A 52-year-old woman with a history of type 1 diabetes mellitus and celiac disease presents with progressive fatigue, weight gain, and cold intolerance over 3 months. On examination, she has a diffusely enlarged, firm thyroid with no nodules. TSH is 18 mIU/L (normal 0.4–4.0), free T4 is 0.6 ng/dL (normal 0.8–1.8), and anti-TPO antibodies are 450 IU/mL (normal <35). Anti-thyroglobulin antibodies are also positive. Thyroid ultrasound shows a diffusely hypoechoic gland with preserved vascularity. Which histopathological finding would be expected on thyroid biopsy?

Explanation

## Histopathology of Hashimoto Thyroiditis ### Clinical Diagnosis: Chronic Autoimmune Thyroiditis (Hashimoto) **Key Point:** Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient regions and is characterized by autoimmune destruction of thyroid follicles with lymphocytic infiltration. ### Diagnostic Criteria Met in This Case | Criterion | Finding | Significance | |-----------|---------|---------------| | **Clinical presentation** | Insidious hypothyroidism (fatigue, weight gain, cold intolerance) | Chronic autoimmune process, not acute | | **TSH/T4 pattern** | TSH elevated (18), free T4 low (0.6) | Primary hypothyroidism | | **Autoantibodies** | Anti-TPO and anti-thyroglobulin positive | Diagnostic hallmark of autoimmune thyroiditis | | **Thyroid appearance** | Diffusely enlarged, firm, no nodules | Chronic inflammation with fibrosis | | **Ultrasound** | Diffusely hypoechoic, preserved vascularity | Chronic lymphocytic infiltration, not granulomatous | | **Associated autoimmunity** | Type 1 DM, celiac disease | Hashimoto is part of autoimmune polyendocrine syndrome | ### Characteristic Histopathology of Hashimoto Thyroiditis **High-Yield:** The pathognomonic histological features are: 1. **Lymphocytic infiltration** — predominantly CD8^+^ T cells and B cells 2. **Germinal centers** — evidence of active B-cell proliferation and antibody production 3. **Hürthle cell change (oncocytic metaplasia)** — follicular epithelial cells with abundant mitochondria, giving a granular, eosinophilic cytoplasm 4. **Follicular atrophy and fibrosis** — progressive destruction of thyroid architecture 5. **Preserved follicular structure** — unlike granulomatous thyroiditis, granulomas are absent **Mnemonic:** **LIGHT** — **L**ymphocytes, **I**nfiltration, **G**erminal centers, **H**ürthle cells, **T**hyroid atrophy ### Phases of Hashimoto Thyroiditis ```mermaid flowchart TD A[Autoimmune activation<br/>Anti-TPO, Anti-Tg antibodies]:::outcome --> B[Lymphocytic infiltration<br/>Germinal center formation]:::action B --> C[Follicular destruction<br/>Hürthle cell change]:::action C --> D[Progressive fibrosis<br/>Thyroid atrophy]:::action D --> E[Overt hypothyroidism<br/>TSH↑, T4↓]:::outcome ``` ### Why Hürthle Cells Are Pathognomonic **Clinical Pearl:** Hürthle cells (also called oncocytes or Askanazy cells) are follicular epithelial cells that have undergone metaplasia in response to chronic immune attack. They are rich in mitochondria and appear as large, granular, eosinophilic cells on H&E staining. This finding is virtually diagnostic of Hashimoto thyroiditis and distinguishes it from other forms of thyroiditis. ### Associated Conditions Hashimoto thyroiditis is part of **autoimmune polyendocrine syndrome (APS)** and commonly coexists with: - Type 1 diabetes mellitus (as in this patient) - Celiac disease (as in this patient) - Addison disease - Pernicious anemia - Systemic lupus erythematosus [cite:Robbins 10e Ch 24]