Nicholas Panzo

Background: Pilomyxoid astrocytoma (PMA) is a rare, aggressive variant of pilocytic astrocytoma (PA) which is associated with shorter progression-free and overall survival than PA.¹ PMA tends to affect infants and younger children and has a higher probability of local recurrence and cerebrospinal spread than PA. ^{2, 3} There are many similarities between these two pathologies, and it is estimated that 10% of previously labeled PA were PMA after histopathology examination.⁴ Clinicians should be aware of the presentations of PMA and the subtle clinical and molecular differences between PMA and typical pilocytic astrocytoma (PA), which are critical to proper diagnosis and treatment. PMAs are most frequently encountered in the hypothalamic-chiasmatic region and, thus, commonly present with loss of visual acuity, endocrine syndromes, and hydrocephalus.⁵ One study found that most PMA patients presented with diencephalic syndrome (DS)⁶, which has fairly non-specific clinical findings making it difficult to diagnose, resulting in an average diagnostic delay of 15.2 months from symptom onset.⁷

Objective: The purpose of this study was to identify the current diagnostics and targeted therapies for pilomyxoid astrocytoma.

Methods: Relevant primary and secondary literature published within the last 5 was identified through a PubMed advanced search using the key words “pilomyxoid astrocytoma”, “therapy”, “diagnosis”, and “targeted therapy”.

Results: Due to the lack of distinct features that PMA presents upon imaging, a definitive diagnosis of PMA requires a biopsy and histopathological examination.⁸ Research into dynamic susceptibility contrast (DSC) perfusion to distinguish PMA and PA has found that DSC perfusion displayed a higher relative cerebral blood volume (rCBV) for PMA compared with PA.⁹ This research shows the potential to use MR imaging to distinguish between PMA and PA. Comprehensive genomic profiling has also provided insight into the molecular characteristics of PMA. ​​Most notably there is an overexpression of the developmental genes H19 and DACT2, extracellular matrix collagen (COL2A1; COL1A1), and IGF2BP3 in PMA. The influence of these variations remains unclear.¹⁰ Although total surgical resection is the preferred treatment for PMA, it is not usually feasible due to its anatomical location. Subtotal resection along with adjuvant therapy is used for tumors at sites where gross total resection is not viable. At resection, a full histopathologic confirmation of PMA and also molecular analysis should be performed to guide the decision for targeted therapy.⁵

Conclusion: PMA should be considered in the differential diagnosis of hypothalamic/chiasmal gliomas. Cases previously labeled as PA may be reclassified PMA after histopathology examination and impact treatment and prognosis.⁴ Continued research shows promising results for molecularly targeted therapy compared to conventional chemotherapy or radiation therapy, but more work is needed to understand the biological mechanism for PMA’s behavior.

Work Cited:

1. Fomchenko EI, Reeves BC, Sullivan W, et al. Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma. Mol Genet Genomic Med. 2021;9(2):e1597. doi:10.1002/mgg3.1597
2. Louis, D.N., Ohgaki, H., Wiestler, O.D. et al. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathol 114, 97–109 (2007). https://doi.org/10.1007/s00401-007-0243-4
3. Komotar RJ, Burger PC, Carson BS, et al. Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurgery. 2004;54(1):72-80. doi:10.1227/01.neu.0000097266.89676.25
4. Bhargava D, Sinha P, Chumas P, et al. Occurrence and distribution of pilomyxoid astrocytoma. Br J Neurosurg. 2013;27(4):413-418. doi:10.3109/02688697.2012.752430
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9. Ho CY, Supakul N, Patel PU, et al. Differentiation of pilocytic and pilomyxoid astrocytomas using dynamic susceptibility contrast perfusion and diffusion weighted imaging. Neuroradiology. 2020;62(1):81-88. doi:10.1007/s00234-019-02310-0
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