Premalignant and Malignant Skin Tumors

Definition

Actinic keratosis: A sharp outlined, homed growth on sun exposed skin with tan or clear scale on an erythematous base. Some potential for malignant degeneration.

Basal cell carcinoma: A malignant epithelial tumor with potential for local invasion and destruction. Small meta static risk. Most common human malignancy with approximately 500,000 new cases annually. Variants include nodular, superficial, morpheaform, pigmented, and infiltrative.

Squamous cell carcinoma: A malignant tumor arising from keratinocytes, generally occurring in sun-exposed areas of older people.

Malignant melanoma: The neoplastic transformation of melanocytes in the epidermis (in situ and biologically benign) that spreads to the dermis and may metastasize. More rapid horizontal growth in superficial spreading melanomas and more rapid vertical growth in nodular melanoma.

History

Symptoms

Actinic keratosis: Dry, rough, warty, scaly lesion on the head or arms.

Basal cell carcinoma: Chronic sore or bump that is generally painless, bleeds easily, seems to heal, and yet never resolves completely. Usually occur in sun-exposed areas.

Squamous cell carcinoma: Chronic ulcers or open, changing, hard bumps on exposed surfaces. Painless until late stages.

Malignant melanoma: New or old pigmented skin lesions that change in size, shape, color, or elevation and may itch or bleed easily.

Age

Actinic keratosis: Middle age and upward.

Basal cell carcinoma: Forties and greater. Occasionally seen in the twenties and thirties if history of extensive childhood sun exposure, especially with bums.

Squamous cell carcinoma: Over forty, increasing incidence into old age. Malignant melanoma: Median age at diagnosis is the mid forties.

Onset

Actinic keratosis: Chronic.

Basal cell carcinoma: Insidious and chronic.

Squamous cell carcinoma: Insidious over months.

Malignant melanoma: Months to years.

Duration

Actinic keratosis: Permanent or malignant degeneration.

Basal cell carcinoma: Permanent.

Squamous cell carcinoma: Indefinite; without treatment, continue to invade surrounding tissues.

Malignant melanoma: Steady, progressive growth or changes.

Intensity Actinic keratosis: Single lesion to many.

Basal cell carcinoma: Single lesions, from a few millimeters to a few centimeters in diameter. Sometimes multiple lesions in various stages of slow growth and development.

Squamous cell carcinoma: Single, isolated lesion to a few scattered discrete tumors. From small, superficial to large deep lesions with potential to metastasize.

Malignant melanoma: One or two primary lesions, rarely multiple.

Aggravating Factors

Actinic keratosis: Significant sun exposure, expecially bums before age 20 in lightly pigmented individuals. Renal transplantation.

Basal cell carcinoma: Extensive sun exposure especially sunburns in childhood, fair skin color and, less frequently, X-ray therapy, thermal injury, or inorganic arsenic exposure.

Squamous cell carcinoma: Extensive sun exposure, especially with bums, prior bum scars, chronic ulcers, discoid lupus lesions, prior X-ray skin damage, industrial carcinogen oils, and tar exposure.

Malignant melanoma: UV sunlight exposure. Intermittent burning exposures are more important than cumulative or chronic exposure time. Environmental exposure to carcinogens. A viral factor is hypothesized.

Alleviating Factors

Actinic keratosis: Good sun protection, sunscreen use, protective clothing, or sun avoidance.

Basal cell carcinoma: Prevention from birth, with sun blocks and clothes to protect light colored skin.

Squamous cell carcinoma: Exposure factor avoidance.

Malignant melanoma: Sunlight protection, avoidance of sunburns and early detection.

Associated Factors

Actinic keratosis: Family history of skin cancers.

Basal cell carcinoma: Not applicable.

Squamous cell carcinoma: Predominate in males, except lower legs where it is more common in women. Fair complexion with skin types I and II more prone.

Malignant melanoma: Phenotypic factors associated with melanoma

include light skin, blond or red hair, blue, green, or gray eyes, or family history of melanoma. Presence of melanocytic nevi nears 100 percent if the patient has dysplastic nevus syndrome and family history of melanoma in two or more first degree relatives.

Physical Examination

Skin

Actinic keratosis: Erythematous macule with overlying clear or tan scale. Easier to palpate than visualize, on face, bare neck, dorsal hands and arms, bare scalp, and occasionally on the upper chest and back. Evaluate all areas of increased sun exposure. Some lesions may have thicker cutaneous hornlike surface.

Basal cell carcinoma: On long term sun exposed skin almost 80 percent are found on the head and neck. Trunk and extremities are the next most common sites. Appear as translucent opal papules and nodules with rolled borders and telangiectasias. They often have depressed or ulcerated centers or appear as a flatter, broader, rough, plaque-like lesions with fine rolled borders. Some have blue, black, or brown pigmentation. Sometimes almost dry and scaly-like. Occasionally a yellowish-waxy, translucent, indurated, deeper plaque, hardly elevated, and diffusely bordered. Squamous cell carcinoma: Indurated papule, plaque, or nodule with adherent keratotic scale. Often eroded, crusted, and/or ulcerated on exposed areas, especially the lip, top of ear, head, neck, and dorsum of the hands and arms. Also occur in old burn scar or radiation sites. All typically present without distinct margins.

Malignant melanoma: The lesions appear as a pigmented macule, flattened papule, plaque, and or nodules. May be a new lesion or a recently changing lesion. Haphazard marked color variegation with two or more of the following: black, brown, pink, red, whitish gray, or blue. Borders are irregularly irregular, often with a notch. The mean size is 1 to 2 cm, but may be as small as 2 mm. The risk of metastasizing is greater after 6 mm size and with more vertical growth. More commonly found on the upper back and legs or under nails in both sexes, the faces of females, and anterior trunk of males. Dark-skinned persons may develop acrallentiginous melanomas on palms, soles, or genitalia. Bathing suit areas generally spared.

Lymphatic

Malignant melanoma: Evaluate for lymphadenopathy.

Pathophysiology

Actinic keratosis: Hypertrophic damaged keratinocytes and thickened dry stratum corneum. Sometimes overlaid with a hyperkeratosis column.

Basal cell carcinoma:Proliferation of basaloid cells in dermis with palisading hyperchromatlc nucleI. One vanant has increased pigment in the melanocytes and melanophages. In another, the morpheaform has increased strands of basaloid cells in a thickened fibrous stroma.

Squamous cell carcinoma: Anaplastic groups of atypical epithelial squamous cells proliferating in strands in the epidermis, dermis, and/or subcutaneous tissue. Cells are of megular shape and size and have large nuclei and variable keratinization.

Malignant melanoma: Melanocytes reside in the basal layer of the epidermis and synthesize melanin. Melanin is important in protecting against DNA damage from UV rays. Neoplastic transformation occurs in these cells and they are able to produce their own growth factors and develop autonomous growth. Four growth patterns are noted in malignant melanoma. The most common type occurring in 60 percent of melanomas is the superficial spreading pattern. It is usually an irregularly pigmented macule with one or more areas of nodularity. Nodular melanoma occurs in 15 to 30 percent of melanomas. It is usually deeply pigmented (blueish black) and raised. It is most common in men and is more aggressive and faster growing than the superficial spreading type. Lentigo melanoma is seen in 5 to 10 percent of melanomas and is usually a facial lesion occuring in Caucasian women. It has a low risk to metastasize. The acrallentiginous type is seen on the palms, soles, and nail beds. It is a rare type occurring in only 2 to 8 percent of melanomas in Caucasians, but in 35 to 60 percent of melanomas in dark-skinned patients. Ulceration is commonly observed in this type.

Diagnostic Studies

Laboratory: Not applicable.

Radiology: Not applicable.

Other

Actinic keratosis: Biopsy: If advanced, thick and raised, and a question of malignant degeneration.

Basal cell carcinoma: Biopsy: Punch, incisional, or deep tangential type.

Squamous cell carcinoma: Biopsy: Any isolated, keratotic, eroded, ulcerating papule, plaque, or nodule that is 6 to 8 weeks old or older to rule out carcinoma.

Malignant melanoma: Biopsy: Excisional biopsy of complete lesion whenever possible.

Differential Diagnosis

Traumatic

Actinic keratosis: Healing wound: Should resolve in less than a month.

Basal cell carcinoma: Wound ulcers: Heal in days to weeks, and rarely have characteristic raised, rolled borders.

Squamous cell carcinoma: Wounds: Should resolve in less than a month.

Malignant melanoma: Wounds: Should resolve in less than a month.

Infectious

Actinic keratosis: Not applicable.

Basal cell carcinoma: Infectious papules and nodules: Have significant erythema, tenderness, and may radiate heat.

Squamous cell carcinoma: Infectious papules, plaques, or nodules: Have more inflammatory response, are more distinct, and heal.

Malignant melanoma: Infectious papules and nodules: Have significant erythema, tenderness, and may radiate heat.

Metabolic

Actinic keratosis: Ichthyosis or dry scaling: Will be more widespread and diffuse without small isolated lesions.

Squamous cell carcinoma: Diabetic ulcers: Occur on lower legs, are more distinct, wide, and deep without the papules or nodularity.

Basal cell carcinoma/Malignant melanoma: Not applicable.

Neoplastic

ctinic keratosis:A Basal or squamous cancers: Difficult to differentiate from advanced actinic keratosis and early malignant change. Usually have more papularity, visibility, and/or ulceration.

Basal cell carcinoma: Malignant melanoma: Usually more irregular in size, shape, and color and rarely have characteristic translucent, rolled borders, but may be difficult without biopsy to differentiate from pigmented nodular basal cell.

Squamous cell skin cancer: Sometimes the superficial and nodular forms are difficult to separate and a biopsy is required.

Squamous cell carcinoma: Bowen's disease (squamous cell carcinoma in situ): Is a hyperkeratotic erythematous patch or plaque with sharp demarcation of a few millimeters to several centimeters. Do not change for years in spite of most treatment for the papulosquamous conditions for which it is most commonly mistaken. Three to 5 percent chance of frank carcinoma.

Erythroplasia of Queyrat: A carcinoma in situ. A bright red, velvety plaque on the penis of older men, particularly the uncircumcised.

Bowenoid papulosis: A fleshy, flat, rough-topped papules of the external genitalia of men and women. Is a squamous carcinoma in situ and often mistaken for condyloma acuminata. Keratoacanthoma: A rapid growing epidermal neoplasm of purported benign, self-healing nature, but difficult to differentiate from squamous cell carcinoma even histologically. Typically occur on sun exposed area, are 1 cm or larger, and appear as domed, rolled border, reddened, fleshy papulo- nodule with central invagination or umbilication having a large keratin plug. Acceptable to treat it as squamous cell carcinoma.

Malignant melanoma: Nodular basal cell carcinoma: May rarely resemble an amelanotic nodular melanoma but biopsy differentiates.

Vascular

Squamous cell carcinoma: VenouS or arterial ulcers: Are more eroded from the surface downward without papule or nodularity. Become larger.

Actinic keratosis/Basal cell carcinoma/Malignant melanoma: Not applicable.

Congenital

Basal cell carcinoma: Nevi: More concentric, uniform, and symmetrical without ulceration; rare umbilication. Malignant melanoma: Cafe-au-Iait: Remain even-colored, tan macules. Black hairy nevi: May be precursors to melanoma (5 percent risks) so they must be followed, and changing areas biopsied. Nevi of melanocytic type: Are possible melanoma precursors and changes in size, shape, color, elevation need evaluation. Other pigmented nevi: No change over lifetime equals low risk for melanoma especially all under 6 mm size.

Actinic keratosis/Squamous cell carcinoma: Not applicable.

Acquired

Actinic keratosis: Small nummular eczema: Are larger, more inflamed, and have flaky dry scale and not as adherent.

Basal cell carcinoma: Fibrous papule: May be whitish and clear but not with rolled border and without telangiectasias. Firm superficial, smaller, and uniform. Trichoepithelioma: Are fleshy papules that do not ulcerate.

Seborrheic keratosis: Has stuck on appearance, no rolled borders, and no central depression or ulcerations.

Treatment

Actinic keratosis: Based on tenderness, cosmetic effect, and malignant potential: Liquid nitrogen cryosurgery without anesthesia Electrodessication and currettage with anesthesia or Topical 5-fluorouracil twice a day for 3 to 4 weeks. Biopsy thick advanced lesions to rule out squamous cell skin cancer.

Squamous cell carcinoma/Malignant melanoma: Not applicable.

Basal cell carcinoma: Multiple modalities exist for treatment including electrodessication and currettage, deep cryosurgery, CO2 laser destruction and currettage, excision, and occasionally X-ray therapy. If aggressive clinicopathological features exist, or if located in strategic areas (e.g., nose area or ear, near eyes), consider micrographic surgery,or MOHS. With microscopic accuracy the tumor is excised in toto with little normal tissue. Ninety-five to 100 percent are permanently cured. The other measures reach 90 to 95 percent cure rates with initial treatment. Each method is performed after biopsy verification.

Squamous cell carcinoma: Based on size, location, and level of invasion. Aggressive biologic or deep invasive histological tumors should be removed by excision or MOHS micrographic surgery Superficial, small, and early in situ forms can be destroyed by electrodessication and currettage or laser. Radiation and cryosurgery can be effective as well.

Malignant melanoma: Deep wide complete excision. If lesion less than 0.5 mm thick, then excise with less than 2 cm margin beyond the lesion border.If lesion greater than 0.5 mm thick then excision margins should be up to 3 cm beyond lesion borders. Elective lymph node dissection is controversial with most waiting for signs or palpability to remove regional nodes. Single agent or combination chemotherapy may be used in metastatic disease but have low overall complete response rates.

Melanoma: A vaccine is being used at centers such as the John Wayne Institute in Los Angeles, California and showing some promise in severe advanced disease. Lesions should be staged. To properly stage the lesion, determine width and depth, and establish the prognosis, the entire lesion should be excised. If anatomic location or function would be jeopardized if biopsy is benign, use a deep incisional biopsy. The CLARK levels of staging melanomas are as follows:

1. All melanoma cells in epidermis.
2. Melanoma penetrating into papillary dermis.
3. Melanoma cells filling the papillary dermis.
4. Melanoma cells extending into the reticular dermis.
5. Invasion of the subcutaneous layer.

Breslow's direct measurements led to C.L. Day's four thickness ranges and survival rates:Less than 0.85 mm, 98 percent survive 10 years. 0.86 to 1.69 mm, 89 percent survive 10 years. 1.7 to 3.59 mm, 67 percent survive 10 years. 3.6 mm or greater, 43 percent survive 16 years. Consider oncology referral.

Pediatric Considerations

Malignant melanomas are uncommon in childhood and appear as pigmented nodules of variegated colors within a single lesion. Melanomas arising in congenital pigmented nevi, which are present in approximately I percent of newborn infants, account for most melanomas of childhood. Giant congenital nevi ( 20 cm) are associated with leptomeningeal melanocytosis and a predisposition for development of malignant melanoma (incidence of 6 to 10 percent with 50 percent developing by age 5). Early total excision is treatment of choice. The approach to medium (1.5 to 20 cm) and small «1.5 cm) sized congenital nevi is less clear but the excision prior to adolescence is strongly recommended.

Prolonged exposure to strong sunlight during childhood and adolescence is recognized as a predisposing factor in the development of basal cell and squamous cell carcinomas. Physician assistants should provide anticipatory guidance to parents regarding the use of sunscreens and sun blocks whenever children are exposed to the sun for prolonged periods of time.