Malignant Tumors

Basal and squamous cell carcinomas are the most common malignant skin tumors, accounting for more than 1 million cases per year in the USA and an estimated 40% of all malignancies. Lifelong environmental exposure to ultraviolet light is the major risk factor, and the annual risk among elderly whites may be 1 to 3% in sunny areas, such as the southwestern USA. Other predisposing factors are exposure to ionizing radiation, exposure to chemical carcinogens (eg, arsenic), and drug- or disease-induced immunosuppression.

Diagnosis is confirmed by biopsy. In general, shave biopsy is adequate for suspected basal and squamous cell carcinomas, whereas excisional biopsy is recommended for pigmented lesions suspected of being melanomas.

Basal Cell Carcinoma

A pearly papule that if neglected may evolve into a superficial ulcer, derived from epidermal basal cells, that is generally slow-growing and rarely metastasizes.

Basal cell carcinoma is responsible for about 75% of the more than 1 million skin cancers diagnosed every year in the USA. More than 99% of patients are white; over half are male. About 95% of cases occur in persons between the ages of 40 and 79 years.

Symptoms, Signs, and Diagnosis

More than 90% of lesions occur on the head and neck. The typical basal cell carcinoma (noduloulcerative subtype) has a pearly appearance, rolled edges, and telangiectasia on its surface. As the lesion enlarges, it may develop central ulceration, creating the classic rodent ulcer. Other subtypes include multicentric lesions that appear as a scaly plaque with a typically raised pearly edge (superficial subtype); pigmented basal cell carcinomas, sometimes mistaken for malignant melanoma (pigmented subtype); and solitary flat or slightly depressed indurated lesions that are whitish or yellowish (sclerosing [morpheaform] subtype).

All basal cell carcinomas should be confirmed histologically by biopsy, preferably before starting therapy. Shave biopsy is usually preferred.

Prognosis

If not detected and treated early, the carcinoma may invade deep tissues and destroy bone and cartilage, especially around the eyes, nose, and ears. Basal cell carcinomas rarely metastasize; however, the sclerosing subtype is more likely than other subtypes to recur. About 33% of patients per year develop another primary basal cell carcinoma.

Treatment

The size of the malignancy, depth of invasion, and patient history determine treatment.

Electrodesiccation and curettage can be used to treat small tumors. The procedure has a 95% cure rate, just below that of surgical excision. This method leaves a round depigmented scar, compared with the linear scar left by surgical excision. Cryotherapy can be used to treat small lesions. Usually, two freeze-thaw cycles are used. However, this method has a lower cure rate.

Surgical excision has the highest cure rate. It can be done on an outpatient basis with use of a local anesthetic. Margins of 5 mm are considered desirable. The procedure can be performed with primary closure or skin grafting, which may necessitate the cooperation of a plastic surgeon.

Mohs' surgery is a micrographically controlled surgical technique of staged excision. The entire tissue margins are examined histologically as surgery proceeds, ensuring complete tumor removal and sparing the maximum amount of uninvolved tissue. Mohs' surgery can be used for large, recurrent, or high-risk carcinomas. The sclerosing subtype of basal cell carcinoma, which has a high recurrence rate after conventional surgical excision, probably is best treated with Mohs' surgery.

Radiotherapy can be used when surgery is undesirable or intolerable and when carcinoma has recurred after surgery.

Intralesional interferon and photodynamic therapy using a hematoporphyrin derivative are recent innovations for managing these lesions.

After tumor removal, patients should be followed at least annually for 5 years for recurrence and for new lesions.

Squamous Cell Carcinoma

Cancers that arise from the malpighian cells of the epidermis and that have a modest propensity to metastasize.

Squamous cell carcinoma is the second most common skin cancer, with > 200,000 new cases occurring every year in the USA. Squamous cell carcinoma may arise from actinic keratoses or Bowen's disease.

These tumors usually occur in sun-exposed areas, although <= 25% occur in sites of chronic inflammation or persistent ulceration, such as long-standing lupus vulgaris (cutaneous tuberculosis), chronic venous ulcers, radiodermatitis, or a burn scar (Marjolin's ulcer). Carcinomas arising in areas of chronic inflammation have the highest risk of metastasizing. Fair-skinned people, who have less melanin and thus less protection from the sun, have a higher incidence of squamous cell carcinoma, both solitary and multiple. Tumors range histologically from well-differentiated to poorly differentiated.

Symptoms, Signs, and Diagnosis

Lesions usually occur on sun-exposed areas of skin such as the face or dorsum of the hand. The earliest signs of squamous cell carcinoma are usually erythema and induration. The overlying epidermis may be scaly or hyperkeratotic. In more advanced lesions, ulceration usually occurs, often with crusting. Advanced lesions may become fixed to underlying tissue.

The diagnosis must be confirmed by biopsy. A shave or 3-mm punch biopsy is usually adequate, provided representative viable tissue is obtained.

Prognosis and Treatment

About 2 to 5% of lesions metastasize. Lesions of the vermilion border of the lip, the pinna, and the genitals are more likely to metastasize than those found elsewhere, such as on the face and limbs.

Surgical excision can be used to treat small well-differentiated tumors. At least 5 mm of tissue beyond the tumor borders must be excised. Squamous cell carcinomas that recur in sites previously treated with another modality (eg, radiotherapy) can also be excised surgically.

Cryotherapy is an alternative method for treating multiple small tumors, which are typically found in fair-skinned patients. The tumors, together with a margin of normal tissue, should be frozen; two freeze-thaw cycles should be used. Although cryotherapy is desirable in that it usually does not require anesthesia, healing can be prolonged in elderly patients.

Radiotherapy is generally used for poorly differentiated tumors of the head and neck and for tumors that recur after surgery. Although the cosmetic results of radiotherapy may be inferior to those of surgery, radiotherapy may be preferable for elderly patients in whom surgery is contraindicated. However, multiple treatments are usually necessary, which may present problems for patients with limited mobility. Radiotherapy is not used to treat tumors on the dorsa of the hands because it may leave friable scars.

Kaposi's Sarcoma

A multicentric malignant vascular neoplasm affecting the skin and subcutaneous tissues and sometimes affecting other organs.

Classic Kaposi's sarcoma (KS) occurs as an indolent tumor in elderly patients of Central European descent, especially men of Jewish or Italian ancestry. Endemic KS tends to occur in the same areas of equatorial Africa in which Burkitt's lymphoma is prevalent. KS also occurs in immunosuppressed organ-transplant recipients and in AIDS patients, who may develop an aggressive lymphadenopathic form of the disease. Herpesvirus type 8 appears to have an etiologic role, particularly among immunosuppressed patients.

Symptoms, Signs, and Diagnosis

KS is characterized by one or more purple or dark blue macules that slowly enlarge to become nodules or ulcers. In classic KS, lesions are usually asymptomatic. However, lesions may be painful. In patients with more aggressive forms, symptoms depend on the site of involvement (eg, wheezing may occur from bronchiolar involvement).

Diagnosis is made clinically and confirmed by biopsy. On histologic examination, the tumor cells are endothelial; proliferating vessels and connective tissue cells are also present.

Prognosis and Treatment

Classic KS usually runs a relatively benign course, even without treatment. The course of lymphadenopathic (AIDS-related) KS is typically more aggressive and may be fulminant.

Intralesional bleomycin can be used if lesions are symptomatic. Alternatively, simple excision, radiotherapy, or laser ablation can be performed. Generalized progressive lesions causing functional impairment require systemic chemotherapy, such as vinblastine, interferon-, doxorubicin, daunorubicin, or paclitaxel. Patients with KS are at increased risk of a second primary malignancy and require regular follow-up.

Melanomas

Highly malignant skin tumors that readily metastasize.

The incidence of all four types of melanoma increases with age. Superficial spreading melanoma accounts for about 60% of all melanomas and is the most common form in the elderly. Although the overall incidence of this melanoma peaks in middle age, its incidence increases through the 8th decade. Nodular melanoma accounts for about 15% of all melanomas and occurs more commonly among elderly patients. Lentigo maligna melanoma accounts for 5 to 10% of all melanomas and occurs mainly in the elderly; it is an invasive melanoma that arises from lentigo maligna. The mean age at diagnosis is 67 years. Acral-lentiginous melanoma accounts for 1 to 2% of all melanomas; it is more common among darker-skinned patients.

Symptoms and Signs

Superficial spreading melanoma is a pigmented plaque with an irregular border and variable pigmentation, often with areas of red, white, black, and brown. Like all melanomas, it is usually asymptomatic. Pruritus and bleeding may occur with advanced lesions.

Nodular melanoma is a darkly pigmented papule (dark brown-black to blue-black) that often enlarges rapidly. Rarely, lesions contain little pigment.

Lentigo maligna melanoma is characterized by nodularity, color change, and/or ulceration occurring in a long-standing lentigo maligna.

Acral-lentiginous melanoma consists of pigmented, usually macular lesions on the nail bed, palms, soles, and fingers.

Diagnosis

Suspicious lesions should be examined clinically by a dermatologist, and a biopsy (optimally, an excisional biopsy) should be performed. After histologic assessment, confirmed cases should be referred immediately to a physician experienced in melanoma management.

In suspected lentigo maligna melanoma, excisional biopsy is often impractical because the lesions are typically > 1 cm and located on the head or neck. Therefore, punch biopsies of areas that are most clinically suspicious are often performed. A nodule, if present, should be included in the specimen.

Prognosis

The rate of progression differs among the melanoma subtypes, but prognosis is always related to tumor thickness at the time of initial excision rather than to histologic type (see Table 125-1). Morbidity rates among elderly men are particularly high, probably because of delayed diagnosis. Because metastatic melanoma is usually fatal, cure depends on early diagnosis and excision while primary tumors are still thin.

Lentigo maligna melanoma is relatively indolent; however, deeply invasive, neglected lesions have the same poor prognosis as other forms of melanoma of equal thickness.

Acral-lentiginous melanoma tends to be diagnosed at a late stage; thus it has usually become deeply invasive before treatment is started.

Treatment

Treatment recommendations depend on the risk category (see Table 125-1). If possible, low-risk lesions are excised with 1- to 2-cm margins, and intermediate- to high-risk lesions are excised with 3-cm margins and at least 1 cm of underlying subcutaneous fat. Removal of all palpably enlarged lymph nodes has also been recommended, but prophylactic lymphadenectomy of clinically normal nodes appears to have no benefit. Follow-up is essential; patients should be seen every 6 to 12 months indefinitely.

Traditional treatment of lentigo maligna melanoma consists of a wide local excision, often requiring a skin flap or split-thickness skin graft to repair the defect. Mohs' surgery, which conserves more tissue, has recently been used successfully. However, long-term follow-up is necessary to determine the risk of metastasis with this approach. High-risk patients (those with thick primary lesions but no apparent metastases) may benefit from prophylactic therapy with melanoma vaccines or other immunomodulatory therapy, for which controlled multicenter trials are under way.

Advanced melanoma with metastases is usually incurable and therefore treated palliatively. Surgery (eg, of a solitary brain lesion) can sometimes prolong survival. Radiation combined with corticosteroids may temporarily ameliorate symptoms. Patients with advanced disease limited to a limb may benefit from hyperthermic limb perfusion together with melphalan and tumor necrosis factor. Opioid analgesics for pain control and end-of-life palliative measures may be needed. Patients should be asked to clarify their wishes about end-of-life care in an advance directive.