Thyroid & parathyroid
Cytology
Bethesda system
Unsatisfactory
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Last author update: 21 April 2022
Last staff update: 20 March 2025 (update in progress)
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PubMed Search: Bethesda[TIAB] thyroid (nondiagnostic OR unsatisfactory)
See Also: Adequacy
Table of Contents
Definition / general | Essential features | Diagnosis | Management | Case reports | Cytology description | Cytology images | Videos | Sample pathology report | Board review style question #1 | Board review style answer #1Cite this page: Suzuki A, Bychkov A. Unsatisfactory. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidnduns.html. Accessed April 2nd, 2025.
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
Diagnosis
- < 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
Management
- ND / UNS nodules should be reaspirated except for pure cyst (Thyroid 2016;26:1, Endocr Pract 2007;13:735, Contemp Oncol (Pozn) 2016;20:491)
- Reaspiration can be done 3 weeks after the first aspiration (Kakudo: Thyroid FNA Cytology, 2nd Edition, 2019)
- Ultrasound guidance with immediate on site adequacy evaluation is recommended (Acta Cytol 2012;56:333)
- If on site evaluation for adequacy is not available, obtain a minimum of 3 separate samples of the nodule (Can Assoc Radiol J 2013;64:220)
- This approach results in a diagnostic interpretation in 60 - 80% of cases (Am J Clin Pathol 2010;134:450, Acta Cytol 2014;58:229, Thyroid 2016;26:1, Endocr Pract 2007;13:735)
- Close clinical and ultrasound followup or surgery for cases with 2 consecutive ND / UNS
- Rapid on site evaluation can help decide whether to reaspirate the nodule immediately
- Additional liquid based preparations may be useful (Cytopathology 2010;21:97)
- Cell block from the residual liquid based preparation sample can convert some ND / UNS cases into satisfactory (Diagn Cytopathol 2016;44:737)
- Cysts
- If the cyst has solid area, FNA should be performed from it
- Possibility of a cystic papillary thyroid carcinoma cannot be excluded
- Specimens from simple and unilocular cyst may be considered clinically adequate, even though they are reported as ND / UNS
- Simple cysts and < 3 cm cysts have low risk of malignancy (Diagn Cytopathol 2008;36:407, Cancer 2009;117:305, ANZ J Surg 2005;75:537, Pathol Annu 1991;26:63)
- Younger patients with only cystic fluid have a slightly higher risk of malignancy contributed by papillary thyroid carcinoma (Pathol Annu 1991;26:63, Thyroid 2009;19:341, Endocrine 2011;39:33)
- In some local reporting systems (Japan), cyst fluid only cases are reported as "adequate, cyst fluid only" because their risk of malignancy is almost the same as benign category and lower than ND / UNS category (Endocr J 2017;64:759)
Case reports
- 19 year old woman with intrathyroidal parathyroid cyst (Endocr Pathol 2011;22:108)
- 42 year old woman with intrathyroidal foregut cyst (Acta Cytol 2009;53:584)
- 45 year old woman with intrathyroidal thyroglossal duct cyst (Int J Clin Exp Pathol 2015;8:7229)
- 49 year old woman with a 4 cm autonomously hyperfunctioning cystic nodule harboring thyroid carcinoma (Int J Surg Case Rep 2018;42:287)
- 55 year old woman with cervical paraganglioma mimicking thyroid nodule (Case Rep Endocrinol 2016;2016:8527279)
- Patient with intrathoracic goiter (Acta Cytol 1987;31:694)
Cytology description
Nondiagnostic / unsatisfactory sample
Cyst fluid only 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
Muscle
Respiratory epithelium
Air dried smear
Cyst fluid only
Images hosted on other servers:
Hemorrhagic background
Muscle
Air dried smear
Cyst fluid only
Poor staining
Videos
Thyroid FNA and smearing techniques
Essential thyroid cytopathology
Head and tail of the Bethesda system for thyroid
Thyroid cytology - Bethesda classification
Sample pathology report
- Diagnosis / category: nondiagnostic
- Nondiagnostic specimen due to insufficient cellularity
- Note: a repeat FNA should be considered
- Diagnosis / category: nondiagnostic
- Unsatisfactory aspirate due to poor fixation and preservation
- Note: a repeat FNA should be considered
- 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
- 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?
- ≥ 6 groups of well visualized follicular cells
- Abundant thick colloid
- A few cells with cytological atypia
- Foamy histiocytes only
- 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.
Comment Here
Reference: Nondiagnostic / unsatisfactory
Comment Here
Reference: Nondiagnostic / unsatisfactory
