Lymphocytic oesophagitis, eosinophilic oesophagitis and compound lymphocytic–eosinophilic oesophagitis I: histological and immunohistochemical findings

Abstract

Based on the literature regarding the significance of intraepithelial lymphocytes (IELs) in the initiation of EoE, we submit that the IEL phenotypes in LyE might differ from those found in EoE as they were unable to elicit the same eosinophilic response. Recent studies disclosed that group 2 innate lymphocytes (ILC2s), enriched in EoE, remain undetected in CD3 immunostain as they lack surface markers for T, B, natural killer (NK) or NK T cells. If ILC2s also participate in the lymphocytic infiltration of EoE, then the frequency of cases with Co LyE-EoE here reported might have been much higher. The four oesophagitis phenotypes described are easy to recognise, provided that the dual staining procedure (H&E-CD3) is implemented.

Lymphocytic Esophagitis

“…In a recent cohort from Rubio et al, out of 311 biopsies with an increased number of intraepithelial lymphocytes, 33 cases were a compound of lymphocytic esophagitis and eosinophilic esophagitis [9]. We can thus ask whether these are two distinct conditions or whether one is the continuum of the other.…”

“…The main histologic indings are a dense peripapillary intraepithelial lymphocytic iniltrate, an intercellular edema known as spongiosis, as well as the absence or rarity of granulocytes (Figure 1) [1]. The intraepithelial lymphocytes express CD3, CD4, and CD8, as shown by immunohistochemistry [1,9,11].…”

Lymphocytic esophagitis updated

“…Regrettably, the lower limit of intraepithelial lymphocytosis used to diagnose LyE was not given . In a subsequent study of LyE, also using H&E‐stained sections, the lower limit was set at 20 IELs …”

“…Moreover, when the CD3 antibody reacts with its cognate antigen present in the cytoplasm, the entire IEL and cytoplasmic fragments included in the sections become clearly visible. With that method, a significantly higher number of CD3 + lymphocytes are highlighted in the area encompassed by the 4 μm thick section than when counting IEL in H&E stain exclusively .…”

“…The result in 311 patients consulting for dysphagia, food impaction, dysphagia with fluids and/or solids, and sense of foreign body revealed four histological/immunohistological esophagitis phenotypes: (1) lymphocytic esophagitis (LyE): ≥40 CD3 + lymphocytes/HPF using CD3 immunostaining; (2) eosinophilic esophagitis (EoE): ≥15 eosinophils/HPF with lymphocytic infiltration (≤39 CD3 + /HPF) in H&E stain; (3) compound lymphocytic esophagitis–eosinophilic esophagitis (Co LyE–EoE), that is, LyE, ≥40 CD3 + lymphocytes/HPF in CD3 immunostaining and ≥15 eosinophils/HPF in H&E stain; and (4) lymphocytic infiltration (≤39 CD3 + /HPF). These four esophagitis phenotypes were easily recognized, provided that sections were stained with H&E and CD3 independently, one at a time . The serendipitous finding that 11% (33/311) of the cases had compound LyE and EoE may explain some of the difficulties experienced by endoscopists while trying to discriminate between LyE and EoE.…”