Page 882 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

868 C H A P T E R 23 Skin

A BCDE

Time
Figure 23–21 Possible steps in development of melanoma. A, Normal skin shows only scattered melanocytes. B, Lentiginous melanocytic hyperplasia.
C, Lentiginous compound nevus with abnormal architecture and cytologic features (dysplastic nevus). D, Early or radial growth phase melanoma (large
dark cells in epidermis) arising in a nevus. E, Melanoma in vertical growth phase with metastatic potential. Note that no melanocytic nevus precursor
is identified in most cases of melanoma. They are believed to arise de novo, perhaps all using the same pathway.

MORPHOLOGY clinical sign is a change in the color or size of a pigmented lesion.
The main clinical warning signs are
Unlike benign nevi, melanomas exhibit striking variations
in pigmentation, including shades of black, brown, red, 1. Rapid enlargement of a preexisting nevus
dark blue, and gray (Fig. 23–22, A). The borders are irreg- 2. Itching or pain in a lesion
ular and often “notched.” 3. Development of a new pigmented lesion during adult

Microscopically, malignant cells grow as poorly formed life
nests or as individual cells at all levels of the epidermis (page- 4. Irregularity of the borders of a pigmented lesion
toid spread) and in expansile dermal nodules; these consti- 5. Variegation of color within a pigmented lesion
tute the radial and vertical growth phases, respectively (Fig.
23–22, B and C). Of note, superficial spreading melanomas These principles are expressed in the so-called ABCs of
are often associated with a brisk lymphocytic infiltrate (Fig. melanoma: asymmetry, border, color, diameter, and evolu-
23–22, B), a feature that may reflect a host response to tion (change of an existing nevus). It is vitally important
tumor-specific antigens. The nature and extent of the to recognize melanomas and intervene as rapidly as pos-
vertical growth phase determine the biologic behav- sible. The vast majority of superficial lesions are curable
ior of melanomas. By recording and using these and other surgically, while metastatic melanoma has a very poor
variables in aggregate, accurate prognostication is possible. prognosis.

Individual melanoma cells usually are considerably larger The probability of metastasis is predicted by measuring
than nevus cells. They have large nuclei with irregular con- the depth of invasion in millimeters of the vertical growth
tours, chromatin that is characteristically clumped at the phase nodule from the top of the granular cell layer of the
periphery of the nuclear membrane, and prominent “cherry overlying epidermis (Breslow thickness). Metastasis risk
red” eosinophilic nucleoli (Fig. 23–22, D). Immunohistochem- also is increased in tumors with a high mitotic rate and in
ical stains can be helpful in identifying metastatic deposits (Fig. those that fail to induce a local immune response. When
23–22, D, inset). metastases occur, they involve not only regional lymph
nodes but also liver, lungs, brain, and virtually any other
Clinical Features site that can be seeded hematogenously. Sentinel lymph
Although most of these lesions arise in the skin, they also node biopsy (of the first draining node[s] of a primary
may involve the oral and anogenital mucosal surfaces, the melanoma) at the time of surgery provides additional
esophagus, the meninges, and the eye. The following com- information on biologic aggressiveness.
ments apply to cutaneous melanomas.
In some cases, metastases may appear for the first time
Melanoma of the skin usually is asymptomatic, although many years after complete surgical excision of the primary
pruritus may be an early manifestation. The most important tumor, suggesting a long phase of dormancy, during which
time the tumor may be held in check by the host immune
response. Recognition of the likely role of the host immune
response has led to therapeutic trials of immunomodula-
tors. Some impressive responses in patients with advanced