Melanocytic neoplasms


Solar lentigo

Key Features

  • Thin rete with bulbous tips “dipped in chocolate”

Differential Diagnosis

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

Fig. 6.1, Solar lentigo

Melanotic macule

Key Features

  • Common on the lips and genitalia

  • Rete are broad and squared-off with pigment at basal layer

Melanotic macules are typically light brown and evenly pigmented, but those in the genitalia may sometimes have strikingly irregular pigment. The histologic changes are the same, regardless of location and clinical appearance.

Fig. 6.2, Melanotic macule

Benign melanocytic nevus

Key Features

  • Sharply defined

  • Well nested at the dermal–epidermal junction

  • Round to oval nests at the tips and sides of rete ridges

  • Matures a

    a These features are only present if there is a dermal component

  • Disperses at the base of the lesion a

  • No deep mitoses a

  • No deep pigment in melanocytic nests a

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.

Pearls

  • 1

    Broad junctional lesions on heavily sun-damaged skin are usually melanoma, regardless of how bland they appear.

  • 2

    Small, well-nested lesions are almost always benign.

  • 3

    Horn cysts can occur in the epidermis overlying melanocytic lesions. Horn cysts visible with dermoscopy are not diagnostic of seborrheic keratosis.

  • 4

    Epithelial crypts are common in conjunctival nevi.

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 wedgelike 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 Nonnested 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

Fig. 6.3, Benign melanocytic nevus. (F and G) Preservation of delicate elastic fibers is typically noted throughout the lesion. See Fig. 6.29 (J) for comparison with melanoma. (H) Conjunctival nevi characteristically demonstrate complex epithelial crypts. See Fig. 6.29 (L) for comparison with conjunctival melanoma

Balloon cell nevus

Key Features

  • Balloon cells

  • Sharply defined

  • Well nested at the dermal–epidermal junction

  • Matures

  • Disperses at the base of the lesion

  • No deep mitoses

  • No deep pigment in melanocytic nests

Balloon change is a degenerative feature. Ultrastructurally, it is characterized by swelling of cellular organelles.

Fig. 6.4, Balloon cell nevus

“Neural” nevus

Key Features

  • S-shaped spindle cells similar to those of a neurofibroma

  • Nevic corpuscles resembling Meissner corpuscles

  • Sharply defined

  • Disperses at the base of the lesion

  • No deep mitoses

  • No deep pigment

Fig. 6.5, Neural nevus

Congenital nevus

Key Features

  • Broad

  • Bland cytologically

  • Matures

  • Cells disperse at base

  • Often within or aggregated about follicles, vessel walls, and nerves

  • Patchy perivascular pattern

  • Single-file interstitial pattern

A typical congenital nevus demonstrates a well-defined melanocytic proliferation with bland nuclei. The lesion is symmetrical from right to left, with a patchy perivascular, periadnexal, and interstitial pattern. Cells mature and disperse in the deeper portions of the lesion.

Fig. 6.6, Congenital nevus

Spitz nevus

Key Features

  • Hyperkeratosis, hypergranulosis, pseudoepitheliomatous hyperplasia (PEH) a

    a These features are only seen if a dermal component is present.

  • Well nested at the dermal–epidermal junction a

  • Nests vertically oriented along rete (“raining-down pattern,” “bananas on the tree”) a

  • Melanocytes within the nests share the vertical orientation a

  • Clefts around nests a

  • Kamino bodies a

  • Large spindle and epithelioid cells

  • Nuclei as large as or larger than keratinocyte nuclei

  • Nuclei vesicular with prominent nucleoli

  • Two-tone cytoplasm

  • Sharply defined laterally

  • Line symmetry from left to right

  • Matures from top to bottom

  • Disperses at the base of the lesion

  • No deep mitoses

  • No deep pigment in nests

  • Buckshot scatter OK in center of lesion a

  • These features are only present if there is a junctional component

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.

Fig. 6.7, Spitz nevus ( PEH, pseudoepitheliomatous hyperplasia)

Fig. 6.8, Kamino body (trichrome stain)

Fig. 6.9, Immunostaining pattern of Spitz nevus

Fig. 6.10, Intradermal Spitz nevus

Pagetoid intraepidermal Spitz nevus

Key Features

  • Buckshot intraepidermal scatter of large epithelioid melanocytes

  • Hyperkeratosis variable

  • Relatively small and very sharply circumscribed lesions of children and young adults

  • Lack nuclear pleomorphism and hyperchromasia

Fig. 6.11, Pagetoid intraepidermal Spitz nevus

Pigmented spindle cell nevus of Reed

Key Features

  • Hyperkeratosis, hypergranulosis, pseudoepitheliomatous hyperplasia

  • Well nested at the dermal–epidermal junction

  • Clefts around nests variable

  • Kamino bodies variable

  • Small spindle cells

  • Sharply defined

  • Line symmetry from left to right

  • Matures from top to bottom if compound

  • Disperses at the base of the lesion if compound

  • No deep mitoses

  • No deep pigment in nests

  • Buckshot scatter OK in center of lesion

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
Characteristic Spitz nevus Pigmented spindle cell nevus of Reed
Age Children Young women
Color Usually pink Usually dark brown
Location Head Legs
Hyperkeratosis, hypergranulosis, and pseudoepitheliomatous hyperplasia Yes Yes
Cytology Large spindle and epithelioid cells Small spindle cells
Kamino bodies Common Variable
Buckshot scatter in epidermis Normal in center lesion Normal in center lesion
S100A6 Strongly + Weak and patchy

“Special site” nevus

Key Features

  • Occur in the anogenital region, axillae, umbilicus, breast, scalp, ears

  • One pattern resembles a dysplastic nevus

  • Second pattern characterized by large junctional nests that appear poorly cohesive (white space surrounding each melanocyte)

Fig. 6.12, Pigmented spindle cell nevus

Fig. 6.13, Genital nevus

Acral nevus

Key Features

  • On volar skin, nests are commonly elongated and follow dermatoglyphs

  • Buckshot scatter OK in center of lesion

  • Sharply defined

  • Well nested at the dermal–epidermal junction

  • Matures

  • Disperses at the base of the lesion

  • No deep mitoses

  • No deep pigment in melanocytic nests

Within the central portion of an acral nevus, melanocytes are commonly noted above the dermal–epidermal junction. As long as it is confined to the center of the lesion, “buckshot scatter” by itself is not a worrisome feature in an acral nevus.

If volar nevi are bisected perpendicular to the dermatoglyphs, the nests will appear round. The rete pattern will be regular. If they are inappropriately sectioned parallel to the dermatoglyphs, the nests will appear long and confluent. The rete pattern may appear effaced in such sections. Oblique sections will give the appearance of irregular nesting and Swiss-cheese rete. It is important to communicate carefully with the laboratory when submitting a specimen from acral skin. Some clinicians prefer to bisect the specimen themselves, perpendicular to the dermatoglyphs.

Fig. 6.14, Acral nevus

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