Home > Thyroid & parathyroid > Hashimoto thyroiditis

Thyroid & parathyroid

Thyroiditis

Hashimoto thyroiditis

Author: Shipra Agarwal, M.D.

Editorial Board Member: Marc Pusztaszeri, M.D.

Deputy Editor-in-Chief: Andrey Bychkov, M.D., Ph.D.

Last author update: 11 October 2023

Last staff update: 11 October 2023

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Hashimoto thyroiditis

See Also: Fibrous (fibrosing) variant

Table of Contents

Cite this page: Agarwal S. Hashimoto thyroiditis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidhashimotosthyroiditis.html. Accessed December 21st, 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

Incidence per year 0.3 - 1.5/1,000 (Best Pract Res Clin Endocrinol Metab 2019;33:101367)
30 - 50 years (Maedica (Bucur) 2019;14:98)
F:M = 3 - 12:1 (Autoimmun Rev 2014;13:391)
- 3:1 for IgG4 related variant
- 5:1 for Hashitoxicosis form
- 6:1 for juvenile variant
- 10:1 for fibrous variant
- 12:1 for classic variant
Polymorphisms associated with other autoimmune diseases in 20% of cases

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, Sjögren 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

Diagnostic workup is similar to any thyroid swelling
- Thyroid function test
- Serum antithyroid antibody levels
- Ultrasound neck
- Fine needle aspiration cytology (FNAC) if thyroid nodule present
References: J Endocrinol Invest 2021;44:883, Autoimmun Rev 2020;19:102649

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

Sonography: diffusely enlarged thyroid gland; diffusely heterogeneous, coarse and hypoechogenic parenchyma with micronodular pattern (Eur J Endocrinol 2019;181:539, AJR Am J Roentgenol 2010;195:208)
IgG4 related variant: more marked hypoechogenicity (Autoimmun Rev 2014;13:391)
Fibrous variant: hypoechogenicity along with prominent nodularity of the parenchyma

Radiology images

Contributed by Ayana Suzuki, C.T.

Isoechoic nodule

Images hosted on other servers:

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

24 year old woman with Hashimoto thyroiditis associated with inflammatory myopathy (Pathology 2017;49:97)
28 year old woman with RET / PTC1 rearrangement in Hashimoto thyroiditis and in associated papillary thyroid carcinoma and hyalinizing trabecular adenoma (AJSP Reviews & Reports 2019;24:13)
31 year old man with Hashimoto thyroiditis presented with myxedema psychosis (J Am Osteopath Assoc 2017;117:50)
41 year old woman with hypothyroidism and multinodular goiter (Arch Pathol Lab Med 2003;127:e253)
43 year old woman with coexisting affective psychosis and brain perfusion abnormalities (Clin Pract Epidemiol Ment Health 2007;3:31)
46 year old woman with thyroid adenoma and Hashimoto thyroiditis (Rom J Morphol Embryol 2017;58:241)
52 year old woman with Hashimoto thyroiditis involving ectopic cervical thyroid tissue (Head Neck Pathol 2021;15:328)

Treatment

Thyroid hormone replacement if hypothyroid
Subtotal thyroidectomy to relieve compression symptoms (Best Pract Res Clin Endocrinol Metab 2019;33:101367)
Hemitotal or subtotal thyroidectomy in case of oncocytic cell neoplasm or suspicious for malignancy cytology
Short course glucocorticoids in IgG4 related variant (Autoimmun Rev 2014;13:391)

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

Images hosted on other servers:

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

Virtual slides

Images hosted on other servers:

Fibrous variant of Hashimoto thyroiditis

Lymphoid follicles and oncocytic metaplasia

Dense infiltrate and atrophied follicles

Oncocytic metaplasia

Fibrous variant with squamous metaplasia

Oncocytic and adenomatous nodules

Oncocytic nodule

Cytology description

Moderately or highly cellular aspirate
Inflammatory infiltrate
- Variable number of lymphocytes in different stages of development (Cureus 2019;11:e5851, J Thyroid Res 2018;2018:5246516)
- Lymphocytes infiltrating follicular epithelial cells
- Lymphoglandular bodies (Acta Cytol 2009;53:507)
- Plasma cells
- Can grade based on lymphocytic infiltration from 0 to 3+ (see Diagrams / tables) but does not correlate with clinical, biochemical, radionuclide and ultrasonographic parameters (Cytojournal 2007;4:10, J Cytol 2016;33:145)
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

Follicular destruction by lymphocytes

Crushed cells

Grade 1, 2 and 3 thyroiditis

Positive stains

High molecular weight keratin, p63 (Hum Pathol 2003;34:764)
May have elevated kappa/lambda ratio (Am J Clin Pathol 2006;125:42)
Mixture of T and B cells (Indian J Pathol Microbiol 2011;54:464)
HBME-1, cytokeratin 19, cyclin D1, galectin3: variable positivity in case of atypia (Virchows Arch 2013;462:557, Endocr Pathol 2021;32:368)

Electron microscopy description

Oncocytic cells have numerous large mitochondria

Molecular / cytogenetics description

Polyclonal (Hum Pathol 1988;19:1444, Indian J Pathol Microbiol 2011;54:464)
No mutations, gene fusions (previously reported RET / PTC rearrangements were erroneous)

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:
- Significant clinical history; shows similar morphologic findings (Hum Pathol 1983;14:737)

Board review style question #1

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

Fibrosis extends into perithyroidal soft tissues
Increased risk of follicular thyroid carcinoma
Increased risk of medullary thyroid carcinoma
Increased risk of primary thyroid lymphoma
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?

Common in iodine deficient areas
Mononuclear cell infiltration of the thyroid parenchyma
More common in males
Not a familial disease
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

Home > Thyroid & parathyroid > Hashimoto thyroiditis