—  SPECIALTY CONFERENCE  —

Neuropathology

Case 5 - Astrocytoma, Pilomyxoid Variant, of Hypothalamic-chiasmatic Region

Anthony T. Yachnis
University of Florida Medical College
Gainesville, Florida


Click on each slide thumbnail image for an enlarged view
Clinical History:
The patient is a 1-year-old male who presented with failure to thrive and recent onset of vomiting. His weight was in the 10 percentile on admission despite an apparently normal caloric intake. Birth history was unremarkable. Imaging studies revealed a 3.3 x 2.4-cm contrast-enhancing mass in the region of the hypothalamus and optic chiasm. A bifrontal craniotomy was performed and extensive internal debulking of the mass was accomplished by a transventricular approach.

Diagnosis - Astrocytoma, Pilomyxoid Variant, of Hypothalamic-chiasmatic Region


Case 5 - Figure 1 - Astrocytoma, pilomyxoid variant. Low magnification photomicrograph showing loose, monomorphous cytoarchitecture. 500X.
Case 5 - Figure 2 - Astrocytoma, pilomyxoid variant. Angiocentric pseudorosette-like arrangement of tumor cells and microcystic, focally myxoid background. 1000X.
Case 5 - Figure 3 - GFAP - Pilomyxoid astrocytoma immunostained for glial fibrillary acidic protein showing strong reactivity of piloid tumor cell processes, especially in perivascular regions. 1000X.

Histologic findings
The tumor is composed of a rather uniform population of small, spindle-shaped cells that are dispersed within a loose, variably myxoid background. In some areas, the radial orientation of tumor cell processes along intra-tumoral blood vessels produces perivascular pseudorosette-like structures. Tumor cells are strongly immunoreactive for glial fibrillary acidic protein (GFAP) and S-100 but negative for neuronal antigens (neurofilament protein, synaptophysin and neuronal nuclear antigen). Mitoses are rare and the Ki67 labeling index is low (3%).

Clinical follow-up
Despite chemotherapy, the patient experienced a recurrence of this tumor, which required a second surgical debulking about one year after the original surgery. Two years from diagnosis, there is significant neurologic impairment and residual tumor.

Discussion:
This one-year-old boy presented with diencephalic syndrome, which is most often encountered in children 1 year of age or less and is characterized by failure to thrive despite a normal or slightly diminished caloric intake and alert appearance.1  The syndrome is usually associated with a space-occupying mass of the hypothalamus-optic chiasm region.1,2  Associated symptoms of increased intracranial pressure, nystagmus and optic atrophy are related to this location.

The most common glioma associated with diencephalic syndrome is the pilocytic astrocytoma: a well demarcated, contrast-enhancing tumor that may arise from the hypothalamus or optic chiasm. Typically, both structures are involved. The lesion may be solid or cystic and may extend into the third ventricle and compress the frontal lobes.2,3  Microscopically, these tumors have a biphasic histology consisting of compact, fibrillated areas and microcystic areas composed of stellate shaped cells.3  Rosenthal fibers and eosinophilic granular bodies are typical. Although pilocytic astrocytomas may present a variety of histologic appearances, the biphasic character is usually apparent to some extent. The biologic behavior is that of a slowly growing, indolent tumor in an eloquent CNS location. Some tumors remain stable for years while others may recur in the form of cystic fluid accumulation. Patients have long survivals but suffer from chronic symptoms of hypothalamic dysfunction and visual problems.

Some hypothalamic-chiasmatic astrocytomas have demonstrated a more aggressive biologic behavior with rapid recurrences after surgery and even a tendency to disseminate in the cerebrospinal fluid pathway .4  Cottingham et al. 5 first reported an "infantile type" pilocytic astrocytoma that was associated with a poor prognosis. Such tumors were composed of a uniform population of cells that were arranged in a loose "cobweb-like" architecture and occasionally formed narrow collars around intra-tumoral blood vessels. The clinicopathologic characteristics of 18 pediatric suprasellar astrocytomas with similar histologic features have been carefully described by Tihan et al. .6  This group emphasized the uniform or monomorphous cytoarchitecture and myxoid stroma displayed by these tumors and introduced the term "pilomyxoid astrocytoma". The myxoid material has been reported to be alcian blue-positive.7  Angiocentric pseudorosette-like structures were a regular feature of this variant.6,7  Unlike the classic pilocytic astrocytoma, the pilomyxoid variant lacks biphasic histology and is devoid of Rosenthal fibers and eosinophilic granular bodies.

Tihan et al. 6 examined the clinical significance of "pilomyxoid" histology in hypothalamic-optic chiasm astrocytomas by comparing the outcomes of patients with such tumors to an age-matched group of patients with classic pilocytic astrocytomas arising in this location. Of 18 patients with the pilomyxoid variant, 14 were 2 years old or less and 15 had subtotal resections. During the period of this study six patients had died of disease; four dying within two years of surgery and the rest were alive with disease. The progression free survival of this group was 38.7%. In contrast, of 13 patients with classic hypothalamic/optic pathway pilocytic astrocytomas, four had no evidence of disease at follow-up, eight were alive with disease and one patient died of non-tumor related causes. Progression free survival was 70%. These results suggest that monomorphous pilomyxoid histology in pediatric hypothalamic region astrocytomas may be important in predicting prognosis of such cases.

It is not clear whether the pilomyxoid variant and classic pilocytic astrocytomas are related or represent distinct morphologic entities. Despite apparent differences in biologic behavior, neither tumor type shows appreciable mitotic activity and Ki67 labeling indices are low and show significant overlap between these neoplasms.6,8  Thus far, immunohistochemistry confirms the glial nature of these tumors but does not significantly aid in their differentiation beyond histologic findings. The pilomyxoid variant may occasionally recur with histologic features more typical of the classic pilocytic astrocytoma 5 (Dr. M. Rosenblum: personal communication). Fuller et al. 7 identified occasional microvilli and rare cilia in an EM study of three hypothalamic region pilomyxoid astrocytomas and noted some similarities with tanycytes. The latter are most numerous in the infralateral walls and floor of the third ventricle.7,9 

Other pediatric gliomas that can rarely be associated with diencephalic syndrome include ganglion cell tumors, pleomorphic xanthoastrocytoma, astroblastoma, dysembryoplastic neuroeithelial tumors and choroid plexus tumors.2  Rarely an ependymoma arising in the third ventricle may mimic a hypothalamic astrocytoma.10 

References

  1. Perilongo G, Carroll C, Salviati L, Murgia A, Pillon M, Basso G, Gardiman M, Laverda AM. Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region. Cancer 80:142-146, 1997.
  2. Burger PC, Cohen KJ, Rosenblum MK, Tihan T. Pathology of diencephalic astrocytomas. Pediatr Neurosurgery 32:214-219, 2000.
  3. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and its Coverings, (Ed 4). St. Louis, MO, Elsevier Science, pp. 203-215, 2002.
  4. Nishio S, Takeshita I, Fukui M, Yamashita M, Tateishi J. Anaplastic evolution of childhood optico-hypothalamic pilocytic astrocytoma: Report of an autopsy. Clin Neuropathol 7:254-58, 1988.
  5. Cottingham SL, Boesel CP, Yates AJ. Pilocytic astrocytoma in infants: a distinctive histological pattern. J Neuropathol Exp Neurol 55:654, 1996.
  6. Tihan T, Fisher PG, Kepner JL, Godfraind C, McComb RD, Goldthwaite PT, Burger PC. Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome. J Neuropathol Exp Neurol 58:1061-1068, 1999.
  7. Fuller CE, Frankel B, Smith M, Rodziewitz G, Landas SK, Caruso R, Schelper R. Suprasellar monomorphous pilomyxoid neoplasm: an ultrastructural analysis. Clin Neuropathol 20:256-262, 2001.
  8. Gianinni C, Scheithauer BW, Burger PC, Christensen MR, Wollan PC, Sebo TJ, Forsyth PA, Hayostek CJ. Cellular proliferation in pilocytic and diffuse astrocytomas. J Neuropathol Exp Neurol 58:46-53, 1999.
  9. Flament-Durand J, Brion JP. Tanycytes: morphology and functions: a review. Int Rev Cytol 96:121-155, 1993.
  10. Oppenheim JS, Strauss RC, Mormino J, Sachdev VP, Rothman AS. Ependymomas of the third ventricle. Neurosurgery 34:350-353, 1994.