Deep Learning Based on B-Mode and Color Doppler Ultrasound for Differentiation of Primary Thyroid Lymphoma and Hashimoto’s Thyroiditis: A Retrospective Single-Center Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Ultrasound Images Acquisition and Reader Comparison
2.3. Deep Learning Model Development
2.4. Model Training
2.5. Statistical Analysis
3. Results
3.1. Cohort and Dataset Characteristics
3.2. Clinical and Ultrasound Feature Analysis
3.3. Image-Level Diagnostic Performance of the Model
3.4. Physician Performance
3.5. Grad-CAM Visualization
3.6. Exploratory External Validation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
| PTL | Primary Thyroid Lymphoma |
| DLBCL | Diffuse Large B-cell Lymphoma |
| MALT | Mucosa-Associated Lymphoid Tissue |
| HT | Hashimoto’s Thyroiditis |
| BMUS | B-mode Ultrasound |
| CDUS | Color Doppler Ultrasound |
| WTConv | Wavelet Transform Convolution |
| ResNet | Residual Network |
| AUC | Area under the receiver operating characteristic curve |
| ROC | Receiver Operating Characteristic |
| Grad-CAM | Gradient-weighted Class Activation Mapping |
| FNA | Fine-Needle Aspiration |
| CNB | Core-Needle Biopsy |
| H&E | Hematoxylin and Eosin |
| 18F-FDG PET | 18F-Fluorodeoxyglucose Positron Emission Tomography |
| PPV | Positive Predictive Value |
| NPV | Negative Predictive Value |
| Acc | Accuracy |
| CI | Confidence Interval |
| t-SNE | t-distributed Stochastic Neighbor Embedding |
| DCA | Decision Curve Analysis |
| CT | Computed Tomography |
| MRI | Magnetic Resonance Imaging |
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| Groups/ Indicators | MALT (64) | DLBCL (129) | HT (120) | χ2 | p-Value | p-Value (MALT vs. DLBCL) | p-Value (MALT vs. HT) | p-Value (DLBCL vs. HT) |
|---|---|---|---|---|---|---|---|---|
| Site | 3.1174 | 0.5384 | 0.4794 | 0.4348 | 0.4329 | |||
| Right lobe | 29 (45.31%) | 69 (53.49%) | 65 (54.17%) | |||||
| Left lobe | 33 (51.56%) | 58 (44.96%) | 50 (41.67%) | |||||
| Isthmus | 2 (3.12%) | 2 (1.55%) | 5 (4.17%) | |||||
| Sex | 15.2505 | 0.0005 | 0.8843 | 0.0008 | 0.0003 | |||
| Man | 18 (28.12%) | 35 (27.13%) | 11 (9.17%) | |||||
| Woman | 46 (71.88%) | 94 (72.87%) | 109 (90.83%) | |||||
| Age | 74.0798 | <0.0001 | 0.0839 | <0.0001 | <0.0001 | |||
| <45 | 10 (15.62%) | 10 (7.75%) | 51 (42.50%) | |||||
| 45–60 | 23 (35.94%) | 37 (28.68%) | 51 (42.50%) | |||||
| >60 | 31 (48.44%) | 82 (63.57%) | 18 (15.00%) | |||||
| Specimen | 8.4769 | 0.0144 | 0.0407 | 0.0039 | 0.3008 | |||
| Biopsy | 34 (53.12%) | 88 (68.22%) | 89 (74.17%) | |||||
| Resection | 30 (46.88%) | 41 (31.78%) | 31 (25.83%) | |||||
| HT background | 12.2795 | 0.0022 | 0.6105 | 0.0046 | 0.0004 | |||
| Present | 59 (92.19%) | 116 (89.92%) | 120 (100.00%) | |||||
| Absent | 5 (7.81%) | 13 (10.08%) | 0 (0.00%) | |||||
| Lesion Type | 7.1692 | 0.0277 | 0.0277 | - | - | |||
| Diffuse | 30 (46.88%) | 78 (60.47%) | - | |||||
| Nodular | 30 (46.88%) | 36 (27.91%) | - | |||||
| Mixed | 4 (6.25%) | 15 (11.63%) | - | |||||
| Abnormal CLN | 59.8963 | <0.0001 | 0.0367 | <0.0001 | <0.0001 | |||
| Present | 26 (40.62%) | 73 (56.59%) | 12 (10.00%) | |||||
| Absent | 38 (59.38%) | 56 (43.41%) | 108 (90.00%) | |||||
| Adler grade | 21.1393 | 0.0003 | 0.5742 | 0.0007 | 0.0003 | |||
| Grade 1 | 21 (32.81%) | 51 (39.53%) | 68 (56.67%) | |||||
| Grade 2 | 33 (51.56%) | 63 (48.84%) | 29 (24.17%) | |||||
| Grade 3 | 10 (15.62%) | 15 (11.63%) | 23 (19.17%) | |||||
| Boundary | 3.1036 | 0.0781 | 0.0781 | - | - | |||
| Distinct | 27 (42.19%) | 38 (29.46%) | - | |||||
| Indistinct | 37 (57.81%) | 91 (70.54%) | - | |||||
| Morphology | 8.2380 | 0.0041 | 0.0079 | - | - | |||
| Regular | 10 (15.62%) | 5 (3.88%) | - | |||||
| Irregular | 54 (84.38%) | 124 (96.12%) | - | |||||
| Aspect Ratio | 1.5119 | 0.2189 | 0.5521 | - | - | |||
| Wider-than-tall | 64 (100.00%) | 126 (97.67%) | - | |||||
| Taller-than-wide | 0 (0.00%) | 3 (2.33%) | - | |||||
| Echogenicity | 27.3216 | <0.0001 | 0.0973 | 0.0010 | <0.0001 | |||
| Hypo echo | 56 (87.50%) | 100 (77.52%) | 119 (99.17%) | |||||
| Marked hypo echo | 8 (12.50%) | 29 (22.48%) | 1 (0.83%) |
| Groups | AUC (95% CI) | Balanced Acc (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) | F1-Score (95% CI) |
|---|---|---|---|---|---|---|---|
| DLBCL | 0.899 (0.858–0.935) | 0.830 (0.785–0.876) | 0.852 (0.778–0.918) | 0.809 (0.747–0.869) | 0.754 (0.679–0.825) | 0.888 (0.832–0.939) | 0.800 (0.737–0.853) |
| HT | 0.937 (0.908–0.963) | 0.841 (0.797–0.887) | 0.748 (0.664–0.826) | 0.935 (0.895–0.969) | 0.892 (0.826–0.950) | 0.837 (0.785–0.892) | 0.814 (0.751–0.870) |
| MALT lymphoma | 0.946 (0.900–0.981) | 0.925 (0.877–0.967) | 0.891 (0.792–0.974) | 0.959 (0.930–0.982) | 0.820 (0.711–0.923) | 0.977 (0.954–0.995) | 0.854 (0.769–0.922) |
| Macro-average | 0.927 (0.889–0.960) | 0.866 (0.820–0.910) | 0.830 (0.744–0.906) | 0.901 (0.857–0.940) | 0.822 (0.739–0.900) | 0.901 (0.857–0.942) | 0.823 (0.753–0.882) |
| Physicians | Groups | Balanced Acc (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) | F1-Score (95% CI) |
|---|---|---|---|---|---|---|---|
| Junior | DLBCL | 0.784 (0.732–0.840) | 0.858 (0.784–0.919) | 0.709 (0.619–0.792) | 0.752 (0.670–0.825) | 0.830 (0.742–0.900) | 0.802 (0.746–0.858) |
| HT | 0.806 (0.753–0.862) | 0.635 (0.537–0.742) | 0.976 (0.945–1.000) | 0.947 (0.885–1.000) | 0.796 (0.727–0.860) | 0.761 (0.680–0.838) | |
| MALT | 0.480 (0.409–0.567) | 0.111 (0.000–0.278) | 0.848 (0.789–0.897) | 0.065 (0.000–0.160) | 0.910 (0.868–0.950) | 0.082 (0.000–0.194) | |
| Macro-average | 0.690 (0.631–0.756) | 0.535 (0.441–0.646) | 0.844 (0.784–0.896) | 0.588 (0.518–0.662) | 0.845 (0.779–0.903) | 0.548 (0.475–0.630) | |
| Intermediate | DLBCL | 0.713 (0.653–0.774) | 0.736 (0.651–0.821) | 0.689 (0.602–0.778) | 0.709 (0.625–0.789) | 0.717 (0.625–0.802) | 0.722 (0.654–0.785) |
| HT | 0.782 (0.729–0.835) | 0.565 (0.458–0.670) | 1.000 (1.000–1.000) | 1.000 (1.000–1.000) | 0.770 (0.700–0.831) | 0.722 (0.629–0.803) | |
| MALT | 0.701 (0.587–0.816) | 0.611 (0.389–0.833) | 0.791 (0.730–0.848) | 0.216 (0.098–0.321) | 0.956 (0.924–0.987) | 0.319 (0.161–0.447) | |
| Macro-average | 0.732 (0.656–0.809) | 0.637 (0.499–0.775) | 0.827 (0.777–0.875) | 0.642 (0.574–0.703) | 0.814 (0.750–0.873) | 0.588 (0.481–0.678) | |
| Senior | DLBCL | 0.858 (0.812–0.902) | 0.783 (0.700–0.862) | 0.932 (0.881–0.978) | 0.922 (0.863–0.973) | 0.807 (0.736–0.874) | 0.847 (0.794–0.898) |
| HT | 0.846 (0.793–0.898) | 0.765 (0.677–0.854) | 0.927 (0.875–0.971) | 0.878 (0.797–0.950) | 0.852 (0.786–0.912) | 0.818 (0.746–0.880) | |
| MALT | 0.777 (0.670–0.877) | 0.722 (0.500–0.917) | 0.832 (0.781–0.882) | 0.289 (0.163–0.419) | 0.970 (0.941–0.994) | 0.413 (0.254–0.543) | |
| Macro-average | 0.827 (0.759–0.892) | 0.757 (0.626–0.877) | 0.897 (0.845–0.944) | 0.696 (0.608–0.781) | 0.876 (0.821–0.927) | 0.692 (0.598–0.774) |
| Physicians | Concordant Cases/Total | Simple Concordance Rate | Cohen’s κ | Interpretation of Concordance |
|---|---|---|---|---|
| Senior vs. Intermediate | 41/63 | 65.1% | 0.458 | Moderate |
| Senior vs. Junior | 45/63 | 71.4% | 0.548 | Moderate |
| Intermediate vs. Junior | 38/63 | 60.3% | 0.328 | Fair |
| Groups | AUC (95% CI) | Balanced Acc (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) | F1-Score (95% CI) |
|---|---|---|---|---|---|---|---|
| DLBCL | 0.806 (0.711–0.891) | 0.675 (0.548–0.799) | 0.581 (0.444–0.725) | 0.769 (0.651–0.873) | 0.676 (0.518–0.821) | 0.690 (0.577–0.800) | 0.625 (0.500–0.738) |
| HT | 0.825 (0.727–0.909) | 0.565 (0.483–0.647) | 0.167 (0.065–0.294) | 0.962 (0.900–1.000) | 0.778 (0.500–1.000) | 0.593 (0.494–0.695) | 0.275 (0.118–0.440) |
| MALT lymphoma | 0.756 (0.620–0.865) | 0.659 (0.457–0.813) | 0.800 (0.500–1.000) | 0.518 (0.414–0.625) | 0.163 (0.068–0.281) | 0.957 (0.881–1.000) | 0.271 (0.122–0.426) |
| Macro-average | 0.796 (0.686–0.888) | 0.633 (0.496–0.753) | 0.516 (0.337–0.673) | 0.750 (0.655–0.833) | 0.539 (0.362–0.700) | 0.746 (0.651–0.832) | 0.390 (0.247–0.535) |
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Share and Cite
Chen, J.; Deng, Z.; Chen, Y.; Ye, R.; Li, J.; Tao, Y.; Ma, B.; He, Y. Deep Learning Based on B-Mode and Color Doppler Ultrasound for Differentiation of Primary Thyroid Lymphoma and Hashimoto’s Thyroiditis: A Retrospective Single-Center Study. Diagnostics 2026, 16, 1909. https://doi.org/10.3390/diagnostics16121909
Chen J, Deng Z, Chen Y, Ye R, Li J, Tao Y, Ma B, He Y. Deep Learning Based on B-Mode and Color Doppler Ultrasound for Differentiation of Primary Thyroid Lymphoma and Hashimoto’s Thyroiditis: A Retrospective Single-Center Study. Diagnostics. 2026; 16(12):1909. https://doi.org/10.3390/diagnostics16121909
Chicago/Turabian StyleChen, Juanmei, Zijian Deng, Yong Chen, Ruiheng Ye, Jiawu Li, Yi Tao, Buyun Ma, and Yushuang He. 2026. "Deep Learning Based on B-Mode and Color Doppler Ultrasound for Differentiation of Primary Thyroid Lymphoma and Hashimoto’s Thyroiditis: A Retrospective Single-Center Study" Diagnostics 16, no. 12: 1909. https://doi.org/10.3390/diagnostics16121909
APA StyleChen, J., Deng, Z., Chen, Y., Ye, R., Li, J., Tao, Y., Ma, B., & He, Y. (2026). Deep Learning Based on B-Mode and Color Doppler Ultrasound for Differentiation of Primary Thyroid Lymphoma and Hashimoto’s Thyroiditis: A Retrospective Single-Center Study. Diagnostics, 16(12), 1909. https://doi.org/10.3390/diagnostics16121909

