Chapter 9. Cutaneous Malignant Neoplasms

Cutaneous malignant neoplasms encompass a large spectrum of tumors that may arise from any of the component cells in skin or its underlying structures. This chapter separates pediatric tumors from those that predominantly affect adults; it further separates nonmelanoma skin cancer from melanoma.

Many lesions are present at birth or shortly thereafter. Some have the potential for malignant transformation later in life; other lesions may be mistaken for a malignant growth.

Benign Neoplasms

Dermoid Cysts

Dermoid cysts may be seen at birth as smooth, cystic tumors that may have both solid and cystic components. The cysts are usually attached to periosteum, are lined with keratinizing epidermis, and may contain hair and fat in addition to keratinous debris. Clinical examination most often shows tumors located in the lateral periocular or nasal areas. Because of tumor fixation to the underlying periosteum, the tumor may feel immobile when palpated. Treatment is simple excision, which may be delayed until later in childhood.

Pilomatrixoma

Pilomatrixoma is usually a benign subcutaneous tumor that originates from the hair matrix and may show calcification. Clinical examination usually shows the tumors as stony-hard, slow-growing, deep subcutaneous masses that develop in early childhood. Rarely, invasive malignant variants with metastases have been reported. Treatment is simple excision.

Sebaceous Nevi

Sebaceous nevi are noted at birth as linear, raised, and tan- to yellow-colored patches on the scalp, face, or neck. The nevi may be several centimeters in size or much larger. Regression of the nevi is common until puberty, when growth of the nevi accelerates and lesions become multinodular and darker. Benign syringocystadenoma papilliferum, as well as various types of malignant neoplasms including basal cell carcinoma, squamous cell carcinoma, and adnexal tumors, may arise in adulthood. To provide optimum cosmesis and to minimize the risk of these malignant growths, patients should be treated in preadolescence with simple excision of the nevi.

Neurofibroma

Neurofibroma may appear singly or may be multiple in von Recklinghausen disease or NF-1 (ie, neurofibromatosis with von Recklinghausen disease) and present as soft, skin-colored nodules composed of nerve cells, mast cells, and oval- to spindle-shaped nuclei in a wavy collagen matrix. The neurofibromatous nodules are usually unencapsulated and may infiltrate fat. Café au lait spots are associated with multiple neurofibromatous lesions and are usually excised for cosmetic or functional reasons. Neurofibrosarcoma may rarely develop in syndromic patients.

Infantile Myofibromatosis

In infantile myofibromatosis, single or multiple fibrous, firm nodules composed of fibroblasts and smooth muscle cells are present at birth or in early childhood. The nodules are palpable, firm, and either cutaneous or subcutaneous. Lytic lesions of the cranium may occur in as many as one-third of children, and visceral nodules are associated with the multicentric form. Visceral nodules may be confused with a malignant growth; indeed, the visceral form of infantile myofibromatosis is frequently fatal. Lesions occurring in the superficial, nonvisceral form usually resolve. Lesions compromising function should be treated with biopsy or excision.

Congenital Melanocytic Nevi

Congenital melanocytic nevi may be seen at birth or several months later as either flat or raised brown lesions, with or without hair, and usually with areas of deeper black or blue pigment. The estimated lifetime risk of developing melanocytic lesions is roughly proportional to the size of the nevus and may be as high as 8%; because of the predictable increased risk, early full-thickness surgical excision for large nevi is advocated where technically feasible.

Benign (Typical) Acquired Nevi

Benign (typical) acquired nevi begin early in childhood and are usually smaller than 5 mm. They may be flat or raised, have symmetric, smooth, and well-defined borders, and have uniform pigmentation, which may range from flesh colored to brown. Evidence supports a higher lifetime risk of cutaneous melanoma in patients who have more than 50 benign nevi.

Malignant Neoplasms

In children, malignant skin tumors may develop sporadically or occur in precursor syndromes with associated abnormalities in other organ systems. The most common precursor syndromes for malignant cutaneous tumors in children are nevoid basal cell syndrome and xeroderma pigmentosum.

Atypical Nevi (Dysplastic Nevus Syndrome)

Atypical nevi (dysplastic nevus syndrome) may be familial or occur sporadically. These nevi are usually flat, but they may have a raised center; they may be dark or pigmented in a variegated distribution. The nevi increase in number over years and show histologic features, such as melanocytic atypia and hyperplasia.

Patients with atypical nevi have an increased risk for either the familial or the nonfamilial forms of cutaneous melanoma; this risk is related both to a large number of nevi and to a family history of cutaneous melanoma. Individuals without a family history of melanoma have a 184-fold increased risk for the familial form of melanoma, whereas individuals with a family history of melanoma have a 500-fold increased risk of the disease. The estimated risk for the sporadic form of melanoma is related to the number of dysplastic nevi: a 12-fold increase in risk is estimated for individuals who have more than 10 dysplastic nevi.

Nevoid Basal Cell Carcinoma Syndrome

Among patients with nevoid basal cell carcinoma syndrome, inactivation of the “patched” PTC tumor suppressor gene has been found in both the sporadic and the autosomal-dominant familial forms. Multiple areas of nevoid basal cell carcinoma may develop before the patient reaches 20 years of age. Clinically, in addition to having many basal cell nevi, patients may present with frontal bossing, mandibular cysts, palmar pits, calcified falx cerebri, and one or more skeletal abnormalities. Treatment for small, well-defined areas of basal cell carcinoma is simple excision; treatment is Mohs micrographic excision for recurrent or poorly defined lesions, or lesions located in anatomic areas at high risk for malignant disease.

Xeroderma Pigmentosum Syndrome

Xeroderma pigmentosum syndrome is inherited as an autosomal-recessive trait in which defects are discovered during the repair of sun-induced DNA damage. Seven genes have been implicated in xeroderma pigmentosum, which manifests in a variety of phenotypes, depending on the specific patterns of mutation. Basal cell carcinoma, squamous cell carcinoma, and cutaneous melanoma may develop in large numbers (preceded by xeroderma pigmentosum) at an early age and in a general anatomic distribution similar to sporadic cases in adults. Clinically, children affected by xeroderma pigmentosum (1) have an onset of extensive freckling early in childhood, (2) are extremely photosensitive, and (3) have an estimated 2000-fold increase in basal cell carcinoma, squamous cell carcinoma, and cutaneous melanoma. These conditions in children occur most commonly on the face, head, and neck; squamous cell carcinoma occurs with notable frequency at the tongue tip. Treatment of xeroderma pigmentosum is total avoidance of the sun, a strategy that is necessary for reducing the number of new tumors.

Malignant Cutaneous Melanoma

Malignant cutaneous melanoma is rare in childhood but is more common among children who have a family history of melanoma, large congenital nevus, large or many dysplastic nevi, xeroderma pigmentosum syndrome, or a history of immunosuppression. In addition, convincing evidence indicates that the incidence of cutaneous melanoma is higher among children who have more than 50 benign melanocytic nevi. The essential aspects of clinical diagnosis are generally the same for children as for adults. Areas of pigment change, pain, or ulceration in large congenital nevi may indicate malignant change.

The overall treatment parallels adult guidelines and is based on the tumor thickness, the presence or absence of tumor ulceration, and the nodal status. However, the prognosis for cutaneous melanoma in children may be worse than in adults because a disproportionate number of nodular cutaneous melanoma cases in children are associated with a rapid vertical growth phase of the tumor.

In situ melanoma is excised with 7-mm margins or with Mohs micrographic frozen-section margins to minimize the surgical defect size. No further work-up is necessary.

Stage I primary tumors <2 mm without histologic evidence of ulceration can be excised with 1-cm margins. If ulceration is present, 2-cm margins should be used and a chest X-ray should be performed.

Stage II lesions are excised with 2-cm margins where feasible; for high-risk lesions, consideration should be given to computed tomography (CT) scanning of the neck as well as sentinel lymph node biopsy or neck dissection. Recent studies have shown benefits from using high-dose interferon alfa-2b in high-risk patients.

Stage III primary neoplasms can also be excised with 2-cm margins down to the fascia, with CT scanning performed and regional lymphatics treated surgically. The postoperative treatment should include radiation as well as high-dose interferon.

Stage IV melanoma carries an extremely poor prognosis, but an attempt should be made to control local and regional disease where possible, as well as defining the extent and the location of systemic disease in order to tailor individual treatment strategies.

The overall survival in childhood melanoma is related to the stage at presentation and generally parallels that of adults: the 5-year survival rate in Stage I disease is about 95%, with the rate dropping to 65% in Stage II and 45% in Stage III disease. There are essentially no survivors in those patients who present with systemic disease.

Subcutaneous Rhabdomyosarcoma

Subcutaneous rhabdomyosarcoma is a poorly differentiated sarcoma; the diagnosis may require immunohistochemical staining. Clinically, the tumor usually presents singly as a firm, reddish or brown, semifixed, noncompressible subcutaneous nodule that becomes enlarged and may deform local structures. These tumors are more common in females and at a mean age of 2–3 years. Currently, surgical excision is recommended where it is technically feasible. Alternatively, radiation and multidrug chemotherapy are recommended.

Many benign lesions of childhood (eg, nevi and vascular malformations) persist into adulthood and may undergo change or be difficult to distinguish from tumors more commonly seen in adults.

Benign Neoplasms

Seborrheic keratoses and chondrodermatitis helicis are the benign tumors most commonly confused with cutaneous malignant tumors. In addition, many varieties of benign skin tumors (eg, dermatofibroma and benign adnexal tumors) may be difficult to distinguish from nonmelanoma skin cancer unless a biopsy is performed.

Seborrheic Keratosis

Seborrheic keratosis is a tumor of unknown origin that is unique to adults. Histologically, it may exist in a variety of forms, all of which show hyperkeratosis, papillomatosis, and acanthosis. When the tumor is chronically irritated, whorls of squamous cells may be present with areas of keratin horn pearls and must be distinguished histologically from squamous cell carcinoma. Clinically, the lesions may be flat, raised, smooth, or verrucous and frequently appear to be “pasted” on the skin (Figure 9–1). Their color may vary from tan to black, and lesions containing pigment may mimic cutaneous melanoma. The lesions have no malignant potential. Treatment may be indicated for cosmetic reasons, and the lesions can be frozen with liquid nitrogen or removed by shave biopsy.

Chondrodermatitis Nodularis Helicis

Chondrodermatitis nodularis helicis typically manifests as an ulcer filled with necrotic dermal debris as well as adjacent granulations with degenerative changes in cartilage. Dystrophic calcification also may be present. The lesions may be seen clinically on the auricular helix as nodules that can be quite painful and may be confused with squamous cell carcinoma. Treatment is intralesional steroid therapy or simple excision.

Malignant Neoplasms

Cutaneous malignant lesions in adults are commonly classified as either nonmelanoma skin cancer or cutaneous melanoma. Many lesions have distinct clinical features that provide clues to the diagnosis; considerable overlap exists, however, and biopsy is almost always necessary to plan treatment. To some extent, the biopsy technique is dictated by the tentative clinical diagnosis: shave biopsy is an adequate treatment for exophytic nodules thought to be nonmelanoma skin cancer, whereas punch biopsy is necessary for flat lesions. Excisional biopsy with a 2-mm margin is preferred for pigmented lesions thought to present a high risk for cutaneous melanoma. Deep punch biopsies into subcutaneous fat in the deepest or darkest portions of the lesion also may be performed in selected lesions. Although no evidence exists showing an adverse effect of biopsy, shave biopsy in cutaneous melanoma is to be discouraged when melanoma is suspected. Moreover, wide, local excision may produce scarring that interferes with lymphatic drainage when sentinel node biopsy is later performed. An adequate amount of tissue must be obtained for processing with special stains in the event that an exact histologic diagnosis is difficult, as is frequently the case with rare or poorly differentiated nonmelanoma skin cancer. Photographs of the lesion or the biopsy defect may be valuable for identifying the exact location of the original lesion when definitive surgery is done at a later date.

Nonmelanoma Skin Cancer

General Considerations

Nonmelanoma skin cancer may be divided into common and rare categories. Basal cell carcinoma, the most common skin cancer, constitutes about 75% of nonmelanoma skin cancer cases; squamous cell carcinoma accounts for about 20% of cases. The remaining 5% of rare nonmelanoma skin cancer cases includes fibrohistiocytic and adnexal cancers. Basal cell carcinoma, squamous cell carcinoma, and some rare types of nonmelanoma skin cancers occur more frequently in sun-exposed areas and in light-skinned individuals with light eye and hair color; they are associated with unrepaired DNA mutations induced by UV-A and UV-B radiation. The incidence of both basal cell carcinoma and squamous cell carcinoma has steadily increased during the past several decades, and nonmelanoma skin cancer is now a clinically significant health problem and a source of morbidity. Both conditions are more common in patients exposed to ionizing radiation. Basal cell carcinoma and squamous cell carcinoma also occur more frequently in patients with HIV; patients with lymphoproliferative disorders, particularly chronic lymphocytic leukemia; and patients receiving long-term immunosuppressive drug therapy after organ transplantation.

Differential Diagnosis

Rare types of nonmelanoma skin cancers include fibrohistiocytic tumors, adnexal cancers, and rare cutaneous sarcoma. Special histochemical stains are frequently necessary for distinguishing varieties of nonmelanoma skin cancer, especially adnexal tumors.

Treatment

Treatment of nonmelanoma skin cancer is determined by many factors, including the exact histologic subtype, the tumor size, the growth characteristics, and the anatomic location. Treatment is also determined by the previous treatment received, current medical problems, and patient expectations. Treatment options for nonmelanoma skin cancer can be categorized as nonsurgical and surgical.

Nonsurgical Measures

Nonsurgical strategies include topical or injection chemotherapy (eg, with 5-fluorouracil [5-FU], a 5% preparation of imiquimod, or interferon), cryotherapy using liquid nitrogen, photodynamic therapy (PDT), and radiation therapy.

Topical Drug Therapy

Topical 5% imiquimod is now widely used by dermatologists as primary treatment for actinic keratoses, superficial basal cell carcinoma, and squamous cell carcinoma in situ (Bowen disease). It may also be used for selected thin nodular basal cell carcinomas, but is not indicated for infiltrating or sclerosing basal cell carcinoma.

Cryotherapy

Cryotherapy is usually done by dermatologists or by primary care physicians. The results of this procedure are related to the skill and experience of the treating physician. The technique is especially useful for treating actinic keratoses, small nodular or superficial lesions of basal cell carcinoma, and squamous cell carcinoma in situ. Treatment is relatively inexpensive and fast but can be painful and leave dense, hypopigmented scars that may conceal deep, multifocal, persistent tumors.

Photodynamic Therapy

PDT with 5 aminolevulinic acid or methyl aminolevulinate activated by unique light source is used to treat actinic keratoses, Bowen disease, and basal cell carcinomas (superficial and nodular types). PDT can be highly effective and cosmesis is typically superior to existing standard therapies.

Radiation Therapy

Radiation therapy is used primarily in patients older than 60 years or who are not suitable candidates for surgery. Radiation therapy is also used postoperatively for aggressive tumors or where perineural spread is noted. Because this therapy is expensive and requires frequent visits over several weeks, it is often not an option for elderly patients with a limited support system. The control rates for basal cell and squamous cell carcinoma are generally reported to be greater than 90%, and the incidence of post-therapy recurrence increases with increasing tumor size. Recent use of the electron beam and more sophisticated techniques used to model treatment fields has improved cure rates and reduced the number of complications. Long-term cosmetic results may be poor, and the complications of tissue necrosis, chondritis, and osteoradionecrosis may occur. Because of the risk of a radiation-induced malignant growth that may occur later, radiation is generally not recommended as the primary treatment modality for patients younger than 50 years of age.

Surgical Measures

Surgical techniques for the treatment of nonmelanoma skin cancer include curettage and desiccation, simple or wide local excision, and Mohs micrographic surgery.

Curettage and Desiccation

Dermatologists most often perform curettage and desiccation for small, well-defined, previously untreated areas of nodular basal cell carcinoma; this procedure is also used for some squamous cell carcinomas. The advantages of this technique are its low cost and rapidity of treatment. Its 5-year recurrence rate ranges from 10% to 20%. The disadvantages of the technique are poor cosmetic results, with hypertrophic scarring as well as multifocal tumor recurrence in the scars.

Simple Excision

Simple excision with 5-mm margins is the appropriate treatment for most well-defined, primary nodular basal cell carcinomas; it is also recommended for low-risk squamous cell carcinoma in anatomic locations where adequate excision with primary closure can be achieved with a good cosmetic result. Five-year recurrence rates of about 10% can be expected. Simple excision is not indicated for tumors that recur after radiation or surgical treatment or for high-risk tumors (eg, sclerosing basal cell carcinoma or poorly differentiated squamous cell carcinoma). It is also not indicated for rare nonmelanoma skin cancer (eg, fibrohistiocytic or adnexal cancer).

Wide Local Excision

Wide local excision generally connotes margins of 2–5 cm and is indicated primarily for (1) well-differentiated squamous cell carcinoma; (2) well-defined, large, nodular-ulcerative basal cell carcinoma; and (3) sarcomas, such as angiosarcoma and malignant fibrous histiocytoma.

Mohs Micrographic Surgery

Mohs micrographic surgery is a technique in which precise surgical margins are obtained by using inverted horizontal frozen sections in conjunction with tumor mapping. The bulk of the tumor is either excised or curetted, and the surrounding perimeter is excised around and deep to the tumor defect. The resulting disk of tissue is then separated into individual quadrants and is inked for orientation, producing a tumor map that is color-coded to represent the inked edges. Histotechnicians specially trained in the technique mount the sections, which are inverted and frozen at −30°C to −50°C. Thin frozen sections are obtained, showing the base in continuity with the epidermis. The slides are stained and are examined microscopically, and tumor locations are graphically noted on the map. Additional margins are then created in the same manner, but only in areas positive for a tumor. This process is repeated until all margins are negative for a neoplasm. The process may be enhanced using rapid selective stains. Some centers perform formalin-fixed horizontal sections (1) on final margins that are shown as negative by frozen section, (2) where the tumor histology is subtle, and (3) where tumor recurrence would be catastrophic. These centers convert selected tissue blocks obtained as frozen-section margins to rush paraffin–formalin fixed slides using the same inverted tissue sectioning techniques and tumor mapping to further ensure true negative final margins on difficult cases.

An advantage of Mohs micrographic surgery is its potential to achieve the highest reported control rates for nonmelanoma skin cancer while maximally conserving normal adjacent tissue. The precise surgical margin control used in Mohs micrographic surgery has largely replaced wide local excision for most nonmelanoma skin cancer; the use of an arbitrary margin size with wide local excision does not benefit the outcome for most skin cancers. The overall cure rates using Mohs micrographic surgery are 99% for primary basal cell carcinoma, 96% for recurrent basal cell carcinoma, and 98% for primary squamous cell carcinoma. Mohs micrographic surgery is the treatment of choice for sclerosing or recurrent basal cell carcinoma, large or poorly differentiated squamous cell carcinoma, and most cases of fibrohistiocytic and adnexal cancer. The disadvantages of this technique are its high cost, lack of easy availability, and long procedure time.

Basal Cell Carcinoma

Basal cell carcinoma is the most common cancer seen in adults. Historically, basal cell carcinoma has been considered most common in persons older than 60 years, but the increased incidence in younger patients has been noted and may be related to a decrease in the atmospheric ozone as well as to the use of tanning salons. Basal cell carcinoma occurs predominantly on hair-bearing skin, and most tumors arise on the face, head, and neck. No precursor lesions are known to exist. In addition to UV radiation, an increased incidence of basal cell carcinoma has been noted in patients exposed to arsenic and insecticides, and at previous vaccination sites and burn scars. Multiple sites of basal cell carcinoma may develop at an early age in patients with basal cell nevus syndrome, xeroderma pigmentosum, Rombo and Bazex syndromes, and sebaceous nevus.

If untreated or recurrent, basal cell carcinoma may produce clinically significant local destruction and cosmetic and functional morbidity. Metastatic behavior, though rare (its occurrence rate is <0.025%), most frequently occurs in patients with cancer that is neglected for many years, who have large or recurrent tumors, who are immunosuppressed, or whose tumors have been previously irradiated. Metastases usually affect bone or lung. Locally advanced, unresectable or metastatic basal cell carcinomas have recently been found to respond to a novel new small molecule (GDC 0449)which inhibits sustained signaling in the sonic hedgehog pathway, essential to the growth of basal cell carcinomas.

Basal cell carcinoma arises from keratinocytes of the epidermis and from adnexal structures and may extend as superficial nests, cords, or filamentous strands surrounded by basement membrane and stroma. These tumors usually grow slowly, spread by direct local extension, and carry the stromal component with them. Some tumors are highly neurotropic and are spread via superficial nerves, a phenomenon that can result in local “skip” areas with false-negative margins. Particularly dangerous anatomic areas are “embryonal fusion planes,” such as those found in the nasofacial sulcus, the medial canthus, and pre- and postauricular areas: in these areas, a neoplasm can proliferate deeply before becoming clinically apparent.

Minimizing exposure to the midday sun is the most important and effective measure to reduce the lifetime risk of developing basal cell carcinoma. This practice may include the use of opaque clothing and hats (microfiber nylon fabrics in particular), as well as eyewear rated to block UV-A and UV-B radiation. Although the efficacy of sunscreens in preventing sunburn is documented, recent large studies seem to suggest that sunscreen use is associated with a reduction in new cases of squamous cell carcinoma, but not of basal cell carcinoma. No benefit has been shown with the use of oral beta-carotene or topical or systemic retinoids. Treatment for small, well-defined basal cell carcinoma is simple excision; for lesions that are recurrent, poorly defined, or located in high-risk anatomic areas, treatment is Mohs micrographic excision.

Basal cell carcinoma is most conveniently divided into four basic categories based on the clinical appearance, the tumor behavior, and the histologic differences between subtypes:

1. Superficial basal cell carcinoma

2. Nodular, ulcerative basal cell carcinoma

3. Sclerosing or morpheaform basal cell carcinoma

4. Basosquamous (keratotic or metatypical) basal cell carcinoma

These categories overlap considerably, and some tumors have features of more than one subtype.

Superficial Basal Cell Carcinoma

Histologically, in superficial, multicentric basal cell carcinoma, basaloid cells proliferate downward at the dermal epidermal junction. This feature also may be found in clinically normal adjacent skin. Clinically, this condition frequently presents as scaling, erythematous plaques that may be pruritic, bleed, and appear almost psoriatic or eczematoid. These plaques may be difficult to distinguish from Bowen disease clinically, and borders may be well defined or indistinct.

Previous treatment with cryotherapy, topical agents, curettage and desiccation, and other methods may render this field change multifocal and discontinuous, leading to high rates of recurrence with surgical removal. Superficial basal cell carcinoma is very slow growing and is not aggressive, but it can affect large areas of skin. Because of this characteristic, selected cases can initially be treated with a topical agent such as 5% fluorouracil or 5% imiquimod. Although most of these lesions can be cured with these regimens, many patients do not tolerate the pain and desquamation associated with topical treatment. Careful follow-up and rebiopsy are indicated if a complete clinical response is not obtained. Although effective, cryotherapy may erratically destroy lesions and produce dense scars with a buried tumor. Photodynamic therapy has been shown effective; the largest series were reported in Europe. Curettage and desiccation, radiation, or Mohs micrographic surgery is used when topical regimens fail or in areas where conservative regimens are not tolerated (eg, the eyelids or the lips).

Nodular, Ulcerative Basal Cell Carcinoma

Histologically, tumors of nodular, ulcerative basal cell carcinoma show solid masses of malignant basal cells with scant cytoplasm and peripheral palisading of nuclei, proliferating with an associated connective tissue stroma. A variety of histologic subtypes exist within this category, and long-neglected neoplasms may have micronodular filaments or sclerosing features at the periphery of the lesion.

Clinically, the tumors are typically discrete, painless, well-defined nodules that may be ulcerated centrally with a waxy, telangiectatic peripheral border. Small, nodular neoplasms of basal cell carcinoma must be distinguished from acneiform eruptions and common benign skin lesions such as nevi or granulomatous skin lesions. Nodular, ulcerative lesions of basal cell carcinoma carry a low risk unless they persist for long durations or are located in high-risk anatomic areas. If untreated or recurrent, these lesions may become quite large and clinically more aggressive and may pose considerable challenges both for adequate tumor removal and reconstruction.

Treatment for the lesions is dictated by patient age and expectations for cosmesis, associated medical problems, the anatomic location and size of the neoplasm, and whether the lesion is primary or has recurred after previous treatment. Curettage and desiccation may be appropriate for small nodular basal cell carcinoma, but recurrence is common and scars are typically hypopigmented and conspicuous. Simple excision with 5-mm margins is the appropriate treatment for lesions smaller than 1 cm located in low-risk anatomic areas (ie, where surgical closure is possible without using a flap or graft). Mohs micrographic surgery is ideal for optimizing the conservation of normal tissue while achieving the highest tumor control rates. It is the technique of choice for neoplasms that recur after prior treatment or where reconstruction with a flap or skin graft is anticipated. Radiation therapy for these tumors is effective, but recurrence rates with this therapy are higher than for Mohs micrographic surgery. Cosmetic results may be poor over time, and subsequent radiation-induced tumors may occur.

Sclerosing Basal Cell Carcinoma

In sclerosing or morpheaform basal cell carcinoma, the histologic examination may show fine, filamentous tumor strands that extend in all directions; these strands account for high tumor recurrence rates. Clinically, the lesions present as white-to-yellow, telangiectatic, indurated plaques with poorly defined margins. Dense stroma associated with the neoplasm gives it a sclerotic appearance, and over time, it may ulcerate. Although many patients have the lesions for long periods, some tumors have a more aggressive growth pattern and widely infiltrate seemingly normal adjacent tissue, resulting in large surgical defects and considerable morbidity.

In general, basal cell carcinoma with sclerosing features should be treated with Mohs micrographic surgery. Radiation may be appropriate for patients who are not suitable candidates for surgery; however, recurrence rates are higher with this mode of treatment, and it may yield cosmetically poor results. To minimize the risk of tumor recurrence, which may be catastrophic in locations such as the medial canthus, Mohs micrographic surgery followed by radiation is the necessary treatment for neoplasms showing perineural spread.

Basosquamous Basal Cell Carcinoma

Keratotic (basosquamous or metatypical) basal cell carcinoma represents a true basal cell carcinoma and is characterized by squamous differentiation and keratinization. Clinically, these tumors can be aggressive locally and may occasionally metastasize, particularly if large or recurrent. The tumors may appear similar to nodular basal cell carcinoma and may be confused clinically with squamous cell carcinoma, fibrohistiocytic lesions, or adnexal tumors. Treatment for this form of basal cell carcinoma is Mohs micrographic surgery or wide local excision. Radiation therapy is effective but yields recurrence rates higher than for Mohs micrographic surgery.

Squamous Cell Carcinoma

Lesions of squamous cell carcinoma, the second most common skin cancer, have an epidemiology and an anatomic distribution similar to basal cell carcinoma. Patients with squamous cell carcinoma may present with keratotic nodules, granular plaques, or ulcerating nodules that may or may not be painful. Common predisposing conditions for squamous cell carcinoma of the face, head, and neck are previous radiation burn scars or long-standing sinus tracts, a history of psoralen and UV-A phototherapy, and immunosuppression. The risk of local recurrence, metastasis, or both is increased by multiple factors and by each of the following:

• The size and depth of the invasion: tumors with a depth of ≥6 mm or a diameter of ≥2 cm.
• The location on the lip (especially near the commissure), ear, and nasal septum.
• The degree of differentiation; the risk of local recurrence and metastatic disease is generally inversely proportional to the degree of differentiation.
• The rapidity of growth (except for patients with keratoacanthomatous tumors), where a history of rapid growth between the diagnoses and the time of treatment is a poor prognostic sign.
• Recurrence after prior treatments; a subsequent recurrence is associated with a high risk of both local recurrence and metastatic disease.
• Perineural spread, which carries a particularly poor prognosis and may be suggested by intense pruritus, pain, hypesthesia, or (rarely) paralysis.
• Immunosuppression in patients with squamous cell carcinoma, either as a result of chronic disease (eg, chronic lymphocytic leukemia) or drugs (eg, cyclosporine, azathioprine); this immunosuppression is associated with an increasing number of lesions over the time of exposure, and many lesions may develop synchronously with a high cumulative risk of metastases and a very poor prognosis. Most of these patients can be shown to have human papillomavirus.

Squamous cell carcinoma may be preceded by precursor lesions such as actinic keratosis (most commonly) or Bowen disease (ie, squamous cell carcinoma in situ). A histologic examination of actinic keratoses shows superficial neoplasms consisting of defined epidermal proliferation of abnormal keratinocytes. In an estimated 1% per year of affected patients, actinic keratoses may evolve into squamous cell carcinoma. Clinically, the lesions are small, scaly, white, red, or occasionally pigmented keratotic crusts with a friable base. Treatment consists of cryotherapy with liquid nitrogen, curettage and desiccation, topical 5-FU, or simple excision.

Squamous Cell Carcinoma In Situ (Bowen Disease)

Bowen disease (ie, intraepidermal squamous cell carcinoma or squamous cell carcinoma in situ) appears histologically as squamous cells with acanthosis and large, hyperchromatic nuclei that proliferate radially along the epidermis. Individual cell keratinization may be present, and the basement membrane is preserved. Bowen disease generally occurs on sun-exposed areas of the face; its occurrence on areas not exposed to sunlight has been linked to arsenic exposure. If left untreated, a small percentage (perhaps 5%) of lesions will develop into invasive squamous cell carcinoma.

Lesions typically present as erythematous superficial plaques with irregular, variably defined borders and may be confused with superficial basal cell carcinoma, psoriasis, or eczema. Induration may indicate invasive squamous cell carcinoma.

If biopsy results fail to show invasion and if the lesion occurs in a suitable area, topical treatment may be administered initially. A 0.025% preparation of tretinoin gel in conjunction with 5% 5-FU is used for 4–6 weeks. Daily application of imiquimod 5% cream for 16 weeks has recently been shown to be a safe and very effective regimen in treating Bowen disease.

Excellent short-term results also have been reported with photodynamic therapy and laser. Mohs micrographic surgery is recommended for treating lesions located in anatomic areas such as the eyelids, lips, and other areas where topical agents are not suitable, or when conservative treatment fails.

Keratoacanthoma

Squamous cell carcinoma can be usefully classified as well-differentiated or poorly differentiated tumors that vary both in terms of their histologic features and their clinical behavior. In addition to tumors in these categories, however, keratoacanthoma should be mentioned because of its clinical and histologic similarities to squamous cell carcinoma; some pathologists consider it a low-grade squamous cell carcinoma.

A biopsy of keratoacanthomatous neoplasms shows histologic features that may be indistinguishable from those of squamous cell carcinoma, except for the absence of epithelial membrane antigen. To exclude a diagnosis of invasive squamous cell carcinoma, the biopsy specimen must include the tumor junction and adjacent normal tissue. A cross section of the tumor shows a central keratinous core, an epidermal lip, and glassy keratinocytes with numerous mitoses in the proliferative phase and a few mitoses in the resolution phase.

Keratoacanthoma is generally considered a benign lesion but is characterized by explosive growth in the proliferative phase, which lasts 2–4 weeks and is associated with a central crater filled with a keratin plug (Figure 9–2). The tumors may grow to a large size and then mature over weeks to months; they usually resolve if left untreated. Special tests to distinguish keratoacanthoma from invasive squamous cell carcinoma include cytokeratin staining and epithelial membrane antigen. Tumors that are believed to be clinically obvious keratoacanthoma or that are confirmed by biopsy frequently respond to intralesional administration of either 5-FU or methotrexate. Larger lesions or those not responding to intralesional agents should be excised, and radiation therapy can be used in patients who are not suitable candidates for surgery.

Well-Differentiated Squamous Cell Carcinoma

In well-differentiated squamous cell carcinoma, microscopic examination shows large, malignant squamous cells that proliferate downward from the epidermis as nests or cords. Intercellular bridges are seen and keratin pearls are seen frequently; peritumoral inflammation also may be present. These tumors stain positive for cytokeratins. Inactivation of the tumor suppressor gene TP 53 appears to be involved in both actinic keratoses and squamous cell carcinoma. Primary lesions with well-defined borders are best treated by simple excision and primary closure. Recurrent tumors or those occurring in immunosuppressed patients should be removed using frozen-section margin control, preferably with Mohs micrographic surgery. Radiation therapy also is effective.

Poorly Differentiated Squamous Cell Carcinoma

In squamous cell carcinoma, the extent of cellular differentiation is directly proportional to amount of keratin and intercellular bridges: The less the differentiation, the fewer keratin and intercellular bridges are present. In anaplastic tumors, no keratin or intercellular bridges are present, and individual cells are markedly atypical with increased mitoses. Immunohistochemical stains or electron microscopy may be necessary to distinguish poorly differentiated squamous cell carcinoma from melanoma, atypical fibroxanthoma, or other poorly differentiated neoplasms. Dedifferentiated squamous cell carcinoma can appear as granular plaques, rapidly growing nodules, or areas of ulceration. Distant metastases occur but are usually preceded by nodal disease; occasionally, tumors originating in the lung present as skin metastases. Patients should be examined carefully for regional adenopathy and have an X-ray of the chest. Other tests, including imaging studies to detect occult nodes, may be indicated, especially in immunocompromised patients.

In poorly differentiated squamous cell carcinoma, the treatment of primary tumors is surgical; ideally, frozen-section margin control should be used (as in Mohs micrographic surgery) or at least 1-cm margins. Defects should be closed without a flap, if possible. Tumors that recur after surgery or after radiation should be excised with Mohs micrographic surgery. Postoperative radiation therapy to the tumor bed and regional lymph nodes is indicated for tumors larger than 2 cm, for perineural invasion, or for tumors occurring in immunocompromised patients. Neck dissection is indicated for adenopathy detected clinically or by imaging; sentinel node biopsy has been shown feasible but remains investigational.

Rare Nonmelanoma Skin Cancer

The most frequently encountered of the many varieties of rare nonmelanoma skin cancer include three types of fibrohistiocytic tumors: (1) atypical fibroxanthoma, (2) dermatofibrosarcoma protuberans, and (3) malignant fibrous histiocytoma. Rare nonmelanoma skin cancer also includes adnexal cancers.

Atypical Fibroxanthoma

Atypical fibroxanthoma is a relatively common tumor thought to represent a superficial form of a low-grade malignant lesion. Histologic examination of the tumor shows densely cellular spindle cell neoplasms in the dermoepidermal junction; pleomorphic, histiocytic cells; giant cells with bizarre nuclei; and fibroblastic spindle cells. By definition, these tumors do not extend into the underlying muscle or fascia. From a histologic perspective, the differential diagnoses include spindle cell carcinoma, malignant fibrous histiocytoma, and melanoma. Special stains are frequently needed to confirm the diagnosis.

Atypical fibroxanthoma generally appears as flat plaques with pigment ranging from yellow to reddish brown in areas of sun-damaged skin; the tumor may grow rapidly. Tumors classified as atypical fibroxanthoma can recur locally if excision is inadequate and rarely metastasize. Lesions proven to invade muscle or fascia should be considered malignant fibrous histiocytoma. Treatment for atypical fibroxanthoma is excision, ideally using Mohs micrographic surgery to minimize local recurrence.

Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans is a slow-growing, fibrous tumor that originates in the dermis, is locally invasive, and occasionally metastasizes. Histologic examination shows packed spindle cells with diffuse infiltration into the dermis and subcutaneous fat as well as (rarely) into deeper structures. Expression of CD34 antigen is positive, and expression of s100 is negative. In younger patients, dermatofibrosarcoma protuberans usually presents as a raised plaque that may appear similar to a keloid in some patients (Figure 9–3). An initial staging evaluation, including a chest X-ray and possibly a CT scan, is indicated because these tumors occasionally metastasize.

Although wide local excision has long been advocated as a treatment for dermatofibrosarcoma protuberans, local recurrence of the disease still occurs, even when 3-cm margins are used. Increasing evidence in the medical literature shows that excision using Mohs micrographic surgery in conjunction with rush paraffin sections provides the highest local control rates; in this technique, the wound is closed only after both frozen and paraffin sections show no tumor. Prophylactic nodal dissection is not indicated for the treatment of dermatofibrosarcoma protuberans because the tumors do not spread to the local nodes. Radiation therapy should be added postoperatively where local recurrence would be catastrophic, but this therapy generally is not used as the primary treatment modality. Patients should be observed at frequent intervals for early detection of local tumor recurrence. Neoadjuvant imatinib therapy has recently been shown to be successful in improving outcomes when used for locally advanced or recurrent dermatofibrosarcoma protuberans.

Malignant Fibrous Histiocytoma

Malignant fibrous histiocytoma is predominately a tumor of adults and rarely occurs on the head and neck. The term defines a spectrum of cellular tumors that may resemble atypical fibroxanthoma or dermatofibrosarcoma protuberans (when well differentiated or superficial) or may appear as a poorly differentiated, deeply invasive fibrosarcoma. The neoplasm is considered to be of fibroblastic origin and seems to be more common in previously irradiated areas. Several general subtypes exist, including storiform pleomorphic, myxoid, giant cell, inflammatory, and angiomatoid forms; a single tumor may contain separate areas with features of each subtype.

Clinically, the tumors may appear as elevated plaques or nodules, and surgical borders may be poorly defined because of the diffuse infiltrative nature of the tumor. Rapidly growing tumors may present with hemorrhage and necrosis. The prognosis for lesions of the head and neck is generally related to the depth of the invasion, the tumor grade, and the tumor size at diagnosis. Tumors invading muscle or fascia have high rates of both local recurrence and metastases, whereas superficial tumors confined to the subcutis have a more favorable prognosis. The differential diagnosis includes other fibrohistiocytic tumors and sarcomas, Hodgkin disease, and pleomorphic carcinoma. Distinguishing between these conditions and malignant fibrous histiocytoma may require immunohistochemical staining.

Patients should undergo initial staging, including CT scans of the chest, head, and neck, as well as an evaluation by an oncologist. Wide excision with 3- to 5-cm margins including fascia is generally recommended. Mohs micrographic surgery with both frozen and rush paraffin sections may be of value for head and neck tumors to achieve comparable (or higher) local control rates and possibly smaller defect size; comparisons of long-term outcomes are lacking because of the rarity of the neoplasm. Nodal metastases are unusual, so neck dissection is not indicated. Postoperative radiation may further reduce the likelihood of local recurrence.

Adnexal Tumors

Adnexal tumors—cutaneous malignant growths arising from adnexal structures—are the rarest types of skin cancer, and several types are highly malignant. Only the more common tumors in this group, that is, proliferating trichilemmal cysts, microcystic adnexal carcinoma, Merkel cell carcinoma, and sebaceous carcinoma, are reviewed here.

Classification

Proliferating Trichilemmal Cysts

Proliferating trichilemmal cysts or tumors are usually composed of proliferating lobules of squamous epithelium with central keratinous debris and are sharply separated from normal surrounding tissue. Malignant variants occur and are usually characterized by sudden rapid growth as well as by an invasion or an erosion of the underlying structures. Regional as well as distant metastases with transformation to invasive squamous cell carcinoma have been reported; indeed, some pathologists consider all proliferating trichilemmal cysts to be low-grade squamous cell carcinoma. The tumors usually occur singly on the scalp in older women as subcutaneous nodules or cysts and are most often confused with a wen or an inclusion cyst. Malignant transformation may be preceded by rapid growth, necrosis, and ulceration. Treatment is simple excision; malignant variants are treated like squamous cell carcinoma.

Microcystic Adnexal Carcinoma

Microcystic adnexal carcinoma (also termed sclerosing sweat duct carcinoma) has microscopic features consisting of basaloid keratinocytes, horn cysts, and abortive hair follicles in desmoplastic stroma. Perineural invasion occurs frequently; these tumors grow aggressively with extensive infiltration beyond the apparent clinical margins, and rates of local recurrence are high. Nodal spread does not occur, and distant metastases have not been reported. Clinically, microcystic adnexal carcinoma usually presents as an indurated papule on the midfacial region (Figure 9–4) and may be confused with trichoepithelioma or basal cell carcinoma. A deep biopsy may be necessary to make the diagnosis.

Treatment is surgical excision, and Mohs micrographic surgery apparently provides optimal local control because of the ability to pursue the unpredictable tumor filaments at the margins (Figure 9–5). The role of radiation therapy for microcystic adnexal carcinoma remains unclear.

Merkel Cell Carcinoma

Merkel cell carcinoma is a rare, highly aggressive skin cancer that probably has a neuroendocrine origin. Histologic examination shows small- to medium-size cells with scant cytoplasm originating in the basal layer. These cells proliferate as cords and contain neuroendocrine granules. Special stains or electron microscopy may be necessary to distinguish Merkel cell carcinoma from small cell lymphoma or metastatic oat cell cancer. Large tumors consisting of small cells with numerous mitoses (10 per high-power field) have the poorest prognosis. Ultraviolet radiation has been implicated as causing Merkel cell carcinoma, which occurs most frequently in patients who received psoralen UV-A treatment. Merkel cell carcinoma has recently been associated with human polyomavirus (MCPyV) infection.

Clinically, Merkel cell carcinoma usually presents as a bland, painless nodule on the head and neck of older patients; it is usually pink to almost purple but can appear cystic. Nodal metastases may be found in up to 15% of patients at the initial presentation and subsequently develop in over 50% of cases. Distant metastases occur frequently in patients with nodal disease and can develop rapidly; the overall mortality remains about 50% and most affected patients die within 3 years after the initial diagnosis. Therefore, the initial diagnostic examination should include not only blood tests and CT scans of the chest and neck, but also should include a positron emission tomography (PET) scan, which may cause some tumors to be reclassified into a higher stage because of the early detection of metastatic disease. When staging is reclassified, treatment strategies must be altered accordingly.

Treatment of Merkel cell carcinoma should be planned in conjunction with an oncologist and generally consists of an initial surgical excision followed by radiation to the primary site and nodes. Although excisional margins of 2 cm are generally recommended, the relation between surgical margins and successful outcome is difficult to evaluate. Available studies suggest that, like excision of melanoma, excision of Merkel cell carcinoma using larger surgical margins does not necessarily increase local disease control or the treatment outcome. Mohs micrographic surgery may therefore be a reasonable choice to minimize defect size (especially on the face); studies have shown local recurrence rates comparable with those obtained by using wide local excision. Although Merkel cell tumors are highly radiosensitive, surgery followed by radiation probably achieves locoregional control more successfully than radiation or surgery alone. However, this comparative result has not been reflected in overall survival rates.

Other treatment modalities include sentinel node technology, which has been shown to be feasible and may correctly identify the nodal basin at risk for metastases. Although sentinel node biopsy in necks without clinical signs of disease may aid in staging disease and may limit the frequency of unnecessary neck dissection, the relation between sentinel node biopsy and a successful outcome ultimately is unclear. Finally, chemotherapy is effective for palliating metastatic disease, but the role of adjuvant chemotherapy remains to be defined.

Sebaceous Carcinoma

Sebaceous carcinoma, the fourth most common skin cancer, is more common in patients with Muir–Torre syndrome and in anatomic areas that have been previously irradiated. Histologic examination of tumor nodules shows variably sized lobules of sebaceous cells that contain lipid globules. Sebaceous carcinoma must be distinguished from basal cell carcinoma with sebaceous differentiation. Patients with sebaceous carcinoma present with tumors as nodules on the head and neck; most tumors occur on the eyelids. Symptoms of ocular irritation are common and may be confused with blepharitis or chalazion. Mortality rates increase with tumor size. About 50% of affected patients with tumors larger than 1 cm die; distant metastases occur in viscera and bone, and orbital invasion may be more common in tumors with pagetoid features. Local recurrence and nodal metastases are common. The initial diagnostic examination should include an ophthalmologic examination; magnetic resonance imaging (MRI) of the orbits and neck should be used to rule out occult metastatic disease in tumors larger than about 6 mm.

Treatment for sebaceous carcinoma is surgical excision; Mohs micrographic surgery using frozen sections followed by rush paraffin sections may optimize local control and tissue conservation. The role of radiation therapy as a primary treatment for sebaceous carcinoma is less clear, but improved technology may make this treatment an option when excision is contraindicated or refused.

Cutaneous Melanoma

General Considerations

Malignant melanoma of the skin is the third most common cutaneous malignant lesion; about 25% of these lesions occur on the head and neck. The incidence of cutaneous melanoma continues to increase exponentially and is currently increasing at a rate of about 5% annually. The overall mortality rate per 100,000 persons continues to increase, but survival rates among patients with lower-staged tumors have increased, and the overall cure rates for melanoma exceed 90%. Both an increased incidence and a decreased mortality may be related to an increased awareness of cutaneous melanoma and its early detection and treatment. Although most cases of the disease are sporadic, some show familial patterns and may be associated with dysplastic nevus syndrome, which carries a 100-fold increased lifetime risk for the development of cutaneous melanoma.

Other precursor lesions associated with an increased risk of cutaneous melanoma include large congenital nevi and the presence of more than 50 benign acquired nevi. A strong correlation with prior intermittent intense sun exposure exists, and active programs for prevention as well as early detection may ultimately help decrease the incidence. The role of sunscreens in preventing melanoma remains unclear. Melanoma of the head and neck can be separated into three general categories: (1) melanoma in situ (ie, lentigo maligna melanoma), (2) superficial spreading melanoma, and (3) nodular melanoma. Primary tumors are also classified using the American Joint Committee on Cancer (AJCC) nomenclature.

Melanoma In Situ

Melanoma in situ is characterized by the proliferation of atypical neoplastic melanocytes at the dermoepidermal junction along adnexal structures. A characteristically prolonged radial growth pattern is present and may last decades; approximately 0.10–0.25% of such lesions annually become invasive melanoma. These lesions occur on the cheek, nose, or temple in elderly patients. Early lesions may be clinically indistinguishable from solar lentigo. Topical imiquimod has been shown to successfully eradicate a significant percentage of in situ lesions and may find increasing utility in older patients who are poor surgical candidates.

Superficial Spreading Melanoma

Superficial spreading melanoma, the most common form, may evolve during a period of several years from a preexisting lesion, such as a nevus, in middle-aged individuals. The lesion is characterized histologically by a predominantly radial growth phase with eventual proliferation of malignant cells into the dermis, as well as upward growth that may present as nodularity and ulceration, which denotes the onset of the vertical growth phase.

Nodular Melanoma

Nodular melanoma occurs most commonly in children and represents approximately 15% of adulthood melanomas. It is characterized by early invasion and a vertical growth phase. The neoplasms can be black or variegated in color and are occasionally amelanotic. These tumors show no radial growth phase and are, by definition, invasive at the time of presentation.

Lesions suspected to be nodular melanomas should be either biopsied with a deep 3-mm punch or excised with a 2-mm margin. Shave biopsy should not be performed because the precise measurement of the tumor depth will not be possible and valuable staging information will not be accurate. A careful search for ulceration, induration of surrounding tissue, satellite or in-transit lesions, and regional adenopathy should be part of the initial examination. Nodular melanomas can become quite large and present significant surgical challenges, both in terms of achieving local control surgically and in reconstructing the defects after removal.

Diagnosis

The early clinical diagnosis of cutaneous melanoma requires a high index of suspicion based on family history, risk factors, and physical examination, which should include an examination for satellite lesions, the presence of ulceration, and regional nodes. To distinguish benign, pigmented lesions from high-risk lesions, the “A-B-C-D-E” approach to physical diagnosis is useful. This approach consists of observing five criteria:

• Asymmetric lesions
• Borders are irregular
• Color may vary with multiple shades from brown to red-black
• Diameter >6 mm
• Evolving lesions that have shown growth or change

Staging Criteria

The review of prior staging and survival data (Table 9–1 and Figure 9–6) suggests that, in addition to tumor thickness, the presence of melanoma ulceration, intransit metastases or satellite lesions, and number of nodes (identified as positive by clinical or pathologic examination) has strong independent prognostic predictive value. The 2001 AJCC staging system incorporated several changes relevant to head and neck surgery. These changes relate to melanoma thickness and ulceration (but not to the level of invasion) that is to be used in all but T1 categories. This strategy essentially changes the classification of tumors based on their thickness in millimeters in Stages II–IV to integers, with the substage based on the presence or the absence of ulceration. The current system for classifying primary tumors and nodes is shown in Table 9–2.

The number of metastatic lymph nodes and the delineation of clinically occult or microscopic nodes is used in the “N” category of the classification system. Macrometastases are defined as clinically, radiologically, or pathologically detectable nodes or as gross nodal extracapsular extensions. Micrometastases are detected with sentinel lymph node biopsy or elective node dissection.

As a result of these changes, the overall staging has changed (Table 9–3). As a result of the new staging criteria, some patients qualify for upgraded treatment strategies. The more recent 7th edition of AJCC guidelines to be published in early 2010 will also incorporate mitotic rate (defined as greater than one mitosis per square millimeter as an additional prognostic factor).

All patients with Stage I, II, and III disease are staged upward (or upstaged) when the primary melanoma is ulcerated.

Satellite metastases around a primary melanoma site and in-transit metastases are merged into a single staging entity grouped into Stage III disease.

A new convention defines clinical and pathologic staging to incorporate the staging information gained from intraoperative lymph node mapping and sentinel node biopsy.

Sites of distant metastases and the presence of an elevated serum lactic dehydrogenase (LDH) level are incorporated into the “M” category.

The role of the initial evaluation after the initial diagnosis is related to the presumed stage of disease. It has been questioned in lesions measuring <1.0 mm because this examination may yield a high rate of false-positive results and lead to unnecessary further studies. Patients who have melanoma in situ or Stage I disease without ulceration or symptoms need no further examination. Patients who have Stage I or II melanoma with ulceration or Stage III lesions may benefit from the addition of CT scanning of the neck, sentinel lymph node biopsy, or both procedures. The following tests are indicated for T4 lesions: (1) CT imaging to include the chest, the abdomen, and the pelvis; (2) an MRI of the brain; and (3) testing of the serum LDH level before sentinel lymph node biopsy. When confirmed by repeated tests, a finding of an elevated LDH level may have an independent predictive value for a poor prognosis. The addition of PET scanning may add additional prognostic information and cause staging of intermediate-risk lesions to be revised upward, thus changing the treatment strategies in high-risk patients. (Current studies are limited to investigational centers.)

Treatment

Surgical Measures

Treatment of melanoma of the head and neck is based on the initial staging and generally consists of surgical excision of the primary lesion; surgical margins are determined on the basis of the T stage. The role of the surgical margin size is particularly important for the head and neck, where conservation of normal structures and function is a high priority, particularly if the effect of larger margins is not manifested in the outcome. It is important to note that if wide local excision is planned, ideally, it should be done in conjunction with sentinel lymph node biopsy; however, it should not be performed before that procedure because of the potential for the altered lymphatic distribution of injected agents. (The role and technique of sentinel, elective, and therapeutic neck dissections are discussed in Chapter 28, Neck Neoplasms & Neck Dissection.)

The generally accepted surgical margins are based on the primary tumor stage. Melanoma in situ can be excised using a Wood's light with a 5-mm margin of clinically normal skin into subcutaneous fat. Mohs micrographic surgery may be beneficial for excising melanoma in situ in certain locations where tissue conservation is of great concern (eg, the eyelid or nose).

Stage I melanomas as deep as 2 mm without ulceration can be excised with a 1-cm margin; Stage I melanoma with ulceration should have 2-cm margins, and consideration should be given to the use of sentinel lymph node biopsy.

Stage II and Stage III lesions should have 2-cm margins and should include subcutaneous fat down to the fascia, if possible. Sentinel lymph node biopsy or elective node dissection, as well as postoperative radiation therapy, other adjuvant treatment, or a combination of these therapies, should be considered.

Nonsurgical Measures

Radiation Therapy

Radiation therapy can be used to treat lentigo maligna or in situ disease when surgery is not feasible. Radiation therapy also has been shown effective in decreasing locoregional recurrence postoperatively in patients with extracapsular spread or bulky nodal disease. Some centers currently recommend radiation therapy for Stage II disease if the nodes are not treated surgically; alternately, these centers recommend postoperative radiation therapy for use in node-positive or recurrent disease.

Adjuvant Therapies

Interferon-alpha can be offered to patients with melanomas greater than 1.5-mm thick and Stage II to III lesions as treatment may extend the relapse-free survival, but as of yet there is no clear long-term survival benefit.