Melanocytic neoplasms

Published on 09/03/2015 by admin

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Chapter 6

Melanocytic neoplasms

Dirk M. Elston

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.

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 6-1 Solar lentigo

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.

Fig 6-2 Melanotic macule

Fig 6-3 Benign melanocytic nevus

Fig 6-4 Malignant melanoma for comparison: Confluent melanocytes involving the arches between rete

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.

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

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)

Acral nevus

Fig 6-12 Pigmented spindle cell nevus

Fig 6-13 Genital nevus

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 lab when submitting a specimen from acral skin. Some clinicians prefer to bisect the specimen themselves, perpendicular to the dermatoglyphs.

Fig 6-14 Acral nevus

“Ancient” nevus

The term “ancient” atypia has been applied to atypical nuclei in benign lesions. Mitoses, confluent growth or an expansile growth pattern (nodule) should never be present.

Halo nevus

Pearl

The pattern of the lymphoid infiltrate of a halo nevus resembles a cocktail party, with lymphocytes and melanocytes mingling together. In contrast, the pattern of the lymphoid infiltrate of a melanoma resembles a wall of riot police trying to hold back an angry mob (band of lymphocytes at the periphery of melanocytic nests).

Fig 6-15 Ancient nevus

Fig 6-16 Halo nevus

Fig 6-17 Melanoma for comparison

Blue nevus

Variants of blue nevus are defined by the cytologic characteristics of the melanocytes. Common blue nevi are often seen on the dorsal hands and feet, face, and scalp. They are composed of dendritic melanocytes. Cellular blue nevi are commonly seen on the buttocks. They are composed of fusiform melanocytes with vesicular nuclei and prominent nucleoli. A closely related lesion referred to as an epithelioid blue nevus is associated with the Carney complex. It lacks the sclerotic stroma usually associated with blue nevi. Deep penetrating nevi are composed of melanocytes with small hyperchromatic nuclei, a smudged chromatin pattern, and inconspicuous nucleoli. Combined blue nevi are common. They include lesions with mixed features of different types of blue nevi, as well as lesions with components of blue and ordinary nevus. Dendritic “equine-type” melanomas are quite rare; they can be differentiated from blue nevi by the presence of nuclear atypia and the lack of sclerotic stroma.

Fig 6-18 Common blue nevus

Fig 6-19 Cellular blue nevus

Fig 6-20 Epithelioid blue nevus

Fig 6-21 Deep penetrating nevus

Combined nevus

Key features

• Two or more populations of nevus cells

Combined nevi most commonly demonstrate a banal (ordinary) nevus component as well as a blue nevus component, but any variant of nevus can be represented within a combined nevus.

Fig 6-22 Combined nevus

Dysplastic nevus

Dysplastic nevi occur in patients with the B-K mole/melanoma syndrome (dysplastic nevus syndrome) as well as sporadically. Any growing mole will have some features in common with a dysplastic nevus. “Special site” nevi can be indistinguishable from dysplastic nevi. Some refer to these as “atypical” nevi.

Grading dysplastic nevi

• Low-grade: atypia restricted to shoulder region

• Moderate: atypia in both shoulder region and central portion, some irregularity and confluence of nests

• High-grade: high-grade cytologic atypia in areas, not entirely well nested at junction, irregular nests, may be marginal in distinction from malignant melanoma in situ

Some have questioned the significance of grading of dysplastic nevi. Others prefer to divide them into high-grade and low-grade lesions.

Management

The management of dysplastic nevi is controversial. Most of the atypical cells are found in the shoulder region at the lateral edges of the specimen. The shoulder extends up to 2 mm beyond the clinically apparent edge of the specimen. A broad saucerization that includes a 0.5–2 mm margin of normal-appearing skin will provide the pathologist with the entire lesion, including the entire shoulder region.

In the author’s opinion, high-grade lesions are best managed like malignant melanoma in situ. The risk of melanoma arising in a lesion with low-grade or moderate atypia is low. A greater risk is that a recurrent nevus within the scar will be misdiagnosed as melanoma. This can lead to overly aggressive management. For a low-grade dysplastic nevus that involves a margin, I will often include a comment:

The patient can be reassured that the lesion appears benign histologically. When they recur, lesions such as these commonly appear atypical clinically and histologically. This creates a potential for diagnostic confusion. In the case of recurrence, it is best if the patient is evaluated by a clinician who is familiar with the preceding lesion. Prompt removal of any recurrent lesion will minimize the potential for future diagnostic confusion.

Fig 6-23 Dysplastic nevus

Fig 6-24 Atypia in the shoulder region of a dysplastic nevus

Junctional lentiginous nevus

Key features

• Club-shaped epidermal hyperplasia

• Round to oval melanocytic nests at the dermal–epidermal junction

• Nests restricted to the tips and sides of rete

Fig 6-25 Junctional lentiginous nevus

Recurrent nevus (persistent nevus, pseudomelanoma)

Key features

• Confluent, poorly nested, or irregularly nested junctional melanocytic proliferation

• Underlying scar

• Melanocytic proliferation confined to the area overlying the scar

• May see residual bland nevus under scar

Recurrent nevi may simulate melanoma. History is critical, and review of the prior biopsy material may be necessary.

Fig 6-26 Recurrent nevus

Nevus of Ota/nevus of Ito

Key features

• Dendritic melanocytes scattered between collagen bundles in the upper third of the dermis

• Melanocytes oriented east to west

• No sclerotic stroma

A biopsy will demonstrate a subtle band of dendritic melanocytes in the upper dermis. There is no associated sclerotic stroma. Clinically, they present as deep blue patches on the face (Ota) or shoulder (Ito).

Fig 6-27 Nevus of Ota

Fig 6-28 Mongolian spot

Table 6-3

Distinguishing features of melanomas

Mongolian spot

Key features

• Dendritic melanocytes scattered between collagen bundles in the lower half of the dermis

• Melanocytes oriented east to west

• No sclerotic stroma

Pearls

1. In the in situ portion of lentiginous types of melanoma, the atypical melanocytes proliferate predominantly at the dermal–epidermal junction, with little to no buckshot scatter.

2. The vertical growth phase is an expansile dermal nodule. It typically invades the reticular dermis (into the zone of bundled collagen or solar elastosis) or appears as a dermal nest larger than the largest junctional nest. Mitoses or necrosis may be noted in the nodule. The vertical growth phase may have different cytologic features from the radial growth phase. Metastases typically resemble the vertical growth phase cytologically.

3. Measure the depth of invasion from the granular layer, the base of an ulcer, or the inner root sheath (if invading outward from a follicle).

4. Clark’s levels:

I Confined to the epidermis (in situ melanoma)

II Into the papillary dermis

III To the papillary dermis–reticular dermis interface

IV Into the reticular dermis

V Into the subcutaneous fat.

Superficial spreading malignant melanoma

Key features

• Broad lesion

• Buckshot scatter of atypical melanocytes within the epidermis

• Non-nested melanocytes outnumber nests in areas

• Nests vary in size and shape (often elongated, bizarre, or confluent)

• Nests not evenly spaced

• Nests not confined to tips and sides of rete

• Typically not symmetrical (right to left)

• Typically fails to mature from top to bottom

• Typically fails to disperse at base

• Dermal nests often larger than junctional nests

• Deep pigment may be present within melanocytic nests

• Lymphoid infiltrate frequent at base, walling off lesion (“riot police”)

• Plasma cells common in infiltrate

• Deep mitoses may be present

• Cytologic atypia

• Melanocytes often have ample amphophilic cytoplasm

• HMB-45 staining typically strong to base

• S100A6 staining typically patchy

• MIB-1 staining of deep melanocyte nuclei common

Fig 6-29 Superficial spreading melanoma

Lentigo maligna

Lentigo maligna typically exhibits asymmetrical growth. As the atypical melanocytes are only one cell thick at the dermal–epidermal junction, the lateral borders are poorly defined clinically. The lesion often extends far beyond the clinically apparent margin.

Pearls

1. Small biopsies are likely to result in misdiagnosis. Skip areas are common. Lichenoid regression can mimic a lichenoid actinic keratosis or benign lichenoid keratosis. Benign pigmented lesions (pigmented actinic keratosis and solar lentigo) occur in collision with lentigo maligna in about half of all cases. Small biopsies may sample only the benign lesion. The false-negative rate of a small biopsy is up to 80%. The best biopsy technique for a large macular facial lesion may be a broad thin shave, or multiple small shave biopsies, to sample every color within the lesion.

2. Although effacement of the rete is typical, lentiginous epidermal hyperplasia may occur, and lentigo maligna may closely resemble a junctional lentiginous nevus or junctional dysplastic nevus. A broad junctional lesion on sun-damaged skin is probably melanoma in situ.

Fig 6-30 Lentigo maligna (DEJ, dermal–epidermal junction)

Lentigo maligna melanoma

Key features

• Lentigo maligna with a vertical growth phase

• Vertical growth phase may be epithelioid, spindled, or desmoplastic

Spindle cell melanoma

Key features

• Spindled cytology

• Most reliable immunostain are S100 and SOX10

Fig 6-31 Spindle cell melanoma

Differential Diagnosis

Spindled melanomas can closely resemble other spindle cell neoplasms. The microscopic differential diagnosis for an atypical spindle cell tumor slammed up against the epidermis includes:

• Squamous cell carcinoma (keratin-positive)

• Leiomyosarcoma (smooth muscle actin-positive, desmin-positive)

• Atypical fibroxanthoma (diagnosis of exclusion)

• Melanoma (S100-positive)

Desmoplastic melanoma

Key features

• Dense desmoplastic stroma

• Nodular lymphoid aggregates

• May see a subtle overlying lentigo maligna

• S100 and SOX10 are generally reliable, but other immunostains like HMB-45 are unreliable in desmoplastic melanoma

• Atypia of spindle cells is variable

• Perineural extension common

Nodular melanoma

Fig 6-32 Desmoplastic melanoma

Fig 6-33 Nodular melanoma

Regressing melanoma

Key features

• Lichenoid regression may occur in lentigo maligna

• Regression in other melanomas is probably secondary to genomic instability rather than inflammatory response

• May appear as zones of fibrosis and melanophages

• Adverse prognostic indicator

• “Tumoral melanosis” may be regressed melanoma

Fig 6-34 Regressing melanoma

Metastatic melanoma

Fig 6-35 Metastatic melanoma

Epidermotropic nevoid metastases typically fail to mature or disperse well at the base. This helps to distinguish them from nevi. In lymph nodes, metastatic melanoma is typically subcapsular in location. Nodal nevi occur, but are typically located within the capsule and are composed of bland nuclei.