Humans ; Neurofibromatosis 1/pathology*

OBJECTIVE: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. METHODS: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. RESULTS: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. CONCLUSION Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Humans ; Neurofibromatosis 1/pathology* ; Neurofibromin 1/metabolism* ; GTPase-Activating Proteins ; Mutation ; Genetic Predisposition to Disease ; Genetic Therapy

Malignant transformation of a neurilemmoma is an exceedingly rare event. We describe a case of intrathoracic ancient neurilemmoma undergoing a malignant change in a 39-yr-old man. The patient presented with right flank and chest pain for several months. Plain radiography and CT scan of the chest showed a soft tissue mass lesion at the extrapleural space with erosion of surrounding ribs at the right basal lung area. The excised mass was encapsulated and measured 4.5 x 3.5 x 2.3 cm. The cut surface showed grayish-white and glistening with a focal cystic change and hemorrhage. Necrosis was not seen. Histologically, the tumor showed the features of classic neurilemmoma composed of the Antoni type A and B areas with perivascular hyalinization. In addition, obviously histo-logically malignant foci manifested by presence of markedly increased cellularity with fascicular arrangement, active mitotic activity, hyperchromasia, and gradual loss of original neurilemmomatous feature were noted.
Adult ; Cell Transformation, Neoplastic* ; Diagnosis, Differential ; Human ; Male ; Neurilemmoma/complications ; Neurilemmoma/pathology* ; Neurofibromatosis 1/complications ; Neurofibromatosis 1/pathology* ; Thoracic Neoplasms/etiology ; Thoracic Neoplasms/pathology* ; Tumor Markers, Biological

A large intrathoracic meningocele, a saccular protrusion of the meninges through a dilated intervertebral foramen or a bony defect of the vertebral column, was diagnosed in a 41-year-old female patient showing clinical features of neurofibromatosis-1 (NF-1), including cafe-au-lait spots, cutaneous neurofibromas, and axillary frecklings and Lisch nodules on the iris. Her daughter and son also had similar manifestations of NF-1. Regular follow-up with periodic imaging was recommended without surgical treatment because there were no signs or symptoms. Meningocele should be differentiated from posterior mediastinal tumors such as neurofibroma, neuroblastoma, and ganglioneuroma because NF-1 has a high risk of tumor formation. We report on this case with a brief review of the literature.
Adult ; Diagnosis, Differential ; Female ; Humans ; Incidental Findings ; Meningocele/*complications/*pathology ; Neurofibromatosis 1/*complications/genetics/*pathology ; Pedigree

Adolescent ; Brain ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Neurofibromatosis 1 ; pathology

Patients with neurofibromatosis-1 (NF-1) have increased susceptibility to a variety of malignancies. Here, we document a rare case of two separated ileal adenocarcinomas in NF-1. The adenocarcinomas were surrounded by a diffuse tubular adenomatous lesion of the mucosa, and ganglion cells were scattered in the NF background. We found this case meaningful for several reasons: two separated adenocarcinomas arising in an unusual ileal segment, the association with precancerous tubular adenoma, and the presence of ganglion cells, which suggests ganglioneuromatosis in NF-1.
Adenocarcinoma/complications/*pathology ; Adult ; Humans ; Ileal Neoplasms/complications/*pathology ; Ileum/pathology ; Intestinal Mucosa/pathology ; Male ; Neurofibromatosis 1/complications/*pathology

Gastrointestinal stromal tumors (GISTs) are rarely noted in association with neurofibromatosis-1 (NF-1, von Recklinghausen disease) as an individual gastrointestinal manifestation. We report here a case of multiple GISTs with an abundant skeinoid fiber in the jejunum of a 43-year-old woman diagnosed as NF-1. Histologically, the tumors were composed of uniform spindle-shaped cells with a fascicular pattern, almost indistinguishable from the histology characteristic of usual GISTs. However, multiple synchronous tumor occurrence, abundant skeinoid fiber, and presence of microscopic miniatures of stromal tumors are additional characteristic features of this case.
Adult ; Female ; Human ; Intestinal Neoplasms/*pathology ; Jejunum/innervation/*pathology ; Myenteric Plexus/pathology ; Neurofibromatosis 1/*pathology ; Stromal Cells/*pathology

PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs. MATERIALS AND METHODS: The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared. RESULTS: Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS. CONCLUSION: NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.
Humans ; Korea ; Multivariate Analysis ; Neoplasm Metastasis ; Neurilemmoma* ; Neurofibromatoses* ; Neurofibromatosis 1* ; Pathology ; Sarcoma ; Seoul

Adult ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Neurofibromatosis 1 ; genetics ; pathology

Neurofibromatosis type 1 (von Recklinghausen's disease, NF-1) is an autosomal-dominant neurocutaneous disorder characterized by abnormal skin pigmentation (cafe au lait spots and axillary freckling), cutaneous and plexiform neurofibromas, skeletal dysplasias, and Lisch nodules (pigmented iris hamartomas). Gastrointestinal stromal tumors (GISTs) are the most common tumors of mesenchymal origin in the gastrointestinal tract, mesentery, omentum, and retroperitoneum. Here, we report a case of GIST in the ileum of a 76-year-old woman previously diagnosed as NF-1. She was admitted due to sudden onset of abdominal pain. Contrast enhanced CT scan revealed a moderately defined, peripherally enhanced soft tissue mass of about 8.8 x 7.3 cm, originating from the small bowel in the left of the abdomen. Surgical excision was performed and the tumor was found to be composed of tumor cells that were positive for c-kit protein. The patient started imatinib treatment a month later, but stopped medication due to dyspepsia after a few months and eventually progressed after 18 months.
Risk Factors ; Neurofibromatosis 1/*diagnosis/pathology/surgery ; Humans ; Gastrointestinal Stromal Tumors/*diagnosis/pathology/surgery ; Female ; Aged ; Abdominal Pain