This issue of Gastroenterology Clinics of North America is focused on challenges faced in everyday clinical practice. Thus rather than reviewing the evolving research literature that details the many experimental models of enteric neuromuscular disease, this article considers the problems faced by the practicing pathologist, who, faced with a single tight-focus histologic “snapshot” of surgically derived tissue must decide whether disease of nerve, smooth muscle, or interstitial cells of Cajal (ICC) are present. This raises several technical and interpretational challenges ( Box 1 ). Several of these points have been addressed in recent publications of an International Working Group (IWG) for GI neuromuscular pathology, and much of this review draws on the IWG’s important contributions to consensus in this field.
Technical
1. Availability of adequate full-thickness tissue for study
2. Standardization of preparative (suitable fixation and orientation) and staining methods
3. Limitations on availability of more complex methods
Interpretational
4. Availability of normative human data
5. Clear definition of abnormality (in the individual)
6. Understanding of relationship of abnormality to observed clinical phenotype
7. Impact on patient management or prognosis
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