Definition/General
Introduction:
Hashimoto thyroiditis (chronic lymphocytic thyroiditis) is the most common cause of hypothyroidism in iodine-sufficient areas
On FNAC, it shows characteristic triad of Hurthle cell metaplasia, lymphocytic infiltration, and absence of colloid
It is an autoimmune disorder with progressive destruction of thyroid follicles.
Origin:
Autoimmune destruction of thyroid follicular epithelium mediated by T-cell and B-cell responses
Anti-thyroglobulin and anti-TPO antibodies are hallmarks
Progressive fibrosis and follicular destruction occur.
Classification:
Classic Hashimoto thyroiditis with goiter
Atrophic variant (Ord thyroiditis) without goiter
Fibrous variant with extensive fibrosis
IgG4-related thyroiditis (subset).
Epidemiology:
Most common thyroid disorder
Female predominance (10:1)
Peak incidence 30-50 years
Prevalence 1-2% in general population, up to 10% in women >60 years
Genetic predisposition (HLA association).
Clinical Features
Presentation:
Diffuse thyroid enlargement (goiter) in classic form
Firm, rubbery consistency
May present with hypothyroid symptoms or euthyroid goiter
Nodular areas possible.
Symptoms:
Hypothyroid symptoms: fatigue, weight gain, cold intolerance, constipation
Goiter may cause compressive symptoms
Initially may be hyperthyroid (hashitoxicosis) due to follicular destruction.
Risk Factors:
Female gender
Genetic predisposition (HLA-DR3, DR5)
Other autoimmune diseases
Iodine excess
Viral infections
Postpartum period
Smoking (protective).
Screening:
Elevated TSH, low T4
Anti-TPO antibodies positive (90-95%)
Anti-thyroglobulin antibodies positive (80%)
Ultrasound shows diffuse heterogeneous hypoechogenicity.
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Gross Description
Appearance:
Diffusely enlarged thyroid with lobulated surface
Cut surface shows gray-tan color with loss of normal translucency
Firm consistency
May show nodular areas.
Characteristics:
Symmetric or asymmetric enlargement
Size varies from normal to markedly enlarged (up to 100g)
Fibrotic areas in advanced cases
Pseudonodular appearance possible.
Size Location:
Involves entire gland diffusely
May be asymmetric with one lobe larger
Size ranges from normal (20g) to massively enlarged (>100g)
Isthmus commonly involved.
Multifocality:
Diffuse process by definition
May show regional variation
Nodular areas may develop (multinodular variant)
Associated papillary carcinoma risk increased (0.5% cases).
Microscopic Description
Histological Features:
Diffuse lymphocytic infiltration with germinal center formation
Hurthle cell (oncocytic) metaplasia
Follicular destruction and atrophy
Progressive fibrosis in advanced cases.
Cellular Characteristics:
Hurthle cells: large cells with eosinophilic granular cytoplasm and enlarged nuclei
Lymphocytes: small mature lymphocytes with plasma cells
Follicular epithelium shows degenerative changes.
Architectural Patterns:
Loss of normal follicular architecture
Lymphoid follicles with germinal centers
Fibrosis separating residual follicles
Hurthle cell change in remaining follicles.
Grading Criteria:
Mild: focal lymphocytic infiltrate, minimal follicular destruction
Moderate: diffuse infiltrate, moderate Hurthle cell change
Severe: extensive fibrosis, marked follicular loss.
Immunohistochemistry
Positive Markers:
Thyroglobulin positive in residual follicular cells
TTF-1 positive
CD3 positive T-cells predominate
CD20 positive B-cells in germinal centers
Cytokeratin positive in epithelium.
Negative Markers:
Calcitonin negative (excludes medullary carcinoma)
Chromogranin negative
Specific lymphoma markers negative (polyclonal process)
Viral markers negative.
Diagnostic Utility:
Thyroglobulin confirms follicular origin
Mixed T and B cell infiltrate (polyclonal)
Ki-67 low in follicular cells, higher in germinal centers
IgG4 staining for IgG4-related disease.
Molecular Subtypes:
Classical Hashimoto with mixed inflammatory infiltrate
IgG4-related subset with increased IgG4-positive plasma cells and fibrosis
Fibrous variant with extensive sclerosis.
Molecular/Genetic
Genetic Mutations:
HLA-DR3 and DR5 associations
CTLA-4 gene polymorphisms
Thyroglobulin gene variants
No specific oncogenic mutations
Polyclonal B-cell population.
Molecular Markers:
Anti-TPO antibodies (hallmark)
Anti-thyroglobulin antibodies
TRAb usually negative
Cytokine profile: Th1 dominant response
Low Ki-67 in follicular cells.
Prognostic Significance:
Progressive hypothyroidism in most cases
Increased risk of thyroid lymphoma (40-80x)
Slight increased risk of papillary carcinoma
Generally benign course with treatment.
Therapeutic Targets:
Levothyroxine replacement for hypothyroidism
No specific anti-inflammatory therapy
Selenium supplementation may help
Surgery only for compressive symptoms or malignancy concern.
Differential Diagnosis
Similar Entities:
Thyroid lymphoma
Subacute thyroiditis
Riedel thyroiditis
Graves disease with lymphocytic infiltrate
Papillary thyroid carcinoma (lymphocytic variant)
IgG4-related thyroiditis.
Distinguishing Features:
Lymphoma: monomorphic lymphoid cells, loss of follicles
Subacute: giant cells, viral history
Riedel: woody hard consistency, fibrosis beyond capsule
Graves: diffuse hyperplasia, TRAb positive.
Diagnostic Challenges:
Distinction from thyroid lymphoma crucial (requires flow cytometry)
Coexistent papillary carcinoma may be masked
Hurthle cell change may mimic neoplasm.
Rare Variants:
IgG4-related thyroiditis with storiform fibrosis
Juvenile Hashimoto with more prominent lymphoid follicles
Hashimoto with eosinophilic infiltrate
Postpartum thyroiditis (transient).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Site and Procedure
Site: Thyroid [right/left/diffuse], Procedure: Fine needle aspiration cytology
Adequacy
Adequate for evaluation
Cellularity
High cellularity with mixed inflammatory and epithelial cells
Inflammatory Infiltrate
Abundant small mature lymphocytes, plasma cells, and histiocytes
Hurthle Cells
Numerous Hurthle cells with eosinophilic granular cytoplasm
Follicular Cells
Decreased follicular epithelial cells with degenerative changes
Colloid
Absent to scant colloid
Background
Inflammatory background with lymphoglandular bodies
Cytological Diagnosis
Consistent with chronic lymphocytic thyroiditis (Hashimoto thyroiditis) - Bethesda Category II
Recommendation
Clinical correlation with thyroid function tests and anti-thyroid antibodies