Response of NF1-related plexiform neurofibroma to high-dose carboplatin

Plexiform neurofibromas (PN) are a hallmark of neurofibromatosis type 1 (NF1). These large nerve tumors can be disfiguring and surgery is the only known standard therapy. Surgical intervention may be suboptimal due to the diffuse nature of PN. Here, we present a case in which we describe the use of high-dose carboplatin to treat the patient's testicular seminoma which resulted in the decrease in size of a PN in a patient with NF1.     

MANAGEMENT OF PLEXIFORM NEUROFIBROMA WITH INTERFERON ALPHA

Plexiform neurofibroma is a relatively common but potentially devastating manifestation of neurofibromatosis type 1 (NF 1). A substantial number of plexiform neurofibroma causes morbidity. Various treatment modalities are considered to decrease pain. In this paper a case with plexiform neurofibroma causing severe pain and in whom alpha-interferon was used is presented.     

Neurological comorbidity in children with neurofibromatosis type 1

Background

The aim of this study was to determine the frequency of central nervous system comorbidities in children with neurofibromatosis type 1 (NF1).

Methods

We performed a nationwide survey to investigate neurological comorbidities in 3–15‐year‐old children with NF1 in Japan by sending questionnaires to pediatricians and pediatric neurologists. A secondary questionnaire was sent to the parents of identified NF1 patients to assess neurological comorbidities including headache, attention deficit–hyperactivity disorder (ADHD) Rating Scale (RS), and the Social Responsiveness Scale 2.

Results

The primary survey identified 760 NF1 patients, and the parents of 565 patients were sent the secondary questionnaire. The parental response rate was 25.7% (145; 63 girls, 81 boys, one unspecified). Among the patients, 42.9% (55/128; 35 girls, 20 boys) were reported to exhibit intellectual problems. On the ADHD‐RS, 40.2% (47/117) of NF1 patients aged 6–15 had ADHD (RS score >93rd percentile), with a rate of 47.7% in boys and 30.8% in girls. Furthermore, 20.2% of patients had suspected autism spectrum disorder (29/143; 10 girls, 19 boys), with Social Responsiveness Scale score ≥76. Headache was reported by 49.6% (61/123) of children over 5 years old, and 25.2% (31/123; 10 girls, 21 boys) reported migraine. Other neurological comorbidities included 20 cases of epilepsy (13.8%), 11 cases of optic nerve glioma (7.6%), five cases of brain tumor (3.4%), six cases of cerebrovascular disease (4.1%), and two cases of hydrocephalus (1.4%).

Conclusion

Intellectual problems, ADHD, autism spectrum disorder, and migraine are major neurological comorbidities in NF1.     

A novel mutation in the NF1 gene in two siblings with neurofibromatosis type 1 and bilateral optic pathway glioma

We present the clinical and ophthalmological findings, genetic analysis, and therapy of two siblings with NF1 and bilateral OPG. In genetic analysis, a heteroduplex profile was detected in exon 4b of the NF1 gene for the affected patients and mother. Sequencing of the DNA samples identified a C > T nucleotide change in exon 4b (c484CAG > TAG). This nonsense mutation resulted in a change of glutamine to a stop codon (Q162X) and is a novel NF1 gene alteration.     

Metronomic therapy for malignant peripheral nerve sheath tumor in neurofibromatosis type 1

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive tumor especially in the patients with neurofibromatosis type 1 (NF1). Without a complete surgical excision, prognosis is guarded. We describe a 10‐year‐old male with NF1 with MPNST, who had a local relapse within 5 weeks of surgical excision. Chemoradiotherapy did not result in tumor regression. Initiation of palliative oral metronomic therapy resulted in complete remission after six cycles. The patient continues to be in remission, 20 months after completion of nine cycles of metronomic therapy. Metronomic therapy may be effective in MPNST where conventional chemotherapy and radiotherapy fails. Pediatr Blood Cancer 2012; 59: 1317–1319. © 2012 Wiley Periodicals, Inc.     

Hepatoblastoma in a child with neurofibromatosis type I

A major hallmark of NF1 is the development of benign tumors, including peripheral neurofibromas, plexiform neurofibromas, gliomas of the optic tract, other low grade gliomas, and pheochromocytomas. Hepatoblastoma have not been previously reported in patients with neurofibromatosis type 1. We present a case of a 9-month-old boy diagnosed with both hepatoblastoma and neurofibromatosis type 1. Hepatoblastoma occurs in association with several well-described cancer predisposition syndromes, including familial adenomatous polyposis, Beckwith-Wiedemann syndrome, Li-Fraumeni syndrome, trisomy 18, and glycogen storage disease type I. This paper describes a case of hepatoblastoma diagnosed in association with neurofibromatosis type 1.     

Plexiform neurofibroma in type 1 neurofibromatosis

A 13-year-old African-American girl was admitted to the hospital for surgery. She was diagnosed with Type I neurofibromatosis at the age of 1 year after she was noted to have multiple café au lait spots. Her past medical history included a history of neurofibroma in the base of the brain, treated with radiation therapy and ventriculoperitoneal shunt, as well as a recent diagnosis of bilateral optic gliomas, treated with chemotherapy. Family history was negative for neurofibromatosis.     

Extensive central nervous system involvement in optic pathway gliomas in neurofibromatosis type 1

Optic pathway gliomas (OPG) in neurofibromatosis type 1 (NF1) usually remain localized to the anterior visual pathway. However, a small number can demonstrate widespread dissemination. We describe three children with NF1 OPGs and extensive central nervous system involvement. In one case, a postmortem examination revealed tumor cells extending continuously from the optic nerves to the conus medullaris. This is the most widespread NF1 OPG reported in the literature. We suggest that rapid visual deterioration in the absence of radiographic changes or increased intracranial pressure can be caused by increasing tumor infiltration within the central nervous system.