Thyroid & parathyroid

Hyperplasia / goiter

Multinodular goiter


Editorial Board Member: Andrey Bychkov, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Swati Satturwar, M.D.
F. Zahra Aly, M.D., Ph.D.

Topic Completed: 11 June 2021

Minor changes: 18 November 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed search: Multinodular goiter[TI] thyroid[TI] full text[SB]

Swati Satturwar, M.D.
F. Zahra Aly, M.D., Ph.D.
Page views in 2020: 34,263
Page views in 2021 to date: 44,506
Cite this page: Satturwar S, Aly FZ. Multinodular goiter. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidnodular.html. Accessed November 29th, 2021.
Definition / general
  • Most common disease of thyroid gland
  • Diffuse or nodular enlargement with distorted outer surface
  • Grossly visible mass / nodule in 10% of thyroid glands at autopsy but microscopic nodularity is present in 40%
  • 3 - 5% risk of thyroid cancer, predominantly follicular variant of papillary thyroid carcinoma or up to 17.5% with papillary microcarcinoma (S Afr J Surg 2014;52:5, Int J Surg Open 2018;15:18)
Essential features
  • Majority asymptomatic and euthyroid
  • Asymmetric diffuse or nodular enlargement of thyroid gland with distorted outer surface
  • Iodine deficiency is most common cause worldwide; however, in the U.S., most goiters are due to autoimmune thyroiditis (i.e. Hashimoto disease) (Endotext: Multinodular Goiter [Accessed 23 December 2020])
  • Histologically, multiple variably sized dilated follicles lined by flattened to hyperplastic epithelium, with or without degenerative changes
Terminology
  • Goiter is clinical term meaning enlarged thyroid, which can be either diffuse or nodular (e.g. multinodular or solitary / dominant nodule)
  • Appropriate morphological term is nodular / multinodular hyperplasia
    • Synonyms: adenomatous / adenomatoid hyperplasia / nodule, colloid goiter, simple goiter, colloid / hyperplastic nodule
  • Simple goiter: also called diffuse nontoxic goiter or colloid goiter
    • Thyroid gland usually 40 g or more
    • Eventually converts into multinodular goiter
  • Multinodular goiter: irregular enlargement of thyroid gland due to repeated episodes of hyperplasia and involution (degeneration) of simple goiter
    • Thyroid gland often 100 g or more; may resemble a neoplasm, particularly if a single firm dominant nodule is present
    • Nodules are clonal or polyclonal and are due to heterogeneous responses of follicular epithelium to TSH
  • Nontoxic goiter: no hyperthyroidism present
ICD coding
  • ICD-10: E04.2 - nontoxic multinodular goiter
Epidemiology
  • 90% of those affected are women (F > > > M)
  • Variable age; develops more frequently during adolescence and pregnancy
Sites
  • Involves entire thyroid gland
Etiology
  • Increase in TSH secretion is the main cause in iodine deficiency related goiter and in autoimmune (Hashimoto) thyroiditis; in persons with normal TSH, oxidative damage to follicular cells and then damage to DNA leads to hyperplasia
  • In individuals with normal TSH, thyroid enlargement is caused by multiple growth factors, including TSH
  • Genetic factors:
  • Some nodules eventually become autonomous due to activating mutations in the TSH receptor or G proteins within the thyroid follicular cells
  • Drug induced goiter: sulfonamides and phenylbutazone inhibit organification of iodine
    • Iodine containing drugs such as amiodarone interfere with thyroglobulin proteolysis
    • Iodine or lithium interfere with thyroglobulin breakdown and release of T3 / T4
  • Goitrogens: cassava, cabbage, cauliflower, Brussels sprouts and turnips interfere with T3 / T4 synthesis
    • Cassava contains a thiocyanate which inhibits iodide transport within the thyroid
  • Hereditary: see dyshormonogenetic goiter
  • Plummer syndrome: hyperfunctioning thyroid nodule within a goiter, without ophthalmopathy or dermopathy of Graves disease
  • Plummer-Vinson (Paterson-Kelly) syndrome: iron deficiency anemia, glossitis, esophageal dysphasia related to webs, may have thyroid enlargement (Orphanet J Rare Dis 2006;1:36)
Clinical features
  • Thyroid enlargement (goiter); neck mass
  • Majority asymptomatic and euthyroid
  • Hypothyroidism due to decreased production of T3 and T4 hormones
  • Hyperthyroidism due to autonomous transformation
  • Pressure symptoms due to compression of trachea and esophagus (uncommon since enlargement is mainly towards strap muscle and subcutaneous tissue); compression of recurrent laryngeal nerve with hoarseness, phrenic nerve paralysis and Horner syndrome
  • Subacute obstructive symptoms with or without pain due to secondary hemorrhage into a nodule
  • Exertional dyspnea when tracheal diameter is less than 8 mm with stridor or wheezing when the diameter is less than 5 mm
  • References: Otolaryngol Clin North Am. 2003;36:35, BMC Emerg Med 2019;19:18, J Endocrinol Invest 2016;39:357
Diagnosis
  • Clinical examination
  • Thyroid function tests: TSH, T3, T4
  • Thyroid peroxidase antibodies
  • Thyroid ultrasound
  • CT or MRI to evaluate extent of goiter
  • Fine needle aspiration is indicated if:
    • History of rapid growth
    • Pain or tenderness
    • Unusually firm areas in the nodule
    • Suspicious sonographic features
Laboratory
  • Usually normal T3 / T4, TSH, normal radioactive iodine uptake, thyroglobulin may be elevated
Radiology description
  • Upper limits of normal for thyroid gland volume:
    • Adult men: 25 mL
    • Adult women: 18 mL
    • 13 - 14 years: 8 - 10 mL
    • 3 - 4 years: 3 mL
    • Neonate: 0.8 - 1.5 mL
  • Ultrasound:
    • Wide variety of appearances which include:
      • Enlarged iso / hyperechoic gland with surrounding hypoechoic halo
      • Sponge-like / honeycomb pattern
      • Anechoic areas may contain colloid
      • Internal calcification
  • Nuclear medicine:
    • 99mTc pertechnetate or radioiodine (123I) demonstrate an enlarged gland, with heterogeneous uptake
  • References: Horm Metab Res 2004;36:645, Clin Endocrinol (Oxf) 1987;26:273
Radiology images

Contributed by Mark R. Wick M.D.

Intrathoracic (ectopic) goiter

Prognostic factors
  • Size
  • Excellent prognosis with either surgery or radioiodine therapy, depending on comorbidities
Case reports
Treatment
Clinical images

Images hosted on other servers:

Large goiter

Giant goiter

Gross description
  • Simple goiters are usually firm with amber cut surface
  • Multinodular goiters are asymmetric, large, 200 - 700 g (up to 2 kg)
  • Increased size: lobe 8 - 15 cm, dominant nodules up to 10 cm
  • Nodular and bumpy outer surface and variegated cut surface, cystic and hemorrhagic with brown gelatinous colloid nodules with focal calcification
  • Reference: Diagn Cytopathol 2007;35:579
Gross images

Contributed by Swati Satturwar, M.D. and Andrey Bychkov, M.D., Ph.D.

External surface

Cut surface

Nodular thyroid



AFIP images

Various images



Images hosted on other servers:

Colloid cyst

Colloid goiter

Nodular goiter

Retrosternal goiter

Microscopic (histologic) description
  • Variable sized dilated follicles with flattened to hyperplastic epithelium
  • Nodules may be present but without thick capsule
  • Nodules with variable histological patterns: from colloid and microfollicular to hypercellular / microfollicular
  • Secondary changes may be seen, including foci of fresh or old hemorrhage, rupture of follicles with granulomatous response, fibrosis, calcification and even osseous metaplasia
  • Some of the cystically dilated follicles may show papillary projections (Sanderson polsters) that may mimic papillary carcinoma; however, they lack the nuclear features of papillary carcinoma
  • Cytologic atypia (in the form of highly atypical nuclei) if exposed to radioactive substances
  • Non nodular thyroid is reduced and compressed
  • Incidental papillary thyroid microcarcinoma may coexist
  • References: Neuro Endocrinol Lett 2015;36:48, Eur Endocrinol 2020;16:131
Microscopic (histologic) images

Contributed by Swati Satturwar, M.D., Andrey Bychkov, M.D., Ph.D. and Rajeshwari K. Muthusamy, M.D.

Dilated follicles

Nodule

Degenerative changes


Reactive fibrosis

False angioinvasion

Sanderson polsters

Adipose metaplasia Adipose metaplasia

Adipose metaplasia



AFIP images

No capsule identified

Sanderson polster

With hypercellular focus

With adipose metaplasia of stroma


Papillary area

Clear cell change

Focal squamous metaplasia

Cytology description
Cytology images

Contributed by Ayana Suzuki, C.T.

Watery colloid

Cracking colloid

Follicular clusters

3D structures

Paravacuolar granules

Cyst fluid only



Images hosted on other servers:

Watery colloid and focal dense colloid

Large amounts of background colloid

Positive stains
Negative stains
  • Loss of PTEN protein in patient with PTEN hamartoma syndrome
Molecular / cytogenetics description
Videos

Thyroid multinodular goiter

Histopathology thyroid: nodular goiter

Histopathology thyroid: colloid goiter

Sample pathology report
  • Thyroid, partial / total thyroidectomy:
    • Multinodular hyperplasia
  • Thyroid, partial / total thyroidectomy:
    • Adenomatoid nodule in a background of diffuse hyperplasia
  • Thyroid, partial / total thyroidectomy:
    • Hemorrhagic nodule in background of multinodular hyperplasia
  • Thyroid, partial / total thyroidectomy:
    • Colloid nodule
Differential diagnosis
  • Adenoma:
    • Usually single, totally surrounded by capsule, dissimilar from remaining parenchyma, compresses adjacent tissue and composed of follicles smaller than normal gland
    • Can mimic monoclonal dominant nodule in nodular goiter
    • Clonal event, such as RAS mutation or PPARG fusion
  • Dyshormonogenetic goiter:
    • Increased cellularity is usually diffuse
  • Follicular carcinoma:
    • Has vascular or capsular invasion, although multinodular goiter may have vascular invasion at periphery of nodule
  • Papillary carcinoma:
    • Distinct nuclear features seen in papillary carcinoma; lacks the Sanderson polsters found in goiters
  • Toxic goiter:
    • Clinical hyperthyroidism
Board review style question #1

Which of the histological features is seen in nodular goiter?

  1. Nodules with distinct thick capsule
  2. Papillary projections of the epithelium with nuclear features of papillary thyroid carcinoma
  3. Variably sized follicles with flattened hyperplastic epithelium, cysts, hemorrhage, granulomatous response, fibrosis, calcification or osseous metaplasia
  4. Vascular invasion
Board review style answer #1
C. Variably sized follicles with flattened hyperplastic epithelium, cysts, hemorrhage, granulomatous response, fibrosis, calcification or osseous metaplasia. Nodules may or may not be present in nodular goiter but generally lack a thick capsule. Prominent features are variably sized dilated follicles with flattened hyperplastic epithelium. Secondary changes include foci of fresh or old hemorrhage, rupture of follicles with granulomatous response, fibrosis, calcification and even osseous metaplasia. Some of the cystically dilated follicles may show papillary projections (Sanderson polsters). Cytologic atypia in the form of highly atypical nuclei occurs in patients exposed to radioactive substances.

Comment Here

Reference: Multinodular goiter
Board review style question #2
Multinodular goiter Multinodular goiter


These images from a thyroid nodule belong in what category of The Bethesda System for Reporting Thyroid Cytopathology?

  1. Category I
  2. Category II
  3. Category III
  4. Category IV
  5. Category V
Board review style answer #2
B. Category II (benign). These images represent a colloid nodule / benign thyroid nodule. They are typically managed by clinical and sonographic followup.

Comment Here

Reference: Multinodular goiter
Back to top
Image 01 Image 02