Thyroid & parathyroid

Benign thyroid neoplasms

Solitary thyroid nodule



Last staff update: 31 March 2025 (update in progress)

Copyright: 2014-2025, PathologyOutlines.com, Inc.

PubMed Search: Solitary thyroid nodule

Momin Iqbal, M.D., M.B.B.S.
Jianhong Zhou, M.D.
Page views in 2024: 197
Page views in 2025 to date: 2,206
Cite this page: Iqbal M, Conway S, Zhou J. Solitary thyroid nodule. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidsolitary.html. Accessed April 2nd, 2025.
Definition / general
  • Lump in the thyroid gland caused by abnormal cell proliferation, identified by manual examination or detected on imaging tests as an incidentaloma
Essential features
ICD coding
  • ICD-10
    • C73 - malignant neoplasm of thyroid gland
    • D17.0 - benign lipomatous neoplasm of skin and subcutaneous tissue of head, face and neck
    • D21.9 - benign neoplasm of connective and other soft tissue, unspecified
    • D34 - benign neoplasm of thyroid gland
    • D44.0 - neoplasm of uncertain behavior of thyroid gland
    • Q89.2 - congenital malformations of other endocrine glands
Epidemiology
Sites
  • Thyroid gland
Pathophysiology
  • Differs among individual lesions
  • Benign (Endocr Pathol 2022;33:27)
    • Toxic adenoma: activating mutations in the TSH receptor proteins, making them independent of thyroid stimulating hormones and 33% of cases have enhancer of zeste, homolog 1 (EZH1) mutation that functions as an epigenetic regulator of gene expression
    • Follicular adenoma: BRAF K601E, EIF1AX, EZH1, DICER1, PTEN or TSHR, PAX8::PPARG has < 10% mutational changes
    • BRAF, RET, NTRK or ALK fusions are not observed
  • Borderline lesions
    • Low malignant potential
    • BRAF K601E, EIF1AX, EZH1, DICER1, PTEN, TSHR or RAS < 10% mutation
    • PAX8::PPARG and THADA fusions up to 30%
  • Malignant
    • BRAF p.V600E, RAS, RET, NTRK, ALK, NTRK1 - NTRK3, TERT promotor mutations are the most common genetic alterations
Etiology
Clinical features
Diagnosis
  • Workup (S D Med 2022;75:569)
    • If nodule is > 1 cm, proceed with thyroid stimulating hormone (TSH) levels
    • If TSH levels are low, which indicates a hyperfunctioning nodule (low probability of cancer), no need for fine needle aspiration (FNA), proceed with T3, T4 levels and scintigraphy / radionucleotide iodine 123 scan
    • If TSH levels are normal to high, which indicates a hypofunctioning cold nodule (high probability of cancer), proceed with ultrasound
      • Thyroid imaging reporting and data systems (TIRADS) 1 and TIRADS 2, FNA is not indicated
      • TIRADS 3 with 1.5 - 2.4 cm nodule, TIRADS 4 with 1 - 1.4 cm nodule and TIRADS 5 with nodule 0.5 - 0.9 cm, proceed with follow up
      • TIRADS 3 with ≥ 2.5 cm nodule, TIRADS 4 with ≥ 1.5 cm nodule and TIRADS 5 with ≥ 1 cm nodule, proceed with FNA
    • On cytology (S D Med 2022;75:569)
      • Thyroid Bethesda System (TBS) 1: repeat FNA
      • TBS 2: follow up
      • TBS 3: repeat FNA or molecular testing
      • TBS 4: molecular testing or lobectomy
      • TBS 5: lobectomy or total thyroidectomy
      • TBS 6: total thyroidectomy
    • Molecular studies (Endocr Pathol 2022;33:27)
Laboratory
  • Thyroid function test (TSH, T3 and T4), could show hyper, hypo and euthyroid state depending upon the lesion
  • Molecular studies (see Diagnosis)
Radiology description
  • Ultrasound (thyroid imaging reporting and data systems [TIRADS], lesion composition, echogenicity, shape, margin and echogenic foci observed) (S D Med 2022;75:569)
    • TIRADS 1 (0 points, benign, no FNA)
    • TIRADS 2 (2 points, not suspicious, no FNA)
    • TIRADS 3 (3 points, mildly suspicious, if ≥ 2.5 cm, then FNA and if ≥ 1.5 cm, then follow up)
    • TIRADS 4 (4 - 6 points, moderately suspicious, if ≥ 1.5 cm, then FNA and if ≥ 1 cm, then follow up)
    • TIRADS 5 (7+ points, highly suspicious, if ≥ 1 cm, then FNA and if ≥ 0.5 cm, then follow up)
  • Thyroid scintigraphy / radionucleotide iodine 123 scan (hot nodule is most likely benign and cold nodule could be benign and malignant)
  • Computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of the extent of the lesion
Radiology images

Images hosted on other servers:
Multiple hypoechoic lesions

Multiple hypoechoic lesions

Prognostic factors
Case reports
Treatment
  • Varies from lesion to lesion, including observation, thyroid lobectomy or total thyroidectomy
Gross description
Gross images

Contributed by Sara Conway, M.D. and Momin Iqbal, M.D., M.B.B.S.
Follicular thyroid lesion

Follicular thyroid lesion

Oncocytic tumor

Oncocytic tumor

Papillary thyroid cancer

Papillary thyroid cancer

Microscopic (histologic) description
  • Varies from lesion to lesion
  • Papillary thyroid cancer (PTC) (Adv Ther 2020;37:3112)
    • Papillary architecture with thin fibrovascular core, the cells can have overcrowded nuclei
    • Nuclei have distinct features with elongated to oval nuclei, open chromatin, nuclear grooves and intranuclear cytoplasmic pseudoinclusions
  • Follicular thyroid cancer: follicular thyroid cancer histologically is very similar to thyroid adenoma except for invasion of capsule or vessels (Endocr Pathol 2022;33:27)
  • Oncocytic / Hürthle cell tumor: encapsulated lesion with predominantly oncocytic / Hürthle cells with intensely eosinophilic granular cytoplasm (Endocr Pathol 2022;33:27)
Microscopic (histologic) images

Contributed by Momin Iqbal, M.D., M.B.B.S. and Sara Conway, M.D.
Papillary thyroid carcinoma

Papillary thyroid carcinoma

Mushroom-like capsular invasion

Mushroom-like capsular invasion

Tall cell variant of PTC

Tall cell variant of PTC

Thyroid oncocytic / Hürthle cell tumor

Thyroid oncocytic / Hürthle cell tumor


Angioinvasive Hürthle cell tumor

Angioinvasive Hürthle cell tumor

Follicular thyroid adenoma

Follicular thyroid adenoma

Follicular thyroid adenoma

Follicular thyroid adenoma

Virtual slides

Images hosted on other servers:

Primary thyroid hemangioma

PTC fine needle aspiration

Medullary thyroid carcinoma

Cytology description
Electron microscopy description
  • Similar to normal thyroid gland and hyperplastic nodules
  • Hyperfunctioning follicular adenomas: organelle rich cytoplasm, especially rough endoplasmic reticulum; numerous, long microvilli on surface (Am J Clin Pathol 1982;78:299)
  • Clear cell follicular adenomas: cytoplasmic vesicles of variable size; these may be dilated cisternae of the rough endoplasmic reticulum or mitochondria, lysosomes or endocytic vesicles (Virchows Arch A Pathol Anat Histol 1978;380:205)
  • Hürthle cell tumor: cytoplasm packed with mitochondria (Endocr Pathol 2022;33:27)
Molecular / cytogenetics description
  • Molecular studies (Endocr Pathol 2022;33:27)
    • BRAF: papillary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid carcinoma, thyroid follicular adenoma
    • HRAS: follicular thyroid carcinoma, follicular thyroid adenoma, anaplastic thyroid carcinoma
    • KRAS: papillary thyroid carcinoma, follicular thyroid carcinoma, follicular thyroid adenoma, anaplastic thyroid carcinoma
    • NRAS: papillary thyroid carcinoma, follicular thyroid carcinoma, follicular thyroid adenoma, anaplastic thyroid carcinoma
    • RET: medullary thyroid carcinoma, papillary thyroid carcinoma, follicular thyroid carcinoma
    • PTEN: follicular thyroid carcinoma, papillary thyroid carcinoma
    • TP53: papillary thyroid carcinoma, follicular thyroid carcinoma, anaplastic thyroid carcinoma
    • TERT: papillary thyroid carcinoma, follicular thyroid carcinoma, anaplastic thyroid carcinoma
    • PAX8::PPARG: follicular thyroid carcinoma, follicular thyroid adenoma
    • GNAS: noninvasive follicular thyroid neoplasm with papillary nuclear-like features, follicular thyroid adenoma
    • AKT1: papillary thyroid carcinoma, follicular thyroid carcinoma, follicular thyroid adenoma
    • EIF1AX: follicular adenoma, follicular thyroid carcinoma, anaplastic thyroid carcinoma, poorly differentiated thyroid carcinoma (Cancers (Basel) 2022;14:6097)
    • CD274 (PDL1): medullary thyroid carcinoma, follicular thyroid carcinoma, papillary thyroid carcinoma (Endocrinol Diabetes Metab 2021;4:e00241, Theranostics 2021;11:1310)
Videos

Solitary thyroid nodule

Thyroid carcinoma I: pathology evaluation

Sample pathology report
  • Thyroid, total thyroidectomy:
    • Follicular thyroid carcinoma (4.8 cm), minimally invasive with capsular invasion (A27, A28, A11), isthmus (see comment)
    • Surgical resection margins, negative for tumor; no vascular invasion identified
    • Nonneoplastic thyroid showing thyroid follicular nodular disease with adenomatous nodules and chronic lymphocytic (Hashimoto) thyroiditis
    • 5 lymph nodes (0/5), negative for malignancy
    • AJCC tumor stage: pT3N0a
    • Comment: Immunohistochemical stains are performed.

    Slide Immunohistochemical stain Result
    A112 CK19 Focally positive
    A113 BRAF V600E Negative
    A182 CD31 Negative
Board review style question #1

What is the most commonly associated genetic abnormality identified in papillary thyroid carcinoma?

  1. BRAF mutation
  2. E1F1AX mutation
  3. PTEN mutation
  4. RAS mutation
Board review style answer #1
A. BRAF mutation. BRAF mutations are frequently linked to papillary thyroid carcinoma. The prevalence of papillary thyroid carcinoma in adults is 80 - 95% of all thyroid cancers and 90% in the pediatric population. Answer D is incorrect because RAS mutation is found in 20 - 30% of follicular adenomas. Answer B is incorrect because E1F1AX mutation is seen in 10 - 20% of follicular adenomas. Answer C is incorrect because PTEN mutation occurs in 10 - 15% of follicular adenomas.

Comment Here

Reference: Solitary thyroid nodule
Board review style question #2
For a patient with thyroid imaging reporting and data systems (TIRADS) 4 thyroid nodule, what is the cut off size for subsequent FNA evaluation?

  1. ≥ 1 cm
  2. ≥ 1.5 cm
  3. ≥ 2.0 cm
  4. ≥ 2.5 cm
Board review style answer #2
B. ≥ 1.5 cm. For a TIRADS 4 thyroid lesion, it is recommended for ultrasound guided FNA if the lesion is ≥ 1.5 cm. Ultrasound TIRADS is based on the lesion composition, echogenicity, shape, margin and echogenic foci observed; based on the scores, the thyroid lesion is categorized as TIRADS 1 (0 points, benign, no FNA), TIRADS 2 (2 points, not suspicious, no FNA), TIRADS 3 (3 points, mildly suspicious, if ≥ 2.5 cm, then FNA and if ≥ 1.5 cm, then follow up); TIRADS 4 (4 - 6 points, moderately suspicious, if ≥ 1.5 cm, then FNA and if ≥ 1 cm, then follow up); and TIRADS 5 (7+ points, highly suspicious, if ≥ 1 cm, then FNA and if ≥ 0.5 cm, then follow up).

Comment Here

Reference: Solitary thyroid nodule
Back to top
Image 01 Image 02