Thyroid & parathyroid

Thyroiditis

Hashimoto thyroiditis


Editorial Board Member: Marc Pusztaszeri, M.D.
Deputy Editor-in-Chief: Andrey Bychkov, M.D., Ph.D.
Shipra Agarwal, M.D.

Last author update: 11 October 2023
Last staff update: 11 October 2023

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PubMed Search: Hashimoto thyroiditis

See Also: Fibrous (fibrosing) variant

Shipra Agarwal, M.D.
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Cite this page: Agarwal S. Hashimoto thyroiditis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidhashimotosthyroiditis.html. Accessed July 13th, 2024.
Definition / general
  • Prototype of autoimmune disease presenting with goiter, elevated circulating antithyroid antibodies, often with hypothyroidism
  • Histopathologically diffuse lymphoplasmacytic infiltration, lymphoid follicle formation, follicular atrophy, oncocytic metaplasia and fibrosis
  • First described in 1912 by Dr. Hakaru Hashimoto, who called it struma lymphomatosa (Thyroid 2013;23:142)
Essential features
  • Most common cause of hypothyroidism in iodine sufficient areas
  • Infiltration of thyroid parenchyma by mononuclear cells, lymphoid follicles with germinal centers, oncocytic cells lining residual thyroid follicles, fibrosis
Terminology
  • Also known as Hashimoto disease, struma lymphomatosa, chronic lymphocytic thyroiditis, goitrous thyroiditis, lymphadenoid goitre
  • Hashitoxicosis: transient thyrotoxicosis due to follicle destruction in Hashimoto thyroiditis
ICD coding
  • ICD-10: E06.3 - autoimmune thyroiditis
Epidemiology
Pathophysiology
  • Breakdown of immune tolerance (Best Pract Res Clin Endocrinol Metab 2019;33:101367)
    • Genetic susceptibility
      • Familial aggregation
      • Polymorphisms in human leukocyte antigen (HLA) genes
      • Polymorphisms in genes involved in immune regulation, including cytotoxic T lymphocyte associated antigen 4 (CTLA4), protein tyrosine phosphatase 22 (PTPN22) and interlukin 2 receptor α chain (IL2RA)
    • Environmental factors (Autoimmun Rev 2014;13:391)
      • Smoking has a protective effect
      • Increased dietary iodine is associated with increased incidence
    • Polymorphisms
    • Decrease in Tregs
  • Autoantibodies against thyroglobulin, thyroid peroxidase (TPO) and antithyroid stimulating hormone (TSH) receptor
  • CD8+ T cell mediated cytotoxicity, cytokine mediated cell death and antibody dependent cell mediated cytotoxicity
Etiology
  • Multifactorial; immunological, genetic and environmental
Diagrams / tables

Images hosted on other servers:

Grading of thyroiditis on cytological material

Clinical features
  • Painless enlargement of thyroid gland
  • Majority (75%) are euthyroid (Autoimmun Rev 2014;13:391)
  • Progressively increasing hypothyroidism
  • May have an initial transient phase of hyperthyroidism
  • May coexist with other autoimmune diseases, like type 1 diabetes mellitus, Addison disease, systemic lupus erythematosus, Sj√∂gren syndrome, pernicious anemia, myasthenia gravis, vitiligo, celiac disease, chronic active hepatitis
  • Increased risk of primary thyroid lymphoma and papillary thyroid carcinoma (PTC) (Front Oncol 2017;7:53, Endocr Pathol 2021;32:368)
  • 6 clinicopathologic forms: classic, fibrous variant, IgG4 related variant, juvenile form, Hashitoxicosis and painless (or silent) thyroiditis (Autoimmun Rev 2014;13:391)
  • Idiopathic myxedema in older patients with fibrous variant
  • Juvenile variant: < 18 years of age, (mean age of 11 years); usually asymptomatic thyroid swelling
  • Hashitoxicosis variant: initial hyperthyroid phase similar to Graves disease, followed by hypothyroidism
  • Painless thyroiditis: sporadic or (more commonly) postpartum (within 12 months of delivery); usually self limited
Diagnosis
Laboratory
  • Deranged thyroid function tests
  • Elevated levels of TSH, with normal or low serum thyroid hormones (T3,T4)
  • Decreased TSH, with normal or increased serum T3,T4
  • Elevated serum antithyroid antibodies
    • Antithyroglobulin
    • Anti-TPO
    • Anti-TSH receptor
  • References: J Endocrinol Invest 2021;44:883, Autoimmun Rev 2020;19:102649
Radiology description
Radiology images

Contributed by Ayana Suzuki, C.T.

Isoechoic nodule



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Ultrasound

Ultrasound

Prognostic factors
  • IgG4 related variant shows a more aggressive clinical course, with more severe and treatment resistant hypothyroidism (Autoimmun Rev 2014;13:391)
Case reports
Treatment
Gross description
  • Diffuse symmetric enlargement of thyroid gland; occasionally asymmetric enlargement or nodular
  • Cut surface: pale, yellow-tan, firm, nodular; resembles lymph nodes
  • May be fibrotic and atrophied
Gross images

Contributed by Mark R. Wick, M.D.

Diffusely enlarged thyroid lobe



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Atrophic gland

Nodular gland

Microscopic (histologic) description
  • Classic form: diffuse infiltration of thyroid parenchyma with lymphocytes and plasma cells; lymphoid follicle formation with germinal centers (Best Pract Res Clin Endocrinol Metab 2019;33:101367)
  • Polymorphic lymphocytic infiltrate, predominantly T cells
  • Thyroid follicular destruction
  • Atrophic thyroid follicles; many lined by oncocytic cells / oncocytes having abundant granular eosinophilic cytoplasm; rarely squamous metaplasia
  • Later fibrosis and nodularity (Virchows Arch 2013;462:557)
  • Fibrous (or fibrosing) variant: extensive keloid-like fibrosis of thyroid parenchyma, fibrous septa divide the parenchyma into lobules, mononuclear cell infiltration, lymphoid follicles, thyroid follicular atrophy, oncocytic cell and squamous metaplasia (Autoimmun Rev 2014;13:391)
  • IgG4 related variant: dense lymphoplasmacytic infiltrate, enriched in IgG4 producing plasma cells (> 20 cells per high power field); interstitial fibrosis; often associated with obliterative phlebitis (Autoimmun Rev 2014;13:391)
  • Juvenile thyroiditis, Hashitoxicosis and painless thyroiditis: rare / absent germinal center formation and follicular atrophy, follicular cell hyperplasia, less pronounced oncocytic cell metaplasia and fibrosis (Autoimmun Rev 2014;13:391)
  • Variable atypia of follicular cells and oncocytic cells, may mimic and act as a precursor (limited evidence) of papillary thyroid carcinoma (Endocr Pathol 2021;32:368)
  • Squamous metaplasia of follicular epithelium can be confused with solid cell nests (J Clin Endocrinol Metab 2012;97:2209)
  • May be associated with colloid goiter, follicular neoplasm, oncocytic cell neoplasm, papillary thyroid carcinoma and primary thyroid lymphoma (Acta Cytol 2009;53:507, Front Oncol 2017;7:53)
Microscopic (histologic) images

Contributed by Andrey Bychkov, M.D., Ph.D. and Shipra Agarwal, M.D.

Lymphoid follicles with germinal centers

Diffuse
lymphoplasmacytic
infiltration

Squamous metaplasia: p63+ cells in many follicles

Evolution of squamous metaplasia

Intense immunostaining


Lobulation of thyroid tissue by fibrotic bands

Vesicular nuclei of thyroid follicles similar to PTC nuclei

Aggregation of lymphoid follicles mimic thyroid nodule

Hashimoto thyroiditis with lymphoepithelial cyst

Nodular Hashimoto thyroiditis


Papillary microcarcinoma and Hashimoto thyroiditis

Oncocytic cell nodule

Oncocytic cell nodule

Virtual slides

Images hosted on other servers:
Fibrous variant of Hashimoto thyroiditis

Fibrous variant of Hashimoto thyroiditis

Lymphoid follicles and oncocytic metaplasia

Lymphoid follicles and oncocytic metaplasia

Dense infiltrate and atrophied follicles

Dense infiltrate and atrophied follicles

Oncocytic metaplasia

Oncocytic metaplasia


Fibrous variant with squamous metaplasia

Fibrous variant with squamous metaplasia

Oncocytic and adenomatous nodules

Oncocytic and adenomatous nodules

Oncocytic nodule

Oncocytic nodule

Cytology description
  • Moderately or highly cellular aspirate
  • Inflammatory infiltrate
  • Aggregates of oncocytic cells / oncocytes
  • Crushed cells, lymphoid tangles
  • Absent or scant colloid
  • Mild anisonucleosis, giant cells, macrophages, epithelioid cells, eosinophils, fire flares
  • Usually Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category II; can be TBSRTC III / IV / V
Cytology images

Contributed by Shipra Agarwal, M.D. and Ayana Suzuki, C.T.

Cellular aspirate

Crushed cells

Lymphocytes and oncocytes



Images hosted on other servers:

Oncocytic cells with atypical nuclei

Sheet of follicular cells with oncocytic change mixed with benign lymphoid cells

Resembles lymphoma


Grade I: mild lymphocytic inflammatory infiltrate

Grade II: moderate lymphocytic inflammation

Grade III: marked
inflammation with
polymorphous
lymphocytes

ThinPrep versus Pap stain


Lymphocytes and oncocytes

Lymphocytes and oncocytes

Follicular destruction by lymphocytes follicular destruction by lymphocytes

Follicular destruction by lymphocytes

Crushed cells

Crushed cells

Grade 1, 2 and 3 thyroiditis

Electron microscopy description
  • Oncocytic cells have numerous large mitochondria
Molecular / cytogenetics description
Videos

Thyroid: compare and contrast

Histopathology thyroid: Hashimoto thyroiditis

Sample pathology report
  • Thyroid, total thyroidectomy:
    • Hashimoto thyroiditis
Differential diagnosis
  • Chronic (focal) lymphocytic thyroiditis:
    • Incidental detection of focal aggregates of lymphocytes, with or without germinal center formation, in thyroid parenchyma
    • Absent or limited oncocytic metaplasia
    • Follicular atrophy and fibrosis
    • Usually absent clinical and laboratory indicators of autoimmune thyroid disease
  • Riedel thyroiditis:
    • Hard fixed mass simulating thyroid carcinoma
    • Active fibroblastic proliferation; storiform fibrosis
    • Inflammation and fibrosis extends beyond the thyroid capsule into perithyroidal tissues
    • Associated with fibroinflammatory lesions in other sites
  • MALT lymphoma:
    • Age: > 60 years
    • Rapid increase in size of thyroid swelling, hard swelling
    • Clonal proliferation of B cells, confirmed on immunostaining and flow cytometry
    • Destructive lymphoepithelial lesions (Rom J Morphol Embryol 2017;58:731)
  • Oncocytic cell neoplasms:
    • Well circumscribed lesion within an echonormal background
    • Composed mainly of oncocytic cells without (or with minimal) mononuclear cell infiltration (Rom J Morphol Embryol 2017;58:731)
  • Papillary carcinoma:
    • Presence of true papillae, more well developed and diffuse nuclear features, infiltrative borders
  • Lithium intake:
Board review style question #1

Which of the following is true regarding the thyroid lesion shown above?

  1. Fibrosis extends into perithyroidal soft tissues
  2. Increased risk of follicular thyroid carcinoma
  3. Increased risk of medullary thyroid carcinoma
  4. Increased risk of primary thyroid lymphoma
  5. Shows monoclonal lymphoid cell proliferation
Board review style answer #1
D. Increased risk of primary thyroid lymphoma. Answer A is incorrect because unlike Riedel thyroiditis, in which the fibrosis extends into perithyroidal soft tissues, it is limited to the thyroid gland in Hashimoto thyroiditis. Answers B and C are incorrect because Hashimoto thyroiditis predisposes to papillary thyroid carcinoma and primary thyroid lymphoma. Answer E is incorrect because Hashimoto thyroiditis is characterized by a polyclonal lymphocytic infiltration of the thyroid parenchyma.

Comment Here

Reference: Hashimoto thyroiditis
Board review style question #2
Which of the following is true about Hashimoto thyroiditis?

  1. Common in iodine deficient areas
  2. Mononuclear cell infiltration of the thyroid parenchyma
  3. More common in males
  4. Not a familial disease
  5. Usually presents with hyperthyroidism
Board review style answer #2
B. Mononuclear cell infiltration of the thyroid parenchyma. Histological examination in Hashimoto thyroiditis reveals a mononuclear cell infiltration of the thyroid parenchyma, composed of lymphocytes and plasma cells. Answer A is incorrect because Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine sufficient areas. Answers C and D are incorrect because the disease shows a female preponderance and is often familial. Answer E is incorrect because the patients usually present with painless diffuse thyroid swelling and are mostly euthyroid.

Comment Here

Reference: Hashimoto thyroiditis
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