Some Thoughts on the Classification of Malformations of Cortical Development

In this issue of the ARCHIVES, Morris, Parisi, and Buchhalter1 describe their findings in a series of 53 patients with malformations of cortical disclosure (MCDs) and use this as a springboard to discuss an approach to classification of these lesions. Historically, there have been many attempts (both radiologic and pathologic) at designing classifications of these lesions with a variety of results2-14

If single carefully sifts through the various described approaches, the lesions being described are more or les the same. The riddles arise in what names are ascribed to the various pathologies, the image of phenotypes that are acceptable for a particularly pathology, the subjectivity of many of the observations (ie, intraobserver variability), definitions of confines used, and the lack of agreement regarding the precise representation of disorders that would fall below the general heading of MCD level the term MCD is a relatively novel appellation that has been applied to this assemblage of disorders that were formerly referr to by the agency of a variety of other names including cortical dysplasia. The authors should be recommended on adopting a more appropriate terminology (MCD) above the term cortical dysplasia. Use of the boundary dysplasia in this context is a misnomer, in that we commonly use the limit to imply a lesion that has a certain quantity of predisposition to progress to neoplasia, which does not look to be the case in the majority of MCD

What is lacking in our popular understanding of these lesions is a real knowledge of the etiology of these lesions and in what manner etiology might relate to morphology. A tremendous amount of work has been done in novel years trying to elucidate the pathogenesis of MCD Clearly, more [i]or[/i] less of them have a genetic constituting whereas others appear to be the accrue of environmental factors that disrupt cortical exhibition In the vast majority of cases, we do not know what the underlying want is that has resulted in the pathology that we are looking at. The pathology we are looking at has repeatedly developed over the course of years. This begs the question about in what manner much of what we are looking at can we directly attribute to the unknown etiology and in what manner much of what we diocese represents secondary consequences. There are a variety of potential mechanisms associated with disruption of cortical disentanglement but we still cannot compute by looking at the pathology, perhaps with rare exception, what the cause is in a given case. single could argue that until we procure a better handle on this, any genuinely morphologic based classification will be limited. The corollary to this is that any literature predicated upon such classification systems is potentially colored by means of the approach an investigator exercises However, because morphologic based classification of MCD appears to be what we have to work with, by what means do we make the best of it?

The basic premise of any approach to a classification schema is that it is reasonably easy to apply (and therefore theoretically reproducible) and that it has a certain number of clinical relevance. There are a number of issues or questions that ne to be considered in the generation of a MCD classification schema. I am not confident there is one correct answer to any of these issues: (1) There are clearly a certain quantity of lesions that are recognizable one as well as the other grossly and radiographically (and more [i]or[/i] less that are not). Should individual include a gross pathology constituting to the schema to include a lesion similar as polymicrogyria or simply stick with a genuinely microscopic approach and incorporate lesions of the like kind as polymicrogyria in that fashion? (2) Is it better to be a loader or splitter? Does it make a difference single way or the other? (3) What is an "appropriate" workup or evaluation of of the like kind a case from a pathology perspective?

In pathology, we do not ofttimes like to mix gross and microscopic patterns in our classifications in a mutually exclusive fashion. In this instance notwithstanding that one could argue that there are certain gros lesions that have been associated with certain syndrome or genetic alterations that make recognizing the gros pathology clinically relevant. For example, lissencephaly or agyria is known to be associated with Miller-Dieker syndrome a rare autosomal dominant disorder associated with a LlS-1 gene abnormality (chromosome 17p133) The gros appearance of a certain number of of these lesions (with their associations) can easily win lost in the general rubric of a microscopic classification.

The validity of a classification approach trunk s from its clinical relevance. As pathologists, we do not operate in a vacuum. Our diagnoses are meant to provide as abundant assistance to our clinical colleagues as possible. There has emerg in the literature recognition that there are certain patterns of MCD that may have a certain quantity of clinical significance. Most notably, patterns of what have been referr to as focal cortical dysplasia or Taylor impressed sign of dysplasia, marked by balloon confined apartments and dysmorphic neurons, tend to be associated with more refractory seizures. Whether individual is a lumper or splitter again becomes a philosophical issue. However, unles at a certain number of level one looks carefully at nuances from a "splitter's perspective," individual may miss out on a relevant correlate that would earn lost in the lumper approach. individual also needs to consider the interobserver variability factor; an approach that is too nuanced may flow in inconsistencies as pathologists attempt to apply it.