Histopathology in gastrointestinal neuromuscular diseases: methodological and ontological issues

Gastrointestinal (GI) neuromuscular diseases (GINMDs) comprise a heterogeneous group of chronic conditions associated with impaired gut motility. These GI disorders, differing for etiopathogenic mechanisms, pathologic lesions and region of gut involvement, represent a relevant matter for public health, since they are very common, can be disabling and determine major social and economic burdens. GINMDs are presumed or proven to arise as a result of a dysfunctioning GI neuromuscular apparatus, which includes myenteric ganglia (neurons and glial cells), interstitial cells of Cajal and smooth muscle cells. Despite the presence of symptoms related to gut dysmotility in the clinical phenotype of these patients, in the diagnostic setting scarce attention is usually paid to the morphological pattern of the GI neuromuscular apparatus. It is also objectively difficult to collect full-thickness gut tissue samples from patients with GINMDs, since their disease, which can be only functional in nature, may not justify invasive diagnostic procedures as a first line approach. As a consequence, whenever available, bioptic gut specimens, retrieved from these patients, must be regarded as a unique chance for obtaining relevant diagnostic information. Based on these arguments, there is an urgent need of standardized and validated histopathological methods, aiming at overcoming the discrepancies affecting current approaches, which usually lead to conflicting definitions of normality and hamper the identification of disease-specific pathological patterns. This review article intends to address current methodological and ontological issues in the histopathological diagnosis of GINMDs, in order to foster the debate on how to discriminate normal morphology from abnormalities.