Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Premalignant and Malignant Nonmelanoma Skin Tumors


Basal Cell Carcinoma

Description

  • ■

    Basal cell carcinoma is a skin cancer derived from the basal layer of keratinocytes of the epidermis.

  • ■

    It is the most common cutaneous malignancy and most common cancer in humans.

  • ■

    If left untreated, basal cell carcinomas will locally invade surrounding skin, destroying underlying tissue.

  • ■

    Rarely, basal cell carcinomas can metastasize.

History

  • ■

    Basal cell carcinoma may occur at any age but is more common in later life.

  • ■

    The highest incidence occurs in people with white or fair skin (types I and II).

  • ■

    It is less common in Hispanic and Asian skin, and is rare in African Americans.

  • ■

    Cumulative ultraviolet light exposure is the major risk factor in developing basal cell carcinoma.

  • ■

    Tumors occur most commonly on the sun-exposed skin of the face, scalp, ears, and neck, and less often on the trunk and extremities.

  • ■

    There are several clinical variants of basal cell carcinoma: nodular, pigmented, superficial, micronodular, morpheaform, sclerosing, and advanced basal cell carcinomas.

  • ■

    Each type varies in clinical appearance, histology, and aggressiveness.

  • ■

    Nodular basal cell carcinoma is the most common type.

  • ■

    Sclerosing basal cell carcinoma has a higher incidence of recurrence.

Skin Findings

  • ■

    In general, basal cell carcinomas are pink, violaceous, or pearly-white, sometimes translucent-appearing papules or nodules.

  • ■

    They may have a smooth surface with overlying telangiectasias.

  • ■

    The papule or nodule enlarges slowly, flattens centrally, or may develop a raised, rolled border.

  • ■

    Tumors frequently bleed, become erosive and crusted, and ulcerate in the center.

  • ■

    Basal cell carcinomas may contain melanin that appears speckled brown, black, or blue in color.

  • ■

    Curettage demonstrates the characteristically soft texture of the tumor compared with the surrounding normal skin.

Fig. 17.1, Basal cell carcinoma distribution diagram.

Nodular Basal Cell Carcinoma

  • ■

    The lesion begins as a pearly-white or -pink, dome-shaped papule or nodule with telangiectasia.

  • ■

    The center may ulcerate and bleed and subsequently accumulates hemorrhagic crust and scale.

  • ■

    The growth pattern may become irregular, forming an oval or multilobular mass.

  • ■

    These features are characteristic and easily recognized by skin experts.

Fig. 17.2, The classical presentation of nodular basal cell carcinoma. A dome-shaped pearly tumor with telangiectasias meanders randomly over the surface.

Fig. 17.3, Basal cell carcinoma. This growing pink pearly tumor on the eyelid margin slowly enlarged. A biopsy confirmed the diagnosis, and it was removed by Mohs' micrographic surgery.

Fig. 17.4, Basal cell carcinomas have a characteristic smooth pearly appearance, with superficial telangiectasias.

Fig. 17.5, Basal cell carcinoma appearing as a pearly nodule with telangiectasias, with central necrosis and erosion.

Fig. 17.6, Nodular basal cell carcinomas are common in any location on the head and neck. This nodular basal cell carcinoma is on the sun-exposed helix of the ear.

Fig. 17.7, Flat, pink, scar-like patch with a shiny border on the helix of the ear, characteristic of a sclerotic basal cell carcinoma.

Fig. 17.8, Typical basal cell carcinoma with a pink, smooth, almost translucent surface and diffuse telangiectasias.

Fig. 17.9, Nodular basal cell carcinoma with pink pearly appearance. A small focus of melanin pigment can be seen with dermoscopy.

Fig. 17.10, Basal cell carcinoma. The sun exposed nose is the most common location for a basal cell carcinoma.

Fig. 17.11, Basal cell carcinomas may present as nonhealing ulcers and may appear on any body surface, including the vulva.

Pigmented Basal Cell Carcinoma

  • ■

    This is the clinical equivalent to nodular basal cell carcinoma, with the addition of speckled melanin pigment within.

  • ■

    The pigment may be sparse or diffuse and resemble malignant melanoma.

  • ■

    The natural history and aggressiveness of the tumor is similar to a nonpigmented basal cell carcinoma.

Fig. 17.12, Basal cell carcinoma. A smooth pearly nodule with telangiectasias and diffuse gray pigmentation is characteristic of a pigmented basal cell carcinoma. Lesions suspected of being a pigmented basal cell carcinoma should be biopsied to ensure they are not melanoma.

Fig. 17.13, Basal cell carcinoma. Pigmented basal cell carcinoma displaying a pearly nodule with focal area of pigmentation.

Fig. 17.14, Pigmented basal cell carcinoma is a nodular basal cell carcinoma that contains melanin. This lesion has the typical pearly appearance with surface telangiectasia along the periphery and ulceration centrally. Melanoma must be in the differential diagnosis.

Superficial Basal Cell Carcinoma

  • ■

    This is the thinnest and the least aggressive form of basal cell carcinoma.

  • ■

    These lesions are typically multiple and appear earlier in life, compared with nodular basal cell carcinoma.

  • ■

    This is found more commonly on the trunk and extremities compared with nodular basal cell carcinoma.

  • ■

    The lesions are flatter, sometimes atrophic, and not as deeply invasive as the lesions of nodular basal cell carcinoma.

  • ■

    The borders are less distinct but have the same pearly-pink quality. Stretching the skin may accentuate the raised border.

  • ■

    The tumor spreads peripherally, sometimes for several centimeters, and invades only after considerable time.

  • ■

    The circumscribed, round to oval, red, scaling plaques may be confused with eczema, psoriasis, extramammary Paget's disease, or Bowen's disease (squamous cell carcinoma in situ).

Fig. 17.15, A, B, Superficial basal cell carcinoma. The circumscribed, round to oval, red scaling plaque resembles a plaque of eczema, psoriasis, extramammary Paget's disease, or Bowen's disease. The superficial basal cell carcinoma spreads peripherally, sometimes for several centimeters, and invades after considerable time.

Fig. 17.16, Superficial basal cell carcinoma may be mistaken for eczema, psoriasis, or ringworm. It bleeds and heals in cycles just like a nodular basal cell. The lesion may increase in size to cover very wide areas before the diagnosis is made. Lesions tend to remain superficial but may eventually penetrate deep into the dermis or subcutaneous tissue.

Micronodular Basal Cell Carcinoma

  • ■

    Micronodular basal cell carcinoma resembles nodular basal cell carcinoma clinically, but microscopically there are islands of tumor cells extending beyond the clinical margins.

  • ■

    Because this histologic variant extends beyond the suspected clinical borders, it recurs more frequently after traditional treatment.

Fig. 17.17, The back is a common place to find superficial basal cell carcinoma. The patient was not aware of the lesion. The sharp border is characteristic. Eczema has a less distinct border. This lesion lacks the silvery scale of psoriasis. The surface of these tumors is often crusted. This lesion was treated with imiquimod cream.

Morpheaform and Sclerosing Basal Cell Carcinomas

  • ■

    Morpheaform and sclerosing basal cell carcinomas are the most subtle and least common variants of basal cell carcinoma.

  • ■

    These types of basal cell carcinomas are also the most difficult to eradicate.

  • ■

    Lesions resemble scar tissue clinically and may appear pale-white to yellow and are waxy on palpation.

  • ■

    Because of the innocuous appearance of these variants, biopsy and diagnosis are often delayed.

  • ■

    The margins are indistinct, and tumor cells may extend more than 7 mm from the clinically apparent border.

  • ■

    Thus, unlike the nodular variant, tumors are more likely to recur after narrow excision.

  • ■

    Both the morpheaform and sclerosing forms are more aggressive, tend to recur more often, and should be followed more closely.

Fig. 17.18, A sclerotic basal cell carcinoma with a flat and atrophic scar-like central patch. Because these types of basal cell carcinomas blend into normal skin and are not elevated, there is frequently a delay in diagnosis.

Fig. 17.19, Morpheaform basal cell carcinoma is a waxy, firm, flat or slightly raised, and either pale pink or flesh colored patch that is difficult to discern, even with palpation.

Advanced Basal Cell Carcinoma

  • ■

    Advanced or locally advanced basal cell carcinoma are those tumor that are large, have been neglected, and have invaded deeper tissues, such as the ocular mucosa.

  • ■

    This designation may also be used for tumors located in areas where surgical excision would lead to deformity or functional impairment.

  • ■

    Treatment options for advanced basal cell cancers include oral therapy with the oral hedgehog inhibitors, vismodigib (Erivedge) and sonidegib (Odomzo), as well as radiation.

  • ■

    Side effects from this class of medications include muscle spasms and dysguesia or aguesia, which may lead to discontinuation.

Fig. 17.20, Large, complex, and advanced basal cell carcinomas occur as a result of neglect and delayed diagnosis. Often, patients simply do not seek dermatologic care. This particularly large fungating basal cell carcinoma of the chest wall had invaded underlying muscle, but not the lymph nodes, and was eventually excised.

Fig. 17.21, Rarely, basal cell carcinomas can be metastatic. This basal cell carcinoma invaded the vertebral bones, was resistant to radiation and vismodegib, and continued to grow and advance.

Fig. 17.22, Some patients with advanced basal cell carcinoma have numerous basal cell tumors that coalesce, frequently recur, and are difficult to get clear surgical margins. This patient was prescribed vismodegib after several recurrent basal cell carcinoma tumors on the face and scalp.

Basal Cell Nevus Syndrome (Gorlin's Syndrome)

  • ■

    Basal cell nevus syndrome is an autosomal dominant condition of multiple basal cell skin cancer and multiple associated anomalies of the skin, skeleton, and central nervous system.

  • ■

    Skin anomalies include multiple basal cell carcinomas appearing early in life and palmar pitting.

  • ■

    Facial anomalies include a broad nose, heavy brow, and hyperteloric (wide-set) eyes.

  • ■

    Skeletal anomalies include odontogenic cysts, frontal bossing, hypertelorism, bifid ribs, kyphoscoliosis, and shortened fourth metacarpals, as well as scoliosis and kyphosis.

  • ■

    Central nervous system anomalies include calcification of the falx cerebri and the development of medulloblastoma.

  • ■

    Blindness, deafness, and seizures can be a part of the syndrome.

  • ■

    These patients are a treatment challenge given the increased number of basal cell tumors, young age, functional alteration after surgical excision, and potential for metastatic disease.

Laboratory and Testing

  • ■

    Histology shows nests of basaloid keratinocyte tumor cells closely distributed in a distinctive stroma in nodular and pigmented basal cell carcinomas.

  • ■

    Superficial basal cell carcinomas appear as multifocal extensions of the basal layer of the epidermis into the superficial dermis.

  • ■

    In nodular basal cell carcinomas, there are larger islands of tumor cells within the dermis; tumor islands may be solid or may contain cystic cavities.

  • ■

    Pigmented basal cell carcinoma is similar to nodular basal cell carcinoma but differs in that tumor islands contain foci or clumps of melanin pigment.

  • ■

    In morpheaform or sclerosing basal cell carcinomas, collagen-like cords and fine strands of tumor cells are embedded within a fibrous stroma.

Course and Prognosis

  • ■

    Without treatment, basal cell carcinomas persist, enlarge, ulcerate, and invade and destroy the surrounding structures.

  • ■

    Inadequately treated basal cell carcinomas recur, often underneath areas of scarring, which may lead to delay in detection.

  • ■

    In patients who develop one basal cell carcinoma, the annual risk for developing another basal cell carcinoma increases to 5%.

Discussion

  • ■

    Basal cell carcinomas are rarely life-threatening, but metastases do occur. This is seen more commonly in immunocompromised patients.

  • ■

    Depending on tumor location, local destruction of normal tissue by the tumor can result in significant impairment. Inadequately treated tumors may extend undetected to destroy large areas of the face, neck, and scalp.

Treatment

  • ■

    The goal of treatment is eradication of the tumor and return of normal anatomic form and function.

  • ■

    Treatment of basal cell carcinoma is determined by the size and location of the tumor, by the histologic variant, and the patient's concerns.

  • ■

    Cosmesis of the wound or defect is an important but secondary concern.

  • ■

    Clinical aggressiveness correlates with histologic pattern.

  • ■

    The various treatment options include cryotherapy, curettage, electrosurgery, traditional excision, Mohs' micrographic surgery, radiation, topical chemotherapy and immunotherapy, and photodynamic therapy.

  • ■

    Inhibition of the transcription of the basal cell carcinoma gene, hedgehog, is now possible with vismodegib (150 mg daily) and sonidegib (200 mg daily).

Cryotherapy

  • ■

    Some thin basal cell tumors and superficial basal cell carcinomas may be eradicated with aggressive cryotherapy.

Curettage

  • ■

    Small, discrete nodular tumors with well-demarcated borders can be removed or destroyed by curettage.

  • ■

    This method is very effective alone or in combination with electrosurgery.

Electrosurgery

  • ■

    Electrosurgery involves curettage with or without electrodessication of basal cell tumor.

  • ■

    It is usually performed for well-defined, small nodular basal cell carcinomas and superficial basal cell carcinomas.

  • ■

    The 5-year cure rate for curettage can approach 92% for primary tumors but is only 60% for recurrent tumors.

Fig. 17.23, Most basal cell carcinomas have a soft core that is easily removed with curettage.

Excision

  • ■

    Outpatient or clinic excision is preferred for well-defined nodular basal cell carcinomas.

  • ■

    Excision allows confirmation of surgical margins and surgical closure and may be preferred over electrosurgery for some tumors.

  • ■

    The 5-year cure rate is >90% for primary tumors and 85% for recurrent tumors with this technique.

  • ■

    This may be the preferred method of removal for nonfacial nodular basal cell carcinomas.

Mohs' Micrographic Surgery

  • ■

    Mohs' surgery is a highly specialized, tissue-sparing method of tumor excision used for difficult tumors with contiguous growth, especially basal cell carcinomas.

  • ■

    It is used for recurrent basal carcinomas, for histologically aggressive forms of basal cell carcinomas, and for tumors in anatomically important locations (e.g., around the eyes, nasal ala, mouth, and ears), and tumors with a high risk for recurrence. It is the treatment of choice for sclerotic or morpheaform basal cell carcinomas.

  • ■

    The procedure involves debulking the tumor, followed by excision with narrow margins, which is performed in stages.

  • ■

    Excision is guided by sequential frozen-section mapping in three dimensions.

  • ■

    This allows histologically confirmed removal of the tumor with the smallest of surgical margin and surgical defect.

  • ■

    The 5-year cure rates for Mohs' excision approach 99% for primary tumors and 96% for recurrent tumors.

  • ■

    Mohs' micrographic surgery is useful when tissue sparing is required because of anatomic location, recurrent tumors, and basal cell carcinomas with indistinct borders.

Radiation Therapy

  • ■

    Radiation may be useful for tumors at difficult sites to treat surgically, such as those on the eyelids, and for patients who are unwilling or unable to tolerate surgery.

  • ■

    Improvements in computerized treatment models now allow the radiation oncologist to precisely treat a localized tumor with high-dose radiation in fractional doses over several weeks.

  • ■

    The 5-year cure rate is roughly 90% for both primary and recurrent tumors.

  • ■

    Cosmesis can be excellent, although expected long-term radiation changes in the treated skin may limit the use of this modality to elderly patients.

Nonsurgical Topical Chemotherapy and Immunotherapy

  • ■

    Imiquimod 5% cream is an immune response modifier shown to be 85% effective, or better, for superficial basal cell carcinomas. Daily application by the patient at home for 6 weeks results in complete eradication in most cases. Inflammation at the treatment site can be significant; rest periods may be needed.

  • ■

    Imiquimod for nodular basal cell carcinoma is less well studied; it is slightly less effective for nodular basal cell carcinomas compared with superficial basal cell carcinomas.

  • ■

    Fluorouracil (Efudex, Carac) 5% cream is a topical chemotherapeutic agent that can also be used to treat superficial basal cell carcinoma.

Fig. 17.24, This superficial basal cell carcinoma had been previously treated by desiccation and curettage. Months later, it recurred at the periphery.

Photodynamic Therapy

  • ■

    The combination of a photosensitizing agent, either aminolevulinic acid (ALA) or methyl aminolevulinate (MAL), and addition of a light source, BLU-Light (415 nm) or RED-Light (diode), can be used to treat superficial tumors, which include squamous cell carcinoma in situ and superficial basal cell carcinomas.

  • ■

    The photosensitizing agent is applied to the skin (tumor) and allowed to be absorbed for 1 to 3 hours.

  • ■

    The agent is converted into protoporphyrin IX, and the light source excites the porphyrin resulting in a singlet oxygen state, which is damaging to most cancerous cells in the treatment area.

Fig. 17.25, The superficial basal cell carcinoma on the left was treated with imiquimod cream applied every other day. Intense inflammation occurred and treatment was stopped. The lesion healed, and there have been no recurrences.

Pearls

  • ■

    The patient should know that basal cell carcinomas are very common, but rarely life-threatening or trivial.

  • ■

    Patients must be followed after diagnosis and treatment because tumors may recur and risk for developing another basal cell carcinoma is increased.

  • ■

    All patients with basal cell carcinomas require follow-up to monitor for the development of new tumors and for recurrence at the treated site, regardless of which treatment is used.

  • ■

    Basal cell carcinomas may present as nonhealing ulcers and may appear on any cutaneous surface, including the genitalia.

  • ■

    Morpheaform or sclerotic basal cell carcinomas present as a firm, flat to slightly raised, pale to white papule, which may resemble a scar; it may be missed clinically, but is confirmed histologically. It is more aggressive than other basal cell carcinoma variants and frequently recurs without adequate treatment.

Actinic Keratosis

Description

  • ■

    Actinic keratoses are very common keratotic lesions with malignant potential.

  • ■

    They are considered intraepidermal, precursor, or early lesions of squamous cell carcinoma and basal cell carcinoma.

  • ■

    Lesions are most commonly found in the sun-exposed areas of elderly patients with fair skin types who have had significant sun exposure in their lifetime.

History

  • ■

    Years of cumulative sun exposure and keratinocyte damage lead to the formation of actinic keratoses.

  • ■

    Individual lesions become progressively more common after age 40 years.

  • ■

    Multiple lesions are common in people with fair skin.

  • ■

    Spontaneous regression and progression to squamous cell carcinoma can occur.

  • ■

    It is difficult to predict which lesions will progress to invasive cancer, but thick, hypertrophic lesions seem to be more worrisome.

  • ■

    Approximately 10% of actinic keratoses progress to invasive squamous cell carcinoma over several years.

  • ■

    Transplant recipients with actinic keratosis must be followed closely because squamous cell carcinoma is more common in these patients, and the potential for metastasis is increased.

  • ■

    Actinic keratoses are found along with other signs of chronic sun exposure, such as uneven pigmentation, atrophy or thinning, and telangiectasias.

  • ■

    Lesions are found predominantly on the face, head, neck, and dorsal hands.

  • ■

    Actinic keratoses initially present as a poorly defined area of redness or telangiectasia.

  • ■

    Over time, the lesion becomes more defined and develops a thin, adherent, yellowish, or transparent scale.

  • ■

    At this stage, lesions are sometimes easier to detect by palpation than by observation.

  • ■

    One may find a discrete sandpaper-like change in skin texture associated with minimal erythema. Patients frequently point out these rough, hyperkeratotic areas to the physician.

  • ■

    With time, the adherent scale becomes progressively thicker and yellow in color.

  • ■

    Retained scale may form an elongated keratinous structure or a cutaneous horn.

  • ■

    Such advanced lesions may be difficult to distinguish from invasive squamous cell carcinoma without skin biopsy, and probably should be treated as a squamous cell carcinoma.

  • ■

    “Spreading pigmented actinic keratoses” describes actinic keratoses with fine reticulated pigmentation and minimal scaling; they may mimic a solar lentigo or melanoma in situ.

  • ■

    Lentigo maligna (melanoma in situ) appears as a pigmented patch and occurs most frequently on sun-damaged skin; it may be confused with a spreading pigmented actinic keratosis, and thus a biopsy may be required to establish the correct diagnosis.

Actinic Cheilitis

  • ■

    Actinic cheilitis is a sun-induced keratinocyte atypia of the lower lip. There is focal crusting and scaling along with blurring of the vermilion border, which appears whitish or gray.

  • ■

    Actinic lesions in this location can be quite subtle clinically and behave aggressively.

  • ■

    Like its cutaneous counterpart, actinic cheilitis may progress to overt squamous cell carcinoma of the lip.

Fig. 17.26, Actinic keratosis distribution diagram.

Fig. 17.27, Actinic keratosis. An early lesion. Scale is yellow, sharp, and tightly adherent.

Fig. 17.28, Actinic keratosis. Numerous lesions are present on the arm. The single dense lesion was excised. The other lesions cleared after a 7-week course of topical 5-fluorouracil.

Fig. 17.29, Actinic keratosis. This typical sun-exposed location on the superior helix has a rough sand-paper feel on palpation.

Fig. 17.30, Pigmented actinic keratosis has all of the features of actinic keratosis. There is sharp adherent surface scale and subtle to dense brown pigmentation.

Fig. 17.31, Extremely sun-damaged skin with multiple actinic keratoses that are too numerous to count.

Laboratory and Testing

  • ■

    Biopsy is often helpful for distinguishing advanced actinic keratoses and actinic cheilitis from invasive squamous cell carcinoma, but this is usually not required because most physicians rely on their clinical expertise.

  • ■

    The histologic hallmark is a disordered epidermis with intraepidermal keratinocyte atypia.

    Fig. 17.32, Thick, yellow scale over a pink papule on photodamaged skin is a typical feature of an actinic keratosis.

    Fig. 17.33, Actinic keratosis on the nose, with thick yellow adherent scale.

  • ■

    By definition, invasion into the dermis of atypical keratinocytes is not seen with actinic keratoses.

  • ■

    Similarly, the lesions of spreading pigmented actinic keratosis show keratinocyte atypia with increased pigmentation, whereas atypical melanocytes are seen in lentigo maligna.

Course and Prognosis

  • ■

    A small percentage of actinic keratosis lesions spontaneously regress with continued sun protection; however, other populations of actinic keratoses progress to squamous cell carcinoma.

  • ■

    The behavior of an individual lesion cannot be predicted by clinical examination, although hypertrophic lesions may be more prone to progress.

  • ■

    It has been estimated that 20% of patients with multiple actinic keratoses develop squamous cell carcinoma in one or more lesions.

  • ■

    Squamous cell carcinomas that develop on the ear, the scalp, or at the vermilion border are more likely to metastasize than squamous cell carcinomas at other skin sites; thus, actinic keratoses at these sites are more worrisome and should be treated aggressively.

Discussion

  • ■

    Inflammatory disorders involving the head and neck, such as seborrheic dermatitis and rosacea, can mimic actinic keratoses. Adequate treatment of these inflammatory disorders helps in the prompt recognition and treatment of actinic keratoses.

  • ■

    Actinic keratoses of the lower legs are frequently multiple, hyperkeratotic, and distributed over a large area.

  • ■

    Numerous lesions may form on the dorsal hand and forearms, which also have the potential to develop into squamous cell carcinoma.

  • ■

    Transplant recipients and other immunosuppressed patients pose a difficult treatment conundrum. These patients have a high incidence of squamous cell carcinoma and metastasis. Thus, adequate and aggressive treatment of actinic keratosis and early squamous cell carcinomas is paramount.

Fig. 17.34, Actinic keratosis may accumulate dense scale on the surface and become a cutaneous horn. These lesions are excised. Squamous cell carcinoma may have an identical appearance and can be difficult to discern from an actinic keratosis.

Fig. 17.35, Actinic keratosis. Almost the entire surface of the scalp is covered with thick hypertrophic actinic keratoses. This volume of actinic keratosis is best treated with topical chemotherapy.

Fig. 17.36, Actinic cheilitis presents with erythema and scaling. There is a loss of lip lines, and the skin becomes smooth and eroded.

Treatment

  • ■

    The patient with multiple actinic keratoses requires at least annual follow-up, if not more often for some patients who have more extensive sun damage.

  • ■

    Visible or detectable lesions represent a fraction of the total number of atypical keratinocytes actually present.

  • ■

    Most of the atypia are scattered within sun-damaged skin and below the level of clinical detection.

  • ■

    These patients will almost certainly develop more clinically apparent actinic keratosis lesions over time.

  • ■

    Adequate sun avoidance with sun-protective clothing and sunscreens should be encouraged to limit further damage.

  • ■

    Destruction with liquid nitrogen (cryotherapy) of solitary superficial lesions is the most common method of removal.

  • ■

    Patients with significant diffuse photodamage or multiple and recurrent lesions present difficult treatment problems.

  • ■

    It is well documented that patients with numerous actinic keratoses have an increased risk for developing squamous cell carcinoma over time.

    Fig. 17.37, This large actinic keratosis had been present for several years, continues to evolve and spread, and is at high risk for transition to squamous cell carcinoma.

    Fig. 17.38, This actinic keratosis covers a wide area. It was treated in segments and cleared after three treatment sessions with cryotherapy (liquid nitrogen).

  • ■

    Topical 5-fluorouracil 5% and 0.5% cream is useful in treating existing, and reducing the number of, atypical keratinocytes in the epidermis and has been the standard in topical, nonsurgical treatment of actinic keratoses.

  • ■

    Treatment should be tailored for specific areas of the skin, in concentration of the cream, the number of applications per day, and the duration.

    Fig. 17.39, Actinic keratosis. Topical chemotherapy with 5-fluorouracil. Lesions can become significantly inflamed during the second and third weeks of treatment.

  • ■

    Although treatment of all sun-damaged areas may be appropriate, it is rarely practical to treat large areas at one time. Some patients may prefer instead to treat limited areas on a rotating basis.

  • ■

    Erythema will appear if actinic keratoses are present. This is followed by warmth, burning, and oozing. Treatment may be stopped before completing the 3-week course if intense inflammation, crusting, or discomfort occurs.

  • ■

    Patients should be evaluated during the treatment period for discomfort and other complications.

  • ■

    Imiquimod 5% cream, an immune response modifier, has been shown to effectively treat multiple actinic keratoses when applied three to five times weekly for up to 4 weeks. A new formulation of imiquimod 3.75% cream (Zyclara) is now available.

  • ■

    Inflammatory changes similar to those with 5-fluorouracil occur with imiquimod.

  • ■

    Photodynamic therapy with either aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is yet another option for treating extensive diffuse photodamage and multiple actinic keratoses, and allows the physician to treat a large surface area.

  • ■

    As with the topical therapies, with photodynamic therapy, there is erythema, inflammation, and discomfort, but these symptoms are shorter in duration.

  • ■

    Electrodesiccation and curettage are also effective and may be necessary for thick lesions.

  • ■

    All destructive methods ablate the epidermis with minimal effect on the dermis. All have some risk for postprocedure hypopigmentation and scar formation, especially in people with darker skin. This should be clearly explained to the patient before treatment.

Actinic Cheilitis Treatment

  • ■

    Actinic cheilitis can be treated via several methods and should be tailored to the patient and side-effect profile.

  • ■

    Cryotherapy can be used to treat actinic cheilitis, for focal or large areas of photodamage of the lip mucosa.

  • ■

    Carbon dioxide laser vermilionectomy is another option for extensive actinic cheilitis.

  • ■

    5-Fluorouracil and imiquimod can also be used on the mucosa (with caution) because the response can be brisk and uncomfortable.

  • ■

    Application of 5-fluorouracil and imiquimod on the oral mucosa should be less frequent compared with the frequency of skin application and for a shorter duration.

  • ■

    Although not yet approved by the U.S. Food and Drug Administration (FDA), photodynamic therapy with aminolevulinic acid is effective for actinic cheilitis, either alone or in combination with the treatments presented earlier.

Pearls

  • ■

    Invasive squamous cell carcinoma can develop from actinic keratosis, especially with thicker, hypertrophic lesions, or lesions not responding to treatment.

  • ■

    Actinic keratosis lesions of the oral mucosa are especially predisposed to convert to squamous cell carcinoma.

    Fig. 17.40, Actinic keratosis. A clinical diagnosis of squamous cell carcinoma was made on this thick lesion. Biopsy, however, showed that this was an actinic keratosis with all of the atypical cells confined to the epidermis.

    Fig. 17.41, Actinic keratosis on the back of the hands and forearms is often very thick. Differentiating an actinic keratosis from invasive squamous cell carcinoma by inspection may be difficult.

    Fig. 17.42, Actinic keratosis. Topical chemotherapy with 5-fluorouracil. Intense inflammation is induced. Thick indurated lesions become inflamed.

  • ■

    A biopsy should be considered in any patient who does not respond appropriately to routine actinic keratosis treatment and in actinic keratoses that are recurrent or hypertrophic.

    Fig. 17.43, Actinic keratosis 3 weeks after treatment with 5-fluorouracil cream. Lesions are inflamed but have not reached the lesion disintegration phase. Treatment was stopped 1 week later when the lesions eroded.

    Fig. 17.44, Actinic keratosis 4 weeks after starting treatment with 5-fluorouracil cream. Lesions on the arms are usually thicker and more resistant to treatment. They may require 6 to 7 weeks of treatment to reach the lesion disintegration phase.

  • ■

    Some severely actinically damaged patients may require two or three visits per year to adequately treat the numerous actinic keratoses present and prevent progression to squamous cell carcinoma.

Squamous Cell Carcinoma

Description

  • ■

    Cutaneous squamous cell carcinoma is an invasive, primary cutaneous malignancy arising from keratinocytes of the skin and mucosal surfaces.

  • ■

    It is most commonly found on the face, head, neck, or hands of elderly patients.

  • ■

    Lesions may develop from precursor actinic keratoses or may arise de novo.

History

  • ■

    Squamous cell carcinoma is the second most common form of skin cancer in the United States.

  • ■

    It comprises 20% of all primary cutaneous malignancies.

  • ■

    The lifetime risk for developing a cutaneous squamous cell carcinoma is estimated to be between 5% and 15%.

  • ■

    More than 100,000 new cases of primary cutaneous squamous cell carcinoma are diagnosed in the United States each year.

  • ■

    Approximately 2500 deaths occur annually from squamous cell carcinoma arising in the skin.

  • ■

    The incidence of squamous cell carcinoma doubles with each 8- to 10-degree decline in latitude.

  • ■

    Primary cutaneous squamous cell carcinomas usually occur on sun-exposed skin from years of accumulated actinic damage.

  • ■

    Nearly 90% of cutaneous squamous cell carcinomas in men and nearly 80% of such tumors in women occur on the face, head, neck, and hands.

  • ■

    Squamous cell carcinoma on the legs occurs more often in women than in men.

  • ■

    White patients with fair skin are at greatest risk.

  • ■

    Although most squamous cell carcinomas are caused by ultraviolet light exposure, other extrinsic factors can play a causal role and include other forms of radiation; chemicals, such as hydrocarbons, arsenic, and tobacco; chronic infections, such as osteomyelitis, chronic inflammation, burns (Marjolin's ulcer), and scars; and human papillomavirus infection.

  • ■

    Historically, squamous cell carcinoma has been considered as a low-grade tumor with a metastatic rate of less than 1%.

  • ■

    With the current epidemic of all primary cutaneous malignancies and recent epidemiologic attention, it is clear that squamous cell carcinoma is far more aggressive than previously believed.

  • ■

    Transplant recipients and other immunocompromised patients develop squamous cell carcinoma much more frequently than the general population, and these tumors can be more aggressive and more likely to metastasize.

  • ■

    “Conduit spread” refers to the perivascular or perineural extension of tumor cells.

  • ■

    Ultimately the tumors may metastasize, usually via the lymphatics, to local lymph nodes.

Skin Findings

  • ■

    As with actinic keratoses, squamous cell carcinomas typically occur on sun-exposed areas.

  • ■

    Tumors are found within a background of sun-damaged skin with atrophy, telangiectasias, and blotchy hyperpigmentation.

    Fig. 17.45, Squamous cell carcinoma distribution diagram.

  • ■

    Early invasive squamous cell carcinoma may have the appearance of a hypertrophic actinic keratosis.

  • ■

    The typical lesion has a pink to dull red, firm, poorly defined dome-shaped nodule with an adherent yellow-white scale.

  • ■

    The untreated lesion becomes larger and more raised, developing into a firm, red nodule with a necrotic, crusted center.

  • ■

    Removal of the crust reveals a central cavity filled with necrotic keratin debris, sometimes with a foul odor.

  • ■

    Multiple lesions may appear on the sun-exposed bald scalp, and in some cases lesions may be too numerous to count.

  • ■

    Actinic keratoses are aggregates of atypical keratinocytes contained within the epidermis.

  • ■

    At the very least, actinic keratoses represent early squamous atypia, if not definitive squamous cell carcinoma in situ.

    Fig. 17.46, Squamous cell carcinoma is commonly found on the ears. The thick verrucous tumor is characteristic of a squamous cell carcinoma.

    Fig. 17.47, Differentiating actinic keratosis from squamous cell carcinoma can be difficult. A biopsy demonstrated invasion of atypical squamous cells into the dermis and proved the diagnosis of squamous cell carcinoma.

    Fig. 17.48, Squamous cell carcinoma. This large mass had been slowly growing for months. Patients are often not concerned until the skin breaks down and ulcerates, which may lead to bleeding.

    Fig. 17.49, Squamous cell carcinoma retains surface scale. The lesion is called a cutaneous horn if it accumulates a large amount of scale.

  • ■

    Unlike the lesions of Bowen's disease (squamous cell carcinoma in situ), which show full-thickness involvement, actinic keratoses show partial epidermal cellular atypia, and squamous cell carcinoma by definition shows atypical keratinocytes with invasion into the dermis.

    Fig. 17.50, A large yellow-red crusted nodule, characteristic of a squamous cell carcinoma.

    Fig. 17.51, This squamous cell carcinoma is multilobular, with hyperkeratotic, verrucous changes superficially and focal areas of hemorrhagic crust.

Variants of Squamous Cell Carcinoma

  • ■

    Actinic keratosis may become thick and hypertrophic, indicating possible progression into squamous cell carcinoma.

  • ■

    Cutaneous horns may begin as actinic keratosis and progress into squamous cell carcinoma, and should be treated as such.

  • ■

    Bowen's disease represents full-thickness squamous cell carcinoma in situ that is slow growing, and usually appears as a pink, scaly, well-demarcated patch. If untreated, invasion may ultimately occur.

  • ■

    Keratoacanthoma is a large, nodular, crateriform, fast-growing nodule with central necrosis, and should now be considered a low-grade variant of invasive squamous cell carcinoma.

  • ■

    Erythroplasia of Queyrat (squamous cell carcinoma in situ of the penis) is a pink, smooth patch, erosion, or ulcer and may also become invasive. Nodular or ulcerated areas in any tumor suspected of being a squamous cell carcinoma should suggest invasion and thus warrant biopsy. Vulvar squamous cell carcinoma is another variant.

  • ■

    Squamous cell carcinoma of the oral mucosa is particularly worrisome and prone to metastasis, especially of the lower lip.

  • ■

    These tumors may arise on an area of actinic cheilitis or chronically sun-damaged mucosa and may develop erosion or ulceration, with an underlying papule or nodule that is usually palpable.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here

Related Posts