Quantitative histology as a diagnostic tool for celiac disease in children and adolescents

The diagnosis of celiac disease relies on a combination of clinical data, serological tests and histopathological features; therefore, the exchange of information between the gastroenterologist and the pathologist is fundamental [1], [2], [3]. The typical histological findings of the duodenum biopsy are an increased intraepithelial lymphocyte (IEL) count, crypt hyperplasia (elongation of the crypts) and villous atrophy (flattening of the villi) [1], [4], [5]. Thus, it is essential to standardize the morphological report of celiac patients and differentiate them from the healthy population and its differential diagnosis such as giardiasis, tropical sprue and common variable immunodeficiency [1], [6], [7], [8], [9], [10].

Many authors determined a spectrum of mucosa alterations, the most well-known ones are the classifications of Marsh [11], Marsh-Oberhuber [12] and Corazza-Villanacci [13]. Even though there is a standardization, these grading systems have as their main limitation the low reproducibility - kappa coefficient under 0,5 - among pathologists, in children and adults studies [14], [15], [16], [17]. One of the reasons is the use of subjective criteria to determine villous atrophy and cryptic hyperplasia, as well as, the variety of cut off values to consider an increased IEL count [2], [3]. It is estimated 13 to 46 % of the histological analyses result in a misdiagnosis of celiac disease [7].

Quantitative histology is an exciting alternative, which measures the villous height and crypt depth in μm and performs the IEL count. The application of this methodology increases the reproducibility and accuracy, and enables the identification of histological changes in a short period of time [3], [18], [19], [20], [21]. Nevertheless, what stands out is its current application in clinical trials of medications which inactivate gluten [22], [23] and the development of biomarkers that correlate with each stage of mucosal damage [24].

Even though morphometric techniques have been available since the 70's [25], [26], [27], quantitative histology has remained in the research field and not in clinical practice; one of the reasons is the lack of its value spreading. Recently, diagnostic classifications were elaborated in the adult population based on quantitative parameters, such as the Q-Marsh scale [3] in 2018 and the Q-histology [20] in 2019. However, these scales were not used in the pediatric age.

Considering the shortage of studies applying quantitative histology to establish the diagnosis of celiac disease or differentiate it from other affections with similar histological features, especially in the pediatric patients, we have decided to carry out this study. The aim is to measure the villous height, the crypt depth and the number of IEL/100 enterocytes of the small intestinal mucosa of children and adolescents with celiac disease; and classify these findings according to Q-Marsh and Q- Histology scales.

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