What is the management approach for abdominal tumors in patients with Neurofibromatosis (NF)?

Management of Abdominal Tumors in Neurofibromatosis

Surgery remains the cornerstone of treatment for high-grade Malignant Peripheral Nerve Sheath Tumors (MPNSTs) in the abdomen, with the aim of achieving clear margins, as this approach has demonstrated benefit even for large abdominal tumors. 1

Types of Abdominal Tumors in Neurofibromatosis

Abdominal tumors in neurofibromatosis type 1 (NF1) can be categorized into several types:

• Neurogenic tumors: Most commonly plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) 2
• Gastrointestinal stromal tumors (GISTs): Arising from interstitial cells of Cajal 2, 3
• Neuroendocrine tumors: Including pheochromocytomas 2, 4
• Embryonal tumors: Such as rhabdomyosarcoma 2

Diagnostic Approach

Clinical Evaluation

• Annual general medical evaluation is recommended for patients with NF1, including assessment for signs/symptoms of MPNST 5
• Key warning signs include:
  • Progressive, persistent pain 1
  • Rapid growth of existing lesions 1
  • Neurologic symptoms 1
  • Deep, truncal location of plexiform neurofibromas 1

Imaging

• MRI is the mainstay of imaging for diagnosis, local staging, and follow-up of abdominal tumors in NF1 1
• 18F-FDG PET/CT is highly valuable for detecting malignant transformation with a sensitivity of 0.89 and specificity of 0.95 1
• A maximum standardized uptake value (SUVmax) of 3.5 is commonly accepted as a threshold for biopsy 1
• Both early (90 minutes) and late (four hours) imaging can be used clinically 1

Biopsy and Pathological Assessment

• For clinically or radiologically suspicious lesions, a standardized biopsy approach is recommended using 14-18G biopsy needles and obtaining at least 6 core biopsies 5
• Core biopsies should be divided with no more than 2 cores per block to preserve tissue 5
• Histologic evaluation should assess:
  • Cytologic atypia 1, 5
  • Loss of neurofibromatous architecture 1, 5
  • Hypercellularity 1, 5
  • Mitotic count 1, 5
  • Presence of necrosis 1, 5
• Immunohistochemical stains should evaluate SOX10, S100, CD34, p16, H3K27me3, and p53 expression 1, 5
• Molecular profiling is recommended for all worrisome noncutaneous lesions, assessing CDKN2A/B inactivation, SUZ12, EED, or TP53 mutations, and aneuploidy 1, 5

Management Approach

Malignant Peripheral Nerve Sheath Tumors (MPNSTs)

• Surgery: The primary treatment for high-grade MPNST with the aim of achieving clear margins 1
  • This approach has demonstrated benefit even for large, abdominal MPNSTs 1
• Adjuvant therapy: While no randomized studies exist, meta-analyses suggest a potential role for adjuvant chemotherapy or radiation in some non-metastatic MPNST patients 1
• Advanced/metastatic disease: Response rates to doxorubicin plus ifosfamide are approximately 21% 1

Atypical Neurofibromatous Neoplasms (ANNUBP)

• Complete surgical resection is recommended when feasible, with close surveillance due to uncertain biologic potential 5
• These are defined by at least 2 of: cytologic atypia, loss of neurofibroma architecture, hypercellularity, and mitotic count >1/50 HPF but <3/10 HPF 5

Desmoid Tumors

• Initial approach: Watchful waiting is recommended as the initial approach for most asymptomatic patients, with progression-free survival rates of 50% at 5 years 6
• Surgery: Indicated when watchful waiting fails, complications occur, or major cosmetic issues are present 6
• For FAP-associated intra-abdominal desmoids: Surgery should be restricted to treating secondary effects and performed only in expert centers 6

Gastrointestinal Stromal Tumors (GISTs)

• Surgical resection is the first-line treatment for NF1-associated GISTs 3
• Unlike sporadic GISTs, NF1-associated GISTs frequently lack KIT and PDGFRA mutations, making imatinib ineffective 3

Surveillance and Follow-up

• MRI surveillance is recommended to assess response to treatment 6
• Serial imaging with CT or MRI every 6-12 months depending on growth rate 6
• For patients with MPNSTs, close follow-up is essential due to high risk of recurrence 1

Special Considerations

• Risk of NF1-associated MPNST increases with age: 8.5% by age 30,12.3% by age 50, and 15.8% by age 85 5
• Life expectancy in NF1 is reduced by 8-15 years compared to the general population, primarily due to malignant neoplasms 5
• Patients with NF1 should be followed in specialized centers with multidisciplinary care including specialized pathology and radiology 2
• For women with NF1, annual mammogram starting at age 30 and consideration of breast MRI with contrast between ages 30-50 is recommended 5