In 1992, M.N. Marsh published a study aimed at measuring degrees of change seen in the structure of intestinal villi under microscopic scrutiny. Villi are finger-like projections which line the intestinal walls; their thin walls and large surface area are what allow for efficient absorption and digestion of nutrients. In patients with celiac disease, the villi erode and flatten, substantially interfering with the body’s ability to process food as it passes through the intestine. Marsh developed a four-level scale categorizing these changes, with Marsh 0 reflecting healthy, normal intestinal villi, and Marsh 4 indicating flat, wholly atrophied intestinal villi. This scale, while not originally intended for diagnostic use, gained widespread popularity as a means of diagnosing celiac disease. In later years, the original scale was modified to seven levels of classification, with Marsh 3 being subdivided into Marsh 3a, 3b, and 3c. This revised scale is called the Marsh-Oberhuber classification system.
A recent study published in the Journal of Clinical Pathology asked the question: is classification of villous atrophy (using the Marsh scale) strictly necessary in the diagnosis of celiac disease? This study by Biagi, et al. looked retrospectively at samples taken from 2,075 patients at an Italian clinic during the period 1999-2015. In each case, samples were viewed using a dissecting microscope (DM) before being sent to pathology for traditional histological testing and classification (TH). The aim of this study was to determine the degree to which the conclusions reached using each method were the same.
For the purposes of this study, samples rated by TH as Marsh 0-2 were considered to have no villous atrophy, those at classification levels 3a and 3b were considered to have mild villous atrophy, and those at levels 3c and 4 were considered severe. Observations made during DM were grouped similarly based on the type of visual cues typically seen in the samples; specifically, samples with a pattern described as “mosaic surface” were judged to be severe (i.e. Marsh 3c level or above). In these latter cases, the mucus membranes appear to have a cracked appearance when viewed under microscopy, indicative of patches of atrophied villi.
Results of this study showed that both techniques were able to nearly equally identify the most severe cases of villous atrophy and give a diagnosis of celiac disease. At lower levels, DM was not sensitive enough to provide a diagnosis, but it is important to note that mild atrophy can have many causes other than celiac disease, making a diagnosis at that stage questionable under any circumstances.
Where DM was particularly helpful was in analysis of samples where TH could not be done, usually because of incorrectly prepared slides. This quick, easy-to-teach method for identifying severe atrophy also allows for earlier intervention with starting a gluten-free diet, setting patients with mosaic surface samples on a path to repair.
The Biagi, et al. study concludes that it is still vital that traditional histological analysis of biopsies be performed whenever possible, though the results of this retrospective study would suggest that detailed Marsh scale classification of each sample is unnecessary. The relative speed of microscopic analysis allows for earlier adoption of the gluten-free diet, setting the patient on a path to alleviated symptoms while waiting for the more detailed histological analysis. While this study was not large, the high correlation between diagnoses reached using the two methods suggests that physicians should strongly consider microscopic analysis, to provide quicker relief to suffering patients.
Necessity of Marsh Scale Classification in Assessment of Villous Atrophy