Thyroid & parathyroid


Bethesda system


Editor-in-Chief: Debra L. Zynger, M.D.
Ayana Suzuki, C.T.
Andrey Bychkov, M.D., Ph.D.

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

Copyright: 2019-2024,, Inc.

PubMed Search: Bethesda[TIAB] thyroid (nondiagnostic OR unsatisfactory)

See Also: Adequacy

Ayana Suzuki, C.T.
Andrey Bychkov, M.D., Ph.D.
Page views in 2023: 3,279
Page views in 2024 to date: 981
Cite this page: Suzuki A, Bychkov A. Unsatisfactory. website. Accessed May 20th, 2024.
Definition / general
  • At the 2007 National Cancer Institute Thyroid Fine Needle Aspiration (FNA) State of the Science conference, the terms nondiagnostic and unsatisfactory were equated and recommended for the category that conveys an inadequate / insufficient sample (Diagn Cytopathol 2008;36:425, Ali: The Bethesda System for Reporting Thyroid Cytopathology, 2nd Edition, 2018)
    • Laboratory should choose the one preferable term and use it exclusively for this category
  • Meta analysis reported 10 - 12% frequency of nondiagnostic / unsatisfactory (ND / UNS) (Acta Cytol 2012;56:333)
    • Ideally should be limited to ≤ 10% of thyroid FNAs, excluding cyst fluid only samples (Am J Clin Pathol 2009;132:658)
    • Nondiagnostic rate of > 20% may require an audit of thyroid FNA workflow
  • Resection rate is 7 - 15% (Acta Cytol 2012;56:333)
  • Risk of malignancy of surgically resected ND / UNS nodules is 9 - 32%
    • This relatively high risk of malignancy is likely influenced by selection bias because only clinically suspicious nodules are resected (Acta Cytol 2012;56:333)
    • A reasonable extrapolation of the overall risk of malignancy for ND / UNS nodules is 5 - 10% (Thyroid 2016;26:1)
Essential features
  • ND / UNS aspirates include inadequate by cellularity, unsatisfactory by quality and cyst fluid only specimens
  • Frequency 10 - 12%, resection rate 7 - 15%, risk of malignancy 5 - 10% of all nodules and up to 30% of resected nodules
  • < 6 groups of well preserved, well stained follicular cell groups with 10 cells each
  • Poorly prepared, poorly stained or significantly obscured follicular cells
  • Cyst fluid, with or without histiocytes and < 6 groups of 10 benign follicular cells
Case reports
Cytology description
Nondiagnostic / unsatisfactory sample
  • Gross of aspirated sample
    • Invisible
    • Abundant fresh blood
  • Cytology
    • Poor cellularity causes difficulty in interpretation
    • Abundant blood contamination causes difficulty in observing cytological findings
    • Poor staining causes misinterpretation of the cytoplasmic and nuclear findings
    • Air dried artifact causes difficulty in observing 3D structure and detailed nuclear findings

Cyst fluid only sample
  • Gross of aspirated sample
    • Brownish liquid, sometimes glittering because of cholesterol crystals
  • Cytology
    • Histiocytes and denatured red blood cells, sometimes cholesterol crystals, calcium oxalate crystals
Cytology images

Contributed by Ayana Suzuki, C.T.

Hemorrhagic background


Respiratory epithelium

Air dried smear

Cyst fluid only

Images hosted on other servers:

Hemorrhagic background


Air dried smear

Cyst fluid only

Poor staining


Thyroid FNA and smearing techniques

Essential thyroid cytopathology

Head and tail of the Bethesda system for thyroid

Thyroid cytology - Bethesda classification

Sample pathology report
  1. Diagnosis / category: nondiagnostic
    • Nondiagnostic specimen due to insufficient cellularity
    • Note: a repeat FNA should be considered
  2. Diagnosis / category: nondiagnostic
    • Unsatisfactory aspirate due to poor fixation and preservation
    • Note: a repeat FNA should be considered
  3. Diagnosis / category: nondiagnostic, cyst fluid only
    • Aspirate consists almost exclusively of histiocytes; interpretation is limited by insufficient follicular cells and / or colloid
    • Note: can be rendered as benign after clinical and radiological correlation; a repeat FNA from the solid area can also be considered
  4. Diagnosis / category: nondiagnostic
    • Obscured by blood, no follicular cells seen
    • Note: a repeat FNA should be considered
Board review style question #1
Which thyroid FNA cytologic appearance is classified as nondiagnostic / unsatisfactory?

  1. ≥ 6 groups of well visualized follicular cells
  2. Abundant thick colloid
  3. A few cells with cytological atypia
  4. Foamy histiocytes only
  5. Numerous inflammatory cells
Board review style answer #1
D. Foamy histiocytes only. When the aspirated material contains only foamy histiocytes and no follicular epithelium or colloid, it is qualified as nondiagnostic / unsatisfactory. However, in some local reporting systems (e.g. Japanese), these cases are reported as "adequate, cyst fluid only" because their malignancy risk is almost the same as the benign category and lower than the nondiagnostic / unsatisfactory category.

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Reference: Nondiagnostic / unsatisfactory
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