Hashimoto’s Thyroiditis Histology: Key Tissue Insights

Hashimoto’s thyroiditis is a common autoimmune disorder that leads to chronic inflammation and progressive destruction of the thyroid gland. As the immune system mistakenly attacks thyroid tissue, characteristic histological changes emerge, which are crucial for diagnosis and understanding disease progression.

A closer look at the microscopic features reveals distinct patterns in cellular infiltration, structural alterations, and immune activity within the thyroid.

Lymphocytic Infiltration

A defining histological feature of Hashimoto’s thyroiditis is the extensive infiltration of lymphocytes into the thyroid parenchyma. This invasion progressively replaces normal thyroid architecture, with T cells predominating alongside a smaller proportion of B cells. These immune cells form dense aggregates that disrupt the follicular structure. Immunophenotyping studies confirm the involvement of CD4+ helper T cells and CD8+ cytotoxic T cells in follicular destruction.

As infiltration intensifies, colloid-filled follicles diminish, and lymphocytic aggregates localize in perivascular and periductal regions before expanding into interfollicular spaces. This distribution suggests a targeted immune response rather than diffuse inflammation. Research in The Journal of Clinical Endocrinology & Metabolism indicates that higher lymphocytic infiltration correlates with more severe thyroid dysfunction.

These lymphocytes actively contribute to tissue damage through elevated levels of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which promote follicular cell apoptosis. Regulatory T cells (Tregs) are present but appear insufficient to counteract destruction. A study in Thyroid found that patients with more aggressive infiltration tend to have lower circulating Treg levels, indicating an imbalance in immune regulation.

Follicular Epithelial Changes

Follicular epithelial cells in Hashimoto’s thyroiditis undergo morphological changes reflecting cellular stress and adaptation to inflammation. A key transformation is the development of Hürthle cells—enlarged epithelial cells with abundant eosinophilic cytoplasm due to mitochondrial accumulation. Electron microscopy confirms mitochondrial swelling and disrupted cristae, indicative of dysfunction.

As Hürthle cells accumulate, the normal cuboidal epithelium becomes heterogeneous, with regions of atrophy interspersed with hyperplasia. Some follicles shrink and lose colloid, while others become irregularly shaped. Immunohistochemical staining reveals diminished thyroglobulin expression, corresponding with reduced thyroid function.

Increased epithelial cell turnover is another notable feature. Ki-67 proliferation indices show higher renewal rates in Hashimoto’s thyroiditis compared to normal thyroid tissue. This heightened activity is a compensatory response to ongoing damage, but it fails to counteract progressive destruction, leading to glandular dysfunction.

Germinal Center Development

Germinal center formation within the thyroid is a hallmark of Hashimoto’s thyroiditis, reflecting localized immune activation. These structures resemble those in secondary lymphoid organs, with a darker mantle zone surrounding a pale germinal center. Unlike reactive lymphoid hyperplasia, germinal centers in Hashimoto’s arise within the thyroid parenchyma, signifying persistent antigen-driven stimulation.

Microscopically, they contain proliferating B cells, supported by follicular dendritic cells that facilitate antigen presentation. These centers enable somatic hypermutation and affinity maturation of B cells, processes typically confined to lymphoid tissues. In situ hybridization studies show that these centers actively produce thyroid peroxidase (TPO) and thyroglobulin antibodies, further driving follicular destruction.

Fibrotic Tissue Patterns

As Hashimoto’s thyroiditis progresses, fibrosis becomes a prominent histological feature. Initially, collagen deposition appears in perivascular and interfollicular regions, forming thin strands that disrupt normal architecture. Over time, these fibers thicken, creating patchy fibrosis rather than diffuse sclerosis.

Extracellular matrix accumulation, particularly type I and type III collagen, stiffens the gland. Masson’s trichrome and Sirius Red staining reveal increased collagen deposition, impairing thyroid follicle expansion and contraction. Fibroblast activation leads to secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), with imbalances in these enzymes exacerbating rigidity.

Immunohistochemical Profile

Immunohistochemical analysis provides insights into the molecular mechanisms driving Hashimoto’s thyroiditis. Thyroglobulin (Tg) and thyroid peroxidase (TPO), essential for thyroid hormone synthesis, show patchy loss in affected follicles. Reduced expression of these proteins correlates with hypothyroidism severity.

Immune cell markers further characterize the inflammatory environment. CD3 and CD20 staining confirm extensive T and B lymphocyte presence, with CD4+ T cells predominating early and CD8+ T cells accumulating as destruction progresses. CD138+ plasma cells indicate active antibody production, while upregulated HLA-DR expression in follicular epithelial cells suggests aberrant antigen presentation, perpetuating inflammation.

Distinguishing Features From Other Conditions

The histological characteristics of Hashimoto’s thyroiditis necessitate differentiation from other thyroid disorders. While lymphocytic infiltration occurs in various inflammatory thyroid diseases, the presence of well-formed germinal centers within the thyroid parenchyma is a distinguishing feature absent in Graves’ disease, where infiltration is more diffuse. Hürthle cell metaplasia is also more pronounced in Hashimoto’s than in other autoimmune thyroid disorders.

Fibrosis helps differentiate Hashimoto’s from Riedel’s thyroiditis, a rare condition with extensive, rock-hard fibrosis extending beyond the thyroid capsule. Immunohistochemistry further aids differentiation, as Hashimoto’s thyroiditis maintains strong thyroglobulin and TPO expression, unlike malignant conditions such as thyroid lymphoma, which often exhibit complete loss of these markers. Ki-67 proliferation indices also distinguish benign lymphocytic infiltration from neoplastic processes, as thyroid lymphoma shows significantly higher proliferative activity.