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Thyroid gland

Bethesda guidelines for Cytology

Atypia of undetermined significance

Reviewer: Michael Constantinescu, M.D. (see Reviewers page)
Revised: 21 March 2011, last major update March 2011
Copyright: (c) 2010-2011, PathologyOutlines.com, Inc.


● Use sparingly (~7% of all thyroid FNAs)
● Use if follicle cells, lymphoid or other cells have architectural or cytologic atypia
● Use when obscuring blood/gel or prep artifact hinders the interpretation (but if interpretation cannot be made due to artifact or obscuring material, it should be rendered “non-diagnostic”)
● The term “follicular lesion of undetermined significance” (FLUS) may be used when the atypia is follicular not lymphocytic


Note: causes of atypia diagnosis:

● Prominent population of follicle cells forming microfollicles, but with a sparse cellularity and scant colloid; cellular material overall is not sufficient for a diagnosis of “follicular neoplasm”
● Predominance of Hurthle cells in a sparse cellularity
● Artifact (air-dried prep, clotting artifact) that hinders interpretation, but atypia still present
● Moderate or marked cellularity with mostly Hurthle cells but clinically Hashimoto or nodular goiter are under consideration
● Focal features suggestive of papillary carcinoma, but predominantly benign appearing sample
● Follicle cells with large nuclei and prominent nuclei, suggestive of radioactive iodine or carbimazole treatment or repair due to cystic degeneration or hemorrhage
● Atypical lymphoid infiltrate not definitely diagnostic for “suspicious of malignancy”

● Suggested to comment about the source of atypia or the reason why this less definitive diagnosis is rendered, along with a recommended course of action


● Repeat FNA, and correlate with clinical and imaging findings
● Repeat FNA results in a more definitive diagnosis in 75-80% of cases
● Malignancy occurs in 20-25% of those with this diagnosis

Sample reports:

(1) Atypia of Undetermined Significance
      - Follicular cells, mostly benign appearing, with rare cytologic atypia
      - Comment: A repeat aspirate after an appropriate interval may be helpful if clinically indicated.

(2) Follicular Lesion of Undetermined Significance
      - The sample consists almost exclusively of Hurthle cells in a sample with moderate cellularity and scant colloid with no apparent increase in lymphoid cells.
      - Comment: In a patient with multiple nodules, these findings are consistent with Hurthle cell hyperplasia in multinodular goiter, but a Hurthle cell neoplasm cannot be completely ruled out. Clinical correlations are necessary.

End of Thyroid gland > Bethesda guidelines for Cytology > Atypia of undetermined significance

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