Nonoptic pathway tumors in children with neurofibromatosis type 1

Objective To define the radiologic features and natural history of nonoptic pathway tumors (non-OPTs) in children with neurofibromatosis type 1 (NF1).

Methods We performed a retrospective cross-sectional analysis of 64 children with NF1 harboring 100 probable non-OPTs. Age at diagnosis, sex, tumor location, number of tumors, symptomology, concurrent OPT, radiographic progression (defined as qualitative and quantitative increases in size), and treatment were assessed. Tumor volumes were measured from initial presentation until treatment or end of disease progression.

Results Sixty-three percent of probable non-OPTs progressed over time, where radiographic progression was concomitantly associated with clinical progression. Fifty-two percent of patients had incidentally identified probable non-OPTs. Twenty-five percent of patients were symptomatic at initial diagnosis, all of whom harbored tumors that grew on subsequent scans and required tumor-directed therapy. There were no clinical differences between probable non-OPTs localized to the brainstem vs other locations with respect to age, sex, concurrent optic pathway glioma, symptomology, and treatment. The average time from diagnosis to stabilization or decrease in tumor size was 2.34 years (SD, 2.15 years). Nineteen biopsied lesions were all histopathologically confirmed as tumor. Six children (9%) had deep extensive tumors, who presented earlier (mean age at diagnosis, 3.88 years), required multiple treatments, and had a shorter mean progression-free survival (48 months).

Conclusions Over half of children with NF1 in this study developed probable non-OPTs, the majority of which were clinically and radiographically progressive. While brainstem and nonbrainstem gliomas share similar clinical features and natural history, deep extensive tumors comprise a distinct aggressive group of tumors that warrant close attention.