Common Melanocytic
Nevus
Epidemiology:
Common sites:
Gross features:
- tan to brown
- uniformly pigmented
- small (<0.6cm usually)
- macule or papule (compound and intradermal nevi
are more elevated than junctional)
- well-defined, rounded borders
Histologic features:
- nests of round cells
- uniform, rounded nuclei
- inconspicuous nucleoli
- maturation:
- superficial cells:
- larger
- melanin producing
- nests
- deeper cells:
- smaller
- little or no melanin
- cords or fascicles similar to neural tissue
- fusiform contours
- type A nevus
cell (intraepidermal):
- round-to-oval nucleus, slightly smaller than
nucleus of adjacent keratinocytes
- finely dispersed chromatin
- occasional single, inconspicuous nucleolus
- prominent cytoplasm
- moderately coarse melanin granules often
- Type B (lymphocyte-like) melanocyte:
- Usually dermal location
- Small round nucleus
- Uniformly dispersed chromatin
- No apparent nucleoli
- Scant, non-pigmented cytoplasm
- Type C (neural) nevus cell:
- Base of melanocytic lesions often
- Rest at, or singly infiltrate, superficial
reticular dermal collagen bundles
- Spindle-shaped or fusiform
- Smaller oval nucleus
- Banal chromatin pattern
- little or no mitotic activity
- junctional
nevus:
- nests only at dermo-epidermal
junction
- compound nevus:
- nests involving dermo-epidermal
junction and underlying dermis
- intradermal nevus:
- nests only involving dermis
Immunophenotype:
Marker:
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Sensitivity:
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Specificity:
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Molecular features:
- frequent somatic mutations in oncogenes
- BRAF (acquired)
- NRAS (giant congenital nevi)
- HRAS (Spitz nevi)
- GNAQ (blue nevi)
- Chromosomal aberrations are infrequent
- Vast majority of nevi have no detectable copy
number changes by CGH
- Note that this does not exclude the
possibility of aberrations in individual melanocytes or random
aberrations in many of the cells
- But none of the cells with aberrations has
undergone any significant clonal expansion
- Spitz is an exception
- Atypical nodular proliferations arising in congenital
nevus is an exception
- Gains and losses of entire chromosomes
- Chromosome 7 losses
- Chromosome 10 gain
- Pathways activated:
- MAP-kinase
- PI3-kinase
- Constitutive activation of these pathways
triggers complex counteracting feedback mechanisms that counteract the growth-promoting
effects via RB and p53 pathways
- p16 (CDK-inhibitor)
- p21 (CDK-inhibitor)
- p14/ARF (blocks p53 degradation)
- DNA replication induced by these constitutively
activated pathways is more likely to involve replication errors
resulting in DNA damage
- The DNA damage then triggers critical
checkpoints
- Typically p53-dependent
- Permanently stops proliferation if the DNA
cannot be repaired (DNA-damage-induced senescence)
- growth may also be limited by replicative or
telomere-induced senescence
- DNA sequence forming the telomere becomes
shorter with each cell division
- After 60-70 divisions, the DNA reaches a
critical length which triggers a DNA damage signal that permanently
arrests the cell
- Note however that 2^60 cell divisions would
allow a nevus to reach several tons in weight potentially
- Secretion of soluble factors which induce
senescence in neighboring cells in a paracrine fashion
- BRAF mutation induces IGFB7 secretion which
induces permanent growth arrest
- Oncogene-induced inflammatory response
- IL-6 and IL-8
- Clearance of senescent cells by immune system
- May result in disappearance of nevi over time
Other features:
References:
- Robbins 2005
- Calonje
JE, Brenn T, Lazar AJ, McKee PH. McKee’s Pathology
of the Skin: Expert Consult - Online and Print 2 Vol
Set, 4e. 4th ed. A Saunders Title; 2011.