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Address reprint requests and correspondence: Genevieve Andrews, MD, Division of Otolaryngology - Head and Neck Surgery, Penn State Hershey Melanoma Center, Head & Neck Oncologic Surgery, Penn State Hershey Medical Center, 500 University Drive, Mail Code H091, Hershey, PA 17033-0850
The spectrum of cutaneous malignancies of the head and neck ranges from tumors that are fairly well behaved, such as the majority of basal cell carcinomas, to very aggressive cancers with a high metastatic rate, such as Merkel cell carcinoma. Most forms of cutaneous malignancy have characteristic clinical presentations, which assist in their clinical diagnosis. The goal of this article is to review the appearances and clinical presentations of common nonmelanoma skin cancers (basal and squamous cell carcinomas), uncommon nonmelanoma skin cancers (Merkel cell carcinoma and dermatofibrosarcoma protuberans), and the various subtypes of cutaneous melanoma.
The majority of cutaneous malignancies affect sun-exposed areas of the body; therefore, head and neck surgeons will commonly encounter patients with skin malignancies. The goal of this article is to review the appearances and clinical presentations of common nonmelanoma skin cancers (basal and squamous cell carcinoma [SCC]), uncommon nonmelanoma skin cancers (Merkel cell carcinoma [MCC] and dermatofibrosarcoma protuberans [DFSP]), and the various types of cutaneous melanoma. For each cancer, the clinical appearance, demographics, etiologic and risk factors, common body locations, and risk of regional lymph node involvement will be discussed.
Basal cell carcinoma (BCC), which is the most common form of skin cancer, is thought to arise from the basal keratinocytes in the epidermis and around adnexal structures. It occurs in men more often than women and usually occurs in those older than 40 years. Ultraviolet radiation, especially prolonged sun exposure, induces mutations in tumor suppressor genes, which leads to uncontrolled proliferation of basal cells.
Fair-skinned individuals are much more likely to develop BCCs than are darker-skinned individuals. Patients with a history of radiotherapy to the head and neck, as well as arsenic ingestion, are also at risk for development of multiple BCCs. Although most BCCs are sporadic, presentation with multiple BCCs might suggest a hereditary disease. Gorlin syndrome (nevoid BCC syndrome), Bazex-Dupré-Christol syndrome, Rombo syndrome, Oley syndrome, and xeroderma pigmentosum are hereditary tumor syndromes associated with the formation of multiple BCCs.
There are several types of BCC including nodular, micronodular, infiltrative, pigmented, morpheaform, and superficial BCC, with the micronodular, morpheaform, and infiltrative types being the more aggressive.
Nodular BCC is the most common type of BCC, and appears as a pearly white or pink dome-shaped papule (Figure 1), with or without ulceration. Telangiectatic vessels on the surface of the lesion become obvious as the lesion enlarges, and the center frequently ulcerates and bleeds. These tumors often have associated blood-tinged crust. Nodular BCCs usually first extend peripherally, and then after a time will penetrate deeply into the subcutaneous tissues. However, as with all tumors, the growth pattern can be irregular.
The morpheaform, or sclerosing, type of BCC is a tumor that has innocuous surface characteristics (Figure 2). The lesion is firm. However, it is waxy, flat or slightly raised, white or yellow, borders are indistinct and blend with normal skin, and can have broad extension beyond the apparent borders. These tumors can mimic the appearance of a scar. Follicular dropout, loss of hair follicle structures, within the area affected is one clue to the diagnosis. The average subclinical extension beyond the apparent borders of morpheaform BCC in one study was 7.2 mm.
In general, Mohs surgery should be used for these subtypes to ensure that negative margins are achieved given the frequent innocuous appearance clinically.
Pigmented BCC is a BCC that contains melanin that imparts blue, brown, or black color to the lesion (Figure 3). Pigmented basal cells can mimic the appearance of melanoma, and in some cases, one cannot clinically distinguish the two with 100% certainty. The tumor most often still has the pearly translucent border more characteristic of BCC, which is a helpful distinguishing factor. The histologic pattern most associated with pigmented BCC is the nodular pattern. The superficial type of BCC is the least locally aggressive of the BCC subtypes because it spreads peripherally first, and invades the subcutaneous tissue late. It appears as a well-circumscribed, round-to-oval, red, scaling patch that can resemble eczema, tinea, or psoriasis. However, careful inspection of edges of the lesion can reveal the thin, raised, pearly white border characteristic of BCC (Figure 4). It most commonly occurs on the trunk or extremities but may occur on the face.
Cutaneous SCC (cSCC) is a malignancy of keratinocytes that arises from the epidermis of the skin. It occurs in men more than women, and usually in those older than 55 years. Ultraviolet radiation exposure is the most frequent etiologic factor for the development of cSCC. However, human papillomavirus infection, immunosuppression, chronic inflammation, industrial carcinogens, and arsenic ingestion are also associated risk factors. SCCs are commonly located on sun-exposed areas of the body.
SCCs of the skin can be divided into well-differentiated or poorly differentiated types, with the poorly differentiated tumors exhibiting a more aggressive biology.
Differentiated SCC often feels hard and hyperkeratotic, and appears as an indurated papule, plaque, or nodule with elevated margins (Figure 5). This lesion may ulcerate and accumulate crust in its center, and a keratotic horn may appear to extend from the margin or center of the lesion.
Keratoacanthoma is a variant of SCC that presents as a dome-shaped nodule with a central keratotic plug. They often present as a firm, round, primarily skin-colored nodule with slight red or brown hues. Keratoacanthomas usually occur in patients older than 50 years. The main risk factors associated with this disease is ultraviolet radiation exposure. As a result, this lesion has a predilection for sun-exposed sites of the body. Human papillomavirus infection and chemical carcinogens are also thought to be associated with this lesion. Keratoacanthoma exhibits rapid growth and can cause cosmetic disfigurement. There are clinical variants of keratoacanthomas, including multiple synchronic tumors, and a giant variant termed keratoacantoma cetifugum marginatum. However, most spontaneously regress in 2-6 months or sometimes after 1 year. Rarely, keratoacanthomas metastasize to lymph nodes and viscera.
Melanoma is a malignancy of melanocytes, the pigment-producing cells, that mainly occurs in the skin; however, it can also arise in mucous membranes, retina, and leptomeninges. The reported incidence of melanoma has been increasing over the past 50 years.
There are four major subtypes of melanoma, including superficial spreading, nodular, acral lentiginous, and lentigo maligna melanoma (LMM), which are discussed herein. The rate of regional lymph node metastasis ranges from 2% to 40% depending on the depth of invasion of the melanoma.
Desmoplastic melanoma (DM), which is also discussed later in the text, is an uncommon type of melanoma, which deserves specific mention owing to the unique behavior of this entity compared with all other types of cutaneous melanoma.
Superficial spreading melanoma (SSM) is the most common type of melanoma that usually presents as a change in a previously existing pigmented lesion such as a dysplastic nevus. Patients will often describe a gradually darkened mole, or change in shape and variation in coloration, or elevation in one of their nevi (Figure 7). SSM displays color mixtures of brown, black, red, and white, with blue and gray being more specific for SSM.
The usual age of onset for SSM is 30-50 years. SSM is more common in women, and 70% occur in Caucasians. Typically, there are no symptoms associated with these tumors, but on occasion, patients will complain of new-onset itching at the site. Risk factors for the development of SSM include the presence of precursor lesions, such as dysplastic nevi or large congenital nevomelanocytic nevi, a history of melanoma in first-degree relatives, fair skin color, and severe childhood sunburns. This tumor usually occurs as an isolated solitary lesion of the anterior trunk, back, and legs. This is the most common type of melanoma, representing 70% of all melanomas.
Nodular melanoma is the second most common type of melanoma that presents as a thick plaque or an exophytic, dome-shaped, or “blueberry-like” nodule (Figure 8). It may ulcerate or exhibit a smooth or crusted surface, and usually has sharply defined borders.
Nodular melanoma usually occurs in middle life (40-50 years of age), and occurs equally in men and women. This melanoma type represents a larger percentage of all melanomas in Japanese people compared with other races. In the United States, 15%-30% of all melanomas are the nodular type.
LMM is a type of melanoma that always starts as a lentigo maligna (LM), a macular intraepidermal neoplasm, which by definition is a melanoma in situ. Focal papular and nodular areas within an LM signal a switch from radial to vertical growth, and thus invasion into the dermis, converting the LM to LMM (Figure 9).
The median age of development of LMM is 65 years and occurs equally in men and women. Chronic ultraviolet radiation exposure is the risk factor for LMM. This lesion occurs on sun-exposed areas such as the face, neck, dorsa of the forearms, and hands. Patients with LMM have associated solar damage to surrounding skin. LMM represents 4%-15% of all melanomas.
Acral lentiginous melanoma is a type of melanoma that develops on the hands or feet, with a specific subtype, subungual melanoma, occurring under fingernails or toenails. This type of melanoma makes up 7%-9% of all melanomas. By definition, this type of melanoma does not occur on the head and neck. Thus, acral lentiginous melanoma will not be discussed in detail here.
Amelanotic melanoma is a descriptive term for a melanoma that does not have the characteristic dark pigment marker (Figure 10). All types of melanoma can be amelanotic, although it occurs more commonly in the desmoplastic and subungual acral lentiginous types, with 1.8%-8.1% of all melanomas being amelanotic (Figure 10).
Owing to the lack of pigmentation of these tumors, clinical diagnosis of amelanotic melanoma often occurs at a later stage than melanomas with the typical dark pigmentation. It is also seen as the primary form of melanoma in patients with albinism.
DM is a rare type of melanoma that presents as irregular sclerotic plaques with little or no pigmentation (Figure 11). DM makes up 1%-4% of all melanomas. Histopathologically, DM displays extensive dermal fibrosis, with two described histologic subtypes, pure and mixed. Pure DM is usually defined as melanoma in which ≥90% of the invasive component of the tumor is desmoplastic, characterized by low cellularity and a fibrotic appearance histologically. Mixed DM also has desmoplasia, but it is not as prominent and contains a variable component of solid spindle cell melanoma.
Although DM is diagnosed at higher Breslow thickness and Clark level compared with other types of melanoma, lymph node and organ metastases are rare, and prognosis is more favorable compared with other Breslow depth–matched forms of melanoma.
The lower incidence of lymph node metastases is intuitive given the sarcoma-like nature of this type of melanoma. Of note, local recurrence rates for DM are higher than for other types of melanoma, with reports documenting rates ranging from 14% to 56%, thus justifying resecting these tumors with generous margins when possible.
MCC is a rare cutaneous neuroendocrine tumor that presents as a cutaneous to subcutaneous papule or dome-shaped nodule (usually 0.5-5 cm) that is pink, red to violet, or reddish brown (Figure 12). MCC usually occurs as a solitary lesion that grows rapidly and may ulcerate when large.
Risk factors for development of MCC include ultraviolet radiation exposure, Merkel cell polyomavirus infection, advancing age, and immunosuppression. It most often occurs on the head and extremities as solitary or multiple lesions. MCC exhibits a remarkably high rate of spread to regional lymph nodes, with a 32% rate of occult nodal disease.
DFSP is a rare, slow-growing, locally aggressive tumor that is initially clinically indolent because it appears like a scar (Figure 13). This lesion presents as a firm indurated plaque that can develop exophytic nodules. They are typically skin-colored to red or brown.
DFSP usually occurs in patients aged 30-50 years, with equal distribution except in the greater-than-70-year-old group, in which DFSP predominates in men. Contrary to all other types of skin malignancies, DFSP is more common in darker-skinned individuals. Development of DFSP or the acceleration of its growth has been associated with trauma, as well as pregnancy.
It has been found that 90% of DFSPs have chromosomal rearrangements that lead to excess platelet-derived growth factor beta expression. Targeting the platelet-derived growth factor receptor in DFSP with imatinib, a selective tyrosine kinase inhibitor, has been approved by the Food and Drug Administration for use in unresectable, recurrent, or metastatic DFSPs.
Although predominantly located on the trunk (42%) and extremities (34%), DFSPs may also occur on the head and neck (15%), and in these locations, it is associated with a greater risk of morbidity and local recurrence.
As demonstrated by the myriad of tumors and their clinical presentations described earlier in the text, the spectrum of cutaneous malignancies of the head and neck ranges from tumors that are fairly well behaved, such as the majority of BCCs, to very aggressive cancers with a high metastatic rate, such as MCC. Each type of cutaneous malignancy has characteristic presentations, which can help in the clinical diagnosis of these lesions. However, there are several skin malignancies, such as amelanotic melanoma, DM, and DFSP, that present late and are difficult to clinically diagnose owing to their lack of pigmentation or subtle subcutaneous spread. Thus, head and neck surgeons, who commonly encounter cutaneous malignancies, need to be familiar with the various presentations of skin cancers so that these lesions can be identified, and subsequently pathologically evaluated and treated in an appropriate manner. For instance, for lesions that appear concerning for melanoma on clinical presentation, appropriate biopsy with an excisional or incisional full-thickness biopsy technique is important in obtaining the correct pathologic diagnosis to direct further evaluation and stage the patient. Shave biopsies, although often adequate for BCCs and cSCCs, are often inadequate for the biopsy of lesions suspicious for melanoma. Apart from using the gross appearance of these lesions, patient demographics, risk factors, and the presence or absence of regional or distant disease to clue one into the diagnosis, dermatoscopy can be used to further characterize the microscopic appearance of the lesion before biopsy. Dermatoscopy is the use of a nonpolarized or polarized light microscope that allows visualization of skin structures from the epidermis to the superficial papillary dermis that are not visible to the naked eye.
Disadvantages of dermatoscopy are the significant amount of training needed in the interpretation of the dermatoscopic images. Most dermatologists have had training in this technique and use it in their practice.
However, dermatoscopy is not part of the typical residency or fellowship training for otolaryngology—head and neck surgeons. One prospective study showed that primary care physicians trained in dermatoscopy significantly improved their accuracy of legitimate referrals to a dermatologist for a suspected skin cancer, thus suggesting that nondermatologists can effectively learn this technique.
Perhaps with the projected continued increase in the incidence of cutaneous malignancies, there will be a demand in the future for head and neck surgeons to use dermatoscopy in addition to history and examination to decide which skin lesions require biopsy.