Common Melanocytic  Nevus

 

Epidemiology:

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Common sites:

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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:

Sensitivity:

Specificity:

 

 

 

 

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
        1. Note that this does not exclude the possibility of aberrations in individual melanocytes or random aberrations in many of the cells
          1. 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
        1. Gains and losses of entire chromosomes
        2. Chromosome 7 losses
        3. 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
        1. p16 (CDK-inhibitor)
        2. p21 (CDK-inhibitor)
        3. p14/ARF (blocks p53 degradation)
      • DNA replication induced by these constitutively activated pathways is more likely to involve replication errors resulting in DNA damage
        1. The DNA damage then triggers critical checkpoints
          1. Typically p53-dependent
          2. 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
        1. After 60-70 divisions, the DNA reaches a critical length which triggers a DNA damage signal that permanently arrests the cell
          1. 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:

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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.