Intraventricular astrocytoma with extensive lipidization (lipoastrocytoma).
Lipidization is a well-documented but unusual phenomenon in primary neuroectodermal tumors of the central nervous system. Lipidization of the tumor cells can give rise to a xanthomatous appearance, such as that seen in pleomorphic xanthoastrocytoma and glioblastoma (7), in which numerous small lipid droplets filled the cytoplasm of the astrocytes. Lipidization may also present as adipocytic change, in which the lipid vacuoles in the cytoplasm are few and large, as exemplified by cerebellar liponeurocytoma (2), medulloblastoma (3), ependymoma (8) and low grade astrocytoma (10, 6, 4).
The presence of adipocyte-like cells in an astrocytoma is rare and only four cases were reported in the literature. The first by Walter A et al. in 1994 (10) occurred in the cerebellum, while another case reported by Roda JM et al. in the following year was intraspinal (6). Both patients were adults. The remaining two were pediatric cases reported by Giangaspero F et al. in 2002 (4), which occurred in the left temporal-occipital area and the left frontal lobe. Giangaspero F et al. also proposed the term lipoastrocytoma for the variant of astrocytoma featuring abundant lipidization of tumor cells resembling mature adipocytes. Our report is the first case of a cerebellar astrocytoma with extensive lipidization occurring in the fourth ventricle.
An unusual observation, in addition to the adipocytic change, is the perivascular arrangement of the tumor cells in a pseudorosette pattern similar to that seen in the cellular ependymoma. This feature was not described in the previously reported cases. Pseudorosettes are a common finding in ependymoma, although not pathognomonic of it. All other defining features of ependymal differentiation, such as true rosettes, cilia, microvilli, and intercellular junctions are absent in our case. In 2005, Jouvet A el al. reported a liponeurocytoma of the fourth ventricle showing similar findings of lipidization and pseudorosette formation (5). However, its immunoreactivity for neuroendocrine markers and ultrastructural finding of dense core granule permits distinction from our case in which neuroendocrine differentiation is lacking.
Our case in some aspects is also morphologically similar to a pilocytic astrocytoma, including a well-demarcated growth and presence of eosinophilic granular bodies and cystic change. However, Rosenthal fibers and the classic biphasic appearance that characterize most pilocytic astrocytomas are not observed.
The pathogenesis of lipomatous change in neuroectodermal tumors is unclear. The proposed mechanisms include a disturbance in cellular metabolism (8), a divergent differentiation of precursor cells with capacity for differentiation into astrocytic and fat cells (1), or a true adipose metaplasia. By virtue of the fact that the fat-laden cells were proved to be of glial nature by ultrastructure, the most plausible explanation for lipidization would be a degenerative/metabolic change rather than a form of metaplasia (transformation into a phenotypically different cell) or differentiation along multiple different lines.
The prognostic significance of lipomatous changes in an astrocytoma is yet to be established. Lipomatous medulloblastomas and central liponeurocytomas have been reported to be generally more favorable than their conventional types (2, 3), while the behavior of the lipomatous ependymomas is possibly similar to that of the ordinary ependymomas (9). The pediatric cases of astrocytoma with extensive lipidization reported by Giangaspero F et al. had a favorable prognosis: both patients were alive and well after 3 and 7 years (4). The adult patients reported by Walter A et al. and Roda JM et al. were both free of tumor after 9 months and two years follow up. In our case, neither recurrence nor metastasis was noted in less than a year follow up. The well-demarcated growth, low proliferation index, and the presence of abundant granular bodies in the tumor reported here are suggestive of a low-grade biological behavior. Therefore, we propose that a lipidized variant of low-grade astrocytoma would have a better prognosis than a typical low-grade astrocytoma. However, this proposal needs further confirmation by study on a larger population.
In conclusion, we have presented an unusual case of low-grade astrocytoma of the fourth ventricle with conspicuous lipidization of the tumor cells and perivascular pseudorosette formation in a young adult. Immunohistochemical and ultrastructural studies are helpful aids in differentiating astrocytoma with extensive lipidization from other neuroectodermal tumors exhibiting lipomatous change as well as providing evidence of glial degeneration exhibited as lipidization. We also propose that astrocytoma with extensive lipidization is a low-grade tumor with favorable prognosis, and total surgical removal is curative for the disease.
Contributed by Fang-Yi Lee, MD, Yee-Jee Jan, MD, Mei-Chin Wen, MD, Mu-Chun Li, MD, John Wang, MD, PhD, Chen Wen-Hsien, MD