Exploring immunoreactivity of TTF-1 and AVP in hypothalamic hamartoma.

INTRODUCTION: Hypothalamic hamartoma (HH) is a rare developmental disorder presenting with gelastic seizures or precocious puberty attributed to gonadotrophin-releasing hormone expression by the hamartoma. The histogenesis of HH is uncertain, and diagnosis of HH is difficult in small biopsies due to its close resemblance to normal hypothalamic nuclei. TTF-1 and arginine vasopressin (AVP) are associated with gonadotropin-releasing hormone release. MATERIALS AND METHODS: In this study, we explored the expression pattern of TTF-1 and AVP in HH and its utility, if any, in diagnosis. We reviewed the clinical, radiologic, and histopathological features of 23 HH diagnosed over the past decade at our Institute. RESULTS: The age at presentation ranged from 11 months to 34 years with gelastic seizures (82.6%), precocious puberty (17.4%), and developmental delay (8.7%) as presenting symptoms. On imaging, all the lesions (n = 9) involved the posterior and tuberal group of hypothalamic nuclei, while 5 cases involved the anterior hypothalamus. Anatomically, the lesions involved mammillary body, arcuate and periventricular nuclei. On histopathology, 52% cases revealed nodular arrangement of small neurocytic cells separated by glial stroma. TTF-1 and AVP immunoreactivity was absent in all the cases, whereas in normal hypothalamus, AVP was expressed in periventricular nuclei. CONCLUSION: Our results suggest that immunoexpression of TTF-1 is absent in HH, particularly in those arising from the posterior hypothalamus, and this can be used in small biopsies to distinguish from a normal hypothalamus as well as from posterior pituitary tumors.

A variant form of mucolipidosis IV: report on 4 patients from the Indian subcontinent.

The clinical manifestations and histopathologic and neuroimaging findings in 4 Indian patients with a variant form of mucolipidosis IV are described. The presenting symptoms were psychomotor delay, spastic paraplegia, and mild mental retardation. One patient also had visual deterioration due to optic atrophy. None had corneal or retinal abnormalities. Magnetic resonance imaging in 3 patients showed a uniformly thin corpus callosum in all patients and white matter changes in 2 patients. Electron microscopic examination of skin biopsy specimens revealed storage bodies characteristic of mucolipidosis IV. These patients differ from previously described patients with this disorder in the absence of corneal abnormalities and in their presentation with spastic paraplegia during the second decade of life. Correct diagnosis is needed for genetic counseling, prognostication. and reduction of additional familial burden of this rare disease.