• CASE 4

During the routine physical examination of a 30-year-old. fair-complexioned white man. you discover a I .5-cm pigmented skin lesion on the posterior aspect of his left shoulder. This lesion is nonindurated, has ill-defined borders, and is without surrounding erythema. Examination of the patient’s left axilla and neck reveals no identifiable abnormalities. No other pigmented skin lesions are observed during your thorough physical examination. According to the patient’s wife, this skin lesion has been present for the past several months, and she believes it has increased in size and become darker during this time. The patient is otherwise healthy.

• What is your next step?

• What is the most likely diagnosis?

• What is the best treatment for this problem?

ANSWERS TO CASE 4: Malignant Melanoma

Summary: A 30-year-old man has a suspicious pigmented skin lesion on his left shoulder.

• Next step: Perform an excisional biopsy.

• Most likely diagnosis: Malignant melanoma.

• Best treatment for this problem: If this proves to be melanoma, wide local excision with an appropriate clear margin is the best initial treatment. Additionally, evaluation and excision of the regional lymph nodes may be appropriate depending on the depth of invasion of the tumor.

Analysis

Objectives

I. Be familiar with the clinical presentation of malignant melanomas.

2. Appreciate the principles involved in performing biopsies of suspected melanomas.

3. Learn about the treatment and prognosis associated with melanomas.

Considerations

Melanoma should be considered whenever a patient presents with a pigniented skin lesion, and lesions should be assessed with the following ABCDE approach. A: asymmetry; B: border irregularity; C: color change; D: diameter increase; E: enlargement or elevation.

All suspicious lesions should undergo a diagnostic biopsy aiid be assessed for depth of tumor invasion. A simple excision can be used to perform a biopsy on small lesions on the extremities. Lesions that are large or involve cosmetically important areas require an incisional biopsy. During the initial biopsy, no attempts are made to achieve a wide margin. Once the melanoma is confirmed and microstaged via biopsy, the patient will require a thorough examination for locoregional metastases and distant metastasis before treatment of the primary melanoma.

APPROACH TO PIGMENTED SKIN LESIONS

Clinical Approach

The incidence of cutaneous melanoma is increasing at an alarming rate. In the year 2000. there were 60.000 new cases and 7700 deaths. Melanoma accounts for 4% of all newly diagnosed cancers in the United States and for I % of all cancer deaths. It is responsible for six out of seven deaths caused by skin cancer. Melanoma is now the tifth most common cancer in men and the seventh most common cancer in women in the United States. The site of occurrence is evenly distributed among the head and neck, trunk, and upper and lower extremities.

Risk factors can be divided into environmental, genetic, and other (Table 4—1), with an associated increase in the overall relative risk. Melanocytes. dendritic cells found at the dermal/epidermal junction. are found in the skin, choroids of the eye, mucosa of the respiratory and gastrointestinal tracts, lymph node capsules. and substantia nigra in the brain. The four types of melanoma are (1) superficial spreading, (2) nodular sclerosis, (3) lentigo maligna, and (4) acral lentiginous. By far the most common is superficial spreading, which accounts for 70% of all cases. It has a slight female predominance and typically has a prolonged radial growth phase (1—10 years) and a late vertical growth phase. In comparison to that for the other types of melanoma, the prognosis is favorable. Nodular sclerosis is the second most common form, accounting for 15% to 30% of all cases. It has no radial growth phase but has an aggressive vertical growth phase that spreads quickly, partially explaining its poorer prognosis. Lentigo maligna occurs in approximately 4% to 10% of patients and has a relatively long radial growth phase (5—15 years) and a good prognosis. Acral lentiginous melanoma represents 35% to 60% of cases occurring in African Americans, Asians, and Hispanics and appears primarily on the palms and soles of the hands and feet and in the nail beds. Similar to nodular sclerosis, it has a very aggressive vertical growth phase and is associated with a poor prognosis.

The incidence of melanoma is directly related to sun exposure. To reduce sun damage, patients should be advised to avoid exposure during the hours of lOAM to 4 PM. seek shade at all times, and apply sunscreen liberally to protect against ultraviolet (UV) radiation, primarily ultraviolet B (UVB). Other measures include the use of titanium dioxide or zinc oxide for ultravio’et A (IJVA) protection, a wide-brimmed hat, sunglasses, darker clothes, and the avoidance of tanning booths and sunlamps.

The treatment and prognosis are determined by the microstage and [he pathologic stage of the tumor. The American Joint Committee on Cancer (AJCC) revised staging system for melanoma from 2002 introduced some important changes and include the following: (I ) Thickness and ulceration continue to be used for the T classification; however, the level of invasion is no longer used except for TI lesions. (2) The number of metastatic lesions (rather than the largest dimension) is now used for the N classification as well as whether the nodes are microscopic versus macroscopic. (3) The site of distant metastases and the serum lactate dehydrogetiase levels are used for the M classification. (4) All patients with stage 1. 11. or 111 disease with an associated primary lesion that is ulcerated should be upstaged. (5) Satellite and in-transit metastases are all combined under stage Ill disease. (6) The information gained from a sentinel lymph node (SLN) biopsy br staging is used in making clinical management decisions, Table 4—2 lists the new melanoma TNM classification and AJCC stage grouping.

The two methods of microstaging have been described by Clark and Breslow. The Clark method of microstaging is based on the level of invasion of the dermal layers (i.e., intraepithelial, into or filling the papillary dermis, into the reticular dermis). The Breslow method of microstaging level is based on the depth of invasion, which is the vertical height of the melanoma from the granular layer to the area of deepest penetration. Most studies have shown that, compared to the Clark method, Breslow depths of invasion are more accurate prognostic indicators; the overall 5-year survival correlates with tumor thickness. The 5-year survival rate for stage I melanoma with a thickness of <0.75 mm is >96%.

Treatment

Primary Tumor

The surgical treatment of melanoma begins with proper management of the primary lesion. Table 4—3 summarizes a treatment plan. Because wide local excision is necessary for treatment of the primary tumor, reexcision of the previous biopsy scar is generally needed. Therefore, orientation of the initial biopsy is extremely important in avoiding unnecessary tissue loss and morbidity. In general, biopsy incisions on the extremities should be oriented longitudinally.

Lymph Nodes

When palpable adenopathy is present, complete lymphadenectomy of the involved lymph node basin should be performed. However, an attempt should be made to obtain a tissue diagnosis (either with fine-needle aspiration or excisional biopsy) before this procedure. Patients with intermediate-depth melanoma (0.76—4 mm) seem to have a longer survival after prophylactic lymph node dissection, suggesting that some patients without clinically evident lymph node involvement may also benefit from regional lymphadenectomy. Because of the morbidity associated with lymphadenectomy. prophylactic dissection is not done routinely, but instead the lymph node basins are generally assessed by SLN biopsy. The SLN is the first node in the lymphatic channel through which the primary melanoma drains and can be identified with

>90% accuracy by using the combined technique of vital blue dye and radiolymphoscintigraphy. This approach offers the advantages of identifying patients with regional nodal metastases who may benefit from therapeutic lymph node dissection and avoids exposing patients without regional lymph node metastases to the morbidity associated with a lymphadenectomy. Additionally, the histologic analysis results from an SLN biopsy can be used to stage the disease process more accurately.

All patients with confirmed lymph node meta.sta.ses should undergo a thorough workup to exclude or identify extranodal spread. Surgery is the primary therapy for patients with nodal involvement, and adjuvant therapy provides minimal benefits for stage I and II disease and only limited benefits for stage III disease. Currently. interferon-2A (lntron-A) is the treatment offered for stage LII disease and provides marginal improvements in overall and disease-free survival. However, because of side effects, Intron-A therapy is generally poorly tolerated.

The prognosis br patients with stage [V disease remains dismal, with a median survival of 6—9 months. Again, it is essential that a thorough workup be pertbmed to develop a therapeutic plan for all sites of disease involvement. Therapeutic options for patients with stage IV disease are limited. The most promising treatment, now approved by the Food and Drug Administration (FDA) for stage IV melanoma patients, is high-dose interleukin-2, which has a known complete, durable response rate of 9% and a partial response rate of 8%.

Comprehension Questions

14.1 j Which of the following is the most common form of melanoma?

A. Superficial spreading

B. Nodular sclerosis

C. Acral lentiginous

D. Lentigo maligna

14.21 Which of the following is the most accurate prognostic indicator during microstaging of a melanoma?

A. Breslow depth of invasion

B. Clark level of invasion

C. T-cell infiltration

D. Size of the primary tumor

[4.3] Based on the current consensus, which of the following is the most appropriate surgical margin for a 2.0-mm-depth melanoma?

A. 0.5 cm

B. 1 cm

C. 2cm

D. 4cm

Answers

14.11 A. Superficial spreading is the most common form of melanoma.

[4.2] A. Although Breslow and Clark staging both use depth of invasion, the Breslow criterion is considered to reflect the prognosis more accurately.

[4.3] C. Margins of 2 cm are considered adequate for a tumor with a depth between 1.5 mm and 4 mm.

CLINICAL PEARLS

+ A full-thickness biopsy should be performed on all suspicious pigmented skin lesions.

Asymmetry, Border irregularity, Color change, Diameter increase, and Enlargement or Elevation is more suspicious for malignant melanoma.

The Breslow system is more accurate than the Clark system for microstaging.

Complete excision of tumor remains the mainstay of therapy for melanoma.