Density and size of lymphoid follicles are useful clues in differentiating primary intestinal follicular lymphoma from intestinal reactive lymphoid hyperplasia

Abstract Background Primary intestinal follicular lymphoma (PI-FL) is a rare and indolent lymphoma and is challenging for diagnosis with endoscopic biopsy specimens. Whole slide imaging (WSI) has been increasingly used for assisting pathologic diagnosis, but not for lymphoma yet, probably because there are usually too many immunostained sections in a single case. In this study we attempted to identify morphological clues of PI-FL in the endoscopic biopsy specimens by measuring various parameters using WSI. Methods We retrospectively investigated 21 PI-FL cases, and scanned the HE sections from 17 of these cases with endoscopic biopsy specimens. Sections from 17 intestinal biopsies showing reactive lymphoid hyperplasia were scanned for comparison. The density and diameter of lymphoid follicles and the shortest distance of these follicles to the surface epithelia were measured on WSI. Comparisons of the aforementioned parameters were made between the neoplastic and reactive follicles. Results The density of follicles was significantly higher in PI-FL than that of reactive hyperplasia (median 0.5 vs. 0.2/mm2; p < 0.01). Furthermore, the neoplastic follicles were significantly larger (median diameter 756.9 vs. 479.7 μm; p < 0.01). The shortest distance of follicles to the surface epithelia tended to be closer in PI-FL (104.7 vs. 177.8 μm, p = 0.056), but not statistically significant. Conclusions In this study we found that in PI-FL the density and diameter of lymphoid follicles as measured from WSI were significantly different from that of intestinal reactive lymphoid hyperplasia. When facing the diagnostic challenge between these two entities in routine practice, pathologists might be alerted by these morphological clues and request for immunohistochemistry for differential diagnosis.