Syndromic and sporadic pediatric optic pathway gliomas: review of clinical and histopathological differences and treatment implications

Abstract

Optic pathway gliomas (OPGs) are the most common primary neoplasm of the optic pathway. These lesions usually present in childhood and can arise anywhere along the optic pathway; they occur more frequently in women; and they rarely undergo late progression. Management strategies after the initial diagnosis are controversial, compounded by the different behaviors exhibited by sporadic and syndromic tumors. Neurofibromatosis Type 1 (NF1), with aberrant oncogenic signaling and consequent predisposition to intracranial tumors, is the most common associated syndrome, with nearly 20% of NF1 patients developing OPGs. A comorbid NF1 diagnosis has implications for tumor location with greater predilection for optic nerve involvement, whereas chiasmal and postchiasmal lesions are more frequently seen in sporadic cases. Syndromic OPGs often exhibit more indolent behavior and lower rates of clinical progression, and the majority of these are diagnosed by routine neuroophthalmological screening. When treatment is indicated, however, the molecular abnormalities that constitute this syndrome can limit the available chemotherapy and radiotherapy options because clinicians fear secondary malignancy and cerebrovascular complications. Furthermore, radiotherapy early in life can impair an individual's intellectual development, endocrine function, and physical growth, thereby limiting the role of this modality in the treatment of this childhood lesion. Differential gene expression and histogenesis among sporadic and syndromic OPGs may account for the different tumor behaviors, but studies correlating specific genetic and proteomic changes with patient outcome are pending. Loss of heterozygosity at 10 and 17q are more common among patients with NF1, and Ki67 labeling intensity of 2-3% and low p53 labeling intensity seem prognostic of aggressive tumor behavior. Recent advances in the development of a preclinical mouse model of NF1-associated OPG will permit investigation into improved detection strategies and chemotherapeutic and radiotherapy treatment protocols.

Clinical and genetic aspects of neurofibromatosis 1

“…175,177 Most children with NF1 who develop optic pathway gliomas do not require treatment, but chemotherapy is the treatment of choice for progressive tumors. 20,24,26,211,212 Surgical treatment of optic pathway gliomas is usually reserved for cosmetic palliation in a blind eye, and radiotherapy is usually avoided because of the risk of inducing malignancy or moyamoya in the exposed field. 31,56 Several controlled trials for treatment of optic pathway gliomas are available to individuals with NF1.…”

Sellar and Parasellar Imaging

“…They are iso-to hypointense on T1 and hyperintense on T2-weighted sequences and usually well demarcated. 73 Enhancement is variable and does not correlate with tumor grade. 74 Calcifications are uncommon and hemorrhage is exceedingly rare.…”

“…72 While it appears that sporadic gliomas are associated with worse outcomes, their presentation differs from syndromic tumors in that the latter are usually found in asymptomatic patients as part of routine screening and their natural history has not been conclusively demonstrated. 73 Syndromic status also has implications for tumor location. Optic pathway gliomas in neurofibromatosis type 1 more frequently involve the optic nerves, while sporadic ones favor a chiasmatic or postchiasmatic location (Figures 10 and 11).…”

“…Optic pathway gliomas in neurofibromatosis type 1 more frequently involve the optic nerves, while sporadic ones favor a chiasmatic or postchiasmatic location (Figures 10 and 11). 72,73 On MRI, they infiltrate and cause enlargement of optic nerves, chiasm, and/or optic tracts. They are iso-to hypointense on T1 and hyperintense on T2-weighted sequences and usually well demarcated.…”

Pediatric Brain Tumors

“…They are astrocytic tumors, typically low grade, and most commonly associated with neurofibromatosis type 1 (NF1) and may occur sporadically, with different biological behavior in each context. 7,8 OPG: NF1 Related NF1 is an autosomal dominant condition caused by a defect in the NF1 gene. The NF1 gene encodes for neurofibromin, also called the NF1 protein, and maps to chromosome 17 q11.2.…”