| Clinical features | - Mean and median age 21 years (range: 2 to 69 years)
- Most commonly affects extremities, head, and neck
- Pink or reddish plaque, papule, or nodule
- Dark brown/black, flat-topped papule, plaque
| - Occurrence at any age; more common in younger patients (<40 years)
- Occurs on extremities, trunk
- Plaque or nodule
- Color variegation, dark brown/black
| - Occurrence at any age (virtually always >10 years, often >40 years)
- Occurs on extremities, trunk
- Asymmetrical
- Enlarged plaque or nodule, ulceration, bleeding
- Color variegation
- Changing lesion
|
| Histopathologic features | - <5 to 6 mm
- Symmetrical
- Well circumscribed
- Epidermal hyperplasia, polypoid, dome shaped, plaque type
- Vertically oriented nests with clefting
- Central focal pagetoid spread (if any)
- Flat base or wedge shaped
- Maturation of dermal component
- Few or no dermal mitoses (0 to 2/mm2)
| - Often >5 to 10 mm, or greater
- Symmetrical or asymmetrical
- Well or poorly circumscribed
- Ulceration possible
- Irregular nesting
- Increased cellularity
- Greater pagetoid spread than in Spitz nevus
- Deeper dermal extension than in Spitz nevus
- Maturation may be partial or absent
- 2 to 6 or more dermal mitoses/mm2
- Deep mitoses
- Possible necrosis
| - Usually >10 mm
- Frequent ulceration
- Usually ≥6 dermal mitoses/mm2
- Invasion of subcutis
- Often asymmetrical
- Often poorly circumscribed
- Irregular and confluent nesting
- Pagetoid spread may be extensive
- Effacement of epidermis
- Lack of maturation
- Deep/marginal or atypical mitoses
- Necrosis
|
| Cytologic features | - Enlarged epithelioid/spindle cells
- Little or no nuclear pleomorphism
- No high-grade cytologic atypia
| - Enlarged epithelioid/spindle cells
- Nuclear enlargement, pleomorphism, and hyperchromatism
| - Enlarged epithelioid/spindle cells
- High-grade cytologic atypia
|
| Immunohistochemistry | - HMB45 and Ki-67 staining diminished with depth in dermal component
- Low Ki-67 proliferation index (<5%)
- Retention of p16
- PRAME negative
| - HMB45 and Ki-67 staining diminished or variable with depth
- Low to intermediate Ki-67 proliferation index (5 to 15%)
- Retention or loss of p16
- PRAME usually negative (false positives occur)
| - HMB45 and Ki-67 deep staining common
- Elevated Ki-67 proliferation index (>20%)
- p16 expression may be completely absent
- PRAME usually positive
|
| Genetic alterations | - Isolated gains of 7p and 11q, tetraploidy
- Activating HRAS mutations
- Kinase fusions
| - Often ≥2 chromosomal abnormalities
- Kinase fusions
- HRAS mutations
- Other mutations possible
- Heterozygous or homozygous loss of CDKN2A may occur
| - >3 chromosomal abnormalities
- Kinase fusions
- HRAS mutations
- BRAF and NRAS mutations absent
- Other mutations possible
- Homozygous loss of CDKN2A often
- TERT promoter mutations
- Other TERT aberrations
|
| Prognosis | - Very low risk of progression
| - Low risk of progression
- Almost always indolent
- Clinical recurrences on occasion
| - Regional clinical lymph node metastases
- Distant metastases and death
|
