Histopathology of Pediatric Celiac Disease (Response)

Abstract

We appreciate the interest in our recent paper on celiac disease (CD) [1], and Dr. Drut’s sharing his perspective on tissue handling and the details of his grading system for villous atrophy [2]. As our paper indicated, and a recent flurry of activity on the Pediatric Pathology listserve has reiterated, there is currently no consensus for optimal tissue handling of small intestinal biopsies. While in our hands, orientation of tissue at the time of embedding by an experienced histotechnologist and examination of multiple levels for selected cases works best, in Dr. Drut’s institution, orientation of tissue on a substrate is preferred. We discuss the advantages and disadvantages of both methods in our paper [1]. We agree with Dr. Drut that a standardized grading scheme for small intestinal biopsies for CD is helpful to the clinician. The Marsh classification is widely used and the modified Marsh classification includes an infiltrative lesion lacking architectural abnormalities and subdivision of villous atrophy into three grades of severity [3]. As CD is currently considered to be predominantly an immune-mediated process, a grading scheme that includes lymphocytic infiltration seems appropriate. As Oberhuber et al. state, “An increase in the number of IEL is the first and most sensitive index of the effects of gluten on the mucosa [their ref. 20], and is therefore the single most important histological feature in CD” [3]. In contrast to Dr. Drut’s experience, our group and others have seen small intestinal biopsies from patients with CD show increased intraepithelial lymphocytes (IEL) and no architectural abnormalities (modified Marsh type I) [3,4], as well as cases of CD with patchy involvement of only some of the biopsy fragments [5]. Thus, although a wider net is cast, we favor a grading system which will call to attention possible cases of CD that would be missed if architectural abnormalities alone were required to suggest diagnosis. Whatever grading scheme is employed, biopsy findings alone are not specific for CD and should be interpreted within the clinical context of each individual case.