Letter to the Editor
Dysplasia, Cytodysplasia and Tuberous Sclerosis
To the Editor:
Within the spectrum of errors in morphogenesis, dysplasia has been defined as an abnormal organization of tissue(s) and its morphologic result is dyshistiogenesis [Opitz and Gilbert, 1982; Spranger et al., 19821. The concept apparently implies that dysplastic lesions should include all abnormalities in the differentiation of tissues. Since tissues are formed by cells, its constitution means an interaction between cells, which when abnormal, results in dysplastic lesions.
I think that there is need for another level of microscopically recognizable alteration that does not necessarily result from dyshistiogenesis but from cellular aberrations arising during cytodifferentiation. This error in morphogenesis I propose to call cytodysplasia, and the process from which it is derived, dyscytogenesis.
A useful way to exemplify this proposal is through the lesions found in tuberous sclerosis. The "tubers" in that disorder are composed of unusual cells (cytodysplasia) resulting from abnormal differentiation (dyscytogenesis) growing discordantly with its own rhythm and producing focal dysplastic lesions. As has been demonstrated by Bender and Yunis, [ 19821 such "tuber" cells express some morphologic (cytologic and ultrastructural) and immunohistochemical features of both astrocytes and neurons. These observations have led to the assumption that the abnormality lies in a precursor cell common to both neurons and astrocytes. The same reasoning may be used for cardiac rhabdomyomas. Its cells not only form an abnormal dysplastic tissue, but appear anomalous. We know they are cardiac muscle cells but they are not like normal myocardial cells. Cardiac rhabdomyomata are composed of cytodysplastic cells. Additional examples may include cells of angiomyolipomas, and stellate "stromal" cells of skin angiofibromas, again lesions found in tuberous sclerosis.
The concept of cytodysplasia is obviously intimately related to that of neoplasia, the first being applied to cases of errors in morphogenesis. However certain points in common may be inferred. Since cell growth and differentiation appear to be regulated by oncogenes, some abnormality of those genes may be operative in dyscytogenesis. Following the line of reasoning, a patient with tuberous sclerosis may be envisioned as a mosaic in whom some cells of the central nervous system, heart, kidney, and skin are abnormally