Scalp and Skin

Basal Cell Carcinomas

Approximately 80% of basal cell carcinomas occur in the head and neck region. These tumors classically present as pearly papular lesions that can ulcerate and invade local tissues, earning them the nickname of “rodent ulcer.” Because basal cell carcinomas also can be pigmented, malignant melanoma may be a consideration in the differential diagnosis. Morpheaform basal cell carcinoma can present as a flat atrophic lesion with poorly defined borders similar to a scar appearance, making clinical diagnosis challenging ( Fig. 3.6 ). After diagnosis of a basal cell carcinoma, there is substantial risk of developing a subsequent basal cell carcinoma within a few years. These tumors rarely metastasize (only in 0.01% of cases) but can cause significant tissue destruction and disfigurement if not diagnosed and treated appropriately. Metastasis is associated with a poor clinical outcome with an expected survival of <10% at 5 years. Recent advances in hedgehog pathway inhibitor drugs offer patients with locally advanced or metastatic basal cell carcinoma another treatment option when further surgery or radiation is no longer possible. Basal cell carcinomas are derived from basal progenitor cells of the epidermis. Histologically these tumors are composed of dark, elongated cells aligned side by side with peripheral palisading and retraction from the adjacent stroma, producing a cleftlike space. This space may contain prominent stromal mucin (hyaluronic acid). The histologic growth patterns include superficial, nodular, infiltrative, morpheaform, and metatypical ( Fig. 3.7 ), and frequently more than one pattern is present in a tumor. Infiltrative, morpheaform, and metatypical (or basosquamous) types are considered more aggressive with greater invasion and increased risk for recurrence. While immunohistochemical studies are not typically required in diagnosis, these tumors are known to be immunoreactive for Ber-EP4 and pankeratin and may even show carcinoembryonic antigen (CEA) positivity.

Although there is no formal staging system for basal cell carcinoma, the National Comprehensive Cancer Network has developed guidelines for treatment based on evidence and consensus expert opinion. The guidelines divide basal cell carcinoma into low and high risk for local recurrence based on clinical and histologic tumor features. The “mask-area” of the face (around eyes, nose, lips, ears, temple, mandible) represents a higher risk location for skin cancer extension and recurrence. High-risk features include large size, location in “mask area,” poorly defined clinical borders, recurrence, site of prior radiation, aggressive histologic subtype, and immunosuppression.

Squamous Cell Carcinomas

Squamous cell carcinomas can be variable in their presentation, ranging from erythematous scaly lesions to highly infiltrative aggressive tumors. Dermal lymphatic permeation presents as distinct intradermal nodules and have an aggressive behavior ( Fig. 3.8 ). More than 70% of all cutaneous squamous cell carcinomas arise in the head and neck region in sun-exposed areas primarily on the ear and upper face. A small proportion of these tumors arise from preexisting actinic keratoses. Although progression has been reported to occur in as many as 25% of untreated cases, the true progression rate for actinic keratoses to squamous cell carcinoma is closer to 0.01% to 0.2% per lesion per year. When actinic damage develops on the lower lips, the term actinic cheilitis is used. Other causes of squamous cell carcinoma include ionizing radiation exposure, chronic nonhealing wounds, and human papilloma virus.

Bowen disease (also known as intraepithelial squamous cell carcinoma ) and keratoacanthoma are unique variants of squamous cell carcinoma. Bowen disease is essentially an in situ squamous cell carcinoma that can progress to invasive cancer if left untreated. Keratoacanthomas are unusual neoplasms that often display rapid growth over a 2- to 4-week period, followed by involution. The precise classification of keratoacanthomas as a variant of squamous cell carcinoma or as a unique entity remains a topic of debate. Histologically, squamous cell carcinomas show a “mosaic” or tile-like pattern of cells with anastomosing intracellular bridges, or desmosomes. Tumors may grow in nests, islands, or single cells and can show variable degrees of intracytoplasmic keratinization, with keratin pearl formation in well-differentiated carcinomas ( Fig. 3.9 ).

Overall, small squamous cell carcinomas (<2 cm) rarely metastasize (metastasis occurs in <5% of cases), but when metastasis does occur, it portends a dismal outcome. Other negative prognostic features include a size larger than 2 cm, prior treatment, immunosuppression, tumor invasion into subcutis or greater (>6 mm), poor differentiation, and neurotropism (perineural invasion). Microscopic perineural invasion does not portend the same poor prognosis as invasion of named nerves such as the trigeminal and facial nerves. Peripheral nerve involvement is indicated by pain, paresthesia, and numbness along sensory nerves and by fasciculation or weakness of muscles of expression, denoting involvement of the facial nerve. Several staging systems have been proposed for squamous cell carcinoma using high-risk features for local recurrence and metastasis, including American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC; eighth edition). The most recent staging criteria include histologic criteria such as depth of invasion (DOI; >6 mm) and perineural invasion.

Melanoma

Melanomas originate from junctional or dermal melanocytes that frequently involve the skin of the head and neck. In addition to skin type and a history of sun exposure, the presence of dysplastic nevi, family history, and immune dysfunction raise the risk for melanoma. Nearly half of all melanomas occur de novo in normal skin, and the remaining ones arise from preexisting nevi. A change in the size or appearance of a preexisting nevus with itching, variegated appearance, ulceration, and bleeding should prompt examination of a biopsy specimen.

Melanomas typically present as an irregularly pigmented lesion with a macular or papular appearance. They can be amelanotic or scarlike (i.e., desmoplastic melanomas), but this presentation is rare. These nonpigmented lesions can be mistaken for the more common basal or squamous cell carcinomas. The four main subtypes of melanoma are (1) superficial spreading melanoma (70% of cases) and has a characteristic horizontal growth pattern; (2) lentigo maligna, which occurs in heavily sun-exposed regions with potential for unpredictable subclinical horizontal extension; (3) acral lentiginous melanoma, which typically occurs in the nail beds, palms, and soles of the feet and is more common in African Americans and Asians; and (4) nodular melanoma, which usually is invasive at presentation and has a predilection for the extremities and trunk, with the scalp being the most common site in the head and neck ( Fig. 3.10 ).

The clinical behavior of melanoma typically is defined by its depth of infiltration, which is assessed microscopically by direct measurement (Breslow's thickness) and is used to define the T stage (except for T1 tumors) by the AJCC. In the past, Clark's Level of Depth of Invasion was used for staging of cutaneous melanoma. However, Breslow thickness is more accurate in prediction of prognosis for melanoma and is currently used in staging. Comparative depth of invasion between Clark's Levels and Breslow thickness are shown in Fig. 3.11 . Other factors included in the staging system are ulceration, mitotic rate, nodal metastasis (i.e., number and size), and distant metastasis (i.e., location and the serum lactate dehydrogenase level). Whereas thin melanomas rarely metastasize, intermediate-thickness melanomas show a high propensity for regional nodal metastasis, and thick melanomas have equal predilection to metastasize to both regional and distant sites. Moreover, melanomas also can produce “in transit” or “satellite” metastases.

Histologically, melanomas may or may not be pigmented and are composed of round to oval or fusiform tumor cells with nuclear pleomorphism and large, cherry-red, prominent nucleoli. These cells generally are located in rounded nests or as solitary units at the dermal-epidermal junction. Within the epidermis, tumor cells may migrate upward to the surface of the epidermis (pagetoid spread). Invasive melanoma may infiltrate the dermis as single cell units or in groups of cells. In some instances the malignant cells may appear epithelioid, whereas in other instances they may appear to be elongated and spindled (fusiform). Hence numerous histologic phenotypes of melanoma exist (e.g., conventional epithelioid, spindle cell, signet ring cell, or balloon cell). Immunohistochemical staining for S-100 protein, Sox 10, Melan-A (MART-1; A103), HMB-45, tyrosinase, and microphthalmia transcription factor can help differentiate melanomas from other nonmelanotic malignant tumors. S-100 protein and Sox 10 also stain myoepithelial and dendritic cells and are found in nevi but are valuable markers for the diagnosis of desmoplastic melanomas. Melanomas are usually negative for epithelial markers. HMB-45 and Melan-A are highly specific for melanocytes, although Melan-A also can label adrenocortical carcinoma and sex cord stromal tumors of the ovary. Molecular diagnosis also may play a role in assessment of melanocytic tumors and help with treatment selection by identifying the presence or absence of a targetable mutation such as BRAF V600E.

Adnexal Tumors

Adnexal tumors in the head and neck region present as intradermal or subcutaneous nodules and represent a wide range of neoplasms that vary in behavior and malignant potential. Nevus sebaceous is a congenital hamartoma that probably arises from basal cells and has a small propensity for transformation to basal cell carcinoma. Cylindromas (turban tumors) can be of either apocrine or eccrine origin and typically arise in the scalp or facial region of young adults. These lesions can occur de novo or may be inherited in an autosomal-dominant pattern. The CYLD 1 tumor suppressor gene is inactivated in both sporadic and familial forms. These tumors have a small propensity for malignant transformation to sweat gland carcinomas. Head and neck syringomas are tumors of eccrine origin that typically arise from the facial skin and eyelids. These lesions are usually multiple, yellowish in color, and have a fleshy covering. Eccrine spiradenomas usually are seen in younger patients and have a small propensity for malignant degeneration. These lesions present as expanding solitary nodules that are painful. Other benign tumors originating in adnexal structures include trichoepitheliomas and pilomatrixomas, but they are relatively rare.

Sweat gland carcinomas are skin appendage tumors derived from eccrine or apocrine glands. Unlike other skin cancers, these tumors do not have a racial predilection. These tumors typically present as 1- to 2-cm, firm, fixed, intradermal, or subcutaneous nodules that may ulcerate and become necrotic ( Fig. 3.12 ). As they grow, they may coalesce and form larger subcutaneous lesions. Apocrine gland carcinomas are less common and occur most often in the axilla of elderly persons. In the head and neck, apocrine gland carcinomas can arise from various sites, including in the eyelid from Moll's gland, a modified apocrine gland. Apocrine gland carcinomas are highly aggressive neoplasms with a mortality rate over 50%. Metastases occur most frequently in regional lymph nodes, and local recurrence after resection is common. Eccrine gland carcinomas arise either de novo or from preexisting benign lesions. Histologic variants of sweat gland carcinomas include primary cutaneous, mucinous carcinoma, eccrine duct carcinoma, porocarcinoma, microcystic adnexal/sclerosing sweat duct carcinoma, endocrine mucin-producing sweat gland carcinoma, cribriform adenocarcinoma, and adenocarcinomas arising in association with a cylindroma or spiradenoma. Eccrine gland carcinomas typically arise from the ocular adnexa, including the meibomian glands, Zeis’ glands, or pilosebaceous glands in older women. Salivary gland–type adenocarcinoma, or a metastasis of breast, pulmonary, or even prostate origin, may come into consideration in the differential diagnosis of eccrine carcinoma such as adenoid cystic carcinoma.

Merkel Cell Carcinoma

Merkel cell carcinoma is a neuroendocrine neoplasm of the skin. The majority of these tumors in North America (80%) are caused by infections with Merkel cell polyomavirus (MCV), a double-stranded DNA virus. Nearly half of all Merkel cell carcinoma lesions occur in the head and neck region. The cheek is the most common site, followed by the upper neck and nose. These lesions typically occur in elderly white persons and appear as a red to violaceous, smooth, dome-shaped lesion with telangiectasias ( Fig. 3.13 ). These tumors have a high propensity for metastatic spread to regional lymph nodes as well as distant sites. Histologically they are composed of basophilic cells with scant cytoplasm and dark powdery chromatin, and they may be morphologically similar to other neuroendocrine carcinomas. Hence metastatic small cell carcinoma, malignant melanoma, or primary neuroendocrine (or “small cell”) carcinoma of the parotid gland may be considerations in the differential diagnosis. Immunohistochemical stains for synaptophysin, chromogranin, and cytokeratin 20 (CK20) (demonstrating a characteristic “dotlike” pattern) or the Merkel cell polyoma virus large T antigen (recognized by the antibody CM2B4) are positive, whereas thyroid transcription factor-1 (TTF-1) is negative.

Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans is an intermediate-grade sarcoma that presents as a unifocal or multifocal nodular lesion. Dermatofibrosarcoma protuberans involves the head and neck region in 10% to 20% of cases, with the scalp and supraclavicular fossae the most common sites for involvement ( Fig. 3.14 ). These slow-growing, locally aggressive tumors have tentacle-like extensions well beyond the visible lesion, and thus the true extent of the disease is often underestimated, leading to local recurrence in more than 50% of patients. Histologically a storiform or fascicular proliferation of spindle cells extends from the dermis into the subcutis, with immunohistochemistry showing CD34 positive staining in most cases. Presence of fibrosarcomatous changes and high mitotic rate may portend a more aggressive course. This tumor frequently has a translocation of a fusion protein involving COL1A1 and PDGFB that functions like PDGFB. Wide excision with margins of ≥2 cm is generally advocated, with adjuvant radiation reserved for larger or recurrent tumors when resection is not feasible.

Angiosarcoma

Angiosarcomas typically have an innocuous presentation, appearing as a purplish bruise, whereas the actual tumor can extend well beyond the visible edge of the lesion ( Fig. 3.15 ). These tumors are thought to arise from vascular endothelial cells and can have a heterogeneous presentation ranging from macular to papular morphology. Angiosarcomas involve the skin in about half of the cases, with 50% arising in the head and neck region. A high degree of clinical suspicion is required, and a biopsy is required to establish tissue diagnosis. These tumors have a high propensity for local recurrence and distant metastasis. Pulmonary metastases can appear as bullous lesions on chest imaging. Surgical resection is feasible only in well-demarcated, nodular lesions. The vast majority of ecchymotic macular lesions are treated with a combination of radiation and chemotherapy. Long-term prognosis is poor despite aggressive treatment.

Topical Therapy

Several topical agents have been used in the management of selected premalignant and superficial skin cancers. In general, this treatment approach is used in patients with multiple lesions or lesions involving large areas of the scalp and facial skin. However, topical agents should not be used for more invasive lesions. Topical chemotherapy with 5-fluorouracil and topical immunotherapy with imiquimod have been effective for actinic keratoses, superficial basal cell carcinoma, and in situ squamous cell carcinoma. Photodynamic therapy also has been used for such lesions with high initial response rates, but the long-term control rates are lower.

Radiation Therapy

Cutaneous malignancies of the scalp and the facial skin, particularly superficial squamous cell carcinoma and basal cell carcinoma, can be treated effectively with radiotherapy. Because skin cancers are superficial in their location with respect to the remainder of the deeper tissues in the body, these tumors preferably are treated with electron beam, superficial, or orthovoltage x-rays. With use of these modalities, an effective dose of radiation can be delivered to the tumor target without delivering excessive radiation to the deeper tissues.

Radiotherapy is an option in patients who present with lesions that require extensive surgery that would affect function and cosmesis, such as compromised oral competence with lesions located near the oral commissure and epiphora with lid retraction for lesions of the eyelid. External radiation is quite effective in basal cell carcinoma of the eyelids, particularly adjacent to the medial canthus ( Fig. 3.16 ). The immediate results of radiotherapy are excellent, with essentially no cosmetic or functional impact on the patient ( Fig. 3.17 ). Atrophy of the underlying cartilage can occur and may result in an unattractive scar over time. Therefore definitive radiotherapy is generally used for elderly patients, for whom cosmesis is not of great concern. Elderly and medically unfit patients with massive skin cancer requiring surgical resection are also considered for treatment with radiation. Radiotherapy can offer excellent palliation and sometimes can be curative. The patient shown in Fig. 3.18 has an extensive basal cell carcinoma of the nose that would have required nasal amputation if treated surgically. Six months after radiation therapy, complete resolution of the tumor was achieved with an excellent cosmetic result ( Fig. 3.19 ). Radiotherapy is also used postoperatively for adverse histopathologic features of the primary tumor (e.g., inadequate surgical margins, extensive perineural invasion, or deep soft tissue infiltration) or in patients with regional lymph node metastasis.

In general, radiotherapy is not recommended in younger patients, because the long-term sequelae of treatment are progressive and can affect cosmesis as the patient gets older. These late effects include telangiectasias, atrophy, and pallor of the skin. In addition, a small risk exists for development of a radiation-induced second cancer in the irradiated field. Although radiotherapy can be curative, a prolonged treatment course, typically over 4 to 5 weeks or 5500 cGy at 250 cGy per day, may limit its applicability in some patients.

The role of radiation therapy in the treatment of head and neck cutaneous melanoma is typically only in the adjuvant setting after surgical resection. Results from in vitro experiments assessing radiation response in several human melanoma cell lines support the use of hypofractionated radiation therapy in the treatment of melanoma. Several nonrandomized studies show that doses of ≥4 Gy per fraction produce higher complete response rates. In particular, 8 Gy fractions given on days 0, 7, and 21 or 6 Gy given in five fractions over 2.5 weeks produce excellent response rates. However, the Radiation Therapy Oncology Group (RTOG) prospective randomized trial, in which measurable melanomas were treated either with 8 Gy per fraction given once every week over 4 weeks or conventional fractionation of 2.5 Gy per fraction given daily over 20 days, showed no differences in outcome. Nonetheless, the shortened treatment time resulting from a hypofractionated course of radiation therapy is preferred, because it allows early initiation of systemic therapy if warranted. Radiation fields should encompass the postoperative bed at the primary site and regional nodes at risk for involvement in the N0 neck or after therapeutic neck dissection for multiple positive lymph nodes, extranodal extension, or recurrent neck disease.

The role of radiation therapy for the treatment of adnexal tumors remains to be defined. The best data are available for Merkel cell carcinoma, for which adjuvant radiotherapy has been shown to be important, especially for larger tumors that are associated with regional metastasis. More recently, reports suggest increased effectiveness with the use of concurrent chemotherapy as well as adjuvant chemotherapy, but the precise role for both these approaches remains to be defined.

Surgical Anatomy

The scalp is a unique adaptation of the epithelial covering of the body. Anatomic variations present in the scalp modify both tumor behavior and the treatment of tumors in this area. The hair-bearing area of the scalp consists of a thick padding of hair follicles, sweat glands, fat, fibrous tissue, and lymphatics that are interspersed with numerous arteries and veins ( Fig. 3.22 ). This thick padding is supported by the galea, a tough aponeurotic layer that is fused in the anterior region with the frontalis muscle and in the posterior region with the occipital muscle. This inelastic layer rests loosely on the periosteum of the skull, creating a potential subaponeurotic space. Laterally, the temporalis muscle provides an additional barrier between the galea and the periosteum.

Three principal arteries provide a rich blood supply to each side of the scalp. The superficial temporal and occipital arteries are branches of the external carotid artery, whereas the supraorbital artery is a branch of the internal carotid artery ( Fig. 3.23 ). The scalp has a rich subdermal and subcutaneous lymphatic network. The general pattern of lymphatic drainage is divided by a coronal plane at the level of the tragus. Malignant tumors located anterior to this plane drain to preauricular, parotid, and anterior triangle lymph nodes in the neck. On the other hand, lesions located posterior to this plane drain to postauricular, suboccipital, and posterior triangle lymph nodes.

Facial skin is also unique in that it has several distinguishing characteristics on various parts of the face, with unique anatomic features providing different functions. For example, the skin around the eyelids is extremely thin, with almost no subcutaneous fat. In contrast, the skin around the central part of the face adjacent to the nose and lips is intimately attached to the underlying facial muscles and offers facial expression. Thus the skin of the central part of the face is mobile, whereas areas of facial skin along the lateral aspect of the nose, the bridge of the nose, and along the preauricular region and temple are relatively immobile. These unique characteristics of the facial skin have significant surgical implications. Similar to the scalp, the facial skin has a rich blood supply through the facial and superficial temporal arteries, and it has predictable patterns of lymphatic drainage to preauricular and periparotid lymph nodes and perivascular facial lymph nodes adjacent to the body of the mandible at level I, eventually draining into the deep jugular chain of lymph nodes.

Principles of Surgical Treatment

Surgical management of skin malignancies is dictated by the location and extent of the tumor. For lesions in the scalp, the extent of surgical resection depends on the surface dimensions of the tumor and the depth of invasion by the tumor. Excision is through partial thickness for superficial tumors or through entire thickness, including the periosteum, for deeply infiltrating tumors. Scalp tumors that are adherent to or involve the underlying cranium require removal of at least the outer table of skull or a through-and-through resection up to and including the dura ( Fig. 3.24 ).

Small lesions of the face and neck can be excised elliptically in the plane of skin tension with excellent aesthetic results. The facial skin lines are at right angles to underlying fibers of the muscles of facial expression. Orientation of facial skin lines and potential directions for elliptical incisions are shown in Fig. 3.25 . Identification and orientation of the long axis for elliptical incision is facilitated by asking the patient to grimace. These lines are horizontal on the forehead and around the bridge of the nose and the outer canthus of the eye. Near the cheek the tension lines run obliquely or perpendicularly, near the lips they run radially from the mouth opening, and on the chin they run horizontally on the midline and obliquely perpendicular at the sides. On the sides of the neck, the wrinkles and tension lines run obliquely downward and forward ( Fig. 3.26 ).

Elliptical excision of a small tumor of the skin of the face along the facial skin lines can be easily closed primarily, with excellent cosmetic outcomes. Meticulous attention should be paid to accurate approximation of the skin with fine sutures, which can be removed as early as 4 days postoperatively. Alternatively, one may elect to use a subcuticular suture, particularly in the area of the eyelids where the skin is very thin.

Most surgical defects resulting from resection of skin neoplasms can be closed primarily after wide undermining. Application of split-thickness or full-thickness skin grafts is best suited to the part of the face with minimal facial motion, such as the tip or lateral aspect of the bridge of the nose or the temple. Similarly, a skin graft can be used in the parotid region where facial movement is minimal with excellent cosmetic results. The most suitable donor sites for obtaining full-thickness skin grafts are from the retroauricular or supraclavicular regions. Local flaps are preferred to repair larger surgical defects or those requiring full-thickness reconstruction, because they provide the best functional and aesthetic outcome. Primary closure of the donor site defect usually can be accomplished with ease with proper planning of local skin flaps. The blood supply of facial skin and soft tissues is extremely rich, because the terminal branches of the external carotid artery provide a major source of blood to the facial skin, which allows use of axial flaps. In addition, an extensive subdermal anastomotic network facilitates the use of random flaps with relative ease. Examples of axial skin flaps are nasolabial, glabellar, Mustardé cheek, and temporal forehead. Examples of random flaps are cervical, rhomboid, and bilobed. If local flaps are not suitable, consideration should be given to regional or free flaps for appropriate repair of large surgical defects.

Metastatic dissemination to regional lymph nodes from primary squamous cell carcinomas of the scalp and face is infrequent. In general, squamous carcinomas <2 cm in diameter have an exceedingly low risk of metastasis, and therefore elective treatment of regional lymph nodes is not recommended because it does not offer significant therapeutic advantage. Lesions >2 cm have a proportionately higher risk of regional lymphatic dissemination, and elective neck dissection should be used selectively. Other more aggressive cutaneous malignancies, such as Merkel cell carcinoma and melanoma, have a higher risk of lymphatic dissemination. Currently, sentinel node biopsy is used to identify occult nodal metastasis.