Neurofibromatosis type 1 (NF1)

 

Epidemiology and Etiology:

    •  Autosomal dominant
    • high penetrance, early on (childhood)
    • NF-1 gene (17q11.2)
      • Encodes neurofibromin protein
        • Inner aspect of plasma membrane
      • Downregulates p21Ras (cell cycle inhibitor) resulting in:
        • Lack of inhibition of cell cycle
        • Increases RAS signal transduction

 

Common sites:

    •  Peripheral nerve and skin:
      • neurofibromas
      • café au lait patches
      • axillary  / groin freckling
      • MPNST
    • CNS :
      • Gliomas (optic nerve, brain stem)
      • meningiomas
    • Eye:
      • Lisch nodules (pigmented hamartomas)(94% of patients > 6y)
    • Adrenal and ANS:
      • Pheochromocytoma
    • Bone (30-50%)
      • Scoliosis
      • Intraosseous cystic lesions
      • Subperiosteal bone cysts
      • Bony dysplasia
      • Pseudoarthrosis of tibia/fibula
      • Sphenoid wing dysplasia
      • Lamboid suture defects
    • GI:
      • GIST (5-25%) (small intestine > stomach)
      • Ganglioneuromatosis
    • Kidney:
      • Wilms
    • Soft tissue:
      • Rhabdomyosarcomas
    • Bone marrow:
      • CML
    • Skin:
      • Glomus (subungual)

 

Gross features:

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Histologic features:

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Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

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Other features:

    •  Reduced intelligence often
    • Intestinal obstruction (mass effect)
    • Hypertension (renal artery mass effect)

 

References:

    •  WHO Tumours of Endocrine Organs (2004)