Hypothalamic Pilomyxoid Astrocytoma in a Child with Lipodystrophy

DISCUSSION

Pilomyxoid astrocytomas are rare pediatric CNS tumors, accounting for approximately 2% of childhood astrocytomas.³ First introduced in 1999 and classified by the World Health Organization in 2007, PMAs were originally identified as a variant of pilocytic astrocytomas.⁴ The discovery of PMAs partially helped explain what had been a befuddling attribute of pilocytic astrocytomas: Though most exhibited indolent growth and favorable prognoses, a subset of pilocytic astrocytomas demonstrated unexpected aggressiveness. PMAs fit nicely into this diagnostic puzzle, offering an explanation for the observed clinical variability.⁵ Patients with PMAs have higher rates of local recurrence and CSF dissemination and shorter progression-free and overall survival than those with pilocytic astrocytomas.^6,7

Given the variability of its clinical behavior and prognosis, in 2007, the World Health Organization had classified this tumor as a grade II disease. However, in its 2016 classification, they removed the grade assignments to PMAs.⁵ PMAs typically occur in younger patients; an average age of onset for PMAs is 18 months, compared with 58 months for pilocytic astrocytomas, leading to early labels of an “infantile” subtype.^4,6 However, cases have been identified across a broad age range, even among adults.⁸ Clinical presentations vary and include developmental delay, failure to thrive, vomiting, feeding difficulties, and generalized weakness.⁶ In infants, the initial clinical manifestations can be more subtle, such as increased head size or bulging fontanelle from increased intracranial pressure.⁵

On imaging, PMAs have an idiosyncratic proclivity for the hypothalamic/chiasmatic region (60%–75% of cases), though they may occur anywhere along the neuraxis, particularly the cerebral hemispheres.^9,10 The tumors are typically well-circumscribed, predominantly solid tumors, with high homogeneous intralesional signal on T2-weighted and T2-weighted FLAIR images and iso- to hypointense signal on T1-weighted imaging, reflecting their myxoid matrix (Fig 5).⁹ The reported frequency of central necrosis varies; some authors believe it to be rare, while a large review of cases noted necrosis in nearly one-third of tumors.^8,11 Peritumoral edema is infrequently seen.¹² PMAs tend to be devoid of calcifications and do not demonstrate reduced diffusivity, helping distinguish them from craniopharyngiomas and germinomas, respectively.¹² Obstructive hydrocephalus may be present, though usually in a minority of patients.⁵

• Download figure
• Open in new tab
• Download powerpoint

FIG 5.

Artistic illustration of a PMA extending from the hypothalamus, with involvement of the suprasellar region and adjacent structures. PMAs tend to be solid and are typically devoid of both calcifications and intratumoral cysts. Used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.

Prior studies have sought to distinguish between PMAs and pilocytic astrocytomas on the basis of imaging features. In general, PMAs demonstrate more homogeneous enhancement, are more susceptible to intratumoral hemorrhage, and are less prone to intralesional cystic changes (Table).^12,13 PMAs are also more prone to leptomeningeal spreading, occurring in approximately 20% of tumors in 1 study; none of the pilocytic astrocytomas in the same study demonstrated such spread.⁶ However, considerable overlap exists between the entities. Even in the hypothalamic/chiasmatic region, most pediatric low-grade tumors are pilocytic astrocytomas.⁶ In this area, about 20%–50% of pilocytic astrocytomas are associated with neurofibromatosis type 1.^14,15 Fernandez et al¹¹ found a higher rate of intratumoral necrosis in PMAs—not surprising, given their relative aggressiveness—though this has not been reported elsewhere. Alkonyi et al¹² found no difference in the size, margins, or intralesional T1 and T2 signal characteristics between PMAs and pilocytic astrocytomas. Ultimately, in its most classic form, a solid hypothalamic mass with leptomeningeal spread in a young pediatric patient, imaging alone might help favor a PMA over a pilocytic astrocytoma. Nevertheless, pathologic analysis is still required to confidently make such a distinction.¹⁶

The tumor in this case was discovered because of the astute diagnostic capabilities of the patient's endocrinologist. Although rare, the connection between hypothalamic astrocytomas and lipodystrophy has been long known.¹⁷ In its original description, “diencephalic syndrome” is characterized by emaciation, normal linear growth, locomotor overactivity, and somewhat incongruous pleasantness and euphoria.^18,19 However, many afflicted patients present with isolated lipodystrophy.²⁰ The mechanism by which hypothalamic astrocytoma results in such a profound loss of subcutaneous fat remains uncertain. Some authors have opined that the pathophysiology may be paraneoplastic, in which either antiadipocyte autoantibodies induce cytotoxicity or hormones/cytokines induce lipolysis. Others have suggested that growth hormone dysregulation and resistance may play a role. Regardless, the symptoms have been described in the setting of both pilocytic (and anaplastic) astrocytomas and PMAs.^21,22 It remains unknown whether certain types of hypothalamic tumor, eg, PMA or pilocytic astrocytoma, are particularly prone to causing sequelae of the diencephalic syndrome.

The patient presented here recently completed his chemotherapy regimen of vincristine and carboplatin and had decreased tumor size on his most recent examination, measuring 1.9 cm in maximum axial diameter compared with 2.2 cm when at its largest size. Serial MRIs will be used to continue to observe the tumor. Currently, his prognosis is considered guarded-but-favorable, particularly given the recent decrease in tumor size. Nevertheless, the patient's body weight continues to be suboptimal. Although his family has reported that he is able to gain some weight during intermittent breaks in chemotherapy, it tends to fall off following re-initiation of treatment, and he continues to exhibit considerable symptoms of lipodystrophy.