3601_e05_p158-170 2/15/02 4:31 PM Page 158 5 Optic Nerve, Chiasmal, and Hypothalamic Tumors JOANN ATER, NANCY J. TARBELL, AND EDWARD LAWS, JR. Gliomas are the most common tumors in the optic ventricle are also strongly associated with neurofi- nerve, chiasmal, and hypothalamic regions of the cen- bromatosis and may be found in tuberous sclerosis, tral nervous system (CNS). As such, they are the fo- another hereditary condition. cus of this chapter. For completeness, the less com- The pathology of optic pathway gliomas runs the mon tumors of these regions—meningiomas and gamut from very benign astrocytomas, considered by craniopharyngiomas—are also covered. Germ cell some to be hamartomas, to tumors that are glioblas- tumors can also occur in this region but are discussed toma multiforme. The typical histologic picture of a in Chapter 7. glioma of the optic nerve is one of dense arachnoid proliferation around an infiltrating pilocytic glioma, with thin hair-like tumor cells intermixed among the GLIOMAS fibers of the optic nerve itself. The low-grade gliomas that tend to affect the optic chiasm, anterior third ven- Gliomas that affect the optic nerves, chiasm, and hy- tricle, and hypothalamus frequently are characterized pothalamus represent a unique type of tumor with a as juvenile pilocytic astrocytomas, having few mitoses, variable clinical course. Histologically, most other no malignant features, or degenerative changes such midline astrocytomas of childhood are of the pilo- as Rosenthal fibers. Despite their relatively “benign” cytic subtype. These gliomas are among the neo- histology, these tumors can progress and cause con- plasms of the nervous system whose tumor type and siderable morbidity in young children. Occasionally, prognosis are age related. Except for infants, the anterior third ventricle tumors are discovered in con- prognosis for patients with these tumors is inversely junction with tuberous sclerosis; these tumors are related to age at onset, with older individuals having generally noninfiltrating, relatively benign subependy- a poorer prognosis. In infancy, tumors affecting the mal giant cell astrocytoma (see Chapter 3). Overall, optic pathways can be malignant in their course, al- approximately 4% to 5% of optic pathway tumors are though the reasons for this are not known. Gliomas frankly malignant, and those usually have many of the of the optic nerves and chiasm are strongly associ- characteristics typical of glioblastoma multiforme. ated with neurofibromatosis type 1. Several large se- The tumors with malignant histology occur most ries report obvious signs of neurofibromatosis in as commonly in adolescents and older individuals. many as 54% of affected children (Alvord and Lofton, In addition to patient age, anatomic distinctions 1988; Hoyt and Baghdassarian, 1969; Listernick et are extremely important in the evolution and prog- al., 1988; Packer et al., 1983; Manera et al., 1994). nosis of these tumors. Optic nerve gliomas can be Gliomas affecting the hypothalamus and anterior third conveniently grouped into two major categories: the 158 3601_e05_p158-170 2/15/02 4:31 PM Page 159 Optic Nerve, Chiasmal, and Hypothalamic Tumors 159 anterior optic nerve glioma, which primarily affects tic nerve function; in other tumors, mixed variants of the optic nerve or nerves; and the posterior optic optic nerve and chiasmal patterns of visual loss can nerve glioma, usually centered in the optic chiasm. occur, with an asymmetric bitemporal hemianopsia Obviously, tumors in both categories affect the visual being the most common finding in a chiasmal glioma. system, but the two types differ in pace and progres- In addition, behavioral changes, possibly related sion. Anterior optic nerve gliomas, which usually oc- to elevated intracranial pressure or hypothalamic in- cur in childhood, are ordinarily quite benign and volvement, are prominent. Irritability, depression, so- progress very slowly. Some of these tumors do not cial withdrawal, somnolence, and aggressive behav- progress at all or progress over many years. Poste- ior have been reported. Because of the frequent rior optic nerve gliomas, which occur in very young involvement of the suprasellar-hypothalamic region, children or older individuals, tend to form larger children with optic nerve tumors of these areas can masses and present with more symptoms. These tu- also present with endocrine abnormalities. Although mors may become large enough to affect the physi- endocrine manifestations can occur with any of the ology of the hypothalamus and/or obstruct the ante- suprasellar lesions, such presentations are particu- rior third ventricle, producing hydrocephalus. In larly common in lesions that arise in the hypothala- infants who present with optic nerve or chiasmal mus or floor of the third ventricle. The hypothalamic gliomas, the spectrum ranges from indolent tumors dysfunction produced by these lesions can range from to aggressive tumors that can spread throughout the varying forms and degrees of hypopituitarism to en- optic pathway from the globe back to the occipital docrine-active syndromes produced by tumors that cortex. secrete hypothalamic-releasing factors. Tumors that Tumors arising primarily in the hypothalamus or affect the physiology of the appropriate nuclei in the anterior third ventricle are less common and less of- hypothalamus or of the pituitary stalk can result in ten associated with neurofibromatosis. Hamartoma- diabetes insipidus. Finally, hypothalamic hamartomas tous lesions also occur in the hypothalamus and in that present in the interpeduncular fossa are also as- the interpeduncular fossa. More typical juvenile as- sociated with precocious puberty. In a report of 33 trocytomas can occur in this region, along with stan- children with optic chiasmatic-hypothalamic tumors, dard anaplastic astrocytomas and other malignant 5 (14%) of 33 presented with symptoms of endocrine forms. dysfunction and 14 (56%) of 25 demonstrated en- docrine abnormalities on laboratory evaluation. Growth hormone deficiency was the most common Clinical Presentation abnormality, followed by precocious puberty, delayed Optic gliomas occur primarily in children, with more puberty, and diabetes insipidus. In addition, 7 (21%) than 71% diagnosed in patients younger than 10 years of 33 patients failed to thrive and had the diencephalic of age and 90% diagnosed during the first two syndrome (Rodriguez et al., 1990), which is charac- decades of life (Dutton, 1991). The tumors can range terized by severe emaciation and an inability to gain from mild fusiform enlargement of the optic nerve or weight even when caloric intake is adequate (Russell, nerves within the orbit to very large, globular exo- 1951). phytic masses that extend from the chiasm and are Evaluations of endocrine function in children with virtually indistinguishable from a primary hypothala- diencephalic syndrome usually reveal normal thyroid mic tumor. function and elevated levels of cortisol and growth hor- In one series, more than 60% of optic pathway tu- mone. Usually the child is young at the time of diag- mors involved the optic chiasm (Tenny et al., 1982). nosis and frequently has been subjected to extensive The signs and symptoms in children with optic path- failure-to-thrive evaluations before the diagnosis is way tumors who presented to The University of Texas made. Because the only neurologic findings on exam- M. D. Anderson Cancer Center between 1975 and ination may be decreased visual acuity, visual field cuts, 1993 are listed in Table 5–1 (Manera et al., 1994). optic atrophy, or nystagmus, which are difficult to eval- The clinical picture of a patient with a lesion affect- uate in a child younger than 3 years, these signs may ing the optic nerves, chiasm, or hypothalamus is usu- be overlooked in a less than thorough examination. ally one of progressive visual loss. In unilateral optic The association of optic nerve gliomas with neu- nerve tumors, this begins as a unilateral loss of op- rofibromatosis is well known. Optic nerve gliomas ac- 3601_e05_p158-170 2/15/02 4:31 PM Page 160 160 PRIMARY CENTRAL NERVOUS SYSTEM TUMORS Table 5–1. Optic Pathway/Hypothalamic Tumors Referred to the Pediatric Brain Tumor Clinic at The University of Texas M. D. Anderson Cancer Center, 1980 to 1993* No. % Demographics Total 60 100 Neurofibromatosis (NF) 31 54 Male 34 57 Female 26 43 Symptoms at diagnosis Decreased visual acuity or blindness 28 47 Visual field deficit 12 20 Nausea/vomiting 17 46 Headache 19 32 Failure to thrive and diencephalic syndrome 6 10 Behavioral problems (irritability, social 12 20 withdrawal, somnolence, aggressive behavior) No symptoms with NF 12 7 Endocrine complaints 4 7 Radiographic findings Multilobular suprasellar-optic chiasmal masses 35 58 Optic nerve and chiasmal swelling 17 32 Isolated optic nerve 6 10 Hydrocephalus 23 38 *Median age at diagnosis was 5.2 (range, 0.75 to 14.3) years. count for only 4% to 8% of all brain tumors in child- tigators (Hoyt and Baghdassarian, 1969) believing hood (Pollock, 1994), but as many as 70% of the op- that these tumors are not neoplasms, but rather are tic nerve glioma cases are found in individuals with hamartomas that do not grow continuously. From the neurofibromatosis type 1 (Stern et al., 1979). In a literature, however, it is clear that the clinical course prospective study of children referred to a neurofi- of optic pathway tumors can be quite variable, rang- bromatosis clinic who had no specific ocular com- ing from rare reports of spontaneous tumor regres- plaints, 15% were found to have optic nerve gliomas, sion (Brzowski et al., 1992), to tumors that remain 30% unilateral, 30% bilateral, and 40% involving the stable for life, as suggested by Hoyt and Baghdassar- optic chiasm (Listernick et al., 1989). In addition, all ian (1969), to aggressive tumors that over time carry children who had plexiform neurofibromas of the considerable risk of visual loss and death (Alvord and eyelid and glaucoma were found through compre- Lofton, 1988). Several factors have now been identi- hensive neuroimaging to have optic nerve gliomas.