CHAPTER 20 Recognition and Treatment of Skin Lesions
Epidermal Neoplasms
Seborrheic Keratoses
Seborrheic keratoses are common lesions, usually appearing around the fourth decade of life.1 They can be single or multiple and can occur anywhere on the body, with the exception of the palms and soles. Clinically, they are sharply demarcated and slightly raised, appearing as if they were stuck on the skin’s surface (Fig. 20-1). Many have a verrucous surface with a soft, friable consistency; however, others may have a smooth surface. Characteristically, all seborrheic keratoses show keratotic plugs on careful surface inspection. Their color is usually brownish to brown-black, although color can vary from flesh color to deep black. The color within the individual lesion is usually uniform. Lesions can measure from a few millimeters to several centimeters. When subjected to trauma, they can become irritated, thereby causing an inflammatory base and occasional bleeding. Occasionally, seborrheic keratoses are pedunculate, especially on the neck.
The etiology of seborrheic keratoses is unknown, although they may be dominantly inherited. They are benign with no malignant potential, although the appearance of hundreds in rapid “showers” may be a sign of internal malignancy; this is the much-debated Leser-Trélat sign.2 The most common tumor seen with this association is colonic adenocarcinoma. In the head and neck, the most common mistaken diagnosis is melanoma; therefore the pathologist sometimes receives a widely excised seborrheic keratosis that has been mistaken for melanoma. If the diagnosis is in doubt, a biopsy before definitive treatment should be performed.
Dermatosis Papulosa Nigra
Dermatosis papulosa nigra is a condition found in approximately 35% of black adults; its onset often occurs during adolescence. The lesions are located predominantly on the face, especially in the malar region, but they may also occur infrequently on the neck and upper trunk. They consist of small (1 to 3 mm), smooth, pigmented, stuck-on appearing, hyperkeratotic papules. Although they have the histologic appearance of a fibroma, many clinicians consider these papules to be a variant of seborrheic keratoses. The treatment of dermatosis papulosa nigra is difficult because of pigmentary problems that occur with the treatment of black skin. Options that have been tried include fine-needle electrosurgery followed by use of a small curette, shave excision, light freezing with liquid nitrogen, and dermabrasion. If the lesions are few, we prefer the first two methods. Cryosurgery can produce spotted hypopigmentation in blacks and should be avoided unless other treatment modalities are not available. Dermabrasion can be of two types: using either a 2-mm wheel or a small cone or pear diamond fraise, the lesions can be removed singly, very quickly, and easily. Dermabrasion can also result in mottled pigmentation after healing, which usually will fade with time. If the lesions are multiple and confluent, total regional dermabrasion may be the treatment of choice for the best cosmetic blend. Judicious use of ablative and pigment-specific lasers can be used to treat these lesions focally; however, meticulous technique is required to avoid pigmentary changes common to this patient population.3
Warts (Verruca Vulgaris)
Warts are common lesions caused by the human papillomavirus (HPV), which is a deoxyribonucleic acid (DNA) virus. Warts are traditionally classified by clinical appearance and location: verruca vulgaris (or common wart), deep hyperkeratotic palmar-plantar; superficial mosaic-type palmar-plantar; verruca plana; epidermodysplasia verruciform; and condyloma acuminatum. Classification may also be based on the genotype of papilloma virus. Hundreds of DNA genotypes have been identified, each with a distinct type-specific antigen, some of which correlate with various benign and malignant conditions.4 The most common facial warts include common warts (including filiform) and flat warts which are most commonly associated with the antigenic serotypes HPV-2 and HPV-3. Clinically, these lesions are hyperkeratotic. The filiform wart is often a pedunculate lesion occurring in isolation on the cheek, nasal tip or columella, or eyelid (Fig. 20-2). Common warts can occur anywhere on the face. Flat warts usually occur in younger patients or on the legs of women who regularly use a razor for shaving; they are small (1 to 2 mm), flat-topped, hyperkeratotic lesions, which can coalesce (Fig. 20-3).
Because the virus survives within cells at the base of the hyperplastic epithelium and within the adjacent normal-appearing skin, eradication of warts can be difficult and recurrences are common. Most common treatments involve destruction of the infected tissue. The filiform wart can be anesthetized at its base and excised with scissors, with the base being lightly curetted and fulgurated under low current; this approach affords the best chance for cure. Filiform warts often are too verrucous and hyperkeratotic to be effectively treated with cryosurgery. Common warts that are thinner can be treated effectively with liquid nitrogen cryotherapy, although several treatments are usually needed. Flat warts present a difficult problem. At times, they can be effectively treated with liquid nitrogen. Perhaps the best method is to individually scrape each small wart off of the skin with a small curette, treating, when possible, all of the flat warts in an area at one time. In young children who do not tolerate surgical therapy well, one may use topical tretinoin at a concentration sufficient to produce erythema and irritation in an attempt to stimulate the body’s own immunity against the wart virus. In healthy children, avoiding treatment is often best, because the vast majority of warts spontaneously involute once the patient’s immune system recognizes the virus.5
Related to the poxvirus family is a group of viruses known as the molluscum contagiosum virus family (EM-2). An infection with one of these viruses appears clinically as a variable number of small, discrete, waxy, skin-colored, dome-shaped papillomas, 2 to 4 mm in diameter, with umbilicated centers (Fig. 20-4). Like all viral lesions, they ultimately will involute spontaneously. Histologically, they have a classic appearance of cytoplasmic inclusion bodies, which are the so-called molluscum bodies. The best treatment is usually superficial cryotherapy or curettage, as is the case with common warts. Topical therapies, including imiquimod cream, liquid podophyllin, cantharidin, and more recently, injectable candidal antigens, have been successfully used for the treatment of warts and mollusca.
Actinic Keratoses
Actinic keratoses, also called solar keratoses, are precancerous lesions.6 Studies indicate that squamous cell carcinoma will develop in one or more lesions in 5% to 20% of persons with solar keratoses.7–10 They are seen on sun-exposed areas of the skin, usually in persons after the fourth decade of life. They are seen most commonly in fair-skinned individuals who get sunburned frequently. Clinically, these lesions are usually erythematous with adherent scale and show little or no infiltration (i.e., they are very superficial) (Fig. 20-5A). Often, the patient can feel the rough, adherent scale before the lesion is clinically visible. Solar keratoses can also be flesh colored or pigmented. They often do not have a sharp demarcation from surrounding skin and can spread peripherally. Occasionally these lesions develop marked hyperkeratosis, giving a clinical appearance of a cutaneous horn. On the vermillion lip, actinic keratoses are known as solar or actinic cheilitis.
Actinic keratoses lesions are best removed and not watched. The most commonly used method for removing discrete lesions is cryosurgery. Shave excision can also be performed, but it would lead to extensive scarring in areas with numerous lesions. In persons with severe sun damage to the face or with diffuse actinic keratoses, regional treatment with topical 5-fluorouracil, imiquimod, or retinoid creams are effective therapies for an entire region of the body such as the arms, hands, scalp, or face.11,12 Because proper use results in severe irritation, sound patient understanding and education, and physician reassurance are necessary to ensure adequate compliance. Photodynamic therapy, laser resurfacing, dermabrasion, and chemical peels are also effective field therapies.13–16
Basal Cell Carcinoma
Basal cell carcinoma is the most common malignancy in humans,17,18 accounting for 75% to 80% of new cancers in the United States each year. Depending on the study cited, approximately 86% of lesions occur initially in the head and neck, with 25% of all primary lesions occurring on the nose. Approximately 96% of recurrences are in the head and neck, with 38% being on the nose. Emmett reported that 75.5% of previously untreated basal cell carcinoma found in Australia occurred in the head and neck, 8.4% on the chest and back, and 16% on the arms and legs.19 When looking at recurrent tumors, 91% occurred on the head and neck, 7.5% on the chest and back, and 1.5% on the arms and legs. Similarly, the primary tumor of metastatic basal cell carcinomas is usually found on the head and neck. However, metastasis of basal cell carcinoma is rare, with reports estimating rates of 0.0028% to 0.1%.20–22 In this discussion, we outline the epidemiology and clinical and histologic variations of basal cell carcinoma. Management of head and neck basal cell and squamous cell carcinomas are addressed in Chapter 82.
Basal cell carcinoma, which is more common in men than in women, is seen most frequently in individuals between 40 and 60 years of age. With the aging of the sunbathing generation, however, basal cell carcinomas are occurring with increasing frequency in younger people. Scandinavians and people of Celtic extraction (particularly Irish), who frequently have Fitzpatrick skin type I or type II (sunburn easily), appear to be more prone to basal cell carcinoma than those with more darkly pigmented skin. Although uncommon in blacks, predilection for occurrence on the head and neck is the same as in whites.23 Exposure to sunlight—primarily to the rays in the ultraviolet B spectrum—is the primary risk factor for basal cell carcinoma; this has been shown experimentally and reproduced clinically. The tumor is more common as one approaches the equator and at high altitudes. Basal cell carcinomas occur most commonly on the head and neck areas, with the nasal tip and the nasal ala being the most common; the cheeks and the forehead are the next most common. The left side of the body is more common than on the right, perhaps because of selective sun exposure in individuals whose occupation preferentially exposes the left side (i.e., driving).
Although sun exposure is the primary etiologic agent of basal cell carcinoma, other risk factors include genetics, occupation,24 immunosuppression, ionizing radiation, and the presence of scars. Farmers, sailors, and fishermen, because of their heavy occupationally actinic exposure, have a higher than average incidence of skin cancer. The most common genetic syndromes include nevoid basal cell carcinoma syndrome and xeroderma pigmentosum.25 The former is an autosomal dominant condition in which basal cell carcinomas arise on any area of the body, with the predilection being toward sun-exposed sites, beginning at an early age and continuing throughout life. These patients also have skeletal abnormalities, including bifid ribs, jaw cysts, frontal bossing, and calcified falx cerebri. Xeroderma pigmentosum is an autosomal recessive disease caused by a defect in DNA repair that leads to the development of basal cell carcinoma and other cutaneous malignancies in response to sun exposure and other carcinogens in childhood and early adulthood.
To the trained and observant eye, the clinical recognition of basal cell carcinoma is not difficult. Typically, lesions are nodular with a smooth, raised, translucent or “pearly” border with prominent telangiectasia (see Fig. 20-5D).26 In addition, they may ulcerate and form a crust (see Fig. 20-5C). A typical history involves a pimple-like lesion that bleeds and does not heal. Pruritus is a common early symptom. Basal cell carcinoma may be pigmented (see Fig. 20-5E) yet maintain the clinical features of pearly, translucent borders and telangiectasia. Superficial multicentric basal cell carcinomas are flat and pink with differing, intercommunicating extensions of tumor that may be either scaly or with raised borders.
Other forms of basal cell carcinoma are clinically more subtle, histologically more aggressive, and more difficult to treat. Approximately 20% of primary basal cell carcinomas demonstrate infiltrative growth patterns with significant subclinical disease and high rates of recurrence.27–29 Importantly, many primary tumors demonstrate histologic heterogeneity with subclinical extension.30 Morpheaform basal cell carcinomas (see Fig. 20-5F) present as yellowish plaques, which develop telangiectasia, may ulcerate, and may have a sclerotic or scarlike appearance. The margins are often indistinct. Histologically, this tumor extends subclinical, finger-like projections intradermally, which make complete excision difficult. This tumor has a scarlike, stromal matrix that gives it a fibrous, sclerotic appearance and nature.
Recurrent basal cell carcinomas (Fig. 20-6A) present with varying clinical appearance, depending on the type of initial treatment. It may appear at the edge of a skin graft, within a scar created by electrosurgery, under a scar created by cryosurgery, or as a nodule developing within a suture line. Recurrent basal cell carcinomas are often nodular and accompanied by a morpheaform or sclerotic histologic picture in the deeper portions of the tumor. This picture may represent an aggressive histologic de-differentiation of the tumor, a factor that may partially account for its clinically aggressive behavior and resistance to treatment. The majority of recurrent basal cell carcinomas demonstrate infiltrative patterns in the original tumor; aggressive behavior may be predicted by careful evaluation of histologic features.31
Chondrodermatitis nodularis helicis (see Fig. 20-6B) is an inflammatory disease of underlying helical cartilage that can mimic and be mistaken for basal cell carcinoma. The condition usually results from chronic trauma on the most protuberant portion of the ear. Surgery is the treatment of choice.
Squamous Cell Carcinoma
Squamous cell carcinoma is the second most common skin cancer and accounts for 10% to 20% of all cutaneous malignancies. Because of their tendency to recur and metastasize, squamous cell carcinomas carry the highest mortality of nonmelanoma skin cancers and account for the majority of deaths due to skin cancer in adults older than 85 years.32 The development of squamous cell carcinoma is multifactorial and involves both environmental and genetic factors. Risk factors for the development of squamous cell carcinoma include fair skin; chronic cumulative sun exposure; history of previous skin cancer; age older than 50 years; smoking; chronic inflammatory, infectious, or scarring skin lesions; chemical carcinogens; PUVA; HPV infection; and various genodermatoses. Similar to basal cell carcinomas, the most important factor is ultraviolet radiation. Fair-skinned individuals with longstanding chronic sun exposure, especially those close to the equator and at high altitudes, are at greatest risk. Men are affected two to three times more than women, and multiple cutaneous carcinomas are common.
Whereas the majority of squamous cell carcinomas may be cured if diagnosed and treated early, some behave aggressively with high rates of metastasis. Risk factors associated with high rates of recurrence and metastasis include chronically sun exposed skin, scarred areas in non–sun-exposed skin, tumors greater than 2.0 cm in diameter, recurrent tumors, chronic immunosuppression, poor histologic differentiation, depth of invasion, and perineural involvement.33,34 The true risk of recurrence or metastasis for each variable is unknown; however, associations are clearly established. Clinically, squamous cell carcinomas can be separated into actinically induced and those that arise de novo on non–sun-exposed skin. The former are the more common and are associated with a low incidence of metastasis (<1% in most series). Some studies suggest that de novo lesions have a higher metastatic potential; approximately 2% to 6%. The mucosal variant of the squamous cell carcinoma, seen clinically as carcinoma of the lip, has a metastatic potential of up to 13.7%; therefore these distinctions are important in prognosis.35 The worst prognostic indicator is perineural invasion, which has been shown to metastasize in 47.3% of cases.
Squamous cell carcinoma may present clinically in several ways.36 Thick, scaling, hyperkeratotic plaques may present on the exposed surface of the body, in particular the ear, lip, or nose (see Fig. 20-6C). Lesions may change slowly over a period of time. If the crust is removed, the base is often ulcerated and has a rolled margin. Lesions may also present as a persistent ulcer, particularly in an old scar, or as a superficial multifocal change in generally sun-damaged skin. The latter is often the most difficult lesion to diagnose, requiring several biopsies at different points. Occasionally, a squamous cell carcinoma will become a vegetative nodular lesion; this lesion often has a cystic feel and can ulcerate and progressively enlarge. Often these exophytic lesions have not invaded deeply. They all have a tendency to ulcerate and become more erosive in appearance than a basal cell carcinoma. As with basal cell carcinoma, they can become pigmented (see Fig. 20-6D) and often appear similar clinically to keratoacanthomas, especially when the latter are in the growth phase. However, these lesions usually grow more slowly than keratoacanthomas, thereby allowing for distinction on clinical as well as histologic grounds. When this occurs, biopsy is always indicated. The treatment of cutaneous squamous cell carcinoma is discussed in depth in another chapter.
Keratoacanthoma is a rapidly growing tumor that presents as an exophytic dome-shaped nodule with central keratin on sun-damaged skin (see Fig. 20-5B). The categorization of keratoacanthoma has been controversial, but it is now thought to be a variant of squamous cell carcinoma. There are some unique features that distinguish it clinically from the common type of squamous cell carcinoma. Keratoacanthomas are characterized by a rapid proliferative phase followed by plateau, then involution. Not all keratoacanthomas, however, involute, and predicting which ones will is difficult. The involution phase can sometimes take up to 1 year. Two rare clinical forms of keratoacanthomas deserve mention. The giant keratoacanthoma can reach 5 cm or more and can cause the destruction of underlying tissues. Eruptive keratoacanthomas often present as many hundreds of characteristic papules that measure 2 to 3 mm in diameter. Metastatic keratoacanthomas have been reported, however, and may represent typical squamous cell carcinoma. Keratoacanthomas can be difficult to treat. Surgical excision is the treatment of choice for most keratoacanthomas, with Mohs micrographic surgery reserved for facial lesions. Because of the involution potential of keratoacanthomas, cytotoxic agents can be used to induce involution. We favor methotrexate at a dose of 12.5 to 25 mg/mL, with approximately 0.5 to 1 mL injected into the lesion at 3- to 4-week intervals. Although complete involution may not occur, it may allow for easier surgical management by reducing the size of the tumor.
Melanocytic Neoplasms
The melanocyte is the pigment-producing cell of the epidermis. However, many tumors of this cell line, which is embryologically from the neural crest, occur in the dermis either by migration or because crest cells fail to reach the epidermis during embryogenesis. The most common of these tumors are nevocellular nevi and melanoma. A wide spectrum of melanocytic nevi and pigmented skin lesions exist, many of which appear similar and can be confused with melanoma.37 This section discusses the clinical manifestations of nevocellular nevi and other melanocytic neoplasms. The presentation, behavior, and treatment of melanoma are discussed elsewhere.
Junctional Nevus
Junctional nevi are tan to brownish macules (flat lesions) of uniform color and smooth border (Fig. 20-7B). Dots of black pigment may be present, but, unlike with melanoma, the normal skin markings are preserved. Lesions vary from a few millimeters to a centimeter or more in diameter. The melanocytes or nevus cells are located at the junction of the epidermis and the dermis (dermoepidermal junction). The lesion can occur anywhere on the body and is the nevus most commonly mistaken for melanoma. When in doubt, one should perform a biopsy of the lesion. Junctional nevi occur anytime after birth and are the common moles found in children before puberty. Their importance lies in their ability to develop into malignant melanoma, although this rarely occurs before puberty. Most junctional nevi remain benign throughout life and can evolve over time into either compound or intradermal nevi. Treatment of these nevi is often dictated by suspicion of melanoma or cosmetic reasons, and usually includes a shave in noncosmetic areas or a fusiform excision with closure in cosmetically important areas. Melanocytes are cold sensitive, and strictly junctional nevi can be removed with deep cryotherapy.
Intradermal Nevus
Intradermal nevi are common mature moles of adults, occurring anywhere on the body but rarely on the palms and soles. It is most common on the scalp or face in adults, varying in size from a few millimeters to several centimeters. It may be flat and smooth or raised and warty, pigmented or nonpigmented, sessile or pedunculate (see Fig. 20-7C). It often contains coarse hairs, reflecting the depth within the dermis of the nevus cells. It is benign and rarely becomes malignant. By definition, all of the nevus cells occur within the dermis. This mole is best treated by shave excision when it is pedunculate and hairless. When it is on the head or neck and contains hair, it is necessary to excise this mole using either the punch excision technique or routine excision to remove the complete depth of the hair follicles within the nevus.
Blue Nevus
Blue nevi present as dark blue or black hairless flat or raised lesions that are usually less than 0.5 cm in diameter, indurated, and palpable. The overlying epidermis is remarkably smooth and the outline regular (see Fig. 20-7D). Blue nevi most commonly occur on the head and neck, the dorsa of the hands and feet, and the buttocks. They are more common in women than men and usually undergo very little change after their initial presentation. The treatment of these lesions is excision or observation. The excision must be deep, because the pigment often extends deep into the subcutaneous fat, thereby resulting in the deep blue color of the lesion. Malignant transformation of blue nevi is rare; however, tumors demonstrate highly aggressive behavior, thus these lesions must be carefully evaluated histologically.38,39
Halo Nevus
The halo nevus is a phenomenon usually associated with a junctional nevus in children or adolescents. Most commonly found on the back, it is often a benign-looking brown papular lesion in the center of a well-circumscribed pale white circle of depigmented skin (see Fig. 20-7E). This appearance reflects the body’s rejection of the nevus cells, because an inflammatory response ensues in which the melanocytes of the nevus and those of the immediately surrounding epidermis are destroyed.40 Often, when left alone, these nevi disappear.
Spitz Nevus
Spitz nevus is also known as a juvenile melanoma or a compound melanocytoma. These rapidly growing pigmented lesions occur principally in children, although they can occur in adults. They are usually less than 1 cm in size and are pink or red, or occasionally brown or black. A Spitz nevus may be soft or hard, but is usually dome-shaped and can be either sessile or pedunculated. It can occur anywhere on the body and is often difficult to diagnose clinically. Its main importance is its histologic resemblance to melanoma, with even experienced pathologists having difficulty distinguishing between the two.41 Very few of these nevi, however, progress to malignancy. Treatment of a Spitz nevus is the same as that for an intradermal or compound nevus.
