Histological Alterations in Hashimoto's Disease: A Case-Series Ultrastructural Study

Abstract

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease exhibiting stromal fibrosis and follicular cell destruction due to lymphoplasmacytic infiltration. Besides deprecated analyses, histopathological approaches have not employed the use of electron microscopy adequately toward delineating subcellular-level interactions.

Methods: Biopsies for ultrastructural investigations were obtained from the thyroids of five patients with HT after a thyroidectomy. Transmission electron microscopy (TEM) was utilized to study representative tissue specimens.

Results: Examination indicated interstitial extravasated blood cells and a plethora of plasma cells, based on their subcellular identity landmarks. These antibody-secreting cells were profoundly spotted near follicular cells, fibroblasts, and cell debris entrenched in collagenous areas. Pathological changes persistently affected subcellular components of the thyrocytes, including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and other intracellular vesicles. Interestingly, significant endothelial destruction was observed, specifically in the larger blood vessels, while the smaller vessels appeared comparatively unaffected.

Conclusions: Our TEM findings highlight the immune-related alterations occurring within the thyroid stroma. The impaired vasculature component and remodeling have not been described ultrastructurally before; thus, further exploration is needed with regards to angiogenesis in HT in order to achieve successful prognostic, diagnostic, and treatment-monitoring strategies.

Keywords: Hashimoto’s thyroiditis; angiogenesis; blood vessels; electron microscopy; ultrastructure.

Figure 1

Immune cells identified with TEM in the HT thyroid gland stroma. (a). Lymphocytes and plasma cells infiltrate the interstitium surrounding the affected thyroid follicles, where plasma cells (PLs) actively attack the follicular cells. The prominent endoplasmic reticulum and Golgi apparatus (asterisk) indicate protein synthesis and secretion. A vessel (v) is present nearby among thyrocytes. (b). Additionally, a macrophage with intracellular debris (arrow) is observed, suggesting its involvement in phagocytic processes. Plasma cells (PLs) were also documented based on ER appearance (asterisk). Scales are denoted in each micrograph.

Figure 2

Thyroid epithelium and follicular impairment. (a). Thyroid follicular cells displayed changes characterized evidently by colloid decomposition appearing as droplets (c) within a follicle. (b). A higher magnification image provides a closer look at the cellular changes, revealing the irregular nucleus (n), enlarged rough endoplasmic reticulum, distended with wider cisternae (asterisk), and other intracellular organelles with abnormal membranes. Furthermore, the degenerated epithelium demonstrates an evident loss of microvilli (arrow) toward the apical surface, which is in direct contact with the colloid. Scales are denoted in each micrograph.

Figure 3

Endothelial cell alterations at the ultrastructural level. (a). Large vessels exhibited extensive damage, showcasing ruptures on the endothelium (arrows) and displaced collagen fibers within the lumen. Additionally, fibroblasts and collagen fibers (inset) were observed in the vicinity of the damaged endothelium, contributing to fibrotic scarring. (b). Endothelial cells exhibited nuclei (n) with irregular outlines, whereas their mitochondria (m) appeared to be denser and smaller in size, implying a perturbed energy metabolism within their cell bodies. Additionally, the majority of endothelial cells displayed disrupted basal lamina, with noticeable alterations and a lack of continuity with the underlying reticular lamina (arrows). Transversely cut collagen fibers can be seen underneath as dark dots. Micrograph pseudocolors: red = red blood cell (RBC), yellow = endothelial cell cytoplasm, orange = mitochondria, purplish blue = endothelial cell nucleus, magenta = basal lamina, and cyan = thyroid intermediate connective tissue. Scales are denoted in each micrograph.