Actinic keratoses, also known as solar keratoses, are common premalignant tumours of the epidermis which occur in sun-exposed skin. Lesions are typically multiple, and may be so numerous as to alter most of the sun-exposed portion of the cutaneous surface. Most commonly, actinic keratoses are flat poorly-defined papules; their colour ranges from pink to dark brown. Characteristically, a surface scale is present, which may be more easily felt than seen. Hypertrophic actinic keratoses are less common, and are fleshier papules or nodules surmounted by a thick scale or horn-like excrescence.

Histologically, actinic keratoses represent the earliest type of neoplastic transformation of the epidermis. Anaplasia and disorderly proliferation of keratinocytes is seen in the lower epidermis, but, unlike squamous cell carcinoma in situ, full-thickness atypism is not seen. An identical process involving the vermilion border of the lower lip is termed actinic cheilitis.

Actinic keratoses are most common in fair-skinned people and are unquestionably the result of chronic ultraviolet exposure. Similar lesions may develop as a result of exposure to other tumour inducers, particularly ionizing radiation and arsenic. As few as 0.1 per cent of actinic keratoses undergo transformation to squamous cell carcinoma.

Because they are very superficial, a variety of modalities may be used to treat actinic keratoses. With the possible exception of large hypertrophic lesions, full-thickness excision is not indicated. In the United States, discrete lesions present in low numbers are most commonly treated with liquid nitrogen cryosurgery (see Section 32.7) 229. Small numbers of lesions may also be treated with curettage. When more diffuse actinic damage is present, topical chemotherapy with 5-fluorouracil cream for 2 to 4 weeks is effective. Patients should be warned that widespread inflammation and crusting will develop. The use of topical tretinoin for the treatment of actinic damage has been studied, but its role in the treatment of actinic keratosis is poorly defined. Regardless of the treatment chosen the patient's skin should be protected from further ultraviolet damage by chemical or opaque sunscreens and physical protection such as hats and long-sleeved shirts. Patients should be educated with regard to the causative role which ultraviolet exposure plays in their disease.

Cutaneous horns are elongated, keratinous projections from the skin, ranging in size from a few millimetres to many centimetres (Fig. 1) 1508. Because they are evidence of anaplasia of the underlying skin biopsy examination is warranted. Most small cutaneous horns arise from actinic keratoses; large horns may develop in hypertrophic actinic keratoses or squamous cell carcinomas.

Squamous cell carcinoma is a malignancy of epidermal keratinocytes. After basal cell carcinoma, it is the most frequently encountered malignant neoplasm of the skin. In caucasian patients, squamous cell carcinoma is most commonly a result of chronic actinic damage; most patients are elderly. However, squamous cell carcinoma also develops at mucocutaneous interfaces as a result of tobacco use or human papillomavirus infection, at sites treated with ionizing radiation, in burn scars, and in chronic ulcers of the skin (Fig. 2) 1509. Sites of chronic inflammation account for the majority of cutaneous squamous cell carcinomas in darkly pigmented races. Although actinically induced squamous cell carcinoma rarely metastasizes, tumours induced by other factors, particularly those at mucocutaneous interfaces, are most aggressive and metastasize frequently. The incidence of squamous cell carcinoma and the rate of metastasis are greater in immunosuppressed patients, especially following organ transplantation.

The clinical presentation of squamous cell carcinoma of the skin is extraordinarily variable. As a rule it presents as an exophytic nodule or a plaque, which may ulcerate. These lesions are typically pink or flesh-coloured in caucasian patients; they may be hypopigmented or hyperpigmented in those with dark complexions. There is often evidence of aberrant keratinization, resulting in the formation of a scale or a cutaneous horn (see above).

Several subtypes of cutaneous squamous carcinoma are worthy of special mention. Squamous carcinoma in situ may occur following chronic actinic damage, or in non-sun-exposed skin. In the latter case, the process is frequently referred to as Bowen's disease. Squamous cell carcinoma in situ arising from the genital skin is referred to as erythroplasia of Queyrat. Both actinically induced squamous cell carcinoma in situ and Bowen's disease (Fig. 3) 1510 present as scaly, well defined plaques with irregular borders. In caucasian patients, lesions are typically pink in colour. Histologically, squamous cell carcinoma in situ does not invade the dermis, although invasive squamous cell carcinoma may develop within lesions.

In the past, squamous cell carcinoma in situ, particularly that in non-sun-exposed skin, has been associated with internal malignancy of various types. A recent population-based study has cast doubt on this concept, however. Squamous cell carcinoma in situ may be treated by excision, although other modalities such as cryosurgery and curettage with electrodesiccation are also effective. Topical chemotherapy with 5 per cent 5-fluorouracil is also occasionally used.

Keratoacanthoma bears many similarities to squamous cell carcinoma, and many clinicians consider it to be a low-grade carcinoma, despite its typically self-limited nature (Fig. 4) 1511. Its classification as a malignancy is because of its tendency to arise from sun-damaged skin, and the fact that keratoacanthoma is commonly seen in immunosuppressed renal transplant patients, in whom tumour surveillance is impaired.

Keratoacanthomas appear suddenly and grow rapidly, often achieving a diameter of several centimetres in a matter of weeks. Classically, the tumour is domed or conical, and has a central crater filled with keratinaceous material. The lesion is pink, and lacks the gelatinous transluscence and telangiectasia of basal cell carcinoma. Keratoacanthomas may be as small as 5 mm in diameter or as large as several centimetres, but most are in the range of 1.0 to 2.0 cm. Most keratoacanthomas are solitary; multiple keratoacanthomas are rare and frequently occur in patients with a family history of the condition.

The pathology of keratoacanthoma resembles squamous cell carcinoma, and differentiation between the two entities may be difficult. Classic, fully developed keratoacanthomas are expansile tumours composed of large, cytologically bland keratinocytes with ‘ground glass’ cytoplasm. Unlike squamous cell carcinoma, the base of the tumour is flat and does not exhibit invasion of the deeper dermis. It is important to include this deeper portion of the tumour in biopsy specimens, as this may be the principal means by which the pathologist can make the correct diagnosis. A thin, radial wedge biopsy that includes the peripheral margin of the tumour as well as the centre, and which extends into the subcutaneous fat, is mandatory.

Keratoacanthomas typically regress spontaneously within 1 year. Post-involutional scarring is common; for that reason the lesions are frequently excised despite their seemingly benign nature. Large keratoacanthomas and those developing in immunosuppressed patients tend to be most aggressive. Their behaviour is more like that of true squamous cell carcinoma, with locally destructive growth and the potential for invasion along neurovascular structures. Surgical excision is the treatment of choice, but may not always be feasible, particularly when lesions are very large or multiple. Intralesional 5-fluorouracil or bleomycin are often used in such cases. Superficial radiation therapy (600–1000 cGy) is effective and safe for the treatment of most lesions. Recently, synthetic retinoids such as etretinate have been used in the management of patients with multiple keratoacanthomas. Although this treatment is effective, little information about its long-term benefit is available.

Basal cell carcinoma is the most common form of skin cancer in caucasian patients. It is rare in oriental populations, and is virtually unheard of in black patients, except in those with predisposing syndrome such as xeroderma pigmentosa or the naevoid basal cell carcinoma syndrome. Basal cell carcinoma is a disease of adults; affected children and infants have only rarely been described. In the vast majority of cases, excess exposure to short wave ultraviolet light length (UVB range, 290–320 nm) precipitates basal cell carcinoma. As a result, these tumours arise in sun-exposed sites, and have a particular predilection for the head and neck. Other risk factors for the development of basal cell carcinoma include ionizing radiation, burn scars, and chronic exposure to arsenic, all of which have also been implicated in the pathogenesis of squamous cell carcinoma. An autosomal dominantly inherited syndrome known as the naevoid basal cell carcinoma syndrome was described in the 1960s. Affected patients develop innumerable basal cell carcinomas beginning in early childhood, in association with odontogenic cysts of the mandible, other bony abnormalities, and medulloblastoma. A characteristic facies, due to prominent frontal bossing, is usually seen. Basal cell carcinoma is also common in patients with xeroderma pigmentosa, in association with multiple squamous cell carcinomas, multiple malignant melanomas, and other cutaneous tumours.

The origin of basal cell carcinoma is controversial. For many years the basal cell of the epidermis was presumed to be the originating cell type, but more recently it has been proposed that a pluripotential epithelial cell, perhaps originating in the pilosebaceous epithelium, is the true progenitor cell type. In either event, the cells of basal cell carcinoma are small and usually not cytologically atypical. In haematoxylin and eosin stained sections these cells appear deep blue and are similar to the normal epidermal basal cells. In addition to proliferation of these basaloid tumour cells, stromal changes are invariably found within and peripheral to the tumour mass. In the nodular and superficial types of basal cell carcinoma, the stromal change consists of abundant deposition of mucopolysaccharides. Sclerosing basal cell carcinoma also exhibits dermal fibrosis as a stromal change. It is not known whether these stromal changes are induced by the tumour cell proliferation or whether they are the cause of the tumour. In any event, the growth and invasive spread of basal cell carcinoma requires the presence of altered connective tissue stroma. Dermal fibrosis is presumably the principal reason that metastases from basal cell carcinoma are rare. In general, invasive growth of tumour nests follows the path of least resistance: rather than invading bone or cartilage, the tumour tends to glide along the perichondrium or periosteum as it grows, sometimes to a distance many centimetres from the original cutaneous origin. Invasion along neurovascular bundles is uncommon and is characteristic of the sclerosing and other ‘aggressive’ types. The three principal types of basal cell carcinoma, and several special subtypes, will be discussed separately.

Nodular basal cell carcinoma is the most common type of basal cell carcinoma (Fig. 5) 1512. The tumour consists of a single expansile nodule of tumour cells and their dermal stroma. The lesions are grossly dome-shaped or spheroidal, and to the naked eye appear shiny, with a translucent or gelatinous optical quality. Numerous small blood vessels are usually seen within the tumour, as a result of tumour-induced angiogenesis. The colour of nodular basal cell carcinoma is typically that of the surrounding skin, although small, greyish-blue foci of pigmentation are often present deep within the substance of the tumour. In extreme cases, this pigmentation may be diffuse within the tumour, and such lesions are referred to as pigmented basal cell carcinoma (Fig. 6) 1513.

Nodular basal cell carcinomas begin as small papules 1 to 3 mm in size. As the papules enlarge, their radial growth tends to be greater than their vertical growth, resulting in flattened hemispherical plaques that may measure up to many centimetres in diameter. Tumours greater than 1 cm in diameter usually outgrow their blood supply, resulting in central ulceration.

Tumours measuring less than 1 cm in diameter are rarely deeply invasive. They are frequently treated with electrodesiccation and curettage, cryosurgery, or excision. Excision is the treatment of choice for lesions more than 1 cm in diameter, although those arising in ‘high-risk’ areas and recurrent tumours are best managed with Mohs' micrographic surgery. Radiation therapy is an acceptable alternative for treatment of these lesions, but is usually reserved for individuals for whom surgery is a high-risk procedure.

Basal cell carcinomas arising in certain areas show a high recurrence rate, because invasive tumour nests may track along cartilage or bone for great distances and because tumour may be sequestered in crevices beneath or between cartilage plates or between cartilage and bone. These sites include the nasal tip, the alar groove, the medial canthus (in which case orbital invasion may occur), the preauricular and postauricular sulci, and the external auditory canal.

Superficial basal cell carcinoma is the second most common type of basal cell carcinoma. It is unusual on the head and neck, appearing primarily on the trunk and proximal extremities. Clinically, superficial basal cell carcinoma resembles squamous cell carcinoma in situ, presenting as a thin, scaly pink plaque with undulating or irregular margins. Frequently, a narrow, thread-like translucent rim, similar in appearance to nodular basal cell carcinoma, is seen at the periphery of the expanding lesion. This tumour primarily spreads by radial extension of small pseudopodia of tumour cells and their stroma. Ulceration and deep dermal invasion usually occur only after the plaque has reached several centimetres in diameter. Excision is not the treatment of choice for superficial basal cell carcinoma: these lesions may be large, and the resultant surgical defect may be difficult to repair primarily. In addition, the microscopic extensions of tumour cells into the adjacent skin are clinically inapparent, so that wide margins may be necessary to ensure removal. Cryosurgery, electrodesiccation and curettage, and topical chemotherapy with 5-fluorouracil offer cure rates similar to those achieved following excision (90 per cent) with less morbidity. Recurrences are treated with Mohs' micrographic surgery or excision with conventional histological frozen section control.

Sclerosing basal cell carcinoma is the third most common type of basal cell carcinoma. Its distribution is the same as that of nodular basal cell carcinoma; most lesions are located on the head and neck. Histologically, sclerosing basal cell carcinoma comprises narrow cords of tumour cells encased in dense scar-like fibrosis. This resemblance to scar tissue is also apparent at the clinical level; the tumour usually lacks the gelatinous appearance of other types of basal cell carcinoma, and most typically mimics scar. Lesions are firm and indurated and may be bound down to the adjacent tissues. The surface of the tumour is usually smooth and slightly atrophic, and it may be lighter in colour than the surrounding skin, as is frequently seen in a scar. Tiny translucent papules typical of basal cell carcinoma may be seen at the edge of the scar-like plaque.

Sclerosing basal cell carcinoma behaves more aggressively than nodular or superficial basal cell carcinomas. Deep invasion along neurovascular bundles, tissue planes, and into adjacent soft tissues is usual. Surgical extirpation of this tumour is fraught with difficulty, and recurrence is likely unless microscopic margin control is undertaken. The Mohs' technique is clearly superior to conventional frozen sections, which do not allow examination of the entirety of the deep margin of an excision specimen.

Although sclerosing basal cell carcinoma is the most commonly encountered ‘aggressive’ form of this disease, a histologically distinct form of basal cell carcinoma with a similar propensity for deep, infiltrative spread has been identified in recent years. This basosquamous or metatypical carcinoma consists of cells typical of basal cell carcinoma, as well as cells that exhibit squamous metaplasia. Like sclerosing basal cell carcinoma, these tumours are locally aggressive and may be difficult to remove without microscopic margin control.

Dermatofibrosarcoma protuberans is a low-grade sarcoma of fibroblast origin, and may be thought of as the malignant equivalent of dermatofibroma. Ninety per cent of cases occur in adults, most often in the third and fourth decades of life. The lesions are firm, intradermal plaques that later become multinodular. Slow extension over many years into the surrounding dermis and subjacent connective tissue is typical. Metastasis to regional lymph nodes and to visceral organs occurs after many years.

Dermatofibrosarcoma protruberans is difficult to remove surgically. Recurrence occurs in up to 50 per cent of cases, although recent series have suggested that a excision margin of 3 cm may reduce the recurrence rate to 20 per cent. Although Mohs' surgery has also been advocated for its treatment, considerable experience is necessary to identify the infiltrating strands of sarcoma cells on frozen sections. The treatment of choice is wide surgical excision with at least 3 cm margins.

Malignant fibrous histiocytoma is an uncommon sarcoma, usually arising on the extremities. Although the tumour may arise within subcutaneous tissue or fascia, cutaneous primary malignant fibrous histiocytoma is occasionally encountered, the presentation of which is similar to that of dermatofibrosarcoma protuberans (see above). The principal prognostic factor for malignant fibrous histiocytoma arising in the skin is whether or not the underlying fascia has been penetrated by the tumour. The incidence of metastases is approximately 10 per cent in cases without fascial involvement, and 30 per cent or more if fascia is invaded. The surgeon should be prepared to excise not only the cutaneous tumour but also the underlying fat, fascia, and a block of subjacent muscle.

Atypical fibroxanthoma is a fairly common tumour of the head and neck of elderly individuals. Histologically, it may be confused with malignant fibrous histiocytoma. Unlike malignant fibrous histiocytoma, atypical fibroxanthoma has little or no tendency to metastasize. Excision is curative.

Juvenile xanthogranuloma is a common cutaneous lesion encountered primarily in young children. Most lesions are solitary; however, patients with multiple juvenile xanthogranulomas have been described. Clinically, the tumour is a yellowish or yellowish-brown papule or nodule that arises rapidly. Histologically, it consists of a proliferation of histiocytoid cells with foamy cytoplasm. Lipid-laden multinucleated giant cells are also seen in fully-developed xanthogranuloma. This benign lesion tends to regress spontaneously. Generally no treatment is needed, although excision is usually curative.

Cutaneous metastases occur in 2.7 to 9 per cent of patients with internal malignancy. Table 1 442 lists the clinical characteristics of cutaneous metastatic carcinoma. The incidence of cutaneous metastases tends to parallel the incidence of primary tumours. Carcinoma of the breast accounts for the vast majority of cutaneous metastases in women, and primary lung carcinoma is the most common source of cutaneous metastases in men. Neoplasms such as hypernephroma that metastasize by haematogenous spread may exhibit cutaneous metastases at presentation.

Cutaneous metastases most commonly present solitary or multiple intradermal nodules, which are typically hard and indurated. On the scalp, which is a common site, an expansile mass of tumour cells may destroy hair follicles, resulting in alopecia. Pigmented metastases are most frequently seen in malignant melanoma. The so-called Sister Joseph's nodule is a solitary, firm umbilical nodule seen as a feature of metastatic carcinoma of gastrointestinal or pancreatic origin.

Several haematological malignancies, including Hodgkin's disease, non-Hodgkin's lymphoma, and myelogenous leukaemias may involve the skin. T-cell lymphomas and adult T-cell leukaemia are particularly prone to cutaneous infiltration, due to the epidermotropic nature of many malignant T-cell neoplasms. Epidermal changes as a result of haematological malignancies are unusual; most commonly, these diseases produce plum-coloured or hyperpigmented dermal plaques or nodules, which may be solitary or multiple. Secondary changes such as purpura due to thrombocytopenia or ulceration are common.

Acute myelogenous leukaemia and T-cell leukaemias and lymphomas may present with cutaneous lesions. In most other haematological malignancies, however, cutaneous lesions develop after diagnosis of the underlying disease. The differential diagnosis of infiltration plaques or nodules in patients with leukaemia or lymphoma often include opportunistic infections due to bacteria, mycobacteria, or fungi. Diagnostic biopsy of the lesions for histopathological examination and bacteriological cultures are appropriate.

Arbesman H, Ransohoff DF. Is Bowen's disease a predictor for the development of internal malignancy? JAMA 1987; 257: 516.

Borel DM. Cutaneous basosquamous carcinoma. Review of the literature and report of 35 cases. Arch Pathol 1973; 95: 293.

Brownstein MH, Helwig EB. Metastatic tumours of skin. Cancer 1972; 29: 1298–307.

Goette DK. Topical chemotherapy with 5-fluorouracil. A review. J Am Acad Dermatol 1981; 4: 633.

Gorlin RJ. Nevoid basal cell carcinoma syndrome. Medicine 1987; 66: 98.

Kumakiri M, Hashimoto K. Ultrastructural resemblance of basal cell epithelioma to primary epithelial germ. J Cut Pathol 1978; 5: 53.

Lupton GP. Cutaneous metastases. J Assoc Milit Dermatol 1990; 16: 18–25.

Montgomery H. Precancerous dermatosis and epithelioma in situ. Arch Dermatol Syphilol 1939; 39: 387.

Roses FD, Valeusi Q, LaTrenta G, Harris MN. Surgical treatment of dermatofibrosarcoma protuberans. Surg Gynecol Obstet 1986; 162: 449.

Spencer PS, Helm TN. Skin metastases in cancer patients. Cutis 1987; 39: 119–21.

Weiss JS, et al. Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study. JAMA 1988; 259: 527.