Re: "Palpebral spring in the management of lagophthalmos and exposure keratopathy secondary to facial nerve palsy".

To the Editor: It is uncontested that optic gliomas (World Health Organization grade I pilocytic astrocytomas) represent tumors. Such terminology, however, while technically correct, remains imprecise and can be misleading. The normal crystalline lens of the eye, for example, also represents a tumor, yet to call it so with patients would unquestionably lead to irresponsible and inappropriate interventions. The situation with juvenile pilocytic gliomas is not entirely dissimilar. By alluding to these masses with terminology more commonly used to designate neoplasms, one leads both family members and physicians alike toward antimitotic and genotoxic therapies that, to date, have had no proven efficacy. It was Hoyt and Baghdassarian, in 1969, who were the first to openly declare these tumors to behave as congenital hamartomata. Indeed, it has recently been confirmed that no spontaneous anaplastic transformation of these masses has been demonstrated. The terms hamartoma and choristoma were created by Albrecht, in 1904, to designate tumors that had the potential to grow in self-limited form during the period of development. Hamartoma signifies a disorganized overgrowth of differentiated tissue normal to a site, while choristoma indicates such growth when it is ectopic to the organ location. This terminology has been used, without controversy, to describe the evident growth of optic disk and retinal glial hamartomas in tuberous sclerosis or of the melanocytic iris hamartomas known as Sakurai-Lisch nodules in NF1. Choristomas, such as dermoids, may certainly also enlarge, often via the accumulation of mucosubstance or glandular secretions. The previous inability to monitor juvenile pilocytic astrocytomas intracranially, however, and the more serious consequences that could entail from enlargement within the limited cavitary space of the skull, understandably led to difficulties in ascertaining their selflimited growth pattern and hesitancy to also call them hamartomas. The subsequent advent of neuroimaging has, however, confirmed only occasional growth during the period of development, along with the possibility for spontaneous regression, previously, and often erroneously, ascribed to various attempted treatments. Since the advent of immunohistochemical labeling indices, such as MIB-1 to detect Ki-67 protein associated with cells during their proliferative phase and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) method to label DNA breaks in cells undergoing apoptosis, histopathologists have understood how there may often be an uneven distribution of both proliferating and apoptotic cells within a tumor. They are also cognizant of the concept of tumor homeostasis: that the relative proportion of both proliferating and apoptotic cells determines whether a tumor remains stable, enlarges, or shrinks. To evaluate a portion of a tumor for proliferative activity, as Walrath et al. and Miller describe, and to ignore the assessment of cells undergoing apoptosis, simply does not provide predictive information regarding potential tumor outcome, including that for a tumor which, parenthetically, had already been irradiated. By their very histopathologic definition, juvenile pilocytic astrocytomas possess only rare, if any, mitotic figures. They are also lacking in other molecular and clinical features associated with glial malignancies, such as characteristic genetic alterations, uncontrolled cell proliferation (when they ever do actually grow, it is only during the period of development, hence the adjective “juvenile”), or a potential for anaplastic transformation. To imply, therefore, that patients with such bona fide tumors, enlarging or otherwise, could benefit from antimitotic treatments, such as radiation or present-day genotoxic chemotherapy, is akin to proposing such therapies to thwart the sometimes undesirable growth of retinal and optic disk hamartomas or of limbal dermoids. In face of our current-day knowledge, persisting on applying such antimitotic and genotoxic nostrums for tumors such as juvenile pilocytic astrocytomas that more specifically are hamartomas, like so many other so-called “controversies,” represents an example of faith-based, rather than evidencebased, medicine.