Pilocytic astrocytomas as hamartomas: implications for treatment
- Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- C F Parsa, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Wilmer 233, 600 North Wolfe Street, Baltimore, MD 21287-9028, USA; cparsa{at}jhmi.edu
Interventional treatment modalities have long been investigated to treat WHO grade I juvenile pilocytic astrocytomas. In some instances, particularly for cerebellar lesions, complete surgical excision, if feasible, can be potentially beneficial and curative.1–5 In other cases, partial resection may be performed to decompress adjacent tissues, or shunts may be placed to treat a resulting hydrocephalus. Despite a lack of demonstrated efficacy,6–13 radiation therapy was promoted for many years for unresectable symptomatic tumours. The grave side effects that ensued, however, such as severe mental retardation in young children, created an impetus for chemotherapy to be advocated in the hopes of postponing radiation therapy. Despite a similar lack of demonstrated treatment effect with chemotherapy,14–16 the continued application of these antimitotic interventional methods has been in part driven by the belief that these tumours could also undergo proliferative as well as anaplastic changes. Limited reported cases of apparent malignant transformation4 17–48 undermined previous arguments emphasising the hamartoma-like qualities of these tumours.25 49 50 It has recently been determined, however, that the malignant transformations demonstrated were rather an iatrogenic phenomenon of the ionising radiation applied.51 Recent neuroimaging evidence, furthermore, has provided confirmation that the great majority of these tumours remain stable and often exhibit spontaneous regression,52–61 with growth generally occurring from accumulation of extracellular mucosubstance.62 Cellular studies emphasise the low cellular proliferative capacity within these tumours5 63 and the lack of genetic changes seen in the more aggressive fibrillar astrocytomas.5 64 Such evidence reaffirms the notion that WHO grade I juvenile pilocytic astrocytomas are, in fact, hamartomas. The rationale and implications of treatment with either radiation therapy or mutagenic chemotherapy when surgical excision is not indicated or feasible are hereby re-examined.
CELLULAR EFFECTS OF IONISING RADIATION AND CHEMOTHERAPY
The antimitotic activity …
