18F-Fluorocholine Positron Emission Tomography/Computed Tomography is a Highly Sensitive but Poorly Specific Tool for Identifying Malignancy in Thyroid Nodules with Indeterminate Cytology: The Chocolate Study

Abstract

Background: Refining the risk of malignancy in patients presenting with thyroid nodules with indeterminate cytology (IC) is a critical challenge. We investigated the performances of 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) to predict malignancy. Methods: Between May 2016 and March 2019, 107 patients presenting with a thyroid nodule ≥15 mm with IC and eligible for surgery were included in this prospective study. Head-and-neck PET/CT acquisitions were performed 20 and 60 minutes after injection of 1.5 MBq/kg of FCH. PET/CT acquisition was scored positive when maximal standardized uptake value in the IC nodule was higher than in the thyroid background. Pathology was the gold standard for diagnosis. Results: At pathology, 19 (18%) nodules were malignant, 87 were benign, and one was a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Sensitivity, specificity, accuracy, positive-predictive value (PPV), and negative-predictive value (NPV) of FCH PET/CT in detecting cancer or NIFTP were 90%, 50%, 55%, 29%, and 96% at 20 minutes and 85%, 49%, 67%, 28%, and 94% at 60 minutes, respectively. Higher specificity (58% vs. 33%, p = 0.01) was observed in nononcocytic (n = 72) than in oncocytic IC nodules (n = 35). The pre-PET/CT probability of cancer or NIFTP in Bethesda III-IV nodules was 11% and the post-PET/CT probability was 19% in PET-positives and 0% in PET-negatives. In retrospective analysis, 42% of surgeries would have been unnecessary after PET/CT and 81% before (p < 0.001), resulting in a hypothetical 48% reduction (95% confidence interval [32-64]). Conclusions: FCH PET/CT offers high NPV to reliably exclude cancer in PET-negative IC nodules, but suffers from low PPV, particularly in those with oncocytic cytology. ClinicalTrials.gov identifier: NCT02784223.

Keywords: 18F-choline PET/CT; PET/CT; fluorocholine PET/CT; indeterminate cytology; thyroid nodules.

Conflict of interest statement

No competing financial interests exist.

Figures

FIG. 1.

Correlation between cytology and pathology in the 107 patients. C-PTC, classic variant of papillary thyroid cancer; FV-PTC, follicular variant of papillary thyroid cancer; HCC, Hürthle cell cancer; TC-PTC, tall-cell variant of papillary thyroid cancer; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

FIG. 2.

Clinical example of a true-positive FCH PET/CT in a 20-year-old female patient with thyroid cancer. She was referred for a right 29 mm thyroid nodule [(A), CT scan, arrow] EU-TIRADS 3, and Bethesda IV (follicular neoplasm). High FCH uptake was observed in the nodule on both PET/CT acquisitions [(B, C), MIP and fused transaxial slice, at 20 minutes; (E, F), MIP and fused transaxial slice, at 60 minutes] (Patient 9, see Table 2 for SUVmax). Pathology revealed a 23 mm FV-PTC (pT2NxMx) [(D), HES staining, × 10]. FCH, 18F-fluorocholine; PET/CT, positron emission tomography/computed tomography; EU-TIRADS, European Thyroid Imaging Reporting and Data System; MIP, maximum intensity projection image; HES, hematoxylin and eosin stain.

FIG. 3.

Clinical example of a false-negative FCH PET/CT result. A 50-year-old female patient with a 24 mm nodule in the left thyroid lobe [(A), CT scan, arrow] EU-TIRADS 4, and Bethesda V. PET/CT did not show any FCH uptake in the thyroid nodule neither at 20 minutes [(B), MIP; (C), fused transaxial slice] nor at 60 minutes [(E), MIP; (F), fused transaxial slice] (Patient 11, see Table 2 for SUVmax). An 18 mm C-PTC (pT1bN0Mx) was found on pathology [(D), HES staining, × 10].

FIG. 4.

Clinical example of false-negative FCH PET/CT result. A 51-year-old female patient was referred for a 15 mm nodule of the right thyroid lobe [(A), CT scan, arrow] EU-TIRADS 5, and Bethesda V. FCH PET/CT showed diffuse thyroid uptake on both acquisitions [(B, C), MIP and fused transaxial slice, at 20 minutes] (SUVmax = 9.29); (E, F) MIP and fused transaxial slice, at 60 minutes (SUVmax = 8.25), which was higher than in the nodule (Patient 10, see Table 2 for SUVmax). A 12-mm FV-PTC (pT1bN0Mx) was found on pathology [(D), HES staining, × 10).

FIG. 5.

Quantitative assessment of FCH uptake in benign, NIFTP, and malignant nodules scanned with PET/CT according to the pathological subtype and the acquisition time [(A), at 20 minutes; (B), at 60 minutes].

FIG. 6.

FCH PET/CT results in two patients with a cytology consistent with oncocytic (Hürthle) cell neoplasm (Bethesda IV). (A–F) True-positive FCH PET/CT in a 65-year-old female patient with a right 53 mm thyroid nodule [(A), CT scan, arrow] and EU-TIRADS 3. High FCH tumor uptake was present on both acquisitions [(B, C), MIP and fused transaxial slice, at 20 minutes; (E, F), MIP and fused transaxial slice, at 60 minutes] (Patient 2, see Table 2 for SUVmax). Pathology showed a 55 mm HCC (pT3aNxMx) [(D), HES staining, × 10). (G–L) False-positive FCH PET/CT in a 71-year-old female patient referred for a 38 mm right thyroid nodule [(G), CT scan, arrow] and EU-TIRADS 4. PET/CT showed high FCH uptake in the nodule on both acquisitions [(H, I), MIP and fused transaxial slice, at 20 minutes (SUVmax = 6.47); (K, L), MIP and fused transaxial slice, at 60 minutes (SUVmax = 6.59)]. A 40-mm oncocytic adenoma was found on pathology [(J), HES staining, × 5].

FIG. 7.

Cancer risk in indeterminate cytology thyroid nodules based on cytology and FCH PET/CT results.