Epidemiology

• Two Types of Neurofibromatosis
  • Neurofibromatosis 1 (von Recklinghausen’s Disease): autosomal dominant inheritance
    • Mutation in NF1 gene at 17q11
  • Neurofibromatosis 2

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Physiology

• Fibrotic neurofibromas of lung

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Pathologic Patterns

• Interstitial Lung Disease: usual interstitial pneumonia (UIP) features may be seen in some cases
• Pulmonary Hypertension
  • May be related to pulmonary fibrosis and/or chronic thromboembolic pulmonary HTN
  • In rare cases, pulmonary arteries and veins manifest intimal hypertrophy and fibrosis
• Systemic Vasculopathy: occasionally complicates the disease
• Neurofibromatosis type 1 gene modulates protein kinase B (a regulator of cell proliferation)

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Diagnosis

• CXR/Chest CT Patterns
  • ILD: upper lobe-predominance
    • Bullous changes eventually appear in upper lung zones
    • Hyperinflation: later
  • Lung nodules: due to metasases from neural tumor (may occur apically producing a Pancoast-like tumor) or due to benign neurofibromas
    • Benign Neurofibroma: solitary lung nodule (usually well-defined)/Location: no lobar predilection/Calcification: rare/Cavitation: none
  • Rib Notching (inferior): due to intercostal neurofibroma
  • Mediastinal mass: due to mediastinal vagal nerve neurofibroma/ meningocele
  • Kyphoscoliosis:
  • Pneumothorax:
• OLB: cellular and fibrotic interstitial pneumonia

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Clinical Manifestations

Dermatologic Manifestations

• Cafe-Au-Lait Spots
• Subcutaneous Neurofibromas: may involve chest wall and intercostal space

Ophthalomologic Manifestations

• Lisch Nodule in Iris

Pulmonary Manifestations

Apical Neurofibroma (Pancoast Syndrome)

• xxx

Intercostal Neurofibromas

• Diagnosis
  • Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]]): inferior rib notching

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease, [[Interstitial Lung Disease]]): occurs in 10-25% of cases

• Epidemiology: interstitial lung disease is the most common lung manifestation in neurofibromatosis
• Diagnosis
  • Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]]): restrictive early, obstructive later (due to later involvement of small airways)
  • Chest CT (see Chest Computed Tomography, [[Chest Computed Tomography]]): lower zone-predominant interstitial infiltrates, eventual appearance of bullous upper zone disease
• Clinical
  • Dyspnea (see Dyspnea, [[Dyspnea]]): first appears between 20’s-50’s

Lung Nodule (see Lung Nodule or Mass, [[Lung Nodule or Mass]])

• Usually asymptomatic

Mediastinal Meningocele (see xxxx, [[xxxx]])

• xx

Mediastinal Vagus Nerve Neurofibroma (see xxxx, [[xxxx]])

• xxx

Neural Tumor Mets to Lung (see xxxx, [[xxxx]])

• May occur in apices (producing Pancoast syndrome)

Pneumothorax (see Pneumothorax, [[Pneumothorax]])

• Epidemiology
• Physiology

Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

• Epidemiology
• Clinical

Scar Carcinoma (see Lung Cancer, [[Lung Cancer]])

• Epidemiology: has been reported

Renal Manifestations

Hypertension (see Hypertension, [[Hypertension]])

• xxx

Rheumatologic Manifestations

Atlantoaxial Instability (see Atlantoaxial Instability, [[Atlantoaxial Instability]])

• xxx

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References

• Type 1 neurofibromatosis complicated by pulmonary artery hypertension: a case report. J Med Invest 2007;54:354–8
• Pulmonary hypertension in neurofibromatosis. Am J Cardiol 2007;99:1177-8
• von Recklinghausen disease complicated by pulmonary hypertension. Chest 2001;119:1606-8
• Pulmonary hypertension secondary to neurofibromatosis: intimal fibrosis versus thromboembolism. Thorax 1999;54:858-9.
• Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy? Chest 2007;132:798-808