Thyroid gland
Bethesda guidelines for cytology
Atypia of undetermined significance

Topic Completed: 1 May 2014

Revised: 7 May 2019

Copyright: 2014-2018,, Inc.

PubMed Search: Bethesda guidelines atypia

Phillip A. Williams, M.D., M.Sc.
Shahid Islam, M.D., Ph.D.
Page views in 2018: 3,655
Page views in 2019 to date: 2,140
Cite this page: Williams P, Islam S. Atypia of undetermined significance. website. Accessed July 17th, 2019.
Definition / general
  • Reported in 3 - 18% of thyroid FNAs (very variable and likely overused), but recommended rate is ~7% according to 2009 Bethesda Guidelines
  • Use if: follicle cells, lymphoid or other cells have architectural or cytological atypia that is inadequate for a diagnosis of follicular neoplasm, suspicious for malignancy or malignant, based upon the 2009 Bethesda system for thyroid cytopathology (Am J Clin Pathol 2009;132:658)
  • Also called "Atypia of Undetermined Significance" (AUS) or "Follicular Lesion of Undetermined Significance" (FLUS)
  • Nine categories according to 2009 Bethesda Criteria (Am J Clin Pathol 2009;132:658):
    • Prominent population of follicle cells forming microfollicles with overall sparse cellularity
    • Predominance of Hürthle cells in a sparse cellularity and scant colloid
    • Artifact (air dried prep, clotting artifact) that hinders interpretation but atypia still present
    • Moderate or marked cellularity with vast majority being Hürthle cells but clinically has lymphocytic thyroditis or nodular goiter
    • Focal features suggestive of papillary carcinoma but predominantly benign appearing sample
    • Atypical cyst lining cells
    • Small population of 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"
    • Not otherwise specified
  • Risk of malignancy: 5 - 15%
  • Repeat FNA (3 - 6 months) (Cancer 2007;111:508), sooner if worrisome clinical features
  • Repeat FNA usually leads to definitive diagnosis in 75 - 80% (Thyroid 2009;19:1215)
  • Malignancy occurs in 20 - 25% of those with this diagnosis
Sample reports
  • 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
  • Follicular lesion of undetermined significance
    • The sample consists almost exclusively of Hürthle 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 Hürthle cell hyperplasia in multinodular goiter, but a Hürthle cell neoplasm cannot be completely ruled out; clinical correlations are necessary
Cytology images

Images hosted on PathOut server:

Contributed by Ayana Suzuki, Cytotechnologist, Japan:

FLUS - cellular

FLUS - architectural

FLUS - Hürthle

Atypical lymphocytes

Images hosted on other servers:

Follicle cells
forming microfollicles
with overall sparse

Blood and air drying artifact: atypical follicular cells

Focal features of PTC: benign macrofollicles

Atypical cyst lining cells

Postradioiodine: atypical cells

Atypical lymphoid cells

Numerous noncohesive spindle cells

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