Thyroid & parathyroid


Bethesda system


Last author update: 21 April 2022
Last staff update: 9 May 2024 (update in progress)

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PubMed Search: Bethesda guidelines thyroid benign

Ayana Suzuki, C.T.
Page views in 2023: 16,061
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Cite this page: Suzuki A. Benign. website. Accessed May 19th, 2024.
Definition / general
Essential features
  • Cytologic sample that is adequate for evaluation and consists of colloid and benign appearing follicular cells
  • 60 - 70% of all thyroid FNA, resection rate 10 - 20%, risk of malignancy (ROM) 0 - 3%
  • Role of benign diagnosis is to avoid unnecessary surgery
  • Equal to negative for malignancy and nonneoplastic
  • Term "benign" preferred over negative for malignancy and nonneoplastic
  • Category II in the Bethesda system
Radiology description
  • Adenomatoid nodules: multinodular goiter on ultrasound
  • Chronic lymphocytic (Hashimoto) thyroiditis: heterogeneous appearance on ultrasound
Radiology images

Contributed by Ayana Suzuki, C.T.

Isoechoic nodule

Hypoechoic nodule

Large cyst

Large multilocular cyst

Case reports
Prognostic factors
  • American Thyroid Association (ATA) recommends that followup should be determined by risk stratification based on ultrasound pattern (Thyroid 2016;26:1)
    • High suspicion: repeat ultrasound and FNA within 12 months
    • Low to intermediate suspicion: repeat ultrasound 12 - 24 months → growth or development of new suspicious ultrasound features → repeat FNA
    • Very low suspicion: ultrasound surveillance is not necessary; if ultrasound is repeated, it should be done after 24 months
  • Repeat FNA or surgery is considered only for a selected subset including those that are large, symptomatic or have worrisome clinical or sonographic characteristics (Thyroid 2016;26:1)
Cytology description
  • Benign follicular nodule
    • Adequate, consists of colloid and benign appearing follicular cells
    • Classified histologically as nodular hyperplasia in nodular goiter, hyperplastic (adenomatoid) nodules, colloid nodules and nodules in Graves disease
    • Cytology: cellularity: sparse to moderate
      • Colloid: viscous, shiny, light yellow or gold (gross), dark blue-violet-magenta (Romanowsky stain), green or orange-pink (Pap stain)
      • Watery colloid: cellophane coating, film with frequent folds (crazy pavement, chicken wire or mosaic appearance)
      • Thick (dense, hard) colloid: a hyaline quality, cracks
    • Macrophages: common, containing hemosiderin pigment
    • Follicular cells
      • Appearance: monolayered sheets, spaces (honeycomb-like) within the sheets, intact 3D variably sized balls
      • Cytoplasm: scant or moderate, stripped (may be misinterpreted as lymphocytes), paravacuolar granules (Cancer 2003;99:217)
      • Nuclei: variable in size, low N/C ratio, round to oval, anisonucleosis, uniformly granular chromatin pattern
      • In abundant colloid: shrunken, spindled, degenerated
      • In cystic lesion: focal reparative changes (cyst lining cells with enlarged nuclei, finely granular chromatin, squamoid or spindle shaped appearance)
      • Minor components: oncocytes, microfollicles, papillary hyperplasia (Cancer 2003;99:217, Cancer Cytopathol 2014;122:666)
      • Liquid based cytology preparations (LBC): decrease in the amount of colloid, superior nuclear details
  • Graves disease
  • Lymphocytic thyroiditis (Hashimoto thyroiditis)
    • Many polymorphic lymphoid cells associated with benign thyroid follicular cells or oncocytes (Acta Cytol 1987;31:687)
    • Oncocytes: flat sheets or isolated, abundant granular cytoplasm, large nuclei, prominent nucleoli, anisonucleosis, mild nuclear atypia (Acta Cytol 1999;43:400)
    • Lymphocytes: background or infiltrating epithelial cell groups, polymorphic (small mature lymphocytes, larger reactive lymphoid cells, occasional plasma cells), variable chromatin pattern (rich and granular heterochromatin in small lymphocytes, diminished and fine in large lymphocytes)
    • Monomorphic lymphoid population should prompt additional samples for flow cytometry if lymphoma suspected
    • LBC: decrease in lymphocytes, oncocytes with irregular nuclei (Acta Cytol 2018;62:93, Diagn Cytopathol 2012;40:404)
  • Granulomatous (de Quervain) thyroiditis (Acta Cytol 1997;41:238)
    • Cellularity: variable (depends on the stage of disease)
    • Granulomas: clusters of epithelioid histiocytes, numerous multinucleated giant cells
    • Early stage: many neutrophils and eosinophils, similar to acute thyroiditis
    • Later stage: hypocellular, giant cells surrounding and engulfing colloid, epithelioid cells, lymphocytes, macrophages, scant degenerated follicular cells
    • Involutional stage: absent giant cells and inflammatory cells
  • Acute thyroiditis (Exp Ther Med;9:860)
    • Numerous neutrophils associated with necrosis, fibrin, macrophages, blood
    • Scant reactive follicular cells and limited to absent colloid
    • Bacterial or fungal organisms (immunocompromised patients)
  • Riedel thyroiditis (Diagn Cytopathol 2004;30:193)
    • Cellularity: acellular
    • Collagen strands and bland spindle cells
    • Rare chronic inflammatory cells, absence colloid and follicular cells
  • Black thyroid (Diagn Cytopathol 1991;7:640, Diagn Cytopathol 2006;34:106)
    • Follicular cells with abundant dark brown cytoplasmic pigment (darker than hemosiderin, similar to melanin)
  • Amyloid goiter
Cytology images

Contributed by Ayana Suzuki, C.T.

Colloid nodule

Adenomatous nodules

Hashimoto thyroiditis

Granulomatous thyroiditis

Thyroglossal duct cyst


Thyroid cytology: colloid nodule

Essential thyroid cytopathology

Differential diagnosis
Board review style question #1
What risk of malignancy is associated with benign thyroid cytology?

  1. 0 - 3%
  2. 5 - 10%
  3. 12 - 15%
  4. 20 - 30%
  5. 40 - 50%
Board review style answer #1
A. 0 - 3% Most published studies reported that a benign FNA diagnosis is associated with a very low false negative rate, estimated to be in the range of 0 - 3%. It should be noted that the precise risk of malignancy for cytologically benign nodules is difficult to assess because only a minority of these patients undergo surgery.

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Reference: Benign
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