Melanocytic neoplasms

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Chapter 6

Melanocytic neoplasms

Solar lentigo

Differential Diagnosis

Reticulated seborrheic keratosis looks similar to a lentigo but with anastomosis of rete and horn cysts.

Benign melanocytic nevus

Benign nevi are bilaterally symmetrical from right to left, but they are asymmetrical from top to bottom. In contrast, melanoma metastases are radially symmetrical in all directions, like a cannonball.

A biopsy of a nevus demonstrates a discrete well-nested melanocytic proliferation in the upper portion of the lesion. Melanocytes disperse into individual units in the deeper portions of the lesion. Maturation refers to melanocytes becoming progressively smaller and spindled in the deeper portions of the lesion. Melanin should not be present in deep melanocytic nests, although melanophages may be present. In cases with questionable maturation, top-heavy HMB-45 immunostaining (loss of staining in the deep component) is a surrogate marker of maturation. Deep mitoses are absent. In unusual lesions, MIB-1 immunostaining is sometimes performed. MIB-1 is expressed in all active phases of the cell cycle – G1, M, G2 and S phase (but not resting G0) – and is not a mitotic marker. There should be no staining of deep melanocytic nuclei.

Table 6.1 gives general rules, and is a good starting point for the evaluation of pigmented lesions. There are exceptions to the rules. For example, blue nevi show no evidence of maturation or dispersion. They are commonly deeply pigmented to the base of the lesion. They are readily recognized by their wedge-like or bulbous outline and characteristic cytologic features.

Table 6-1

Characteristics of nevus versus melanoma

Characteristic Nevus Melanoma
Lateral circumscription Sharp Variable
Bilateral (right to left) symmetry Yes Commonly asymmetrical
Top to bottom symmetry No Variable
Size Small Usually quite broad
Dermal–epidermal junction Well nested Non-nested melanocytes usually outnumber nests in areas
Shape of junctional nests Round to oval Often elongated and bizarre
Location of junctional nests Tips and sides of rete Tops of dermal papillae often involved as well
Spacing of junctional nests Regular Usually irregular
Buckshot scatter in epidermis Absent except in the center of Spitz nevi, pigmented spindle cell nevi, acral nevi, traumatized nevi, and sunburned nevi Variable (present in superficial spreading malignant melanoma, usually not prominent in lentigo maligna and acral lentiginous malignant melanoma)
Maturation Cells become smaller and more neuroid from top to bottom Typically fails to mature
Dispersion Disperses to single units at base of lesion Generally remains nested at base
Junctional vs dermal nests Dermal nests smaller than junctional nests; from top to bottom, nests become smaller, melanocytes disperse Dermal nests often larger than junctional nests
Deep mitoses Rare Variable
Deep pigment No Variable
HMB-45 Top-heavy Commonly stains strongly to base
MIB-1 No deep nuclei positive Deep nuclei commonly positive
S100A6 Spitz nevi usually stain diffusely Usually patchy

Spitz nevus

Benign spindle and epithelioid cell (Spitz) nevi occur in adults, but most commonly present as pink papules on the face or scalp of a child. Unfortunately, melanomas can demonstrate large spindle and epithelioid cells, hyperkeratosis, hypergranulosis, and pseudoepitheliomatous hyperplasia. These features are especially common among melanomas in the pediatric age group. Critical distinguishing features include sharp lateral circumscription, maturation, and dispersion, all of which should be present in benign Spitz nevi. Deep mitoses should be absent. Kamino bodies are dull pink areas of trapped basement membrane material within the epidermis. They stain blue to green with a trichrome stain and mark with immunostains for type IV collagen.

In lesions with any atypical feature, immunostaining is commonly performed. HMB-45 immunostaining should be top-heavy, and the lesion should stain diffusely for S100A6. MIB-1 staining should be absent in melanocyte nuclei at the base of the lesion.

Comparative genomic hybridization and chromosome deletion analysis by fluorescent in situ hybridization are promising techniques. The majority of Spitz nevi have a normal chromosome complement. Some large Spitz nevi have an 11p gain.

Pigmented spindle cell nevus of Reed

Benign pigmented spindle cell nevus is considered by many to be a variant of Spitz nevus. They typically present as deeply pigmented macular lesions on the thighs or lower legs of young women. The spindled melanocytes are smaller than those in a Spitz nevus. Epithelioid cells are rare.

Table 6-2

Characteristics of Spitz nevus versus pigmented spindle cell nevus of Reed

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Characteristic