Cutaneous melanoma: Detecting it earlier, weighing management options

Most important for the prognosis is a determination of the tumor’s depth of invasiveness.

In situ or invasive?

Melanoma in situ lesions are confined to the epidermis and may extend along hair appendages. It often occurs on sun-exposed areas (FIGURES 1 AND 2). Histologically, melanoma in situ is an asymmetric and poorly circumscribed proliferation of melanocytes usually larger than 6 mm in diameter (FIGURE 3).

Melanocytes form irregular nests that are not equidistant and have areas of confluence (FIGURE 3). Single melanocytes predominate over nests in some areas and may entirely replace the basal layer.

Additional histologic features include single melanocytes above the dermal-epidermal junction (Pagetoid spread) and uneven distribution of pigment. In many cases the dermis has inflammatory infiltrates, melanophages, and evidence of solar-damage. Particularly in anatomical areas rich in hair follicles, the neoplastic cells may spread into the epithelium of the hair follicles without extending to the dermis.

Melanoma in situ may be quite large in diameter (horizontal growth phase) without becoming invasive; however, always be concerned about invasion.

Invasive melanoma shares the same histologic features but invades the dermis or subcutaneous fat (vertical growth phase). Aside from the conventional criteria used for the histologic diagnosis of melanoma, acral melanomas may show an increased number of dendritic melanocytes loaded with melanin (FIGURE 4). Desmoplastic melanoma is most commonly found on the head and neck; however, it varies in clinical presentation (FIGURE 5). It is often associated with other types of melanoma, is common in older persons, and has a slight male predilection.

FIGURE 3
Melanocytes

FIGURE 4
Acral melanoma

FIGURE 5
Dermoplastic melanoma

Microstaging: The key to good management

The categories “superficial spreading” and “nodular” are based on the seminal work of Wallace Clark, who described putative growth phases of cutaneous melanoma.¹² Clark hypothesized that melanoma initially grows horizontally and only later begins an invasive vertical growth phase.

The horizontal growth phase is common in sun-exposed sites and often occurs over a long period of time. The vertical growth phase is a much more aggressive growth pattern that, if left unchecked, can be lethal. This is often seen in nodular melanoma (FIGURE 6).

Measurement of vertical growth (“microstaging”) is the most important prognostic indicator for localized cutaneous melanoma.¹³

Clark described 5 levels (“Clarks’ levels,” I–V) of invasion (FIGURE 7).

Independently of Clark, Breslow described tumor thickness as an important prognostic factor.^14,15 Breslow thickness is measured from the granular layer of the epidermis to the deepest area of invasion (FIGURE 7). Most reports indicate that, overall, Breslow tumor thickness more closely correlates with clinical outcome.¹⁶

Special circumstances that affect microstaging. Although Clark and Breslow measurements are both conceptually simple, a number of factors, including hair follicle involvement and ulceration, must be considered when measuring melanoma depth. It is often useful to have a Breslow thickness and a Clark’s level for primary cutaneous melanomas (both methods are used for staging thin primary lesions).

The location of the primary lesion affects interpretation of measurement results. For example, a Breslow thickness of 0.5 mm confers a different meaning on the eyelid (very thin skin, Clark’s level proportionately deeper than tumor thickness might indicate) than the back (thick skin, proportionately more superficial Clark’s level than tumor thickness would indicate).

Measurement of vertical involvement is used to stage the tumor with the TNM classification. This was recently updated as outlined by Balch et al¹³ in 2001 (TABLE 1).

FIGURE 6
Nodular melanoma

FIGURE 7
Classifying melanoma: Both Clark’s level and Breslow measurement are often used for staging