Dependence of Renal Uptake on Kidney Function in [68Ga]Ga-PSMA-11 PET/CT Imaging.

(1) Background: PSMA ligand PET/CT is increasingly important for diagnostics of prostate cancer and other tumor diseases. In particular, the radiopharmaceutical [68Ga]Ga-PSMA-11 is widely used. Besides its tumor-specific binding, the uptake within the kidneys is dominant and seems to visualize the renal cortex specifically. Kidney diseases may alter the uptake of radiopharmaceuticals. Therefore, the correlation between renal uptake in PET/CT imaging and renal function should be investigated. (2) Methods: A group of 103 male patients were retrospectively evaluated for eGFR according to the CKD-EPI equation, tracer uptake intensity (SUVmax, SUVpeak, SUVmean), the molecular volume of the renal cortex, morphological kidney size, and total renal uptake. Manual and three different computer-assisted contouring methods (thresholds at 50% of SUVmax, 30% of SUVmax, and absolute SUV of 20) were used for measurements. Correlations between parameters were calculated using linear regression models. (3) Results: Renal SUVmax, SUVpeak, and SUVmean do not correlate with eGFR for manual or computer-assisted measurements. In contrast, molecular cortex volume shows a moderate correlation with eGFR (R2 = 0.231, p < 0.001), superior to morphological kidney size. A contouring threshold of 30% of SUVmax outperformed the other settings for renal cortex volume and total renal uptake. (4) Conclusions: Renal uptake of [68Ga]Ga-PSMA-11 cannot predict eGFR, but the functional renal cortex can be quantified by PET/CT imaging.

Transarterial Radioembolization (TARE) in Patients with Hepatocellular Carcinoma: A Comparison of Palliative with Bridging-to-Transplant Concepts.

We investigated transarterial radioembolization (TARE) as a palliative measure and bridging-to-transplant therapy in hepatocellular carcinoma (HCC) patients. A total of 167 patients (50 bridging, 117 palliative) with 245 TARE procedures were assessed. Fourteen patients underwent subsequent liver transplantation (LT). Patients undergoing LT exhibited significantly prolonged progression-free survival (PFS) compared to those with bridging-without-transplant (p = 0.033). No significant differences were observed between patients with bridging-without-transplant and palliative cases (p = 0.116). Median overall survival (OS) post-TARE was 16.6 months, with estimated OS rates at 6/12 months of 82.0%/60.5%, respectively. Patients who underwent LT demonstrated statistically significantly longer OS compared to those with bridging-without-transplant (p = 0.001). No marked outcome distinctions were found between bridging-without-transplant and palliative groups. The findings underscored the superiority of LT over alternative treatments. TARE served as an important component in non-LT scenarios, allowing for subsequent therapeutic options. The study reflected the highly variable and complex situations of patients with HCC, emphasizing the need for further investigations to define an optimal multimodal approach.

Thyroid Imaging Reporting and Data Systems: Applicability of the "Taller than Wide" Criterium in Primary/Secondary Care Units and the Role of Thyroid Scintigraphy.

BACKGROUND: To examine the applicability of the "taller than wide" (ttw) criterium for risk assessment of thyroid nodules (TNs) in primary/secondary care units and the role of thyroid scintigraphy therein. METHODS: German bicenter study performed in a setting of primary/secondary care. Patient recruitment and analysis in center A was conducted in a prospective manner. In center B, patient data were retrieved from a database that was originally generated by prospective data collection. TNs were assessed by ultrasound and thyroid scans, mostly fine needle biopsy and occasionally surgery and others. In center A, only patients who presented for the first time were included. The inclusion criterion was any TN ≥ 10 mm that had at least the following two sonographic risk features: solidity and a ttw shape. In center B, consecutive patients who had at least ttw and hypofunctioning nodules ≥ 10 mm were retrieved from the above-mentioned database. The risk of malignancy was determined according to a mixed reference standard and compared with literature data. RESULTS: In center A, 223 patients with 259 TNs were included into the study. For further analysis, 200 nodules with a reference standard were available. The overall malignancy rate was 2.5% (upper limit of the 95% CI: 5.1%). After the exclusion of scintigraphically hyperfunctioning nodules, the malignancy rate increased slightly to 2.8% (upper limit of the 95% CI: 5.7%). Malignant nodules exhibited sonographic risk features additional to solidity and ttw shape more often than benign ones. In addition to the exclusion of hyperfunctioning nodules, when considering only nodules without additional US risk features, i.e., exclusively solid and ttw-nodules, the malignancy rate decreased to 0.9% (upper limit 95% CI: 3.7%). In center B, from 58 patients, 58 ttw and hypofunctioning TNs on thyroid scans with a reference standard were available. Malignant nodules from center B were always solid and hypoechoic. The overall malignancy rate of hypofunctioning and ttw nodules was 21%, with the lower limit of the 95% CI (one-sided) being 12%. CONCLUSIONS: In primary/secondary care units, the lowest TIRADS categories for indicating FNB, e.g., applying one out of five sonographic risk features, may not be appropriate owing to the much lower a priori malignancy risk in TNs compared to tertiary/quaternary care units. Even the combination of two sonographic risk features, "solidity" and "ttw", may only be appropriate in a limited fashion. In contrast, the preselection of TNs according to hypofunctioning findings on thyroid scans clearly warranted FNB, even when applying only one sonographic risk criterion ("ttw"). For this reason, thyroid scans in TNs may not only be indicated to rule out hyperfunctioning nodules from FNB but also to rule in hypofunctioning ones.

[Technical innovations to optimize ultrasound imaging]. / Technische Innovationen zur Optimierung der Ultraschallbildgebung.

Due to the high incidence of thyroid disease, ultrasound examination of the neck has high priority in many nuclear medicine departments. A precise sonogram with high spatial resolution and image sharpness over the entire imaging area, combined with minimal artifacts, is the prerequisite for meeting the demand for high diagnostic accuracy in modern medicine. In the last 20-30 years, a number of significant technical innovations have been implemented, such as the development of the matrix array, electronic image focusing, realtime compound imaging, artifact limitation by speckle reduction and harmonic imaging, as well as the possibility to extend the field of view.

[Standardized acquisition and documentation of cine loops on conventional thyroid ultrasound]. / Standardisierte Akquisition und Dokumentation von Videosequenzen bei der konventionellen Schilddrüsensonografie.

Ultrasound is the basic imaging method for the assessment of the thyroid gland. Due to the high prevalence of structural disease, the examination procedure is used very frequently in Germany, in many cases in the context of follow-up. The assessment of thyroid pathologies and their dynamics is subjected to relevant inter- and intraobserver variability. Findings that were not identified during live ultrasound cannot be assessed retrospectively. Applying an SOP for the acquisition and documentation of standardized video sequences of ultrasound images (so-called cine loops), allows for a secondary retrospective evaluation of the thyroid gland, taking into account previously acquired images analogous to other cross-sectional imaging methods such as CT or MRI. The cine loops can be acquired by non-physician personnel, stored to the local PACS and used for educational and research purposes.

Correct and Incorrect Recommendations for or against Fine Needle Biopsies of Hypofunctioning Thyroid Nodules: Performance of Different Ultrasound-based Risk Stratification Systems.

PURPOSE: To evaluate the recommendations for or against fine needle biopsy (FNB) of hypofunctioning thyroid nodules (TNs) using of five different Ultrasound (US) -based risk stratification systems (RSSs). METHODS: German multicenter study with 563 TNs (≥ 10 mm) in 534 patients who underwent thyroid US and surgery. All TNs were evaluated with ACR TI-RADS, EU-TIRADS, ATA, K-TIRADS 2016 and modified K-TIRADS 2021. A correct recommendation was defined as: malignant TN with recommendation for FNB (appropriate) or benign TN without recommendation for FNB (avoided). An incorrect recommendation was defined as: malignant TN without recommendation for FNB (missed) or benign TN with recommendation for FNB (unnecessary). RESULTS: ACR TI-RADS demonstrated the highest rate of correct (42.3 %) and lowest rate of incorrect recommendations (57.7 %). The other RRSs showed similar results for correct (26.5 %-35.7 %) and incorrect (64.3 %-73.5 %) recommendations. ACR TI-RADS demonstrated the lowest rate of unnecessary (73.4 %) and the highest rate of appropriate (26.6 %) FNB recommendation. For other RSSs, the rates of unnecessary and appropriate FNB were between 75.2 %-77.1 % and 22.9 %-24.8 %. The lowest rate of missed FNB (14.7 %) and the highest rate of avoided FNB (85.3 %) was found for ACR TI-RADS. For the other RSSs, the rates of missed and avoided FNB were between 17.8 %-26.9 % and 73.1 %-82.2 %. When the size cutoff was disregarded, an increase of correct recommendations and a decrease of incorrect recommendations was observed for all RSSs. CONCLUSION: The RSSs vary in their ability to correctly recommend for or against FNB. An understanding of the impact of nodule size cutoffs seems necessary for the future of TIRADS.

[Normal values for adult thyroid volume on ultrasound - where do they come from and how should they be evaluated?] / Sonographische Normwerte für das Schilddrüsenvolumen Erwachsener ­ woher kommen sie und wie sind sie zu bewerten?

The upper limit for the thyroid volume is 18 ml for women and 25 ml for men. These reference values are used and taught in many clinics and practices across several disciplines. The thyroid volume is a relevant factor for the treatment course. But where do the standard values for thyroid volumes come from, what kind of studies have been carried out to establish them? Should these upper limits be used as an universal standard in clinical routine, and which factors can influence the physiological organ size? The following article is dedicated to a critical review of the commonly used reference values for the thyroid volume of adults.

Image-Guided Fine-Needle Aspiration Cytology for BRCA Mutation Assessment of PSMA-Positive Lymph Node Metastases in a Patient With Metastatic Castration-Resistant Prostate Cancer.

ABSTRACT: A 64-year-old man with metastatic castration-resistant prostate cancer presented for prostate-specific membrane antigen (PSMA) PET/CT in preparation for 177 Lu-PSMA radioligand therapy. For precedent BRCA mutation assessment, fine-needle aspiration cytology of 2 PSMA-positive lymph node metastases was conducted. The acquired material was suitable for next-generation sequencing-based gene panel diagnostics and did not show a BRCA1 / 2 mutation, thus PSMA radioligand therapy was initiated. Fine-needle aspiration cytology of lymph node metastases may be a viable option in evaluating further therapeutic alternatives.

Noninvasive Verification of a Very Small Intraocular Prostate Carcinoma Metastasis by 68Ga-PSMA-11 PET/CT.

ABSTRACT: A male patient underwent 68Ga-PSMA-11 PET/CT for the evaluation of a suspected intraocular metastasis in the right eye. Although the choroidal thickening was very small (4 × 2 mm), and ophthalmoscopy as well as MRI were inconclusive, PET/CT imaging showed distinct PSMA expression in the suspected lesion, confirming prostate cancer metastasis. The ability of dedicated PSMA ligand PET/CT imaging to detect small metastases, even with 68Ga-labeled ligands, has been demonstrated. Therefore, the use of further invasive diagnostic procedures could be avoided. Thus, the possibility of detecting intraocular metastases of prostate cancer should be considered in routine PET/CT imaging.

Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification.

Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.

Clinical Results of Transarterial Radioembolization (TARE) with Holmium-166 Microspheres in the Multidisciplinary Oncologic Treatment of Patients with Primary and Secondary Liver Cancer.

Holmium-166 microspheres are used for the transarterial radioembolization (TARE) treatment of primary and secondary liver cancers. In this study, its efficacy regarding local tumor control and integration into the oncological treatment sequence of the first 20 patients treated in our institution were examined. A total of twenty-nine 166Ho-TARE procedures were performed to treat hepatocellular carcinoma (HCC, fourteen patients), metastatic colorectal cancer (mCRC, four patients), intrahepatic cholangiocarcinoma (ICC, one patient), and hemangioendothelioma of the liver (HE, one patient). In eight patients, 166Ho-TARE was the initial oncologic treatment. In patients with HCC, the median treated-liver progression-free survival (PFS), overall PFS, and overall survival after 166Ho-TARE were 10.3, 7.3, and 22.1 months; in patients with mCRC, these were 2.6, 2.9, and 20.6 months, respectively. Survival after 166Ho-TARE in the patients with ICC and HE were 5.2 and 0.8 months, respectively. Two patients with HCC were bridged to liver transplantation, and one patient with mCRC was downstaged to curative surgery. In patients with HCC, a median treatment-free interval of 7.3 months was achieved. In line with previous publications, 166Ho-TARE was a feasible treatment option in patients with liver tumors, with favorable clinical outcomes in the majority of cases. It was able to achieve treatment-free intervals, served as bridging-to-transplant, and did not prevent subsequent therapies.

The effect of butylscopolamine on [18F]FDG uptake in the gastrointestinal tract is negligible and regionally variable.

BACKGROUND: Butylscopolamine (or hyoscine butylbromide, trade name Buscopan®) is occasionally administered as a premedication to reduce non-specific FDG uptake in the gastrointestinal tract based on its antiperistaltic effect. To date, there are no consistent recommendations for its use. The aim of this study was to quantify the reduction in intestinal and non-intestinal uptake by butylscopolamine administration and to derive relevance for clinical evaluation. RESULTS: 458 patients (PET/CT for lung cancer) were retrospectively reviewed. 218 patients with butylscopolamine and 240 patients without butylscopolamine had comparable characteristics. While the SUVmean in the gullet/stomach and small intestine was significantly reduced with butylscopolamine, the colon and rectum/anus showed no difference. The liver and salivary glands showed a reduced SUVmean, while skeletal muscle and blood pool were unaffected. An effect of butylscopolamine was particularly evident in men and patients under 65 years of age. There was no difference in the perceived confidence in the assessment of intestinal findings in the subjective evaluation, although in the butylscopolamine group further diagnostics appeared advisable more frequently. CONCLUSIONS: Butylscopolamine reduces gastrointestinal FDG accumulation only in selected segments and, despite a significant effect, only to a small extent. A general recommendation for the use of butylscopolamine cannot be derived from these results, its use for specific issues could be considered individually.

Medical Students' and Radiology Technician Trainees' eHealth Literacy and Hygiene Awareness-Asynchronous and Synchronous Digital Hand Hygiene Training in a Single-Center Trial.

Next to the known nosocomial infections, the COVID-19 pandemic was an example for the need for the immediate implementation of functioning hygiene concepts and knowledge transfer. The aim of this study was to evaluate the self-assessment of ehealth literacy in terms of finding, using and critically evaluating health information and theoretical and practical hygiene awareness on a voluntary participation basis at the Jena University Hospital in 2022. The well-established and validated eHEALS and WHO questionnaire on hand hygiene (HH) knowledge for healthcare workers was completely filled by 204 participants (191 medical students; 13 healthcare trainees). In a second step, after the questionnaire, 77 participants completed additional asynchronous, digitally guided self-training using DesiCoach 2Go. In the end, a synchronous hand disinfection was carried out in the hospital using Visirub, by separating it into a group without (n = 191; with and without HH questionnaire) and a group with (n = 31; with HH questionnaire) previously completed self-training. For the eHL, the respondents tended to have a positive self-assessment of finding, using and critically evaluating health information. The voluntary participants of the practical hand disinfection who had received self-training were able to achieve significantly better results (p = 0.0047), resulting in fewer wetting gaps in a subsequent performance with Visirub than those who had not received digital self-training. The survey showed that healthcare-related participants belonging to the "digital native" generation have above-average knowledge on HH and profit by digitally guided self-training.

PET/CT of the Spleen with Gallium-Oxine-Labeled, Heat-Damaged Red Blood Cells: Clinical Experience and Technical Aspects.

Several scintigraphic techniques have been supplemented or replaced by PET/CT methods because of their superior sensitivity, high resolution, and absolute activity quantification capability. The purpose of this project was the development of a PET tracer for splenic imaging, its radiopharmaceutical validation, and its application in selected patients in whom unclear constellations of findings could not be resolved with established imaging methods. Heat-damaged red blood cells (RBCs) were labeled with [68Ga]gallium-oxine, which was produced from [68Ga]gallium and 8-Hydroxyquinoline (oxine) on an automated synthesizer. Ten patients underwent [68Ga]gallium-oxine-RBC-PET/CT for the classification of eleven unclear lesions (3 intra-, 8 extrapancreatic). [68Ga]gallium-oxine and [68Ga]gallium-oxine-labeled RBCs could be synthesized reproducibly and reliably. The products met GMP quality standards. The tracer showed high accumulation in splenic tissue. Of the 11 lesions evaluated by PET/CT, 3 were correctly classified as non-splenic, 6 as splenic, 1 as equivocal, and 1 lesion as a splenic hypoplasia. All lesions classified as non-splenic were malignant, and all lesions classified as splenic did not show malignant features during follow-up. PET/CT imaging of the spleen with [68Ga]gallium-oxine-labeled, heat-damaged RBCs is feasible and allowed differentiation of splenic from non-splenic tissues, and the diagnosis of splenic anomalies.

Optimization of Thyroid Volume Determination by Stitched 3D-Ultrasound Data Sets in Patients with Structural Thyroid Disease.

Ultrasound (US) is the most important imaging method for the assessment of structural disorders of the thyroid. A precise volume determination is relevant for therapy planning and outcome monitoring. However, the accuracy of 2D-US is limited, especially in cases of organ enlargements and deformations. Software-based "stitching" of separately acquired 3D-US data revealed precise volume determination in thyroid phantoms. The purpose of this study is to investigate the feasibility and accuracy of 3D-US stitching in patients with structural thyroid disease. A total of 31 patients from the clinical routine were involved, receiving conventional 2D-US (conUS), sensor-navigated 3D-US (3DsnUS), mechanically-swept 3D-US (3DmsUS), and I-124-PET/CT as reference standard. Regarding 3DsnUS and 3DmsUS, separately acquired 3D-US images (per thyroid lobe) were merged to one comprehensive data set. Subsequently, anatomical correctness of the stitching process was analysed via secondary image fusion with the I-124-PET images. Volumetric determinations were conducted by the ellipsoid model (EM) on conUS and CT, and manually drawn segmental contouring (MC) on 3DsnUS, 3DmsUS, CT, and I-124-PET/CT. Mean volume of the thyroid glands was 44.1 ± 25.8 mL (I-124-PET-MC = reference). Highly significant correlations (all p < 0.0001) were observed for conUS-EM (r = 0.892), 3DsnUS-MC (r = 0.988), 3DmsUS-MC (r = 0.978), CT-EM (0.956), and CT-MC (0.986), respectively. The mean volume differences (standard deviations, limits of agreement) in comparison with the reference were -10.50 mL (±11.56 mL, -33.62 to 12.24), -3.74 mL (±3.74 mL, -11.39 to 3.78), and 0.62 mL (±4.79 mL, -8.78 to 10.01) for conUS-EM, 3DsnUS-MC, and 3DmsUS-MC, respectively. Stitched 3D-US data sets of the thyroid enable accurate volumetric determination even in enlarged and deformed organs. The main limitation of high time expenditure may be overcome by artificial intelligence approaches.

Warthin-Like Papillary Thyroid Microcarcinoma With Coincidental Ipsilateral Warthin Tumor of the Parotid Gland Detected on 131 I-SPECT/US and 18 F-PET/US Fusion Imaging.

ABSTRACT: A 66-year-old woman was referred with an incidental finding of a bilateral papillary thyroid microcarcinoma after thyroidectomy. On the right side, a Warthin-like variant was observed. After radioiodine therapy, whole-body scan revealed an unclear iodine uptake on the right-sided neck. For further clarification, 131 I-SPECT/US and 18 F-PET/US fusion imaging were performed, unambiguously revealing iodine and glucose uptake within a hypoechoic lesion located in the parenchyma of the right parotid gland. Surgical excision confirmed a Warthin tumor ipsilateral to the Warthin-like variant of the papillary thyroid microcarcinoma. Because the extensive imaging, targeted minimal-invasive surgery was possible.

Excellent Response to Multimodal Therapy Approach in Hyperfunctioning Metastatic Follicular Thyroid Carcinoma Diagnosed on 123 I-SPECT/Ultrasound Fusion Imaging.

ABSTRACT: An 83-year-old woman presented with new-onset hyperthyroidism and suspicious thyroid nodules on ultrasound (US). Conventional 99m TcO 4 thyroid scintigraphy showed hyperfunctioning areas that could not be clearly assigned to the US findings. With the aid of 123 I-SPECT/US fusion imaging, suspicious nodules were unambiguously identified as autonomously hyperfunctioning lesions. Additional 123 I whole-body scan revealed iodine-avid lymphonodular and pulmonal metastases. Clinical diagnosis of hormone-active thyroid carcinoma was made and histologically confirmed. Because of significant hyperthyroidism as well as multiple partially iodine-negative metastases, a multimodal treatment regime consisting of 131 I radioiodine therapy, surgery, and radiation therapy was conducted, leading to almost complete remission.

Synchronous Metastatic Medullary Thyroid Carcinoma and Paraesophageal Parathyroid Adenoma Detected on 18 F-Ethylcholine PET/US Fusion Imaging.

ABSTRACT: An 80-year-old woman with osteoporosis without fractures was referred with asymptomatic primary hyperparathyroidism and elevated calcitonin level. Ultrasound, 99m Tc-pertechnetate scintigraphy, 99m Tc-MIBI scintigraphy, and CT revealed a suspicious thyroid nodule and enlarged submandibular lymph nodes. However, no parathyroid adenoma was depictable. 18 F-choline PET/CT showed increased uptake of the proximal esophagus, but neither CT nor US revealed a parathyroid lesion, and only 18 F-choline PET/US fusion imaging confirmed a paraesophageal parathyroid adenoma. Resection of both medullary thyroid carcinoma and ectopic parathyroid adenoma through a single cervicotomy was conducted (thyroidectomy, neck dissection, extirpation of parathyroid adenoma); parathyroid hormone and calcitonin dropped to normal. Multiple endocrine neoplasia IIa syndrome was suspected.

Introducing a Pole Concept for Nodule Growth in the Thyroid Gland: Taller-than-Wide Shape, Frequency, Location and Risk of Malignancy of Thyroid Nodules in an Area with Iodine Deficiency.

Purpose: (i) To examine the criterion taller-than-wide (TTW) for the sonographic assessment of thyroid nodules in areas of iodine deficiency in terms of frequency, anatomical distribution within the thyroid gland and risk of malignancy. (ii) To develop a model for nodule growth in the thyroid gland. Methods: German multicenter study consisting of two parts. In the prospective part, thyroid nodules were sonographically measured in all three dimensions, location within the thyroid gland and contact to a protrusion-like formation (horn) in the dorsal position of thyroid gland was noted. In addition, further sonographic features such as the composition, echogenity, margins and calcifications were investigated. All nodules from the prospective part were assessed for malignancy as part of clinical routine at the decision of the treating physician adhering to institutionally based algorithms. In the retrospective part, only nodules with fine needle aspiration and/or histology were included. The risk of malignancy in TTW nodules was determined by correlating them with cyotological and histological results. Results: Prospective part: out of 441 consecutively evaluated thyroid nodules, 6 were found to be malignant (1.4%, 95% CI 0.6-2.7%). Among the 74 TTW nodules (17%), 1 was malignant (1%, 95% CI 0-4%). TTW nodules were more often located in the dorsal half of the thyroid than non-TTW nodules (factor 2.3, p = 0.01, 95% CI 2.1-2.5) and more often located in close proximity to a horn than non-TTW nodules (factor 3.0, p = 0.01, 95% CI 2.4-3.8). Retrospective part: out of 1315 histologically and/or cytologically confirmed thyroid nodules, 163 TTW nodules were retrieved and retrospectively analyzed. A TTW nodule was 1.7 times more often benign when it was dorsal (95% CI 1.1-2.5) and 2.5 times more often benign when it was associated with a horn (95% CI 1.2-5.3). The overall probability of malignancy for TTW nodules was 38% (95% CI 30-46%) in this highly preselected patient group. Conclusion: TTW nodules are common in iodine deficient areas. They are often located in the dorsal half of the thyroid gland and are frequently associated with a dorsal protrusion-like formation (horn) of the thyroid. Obviously, the shape of benign nodules follows distinct anatomical preconditions within the thyroid gland. The frequency of TTW nodules and their predominant benignity can be explained by a pole concept of goiter growth. The difference between the low malignancy risk of TTW nodules found on a prospective basis and the high risk found retrospectively may be the result of a positive preselection in the latter.