Keratoacanthoma (KA) is a tumor derived from hair follicle epithelium and associated with HPV 9, 16, 19, 25, and 37. It is a rapidly growing neoplasm that resembles SCC. Whites are more commonly affected than other racial groups and the tumors present in sun-exposed areas of the extremities, head, and neck. KA affects all age groups (occurring most often in the middle-aged and elderly) and it has a 3:1 predominance in men. Sun exposure is the main predisposing factor, but immuno-suppression and exposure to tar are also important (132). The five clinical variants are described here.

Common solitary KA starts as a keratotic papule or nodule that reaches 13 cm in size. The tumor is erythematous, firm, and has a keratin-filled crater. There is spontaneous involution in a few weeks leaving an atrophic scar.

Giant KA (Fig. 25) is clinically similar to the common variant but grows up to 10 cm in diameter.

KA Centrifugum marginatum is a keratotic erythematous enlarging plaque.

Multiple self-healing KA (Ferguson-Smith type) involves multiple lesions, autosomal dominant inheritance, and a positive family history.

Eruptive KA (Gryzbowski type) is characterized by innumerable, disseminated, 2-3 mm lesions with mucosal involvement and severe pruritus.

The majority of KAs have a benign course. The risk for malignant transformation seems minimal and, when it occurs, the possibility of misdiagnosed SCC should be considered. Many authors believe that malignant transformation from KA into SCC is frequent, although this is controversial. We think of KA as having a continuous spectrum of manifestations, from the most benign to the locally invasive, to those that can rarely metastasize.

On histological examination KA is a flask-shaped lesion with well-developed a lateral borders (so-called collarette) and a central keratin-filled epithelial invagination. The epithelium is well differentiated, shows marked keratinization, and has a ground-glass appearance (133).

KA should be treated because clinical differentiation with SCC is not always possible. Treatment is also provided to hasten resolution for cosmetic reasons, to reduce recurrences, and because treatment is simple and effective in most cases.

Figure 25 A large, asymptomatic, ulcerated nodule on the left cheek of an elderly woman with extensive solar damage. The lesion corresponds to a giant keratoacanthoma but differentiation from invasive squamous cell carcinoma cannot be done on clinical grounds; a biopsy is always indicated.

Surgical excision is the treatment of choice. The recurrence rate is 4-6% but higher figures are reported for lesions on lips, hands, and fingers, and for giant KA (134).

Mohs' micrographic surgery is indicated for tumors with a greater probability of recurrence, such as giant KA, and tumors located on digits or lip. It is also recommended for tissue preservation in cosmetically or functionally relevant areas (135).

Curettage and electrodesiccation are also effective therapy for KA. A drawback is the hypopigmented residual scar (136).

Radiation therapy is indicated for poor surgical candidates, patients who refuse surgery, and for inoperable tumors (137).

Chemotherapy with intralesional bleomycin or 5-FU is indicated for inoperable tumors, multiple tumors, and to reduce the size of giant KA lesions (138). Therapy is convenient, relatively inexpensive, and produces minimal side effects. Weekly doses of oral methotrexate have proven effective for speeding the resolution of large lesions that are not amenable to surgical treatment (139). |

Oral retinoids (isotretinoin and etretinate 1 mg/ kg/ day) have proven effective ยป

for the treatment and prevention of KA. Common, giant, eruptive, and recurrent lesions have all been treated successfully (140). ^

Malignant Melanoma 1

Melanoma (MM) is a malignant and potentially fatal neoplasm derived from mela-nocytes. It may arise de novo or from precursor lesions, and is more common in fair-skinned individuals with poor tanning ability. Acute intermittent sun exposure and number of childhood sunburn episodes are more important than chronic sun exposure. The association with tanning bed use is more controversial. Estrogen, oral contraceptives, and pregnancy are no longer considered risk factors (141).

Risk for MM ranges from 1.8 to 13% in congenital melanocytic nevi (estimates are 6.3% risk for giant lesions) (142). The risk is less for common acquired nevi, but there is a significant association in patients with more than 100 lesions. Dysplastic nevi (DN) occur in 2-18% of whites. All studies have demonstrated an increased risk for melanoma in patients with these nevi (143). In the familial melanoma/dysplastic nevus syndrome, several members present with DN and/or a history of MM. Approximately 50% of individuals carry the trait. MM risk approaches 100% over the course of a lifetime. There is a 56% risk between the ages of 20 and 59. Studies have identified two sites for melanoma genes: chromosomes 1p and 9p (144).

The clinical identification of MM is based on the ABCDE of pigmented lesions: asymmetry, border irregularity, color variegation, diameter >6 mm, and elevation (145). Once diagnosed, MM is better thought of in terms of its growth pattern. Lesions with vertical growth are capable of metastasis, while those with only radial growth are confined to the skin. The most common locations are the trunk, head, and neck in men; and the lower extremities in women.

Superficial spreading melanoma (SSM) occurs in 70% of cases. It presents as a pigmented plaque with different shades of brown/black, and a notched border. Sometimes there is erythema or ulceration (Fig. 26). Differential diagnoses includes dysplastic nevus, Spitz nevus, pigmented BCC, seborrheic keratosis, and common nevus.

Scar Leg From Melanoma Surgery
Figure 26 Recurrent superficial spreading melanoma of the leg along a surgical scar. As evident in this case, operative margins in melanoma do not correlate with prognosis. The lesion was treated initially using 5 cm margins.

Lentigo maligna melanoma (LMM) occurs in 5% of cases. It develops from a precursor lesion called lentigo maligna, which is a hyperpigmented flat patch occurring on the face of elderly individuals. Malignant transformation (progress from a radial to vertical growth phase) occurs in 20-50% of cases.

Nodular melanoma (NM) occurs in 15% of cases. It has no radial growth phase and presents as a growing dark nodule with color variation (Fig. 27). The differential diagnosis includes thrombosed skin tag, hemangioma, pigmented BCC, common nevus, blue nevus, and seborrheic keratosis.

Acral lentiginous melanoma (ALM) occurs in 8% of cases. It is the most common MM in dark-skinned persons and presents as an irregular pigmented patch with notched border and color variation (Fig. 28). The most common locations are the volar surfaces of the hands and feet, and subungual. Differential diagnosis includes melanocytic nevi, hematoma, and paronychia. A pigmented nail streak with pigmentation of surrounding skin constitutes Hutchinson's sign.

Figure 28 Acral lentiginous melanoma is the most frequent form of melanoma in dark-skinned individuals. This large patch shows various tones of black and brown and has ill-defined borders.

Desmoplastic neurotrophic melanoma presents as a nonpigmented scar without history of previous trauma. Preoperative diagnosis is difficult since it resembles keloid scar, morpheaform BCC, or dermatofibroma.

Amelanotic melanoma does not produce pigment. It presents as erythematous or skin-colored papules, nodules, or plaques. It resembles insect bite, folliculitis, BCC, adnexal tumor, or sarcoma.

Mucosal lentiginous melanoma presents in the oral cavity as a pigmented area showing the ABCDE changes. It resembles a nevus or a venous lake.

On histological examination, MM is identified by the presence of highly atypical melanocytes (Fig. 29). A pagetoid pattern refers to scattering of individual mel-anocytes and nests throughout all layers of epidermis. This pattern is seen in SSM. A lentiginous pattern is characterized by proliferation of atypical cells in the basal layer of epidermis with involvement of skin appendages. This pattern is seen in LMM and ALM. Amelanotic melanoma makes up 1.8% of most series. MM cells stain positive "S

The prognosis and management of melanoma are based on the histological findings; therefore, the pathologist's report should include: c

1. Breslow depth: Thickness in millimeters measured from the granular layer to greatest depth. If ulcerated, from surface of ulcer to greatest depth.

2. Clark's level of invasion: I, cells localized to epidermis; II, through dermoepidermal junction into papillary dermis; III, filling papillary dermis; IV, reticular dermis; V, subcutaneous fat.

Figure 29 Characteristic lentiginous proliferation of neoplastic melanocytes in malignant melanoma. The darker areas show positive immunostaining reaction with S-100 monoclonal antibodies.

3. Radial vs. vertical growth phase.

4. Pagetoid vs. lentiginous pattern.

5. Mitotic rate (number of mitoses per mm2) and prognostic index (mitotic rate x thickness in mm)

6. Presence or absence of ulceration, desmoplasia, neurotropism, regression, and satellite lesions (focus of MM larger than 0.5 mm, located on reticular dermis, and separated from main tumor by normal tissue)

7. Surgical margins

Staging of Melanoma According to the American Joint Commission for Cancer (AJCC).






5 years

10 years




















Any T






Any T

Any N




Tis = in situ/Clark I; T1 = <0.75mm/Clark II; T2 = 0.76-1.49mm/Clark III; T3 = 1.5-3.99mm/Clark IV; T4 = > 4.0mm/Clark V; N1 = Nodes < 3 cm; N2 = Nodes > 3 cm; M1 = Distant metastases

Tis = in situ/Clark I; T1 = <0.75mm/Clark II; T2 = 0.76-1.49mm/Clark III; T3 = 1.5-3.99mm/Clark IV; T4 = > 4.0mm/Clark V; N1 = Nodes < 3 cm; N2 = Nodes > 3 cm; M1 = Distant metastases

Indicators of a bad prognosis include the following findings:

Breslow's thickness: The 5 year survival rate is 99% for melanomas < 1mm;

80-90% for 1-3 mm; 58% for 3-4mm; and 30% for > 4mm. Clark's level: The 5 year survival rate is 100% for levels I and II; 90% for level

III; 66% for level IV; and 15-25% for level V. Male gender Ulceration

Mitotic rate > 5/mm2 Axial location (trunk, arm) Age > 50 years Tumor size > 2 cm Satellitosis

Tumor volume > 200 mm3

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