyrin is the first systemically
examination of the entire tumor margin. This cycle of studied photosensitizer for clinical PDT. The cutaneous
 SKIN CANCER OF THE HEAD AND NECK/OUYANG 121

accumulation of photosensitizer and its slow clearance MALIGNANT MELANOMA

from the skin leads to long-lasting cutaneous photo- Malignant melanoma is an aggressive neoplasm of skin.
sensitivity, up to 4 to 6 weeks, and an approach (topical Although it is less common than NMSC, it has been
PDT) to avoid this side effect has been developed. The estimated to be the seventh most frequent cancer in
standard procedure for topical PDT for a skin tumor is whites in the United States. Because one third of
application of 20% d-aminolevulinic acid (ALA) over melanomas arise in the head and neck, a surgeon should
lesional skin; the lesions are then exposed to light at 630 have a thorough working knowledge of the disease. The
to 635 nm for 3 to 6 hours after ALA application. Based lifetime risk of an individual developing malignant
on a literature review, the procedure is safe and eff- melanoma in the United States was expected to climb
icacious for treatment of cutaneous precancer and to 1 in 75 by the year 2000; during the past decade, the
cancer, and encouraging results have been reported in annual increase in malignant melanoma was
5 to 6%
treating AK, Bowen’s disease, and superficial BCC and per year, the most rapidly increasing rate for any cancer
SCC. in America.1
In contrast with many conventional therapeutic Malignant melanoma is a lethal cancer but is not
modalities, PDT has comparatively insignificant side uniformly fatal. Although melanoma comprises only 5%
effects such as burning pain, stinging, or itching re- of all skin cancers, more than three of four deaths from
stricted to the illuminated areas. The most frequent skin cancer are due to melanoma. Owing to earlier
cosmetic problem is residual hyper- and hypopigmenta- detection, the case fatality rate for melanoma has been
tion induced by PDT. There are still some problems dropping in recent decades.1,27
with PDT, including the cost, consumption of time, and
the need for special, expensive equipment.23
Etiology and Risk Factors
INTERFERON Similar to NMSC, there is a strong correlation between
Interferons (IFNs) are a group of naturally occurring sun exposure and the development of malignant mela-
cytokines that have multiple biologic effects, including noma. In contrast with NMSC (SCC and BCC), whose
control of cell growth and differentiation, modulation of development correlates with chronic sun exposure, the
immune responses, and antiviral activity. The intrale- development of malignant melanoma correlates better
sional administration of IFN-a has shown promise in with intermittent intense exposure to UV radiation.
the treatment of superficial and nodular BCCs, produc- Individuals who suffered blistering or other severe
ing cure rates of more than 80%.24,25 Further studies are sunburn during childhood or adolescence appear to be at
needed to determine the amount of IFN and the dura- increased risk for developing a melanoma later in life.
tion of therapy. Fair-skinned persons who have blue eyes, red or blond
hair, light complexion, and freckling tendency are at
RETINOIDS increased risk for the development of melanoma. This
Vitamin A and its physiologic metabolites and synthetic observation emphasizes the importance of educating this
derivatives (retinoid) have been shown to have protective population, and protection from the sun should begin at
effects against the development of certain types of an early age.1,28
cancer. Clinically, isotretinoin (13-cis-retinoic acid) sig- Most malignant melanomas (70% or more) arise
nificantly decreases the incidence of second primary in normal skin rather than from a preexisting melano-
tumor in patients with head and neck cancer and reduces cytic lesion.1 At least three types of lesion are known to
the appearance of NMSC in patients with xeroderma be precursors to malignant melanoma. In a literature
pigmentosum. Generally speaking, they are more effec- review, the percentage of histologically associated ma-
tive as chemopreventive agents than as chemotherapeu- lignant melanomas with large numbers of melanocytic
tic agents.26 nevi (including common melanocytic nevi and dys-
plastic nevi) varied between 4% and 72% and the
maximal frequency between 20% and 30%.29Congenital
Conclusion melanocytic nevi (CMN), which are present at birth,
NMSC of the head and neck is quite common. Once a may give rise to melanoma. A significant increased risk
diagnosis of NMSC is considered, a complete history, of melanoma in patients with giant CMN (>20 cm in
review of systems, and physical examination should be diameter) from 5 to 40% has been reported.30Lentigo
performed. Because of the variety of surgical and non- maligna (LM) is regarded as a form of melanoma in
surgical options that are available for the treatment of situ; the exact percentage of LM that progress to
NMSC, careful preoperative assessment, including di- lentigo maligna melanoma (LMM) is unknown. The
agnostic imaging and consultation with an experienced lifetime risk of LMM developing from LM is estimated
reconstructive surgeon, radiologist, or oncologist, may be to be 4.7% at 45 years of age and 2.2% for a person
needed. 65 years old.28
122 SEMINARS IN PLASTIC SURGERY/VOLUME 24, NUMBER 2 2010

Another important constitutional risk factor for with sun-damaged atrophic skin. Histopathologically,
melanoma is a family history of melanoma (particularly if the epidermis usually shows atrophic change with thin-
associated with a personal and family history of dys- ning and loss of rete ridges and an increased number of
plastic nevi). The patients with familial dysplastic nevus atypical melanocytes in the basal cell layer. The mela-
syndrome and sporadic dysplastic nevi are at significantly nocytes vary in appearance, size, and shape and show
greater risk for malignant melanoma than the general atypical changes in the nuclei.28,32
population. It is important to establish accurate baseline
photographs and maintain close clinical follow-up. LENTIGO MALIGNA MELANOMA
Biopsies are reserved for the initial diagnosis of dys- Lentigo maligna melanoma (LMM) is the least common
plastic nevi and for lesions suspected of being malignant type of melanoma (usually 4 to 15% of all types). It is
melanoma. Xeroderma pigmentosa is a genetic syn- almost exclusively located on sun-exposed skin of the
drome associated with melanoma.4 head and neck, with the nose and cheeks the most
common sites. The clinical appearance is a flat patch
with irregular borders, with or without a papulonodular
Clinical Evaluation portion. The color is variegated and may include tan,
To summarize the important risk factors, Dr. T.B. brown, black, blue-gray, and white. The histopathology
Fitzpatrick proposed the acronym MMRISK: of LMM is extensive hyperplasia of typical melanocytes
M ¼ Moles: atypical; M ¼ Moles: common; R ¼ Red along the dermal-epidermal junction and nesting of
hair and freckling; I ¼ Instability to tan: skin phototypes atypical melanocytes invading the papillary dermis. In
I and II; S ¼ Sunburn: severe sunburn before age addition, there is always severe solar elastotic degener-
14 years; K ¼ Kindred: family history of melanoma.28 ation in the upper dermis.28,32
On physical examination, the mnemonic ABCD
developed years ago to aid in the diagnosis of melanoma SUPERFICIAL SPREADING MELANOMA
is helpful in assessing a patient with a pigmented lesion. Superficial spreading melanoma (SSM) represents
The ABCD of melanoma is as follows: Asymmetry: the
70% of all melanomas and is the most common type
melanoma is not symmetrical; Border: note the highly of cutaneous melanoma. SMM may present as a deeply
irregular and uneven border; Color: the color is varie- pigmented macule or plaque with pigment variegation.
gated with different shades of brown, black, and tan; The most common sites of SMM are the legs of women
Diameter: the diameter is usually >6 mm.28 and the backs of men. The histopathology of SSM is
Aids to clinical diagnosis include a Wood’s lamp, irregular epidermal hyperplasia with a pagetoid distri-
dermatoscopy, and photography. The ultimate diagnosis bution of large melanocytes. These large cells may occur
of a melanoma depends on the biopsy. In general, the singly or in nests and have uniform cytologic atypia.28,32
lesion should be excised with narrow margins whenever
possible. Otherwise, an incisional biopsy is appropriate NODULAR MELANOMA
when the suspicion for melanoma is low, the lesion is The second most common subtype of melanoma is
large, or it is impractical to perform an excision. Needle nodular melanoma (NM), with a frequency of 15 to
and shave biopsies of primary lesions are discouraged 30% of all types. NM presents as a uniform dark blue-
because they do not adequately assess thickness.31 black nodule on the trunk, head, and neck. Early
recognition of NM can be difficult because it lacks
many of the conventional clinical features of melanoma.
Classification and Histopathology of Cutaneous But NM is remarkable for its rapid evolution within
Malignant Melanoma several weeks to months. The histopathology of NM is
Melanoma results from the malignant transformation of contiguous proliferation of neoplastic melanocytes in the
melanocytes. According to their gross and microscopic dermis, forming a tumor mass that is larger than the
characteristics, melanoma can be classified into four largest nest in the overlying epidermis. Pagetoid spread-
main growth patterns: ing of the epidermis with neoplastic melanocytes may be
absent or may be limited to that portion overlying the
 lentigo maligna dermal mass.28,32
 superficial spreading
 nodular ACRAL LENTIGINOUS MELANOMA
 acral lentiginous melanoma. Acral lentiginous melanoma (ALM) occurs relatively
infrequently in light-skinned whites but represents the
LENTIGO MALIGNA most common form in those of darker complexion. The
The clinical manifestation of lentigo maligna (LM) is an histopathology shows proliferation of neoplastic mela-
irregularly mottled pigmented macule or patch on sun- nocytes with heavily pigmented granules along the
exposed areas. It occurs most often in elderly patients dermal-epidermal junction. As the name implies,
 SKIN CANCER OF THE HEAD AND NECK/OUYANG 123

ALM always occurs on acral parts, the most common In the AJCC staging system, tumor thickness is
site being the sole of the foot. We will not therefore the most powerful independent prognostic factor for
discuss ALM here.28,32 patients with primary cutaneous melanoma. Mela-
noma thickness is measured from the granular layer
of the epidermis to the greatest depth of tumor
Staging invasion. This was originally described by Breslow.
Once the diagnosis of a melanoma is confirmed, the Now it is correlated with a thickness of 1 mm (T1),
history should be reviewed. This should include a 1.01 to 2 mm (T2), 2.01 to 4 mm (T3), or 4 mm
review of systems and a family history of atypical moles (T4). Ulceration is the second most powerful factor for
and melanoma. A thorough physical examination poor prognosis.
should be performed. The requirement of sentinel The anatomic level of invasion (Clark’s level) is an
lymph node biopsy and extensive laboratory investiga- independent factor only for thin melanomas (<1 mm, or
tion should be evaluated. category T1). It is classified into levels I to V. Level I
The American Joint Committee on Cancer indicates melanoma confined to the epidermis. Level II
(AJCC) Tumor Node Metastasis Committee has ap- indicates tumor cell extended into the papillary dermis
proved a new melanoma staging system, which was im- but not reaching the papillary-reticular dermal interface.
plemented in 2002.33 Tables 1 and 2 present the TNM Level III indicates invasion of neoplasm to fill and
categories and staging groups, respectively. There are expand the papillary dermis but not penetrating the
three prognostic factors included in AJCC staging system: reticular dermis. With level IV, there is a clear extension
of tumor cells into the reticular dermis. Finally, level V
1. tumor thickness indicates subcutaneous invasion.33
2. ulceration The other prognostic factors also significantly
3. level of invasion (Clark’s level). correlate with survival. The worse prognostic factors

Table 1 TNM Classification of Melanoma

T Classification Thickness Ulceration Status

T1 1.0 mm a: without ulceration and level II/III

b: with ulceration or level IV/V
T2 1.01–2.0 mm a: without ulceration
b: with ulceration
T3 2.01–4.0 mm a: without ulceration b: with ulceration

T4 >4.0 mm a: without ulceration

b: with ulceration
Number of
N Classification Metastatic Nodes Nodal Metastatic Mass
N1 1 a: micrometastasis*
b: macrometastasisy
N2 2–3 a: micrometastasis*
b: macrometastasisy
c: in-transit metastases/satellite(s)
without metastatic nodes
N3 Four or more metastatic nodes,
or matted nodes, or in-transit
metastases/satellite(s) with
metastatic node(s)

M Classification Site Serum Lactate Dehydrogenase

M1a Distant skin, subcutaneous, Normal

or nodal metastasis
M1b Lung metastasis Normal
M1c All other visceral metastases Normal
Any distant metastasis Elevated
*Micrometastases are diagnosed after sentinel or elective lymphadenectomy.
y
Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal
metastasis exhibits gross extracapsular extension.
124 SEMINARS IN PLASTIC SURGERY/VOLUME 24, NUMBER 2 2010

Table 2 Proposed Staging Groups for Cutaneous Melanoma

Clinical Staging* Pathologic Stagingy
T N M T N M

0 Tis N0 M0 Tis N0 M0
IA T1a N0 M0 T1a N0 M0
IB T1b N0 M0 T1b N0 M0
T2a T2a
IIA T2b N0 M0 T2b N0 M0
T3a T3a
IIB T3b N0 M0 T3b N0 M0
T4a T4a
IIC T4b N0 M0 T4b N0 M0
IIIz Any T N1 M0
N2
N3
IIIA T1 to 4a N1a N2a M0
N2a
T1-4a
IIIB T1 to 4b N1a M0
T1 to 4b N12a M0
T1 to 4a N1b M0
T1 to 4a N1b M0
T1 to 4a/b N2c M0
IIIC T1 to 4b N1b M0
T1 to 4b N2b M0
Any T N3 M0
IV Any T Any N Any M1 Any T Any N Any M1
*Clinical staging includes microstaging of the primary melanoma and clinical/radiologic evaluation for metastasis. By convention, it should be
used after complete excision of the primary melanoma with clinical assessment for regional and distant metastasis.
y
Pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after partial or
complete lymphadenectomy. Pathologic stage 0 or stage 1A patients are the exception; they do not require pathologic evaluation of their lymph
nodes.
z
There are no stage III subgroups for clinical staging.

include increasing age, male tumor on head and neck, surgeon must think in three dimensions; that is, how
increasing mitotic rate, diminished tumor-infiltrating best to obtain a deep margin as well as lateral margins
lymphocytes, microscopic metastasis, and vascular (e.g., whether or not resection of muscle and facial bones
invasion.28,34 is required for adequate margins). When tissue conser-
vation is important, intraoperative frozen section analy-
sis may be helpful.
Treatment
MOHS’ MICROGRAPHIC SURGERY
SURGICAL EXCISION Mohs surgery has been advocated for the treatment of
The standard treatment for cutaneous melanoma is primary cutaneous melanoma, especially those located
complete surgical excision of the primary lesion. The on the head, neck, hands, and feet.31 The other selective
current American Academy of Dermatology (AAD) criteria of Mohs’ micrographic surgery (MMS) are
guidelines of care for cutaneous melanoma recommends desmoplastic melanoma with invisible extensions from
an 0.5-cm margin for melanoma in situ, a 1-cm margin perineural invasion, locally recurrent melanoma, and
for invasive melanomas <2 mm thick, and 2-cm margins melanoma located in areas in which tissue preservation
for melanomas >2 mm thick.31 is mandatory.21,35
It is important to note that strict guidelines
should not be routinely recommended in the surgical SENTINEL LYMPH NODE BIOPSY AND ELECTIVE LYMPH
management of cutaneous primary melanoma. Mela- NODE DISSECTION
noma excision at special sites, such as ear, nose, or other The sentinel lymph node is the first node or nodes to
site of head and neck, also requires separate surgical, drain a primary neoplasm. Sentinel lymph node biopsy is
functional, and cosmetic consideration. In addition, the performed to determine whether regional metastases are
 SKIN CANCER OF THE HEAD AND NECK/OUYANG 125

present. The head and neck area is notorious for being cutaneous melanoma. The chemotherapeutic agent
harder to map. The previously reported success rate was most commonly used to treat disseminated melanoma
70 to 80%, but, by using two mapping techniques, the is dacarbazine, which produced 20 to 25% response rates
success rate is increased to 95%. in treated patients with metastatic or recurrent dis-
From a review of literature, it is considered that a ease.37,38
sentinel lymph node biopsy should be performed on Melanoma is considered to be relatively radio-
patients with a melanoma greater than 1 mm thick; the resistant, thus limiting the role of radiation therapy in its
staging information can then be used to plan elective management. The optimal dose fraction is unclear.
lymph node dissection and adjuvant therapy. This tech- Based on encouraging results with a few large-dose
nique can be used to make the surgical care of the fractions, the Radiation Therapy Oncology Group be-
melanoma patient more conservative, so that only gan a prospective randomized trial of regional adjuvant
those patients with evidence of regional node metastasis radiotherapy after lymphadenectomy in patients with
are subjected to the morbidity and expense of a complete node-positive head and neck melanoma.37
node dissection and the toxicity of adjuvant therapy.36

INITIAL DIAGNOSTIC WORKUP AND ONGOING CONCLUSION

FOLLOW-UP The rate of malignant melanoma is currently rising faster
The current AAD guidelines for care of primary cuta- than that of any other cancer, and it has become an
neous melanoma recommend that routine laboratory important public health problem. Most melanomas are
tests and imaging studies are not required for initial amenable to cure with early diagnosis and appropriate
staging or follow-up in asymptomatic patients with treatment. Several options for the treatment of skin
primary cutaneous melanoma that is 4 mm or less in cancer are available to the patient and physician, allow-
thickness. Indications for such studies are directed by a ing high cure rates and excellent functional and cosmetic
thorough medical history and physical examination. outcomes. Until further research yields a cure for ad-
The goal of follow-up of patients with melanoma vanced malignant melanoma, sunscreen protection and
is to reduce morbidity and mortality through the detec- early evaluation of suspicious areas remain the first line
tion of asymptomatic metastases and additional primary of defense in the fight against malignant melanoma.6,27
melanomas. Although there is no evidence to support a
specific follow-up interval, the AAD recommends fol-
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