Thyroid Nodule Risk Stratification

ACR TI-RADS Calculator

ACR TI-RADS 2017 (Tessler et al.) — point-based scoring system; select one option per category, all applicable echogenic foci

1. Composition (choose one)

Cystic or almost completely cystic 0 pts

Spongiform ≥50% composed of small cystic spaces 0 pts

Mixed cystic and solid 1 pt

Solid or almost completely solid 2 pts

2. Echogenicity (choose one; for solid component)

Anechoic 0 pts

Hyperechoic or isoechoic 1 pt

Hypoechoic 2 pts

Very hypoechoic More hypoechoic than strap muscles 3 pts

3. Shape (choose one; measured on transverse view)

Wider-than-tall 0 pts

Taller-than-wide AP dimension exceeds transverse dimension 3 pts

4. Margin (choose one)

Smooth 0 pts

Ill-defined 0 pts

Lobulated or irregular 2 pts

Extra-thyroidal extension (ETE) 3 pts

5. Echogenic Foci (select all present — points are additive)

None or large comet-tail artifacts Comet-tail artifacts >1 mm 0 pts

Macrocalcifications Coarse calcifications causing acoustic shadowing 1 pt

Peripheral (rim) calcifications Complete or incomplete eggshell calcification 2 pts

Punctate echogenic foci ≤1 mm, may have small comet-tail artifact; microcalcifications 3 pts

FNA & Follow-up Recommendation (ACR 2017)

ACR TI-RADS Level Reference

Level	Points	Malignancy Risk	FNA if ≥	Follow-up US if ≥
TR1 — Benign	0	<0.3%	No FNA or routine follow-up needed
TR2 — Not suspicious	2	<1.5%	No FNA or routine follow-up needed
TR3 — Mildly suspicious	3–4	~5%	≥2.5 cm	≥1.5 cm (at 1, 3, 5 yrs)
TR4 — Moderately suspicious	5–6	~5–20%	≥1.5 cm	≥1 cm (at 1, 2, 3, 5 yrs)
TR5 — Highly suspicious	≥7	~20–80%	≥1 cm	≥0.5 cm (at 1, 2, 3, 5 yrs)

Clinical disclaimer: ACR TI-RADS 2017 is a radiologist-applied scoring system based on a comprehensive neck ultrasound report. This calculator requires accurate identification of all sonographic features from a full diagnostic study. Scores should be interpreted alongside clinical context. ACR recommends follow-up intervals be adjusted based on growth rate, patient risk factors, and clinical judgment.

ATA 2015 Sonographic Risk Calculator

Select all ultrasound features present → receive ATA risk tier and FNA size threshold (per ATA 2015 Management Guidelines)

First, select the echogenicity / composition pattern:

Nodule Composition & Echogenicity

Purely cystic No solid component

Spongiform / predominantly cystic ≥50% cystic with microcystic spaces

Isoechoic or hyperechoic solid OR partially cystic with eccentric solid areas

Hypoechoic solid Compared to strap muscles

Markedly hypoechoic solid More hypoechoic than strap muscles

FNA Recommendation

Clinical disclaimer: This tool applies ATA 2015 guidelines for educational and reference purposes. Clinical decisions should incorporate the full clinical picture, patient preference, and institutional expertise. ACR TI-RADS (2017) and BTA (2014) guidelines offer alternative frameworks.

Bethesda System for Reporting Thyroid Cytopathology

BSRTC 2023 (3rd Edition) — malignancy risk estimates with molecular ancillary testing context

Category	Diagnosis	Malignancy Risk	Usual Management
I	Nondiagnostic / Unsatisfactory Inadequate cellularity; obscuring blood or clot; cyst fluid only	5–10%	Repeat FNA under ultrasound guidance; consider core needle biopsy if repeatedly nondiagnostic
II	Benign Benign follicular nodule, colloid nodule, Hashimoto thyroiditis, granulomatous thyroiditis, simple cyst	0–3%	Clinical and sonographic follow-up per ATA guidelines; no routine surgery
III	Atypia of Undetermined Significance (AUS) Also reported as Follicular Lesion of Undetermined Significance (FLUS)	13–30%	Repeat FNA, molecular testing (AFIRMA/Thyroseq), or diagnostic lobectomy based on clinical and imaging features
IV	Follicular Neoplasm (FN) Suspicious for Follicular Neoplasm (SFN); includes Hürthle cell variant	25–45%	Molecular testing strongly recommended; if suspicious → diagnostic lobectomy or total thyroidectomy
V	Suspicious for Malignancy Suspicious for PTC, MTC, lymphoma, or other malignancy	50–75%	Near-total thyroidectomy or diagnostic lobectomy; consider molecular testing to guide extent of surgery
VI	Malignant PTC, MTC, anaplastic carcinoma, lymphoma, metastatic carcinoma	97–99%	Appropriate definitive surgery (usually near-total thyroidectomy ± neck dissection); staging workup

Note: Malignancy risk estimates reflect the 2023 BSRTC 3rd edition. Rates vary by institution, patient population, and whether molecular testing is used to triage indeterminate categories. "Malignancy" in categories III–V includes noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in some series.

Molecular Testing: AFIRMA vs. Thyroseq

Used primarily for Bethesda III & IV indeterminate cytology to avoid unnecessary surgery

AFIRMA GSC

Gene Sequence Classifier · Veracyte Inc.

MethodRNA microarray (whole transcriptome)

SampleFNA specimen (≥60 follicular cells)

Benign call rate~68% of tested nodules

Sensitivity~91%

Specificity~68%

NPV (Bethesda III)~97%

PPV (Bethesda III)~38%

✅ Benign result: Malignancy risk ~4–5% — supports active surveillance over surgery in appropriate patients

⚠️ Suspicious result: Malignancy risk ~47% — surgical evaluation recommended. Paired with AFIRMA Xpression Atlas (AXA) to identify specific driver mutations and fusions.

Thyroseq v3

Genomic Classifier · CBLPath / Univ. of Pittsburgh

MethodNext-gen DNA + RNA sequencing

SampleFNA specimen (preservative-fixed)

Alterations detectedBRAF V600E, RAS, TERT, RET, NTRK, PAX8-PPARG, others

Sensitivity~94%

Specificity~82%

NPV (Bethesda III/IV)~97%

PPV (Bethesda III/IV)~66%

✅ Negative result: Malignancy risk ~3–5% — supports lobectomy avoidance or active surveillance

⚠️ Positive result: Risk varies by alteration — BRAF V600E → near-certain PTC; RAS → 20–40% risk; guides extent of surgery (lobectomy vs. total thyroidectomy)

Quick Comparison

Feature	AFIRMA GSC	Thyroseq v3
Platform	RNA expression	DNA + RNA sequencing
Best for	Bethesda III/IV rule-out	Bethesda III/IV rule-out + mutation profiling
Report format	Benign / Suspicious	Negative / Positive + specific alteration(s)
Guides surgery extent?	Limited (AXA add-on)	Yes — alteration type informs lobectomy vs. TT
Turnaround	~10 business days	~10 business days
Insurance coverage	Medicare & most commercial	Medicare & most commercial

Performance data from published validation studies (Alexander 2019 for AFIRMA GSC; Steward 2019 for Thyroseq v3). Real-world NPV depends on pretest probability (institution malignancy rate). Both tests have limitations with Hürthle cell neoplasms and oncocytic variants.

In-Office FNA — Specimen Handling Tips

For AFIRMA and Thyroseq collection at the clinic

AFIRMA (Veracyte)

✔ 1–2 passes into proprietary CytoLyt® preservative vial
✔ Minimum 10,000 follicular cells required
✔ Refrigerate at 2–8°C; ship within 6 weeks
✔ Order kit from Veracyte in advance
✔ Can be sent concurrently with cytology slides
⚠ Avoid passes with heavy blood contamination

Thyroseq (CBLPath)

✔ 1–2 passes into PreservCyt® (ThinPrep) vial
✔ Dedicated pass preferred (separate from cytology)
✔ Store at room temp or refrigerated
✔ Ship at room temperature within 8 weeks
✔ Order collection kits from CBLPath
⚠ Label clearly: patient ID + collection date

Always consult the current collection instructions from Veracyte and CBLPath, as protocols may update. Contact lab directly for questions about specimen adequacy or rejection criteria.