Abdominal neoplastic manifestations of neurofibromatosis type 1

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary tumor syndrome, with a wide clinicopathologic spectrum. It is defined by characteristic central nervous system, cutaneous and osseous manifestations, and by mutations in the NF1 gene, which is involved in proliferation via p21, RAS, and MAP kinase pathways. Up to 25% of NF1 patients develop intra-abdominal neoplastic manifestations including neurogenic (commonly plexiform neurofibromas and malignant peripheral nerve sheath tumors), interstitial cells of Cajal (hyperplasia, gastrointestinal stromal tumors), neuroendocrine, and embryonal tumors (rhabdomyosarcoma). Nonspecific symptoms, multifocal disease, or coexistence of 2 or more tumor types make patients challenging to diagnose and manage. Screening for intra-abdominal tumors in NF1 patients remains controversial, and currently no guidelines are established. Management decisions are complex and often informed by single-center experiences or case studies in the literature, though the field is rapidly evolving. Thus, NF1 patients should be followed in specialist centers familiar with their wide spectrum of pathology and with multidisciplinary care including specialized pathology and radiology. This review will (1) provide a contemporaneous synthesis of the literature and our multi-institutional clinical experiences with intra-abdominal neoplasms in NF1 patients, (2) present a classification framework for this heterogeneous group of disorders, and (3) outline approaches to screening, surveillance, diagnosis, and management.

Keywords: gastrointestinal stromal tumor; malignant peripheral nerve sheath tumor; neoplasms; neurofibromatosis type 1; plexiform neurofibroma.

Figure 1.

Imaging characteristics of abdominal neoplasms in NF1 patients. Axial postcontrast T1-weighted fat-saturated MR image demonstrates an infiltrative enhancing plexiform neurofibroma in the proximal left obturator region with components extending into the perineum and pelvic floor (A). Axial fused PET/CT image of the plexiform neurofibroma demonstrates low levels of FDG uptake with SUV_max 3.6–3.8; however, no definite areas for were suspicious for malignant transformation (B). Axial T2-weighted MR image demonstrates a heterogeneous mixed solid and cystic mass in the left retroperitoneum arising from the left L3 nerve root. Core biopsy was performed and pathology was consistent with malignant peripheral nerve sheath tumor (MPNST) (C). Axial and coronal postcontrast T1-weighted fat-saturated images demonstrate heterogeneous enhancement of the periphery and soft tissue components of the MPNST (D and E). Axial postcontrast CT image demonstrates a heterogeneous right adrenal mass in keeping with pheochromocytoma. There is also infiltrating low-attenuation soft tissue around the imaged portal structures (F). Coronal postcontrast CT image further demonstrates the infiltrating periportal soft tissue mass, in keeping with a plexiform neurofibroma. There is also patulous distension of the duodenum with oral contrast. In the proximal jejunum, there is a soft tissue mass in keeping with gastrointestinal stromal tumor (GIST) which was subsequently resected (G). Axial postcontrast CT image demonstrates routine surveillance of further intraluminal masses in the distended proximal duodenum, in keeping with further GISTs (H).