Can ultrasound scores sort unclear thyroid biopsies?
For thyroid nodules whose needle biopsy was inconclusive, combining the biopsy category with a standard ultrasound risk score picked out low-risk nodules that were almost always benign.
Source
ACR TI-RADS and ATA US scores are helpful for the management of thyroid nodules with indeterminate cytology
Study at a glance
- Design
- Cross-sectional — Retrospective diagnostic-accuracy study: blinded re-scoring of pre-biopsy ultrasound images compared with post-thyroidectomy histology as reference standard
- N
- N=140 · 140 cytologically indeterminate thyroid nodules in 139 patients who had surgery, drawn from all thyroid biopsies at two pathology centres
- Population
- Adults (mostly women) in Paraná, Brazil (a university hospital plus one private centre), with Bethesda III, IV or V thyroid nodule cytology who underwent thyroidectomy, 2012-2016
- Outcome
- Malignancy on final histopathology; sensitivity, specificity, PPV, NPV and accuracy of ACR TI-RADS and 2015 ATA ultrasound categories alone and combined with Bethesda category
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What they did
The team searched biopsy records from two pathology centres in Brazil for thyroid nodules with indeterminate cytology (Bethesda III, IV or V) that also had stored ultrasound images and a surgical pathology result. A radiologist blinded to cytology and histology re-scored each nodule's ultrasound using the 2017 ACR TI-RADS points system and the 2015 American Thyroid Association (ATA) patterns. Nodules were labelled favourable or unfavourable by ultrasound and by cytology, and these labels were compared with whether surgery found cancer.
What they found
Of the 140 nodules, 66 (47.1%) were malignant, and malignancy rose with cytology category (15.9% for Bethesda III, 40.4% for IV, 86.4% for V) and with ultrasound suspicion. On their own, both ultrasound systems had modest sensitivity (69.7%) with specificity of 81.1% (TI-RADS) and 86.5% (ATA), and the two systems agreed closely (kappa 0.91). Combining them with cytology worked better: Bethesda III nodules with a low-risk ultrasound were malignant only 5.9% (TI-RADS) or 5.7% (ATA) of the time, giving negative predictive values around 94%, while Bethesda IV/V nodules with high-risk ultrasound were mostly cancers.
The limits
What it doesn't show
Only nodules that went to surgery and had retrievable images could be included, so the sample is heavily filtered and malignancy (47%) is much higher than in all indeterminate nodules, which inflates predictive values; the authors note the high NPV may not hold where cancer risk differs. A single radiologist re-read static stored images rather than scoring live scans, and reader agreement between radiologists was not tested. The study is retrospective, from one region, and lacked data such as TSH and thyroid autoimmunity.
Key terms
- Bethesda system (TBSRTC)
- A six-category scheme for reporting thyroid needle-biopsy cytology; categories III, IV and V are 'indeterminate' because they neither confirm nor exclude cancer.
- ACR TI-RADS
- An ultrasound scoring system that adds points for features such as composition, echogenicity, shape, margins and echogenic foci to place a nodule in a risk category.
- Negative predictive value (NPV)
- The proportion of test-negative cases that truly do not have the disease; it depends on how common the disease is in the tested group.
- Reference standard
- The best available method for establishing true disease status; here, histopathology after thyroidectomy.
- Cohen's kappa
- A statistic measuring agreement between two classifications beyond what chance would produce.
- Verification bias
- Distortion that arises when only patients who received the reference test (here, surgery) are included in an accuracy study.
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Quiz yourself
What was the reference standard used to judge each nodule?
Common questions
Why does an indeterminate biopsy matter clinically?
Many such nodules are benign, so sending all of them to diagnostic surgery exposes patients to unnecessary operations; a cheap way to reassure some patients could avoid that.
Does a 94% NPV mean ultrasound can safely replace surgery for Bethesda III nodules?
Not on its own. The NPV comes from a surgically selected, high-malignancy sample in one region, so it needs confirmation in unselected cohorts before guiding conservative management everywhere.
Why did the authors split TI-RADS category TR4 into 4a, 4b and 4c?
Cancer risk varied widely within TR4 in their data, with TR4a behaving like low-risk nodules and TR4b/4c like high-risk ones, so splitting it sharpened the favourable/unfavourable cut-off.
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