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The well-developed facial lesions (adenomas of Pringle), pathognomonic of tuberous sclerosis, are present in 90 percent of patients over 4 years of age Typically they are red to pink nodules with a smooth, glistening surface, and they tend to be limited to the nasolabial folds, cheeks, and chin; sometimes they also involve the forehead and scalp Although called adenoma sebaceum, these nodules are actually angio bromas; the sebaceous glands are only passively involved (Fig 38-5) The earliest manifestation of facial angio bromatosis may be a mild erythema over the cheeks and forehead, intensi ed by crying The occurrence of large plaques of connective tissue on the forehead is usually expressive of a severe form of the disease On the trunk, the diagnostic lesion is the shagreen patch (in reality a plaque of subepidermal brosis) found most often in the lumbosacral region It appears as a at, slightly elevated, eshcolored area of skin 1 to 10 cm in diameter, with a pigskin, elephant hide, or orange peel appearance (Fig 38-6) Another common site of bromatous involvement is the nail bed; subungual bromas usually appear at puberty and continue to develop with age Other common skin changes, not in themselves diagnostic, include broepithelial tags (soft bromas), cafe au lait spots, and port-wine hemangiomas Pathology The brain exhibits a number of diagnostic anomalies Broadening, unnatural whiteness, and rmness of parts of some of the cerebral convolutions are simulated by no other disease These are the tubers after which the disease is named On the surface of the brain, they range in width from 5 mm to 2 or 3 cm Their cut surface reveals a lack of demarcation from cortex and white matter and the presence of white ecks of calcium; these, which are readily seen on CT scans and MRI, are called brain stones (see below and Fig 38-7) The walls of the lateral ventricles may be encrusted with white or pink-white masses resembling candle gutterings When calci ed, they appear in radiographs as curvilinear opacities that follow the outline of the ventricle Rarely, nodules of abnormal tissue are observed in the basal ganglia, thalamus, cerebellum, brainstem, and spinal cord Under the microscope the tubers are seen to be composed of interlacing rows of plump, brous astrocytes (much like an astrocytoma, though lacking in glial brillar protein) In the cerebral cortex and ganglionic structures, derangements of architecture re-
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Figure 38-6 Shagreen patch on the skin of the lower back in a young patient with tuberous sclerosis
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sult from the presence of abnormal-appearing cells: greatly enlarged monstrous, or balloon neurons and glial cells often dif cult to distinguish from one another Also, displaced normalsized neurons contribute to the chaotic histologic appearance Gliomatous deposits may obstruct the foramina of Monro or the aqueduct or oor of the fourth ventricle, causing hydrocephalus Neoplastic transformation of abnormal glial cells, a not infrequent occurrence, usually takes the form of a large-cell astrocytoma, less often of a glioblastoma or meningioma Recently, certain relationships have been drawn between the balloon cells of this disease and similar cells in focal cortical dysplasias (see Crino for details) The phakomas of the retina are also composed mainly of neuronal and glial components, but occasionally there is an admixture of brous tissue Diagnosis When the full combination of seizures and mental and dermal abnormalities is conjoined, the diagnosis is self-evident It is the early stage of the disease and the formes frustes that give trouble, and here the experienced dermatologist can be of great help Epilepsy ie, exion spasms in infancy and delay in psychomotor development are by no means diagnostic of tuberous sclerosis, since they occur in many diseases It is in these cases and also in every sizable population of the epileptic or mentally retarded, especially when the family history is unrevealing, that a search for the dermal equivalents of the disease the hypomelanotic ash-leaf spots, adenoma sebaceum, collagenous skin patch, phakoma of the retina, or subungual or gingival bromas is so rewarding The nding of any one of these lesions provides con rmation of the partial and atypical case Adenoma sebaceum may occasionally occur alone and is easily confused with acne vulgaris in the adolescent The history of epilepsy and/or the demonstration of a dull mentality are helpful, but neither is a requisite for the diagnosis of tuberous sclerosis (see the monograph by Gomez) The most useful laboratory measures for corroborating the disease are the CT scan and MRI (Fig 38-7) The calci c lesions tend to be periventricular and are particularly well shown on the CT scan, whereas MRI is more sensitive in detecting hamartomatous subcortical lesions There is an absence of edema in the surrounding tissue Roach and colleagues have indicated that an increasing number of cortical lesions demonstrated with MRI appears to correlate with an increased impairment of neurologic function
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