Cracking Spaces in Hashimoto Thyroiditis Are Lymphatic and Prelymphatic Vessels

Abstract

A century ago Hashimoto described the histologic hallmarks of struma lymphomatosa: (1) lymphoid follicles, (2) changes in the epithelial cells, (3) formation of connective tissue, and (4) diffuse round cell infiltration. He also showed some cracking spaces close to lymphoid follicles resembling vessels. The aim of this study was to investigate the possible lymphatic nature of these spaces and their prevalence in non-neoplastic thyroid tissue. Ten cases of Hashimoto thyroiditis (HT), 5 of Basedow-Graves disease (BG), and 5 of normal thyroid tissue (NT) were selected. Tissues were stained with hematoxylin and eosin, CD31 (Dako), and D2-40 (Dako) stains. Cracking spaces staining positive for CD31 and D2-40 stains were considered as lymphatic vessels. Site, distribution, intravascular valves and lymphocytes, perivascular lymphoid aggregates, and number and surface of lymphatic vessels were evaluated using a computer-assisted digital videocamera microscope (Nikon digital sigh, DS-2Mv). The number of lymphatic vessels increased from NT [3 (range, 2 to 13)] to BG [8 (range, 5 to 9)] to HT [12.5 (range, 10 to 16)]. A significant statistical difference was observed within the group (P=0.003): HT differed from NT (P=0.016) and BG (P=0.002). The area of lymphatic vessels increased from NT [0.01 mm (range, 0.01 to 0.12 mm2)] to BG [0.03 mm2 (range, 0.01 to 0.19 mm2)] to HT [0.03 mm (range, 0.01 to 0.6 mm2)]. A significant statistical difference was observed among the groups (P=0.001): NT differed from HT (P<0.001) and from BG (P<0.001). Lymphatic vessels showed valves, perivascular lymphoid aggregates, and intravascular lymphocytes. The cracking spaces shown by Hashimoto are mainly lymphatic vessels and represent a characteristic feature of autoimmune thyroid diseases.