Review of clinical and diagnostic imaging of the thymus: from age-related changes to thymic tumors and everything in between.

The thymus, a primary lymphoid organ of the immune system, undergoes several changes due to a variety of reasons, ranging from aging to pathological conditions. These changes can make distinguishing between benign and neoplastic changes in the thymus challenging, thereby complicating the histopathological diagnoses of thymic tumors. Moreover, most patients with thymic tumors are asymptomatic at the time of diagnosis. Therefore, imaging plays an extremely important role in the evaluation of thymic lesions. In this review, we introduced the imaging characteristics of the thymus, ranging from benign findings, such as normal maturation and benign lesions, to neoplasms.

The thymus: what's normal and what's not? Problem-solving with MRI.

Anterior mediastinal masses can be difficult to characterise on computed tomography (CT) due to the wide spectrum of normal appearances of thymic tissue as well as the challenge of differentiating between benign and malignant pathologies. Additionally, attenuation of cystic mediastinal lesions can be misinterpreted on CT due to varying attenuation values. Anecdotally, non-vascular magnetic resonance imaging (MRI) of the thorax is underutilised across radiology departments in the UK, but has been shown to improve diagnostic certainty and reduce unnecessary surgical intervention. T2-weighted MRI is useful in confirming the cystic nature of lesions, whereas chemical shift techniques can be utilised to document the presence of macroscopic and intra-cellular fat and thus help distinguish between benign and malignant pathologies. In this review article, we present a practical approach to using MRI for the characterisation of anterior mediastinal lesions based on our clinical experience in a UK district general hospital.

Predicting model of mild and severe types of COVID-19 patients using Thymus CT radiomics model: A preliminary study.

OBJECTIVE: To predict COVID-19 severity by building a prediction model based on the clinical manifestations and radiomic features of the thymus in COVID-19 patients. METHOD: We retrospectively analyzed the clinical and radiological data from 217 confirmed cases of COVID-19 admitted to Xiangyang NO.1 People's Hospital and Jiangsu Hospital of Chinese Medicine from December 2019 to April 2022 (including 118 mild cases and 99 severe cases). The data were split into the training and test sets at a 7:3 ratio. The cases in the training set were compared in terms of clinical data and radiomic parameters of the lasso regression model. Several models for severity prediction were established based on the clinical and radiomic features of the COVID-19 patients. The DeLong test and decision curve analysis (DCA) were used to compare the performances of several models. Finally, the prediction results were verified on the test set. RESULT: For the training set, the univariate analysis showed that BMI, diarrhea, thymic steatosis, anorexia, headache, findings on the chest CT scan, platelets, LDH, AST and radiomic features of the thymus were significantly different between the two groups of patients (P < 0.05). The combination model based on the clinical and radiomic features of COVID-19 patients had the highest predictive value for COVID-19 severity [AUC: 0.967 (OR 0.0115, 95%CI: 0.925-0.989)] vs. the clinical feature-based model [AUC: 0.772 (OR 0.0387, 95%CI: 0.697-0.836), P < 0.05], laboratory-based model [AUC: 0.687 (OR 0.0423, 95%CI: 0.608-0.760), P < 0.05] and model based on CT radiomics [AUC: 0.895 (OR 0.0261, 95%CI: 0.835-0.938), P < 0.05]. DCA also confirmed the high clinical net benefits of the combination model. The nomogram drawn based on the combination model could help differentiate between the mild and severe cases of COVID-19 at an early stage. The predictions from different models were verified on the test set. CONCLUSION: Severe cases of COVID-19 had a higher level of thymic involution. The thymic differentiation in radiomic features was related to disease progression. The combination model based on the radiomic features of the thymus could better promote early clinical intervention of COVID-19 and increase the cure rate.

Diagnostic approach for mediastinal masses with radiopathological correlation.

PURPOSE: Mediastinal masses have various histopathological and radiological findings. Although lymphoma is the most common type of tumor, thymic epithelial and neurogenic tumors are common in adults and children, respectively, but several other types are difficult to distinguish. No previous review has simply and clearly shown how to differentiate mediastinal masses. METHOD: We conducted a review of the latest mediastinal classifications and mass differentiation methods, with a focus on neoplastic lesions. Both older and recent studies were searched, and imaging and histopathological findings of mediastinal masses were reviewed. Original simple-to-use differentiation flowcharts are presented. RESULTS: Assessing localizations and internal characteristics is very important for mediastinal mass differentiation. The mass location and affected organ/tissue should be accurately assessed first, followed by more qualitative diagnosis, and optimization of the treatment strategy. In 2014, the International Thymic Malignancy Interest Group presented a new mediastinal clinical classification. In this classification, mediastinal masses are categorized into three groups according to location: prevascular (anterior)-, visceral (middle)-, and paravertebral (posterior)-compartment masses. Then, the internal characteristics and functional images are evaluated. CONCLUSIONS: Differentiation of mediastinal masses is very difficult. However, if typical imaging findings and clinical characteristics are combined, reasonable differentiation is possible. In each patient, proper differential diagnosis may contribute to better treatment selection.

Finding the best method for screening for gestational diabetes mellitus: fetal thymic-thoracic ratio or fetal thymus transverse diameter.

OBJECTIVE: The aim of this study was to compare the efficiency of fetal thymic-thoracic ratio and fetal thymus transverse diameter measurements in gestational diabetes mellitus. METHODS: Fetal thymic-thoracic ratio and fetal thymus transverse diameter were assessed in 360 pregnant women. Patients were examined in two groups: 180 gestational diabetes mellitus (study group) and 180 healthy pregnant women (control group). RESULTS: There were no statistically significant differences between the cases with gestational diabetes mellitus and the control group in terms of fetal thymus transverse diameter; however, the fetal thymic-thoracic ratio was found to be significantly lower in cases with gestational diabetes mellitus compared to that in the control group (p<0.001). CONCLUSION: The fetal thymic-thoracic ratio is superior to the fetal thymus transverse diameter in evaluating the fetal thymus size.

Radiología de las tumoraciones palpables en el paciente pediátrico. Parte 2 / Imaging palpable tumors in pediatrics: Part 2

Las tumoraciones palpables en los niños son un motivo de consulta muy habitual para el radiólogo. El origen de las lesiones es muy variado, y algunas de ellas no reciben atención en los libros clásicos de Radiología, pese a encontrarse frecuentemente.El objetivo de esta serie de 2 artículos es revisar las características clínico-radiológicas de una selección de estas entidades que consideramos importante conocer. (AU)

Palpable tumors in children are a common reason for consulting a radiologist. The origin of these lesions varies widely, and although they are common, classic radiology books do not cover some of them.This series of two articles aims to review the clinical and radiological characteristics of a selection of palpable tumors in children that radiologists need to be familiar with. (AU)

Evaluation of thymic dimensions in patients with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome (MIS-C) is the most important complication of COVID-19 in the pediatric population. Unfortunately, this problem is an unpredictable situation in patients with COVID-19. We aimed to evaluate the effects of MIS-C on thymus dimensions in pediatric patients. METHODS: We retrospectively analyzed the files of 368 pediatric patients aged 2-18 years, who were diagnosed with COVID-19. Computer Tomography (CT) images of 22 patients diagnosed with COVID-19 and 10 patients diagnosed with MIS-C were evaluated in detail by two board-certified radiologists. Eighteen age and sexmatched patients who applied to the emergency department of our hospital for any reason and had a CT scan for any reason were selected as the control group. The data of both groups were statistically compared. RESULTS: Considering the differences between the groups in terms of laboratory data, monocytes, hemoglobin, and platelet were significantly lower in the MIS-C group than the other groups. Procalcitonin, C- reactive protein, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and proBNP levels were statistically significantly higher in the MIS-C group compared to the other groups Regarding the differences in thymus dimensions, thymus AP diameter, transverse diameter, length, thickness, and volume were significantly higher in the MIS-C group than in the other groups There was a significant positive correlation between the transverse diameter of the thymus and CRP, procalcitonin, pro-brain natriuretic peptide (proBNP), and NLR levels. CONCLUSIONS: Our study shows that thymus dimensions and acute phase reactants are higher in pediatric patients in the MIS-C group. Also, thymus transverse diameter, thymus thickness, and PLR values pose a risk for the development of MIS-C. More research is needed on the role of the thymus gland in the pathogenesis and diagnosis of MIS-C.

Intrathyroidal ectopic thymus: an important entity in the differential diagnosis of thyroid nodules.

BACKGROUND: Intrathyroidal ectopic thymus (IET), a benign lesion due to aberrant thymic migration during embryogenesis, is often discovered incidentally. We aimed to present the ultrasound (US) features, diagnostic methods, and follow-up of IET in children and adolescents. METHODS: We searched our database of patients with a nodular thyroid lesion detected by US, between January 2007 and December 2019. In 30/255 (11.7%), IET was diagnosed. RESULTS: The study included 30 patients (20 males/10 females), mean age 5 years (0.1-12.2, median 5.6) with 34 lesions diagnosed by US as `incidentalomas.` None of the patients had palpable nodules. On US, IET appeared as a hypoechoic lesion, with multiple punctuate internal echoes. 29/34 of lesions had well-defined margins. The most common location of IET was in the middle part (27/34) of the left lobe (19/34). The mean longest diameter at diagnosis was 6.4 mm (2.5-21, median 4.5). Sonographic follow-up was available in 25 patients with 27 lesions. The mean time of observation was 2.7 years (0.3-7.5, median 2.1). While 13/27 cases showed decreased size or regression during follow-up, the other 13 increased in size, and there was no change in size in one. Pubertal progression was associated with both increment and decrease in size of IET. Fine needle aspiration (FNA) was performed in 5 patients and surgery in one. CONCLUSIONS: IET should be considered in the differential diagnosis of pediatric thyroid nodules as a cause of FNA and/or surgery. Regular US monitoring can be used safely in the follow-up of this lesion. We present one of the largest series in the literature with long-term follow-up and description of patients` pubertal status. IET prevalence was 11.7% among children and adolescents with a nodular thyroid lesion, higher than that stated in the literature.

Evaluation of age-related thymic changes using computed tomography images: A retrospective observational study.

We aimed to investigate if Computed tomography (CT) attenuation values can help improve the identification of age-related changes in the thymus. We assessed CT images of 405 patients aged 0 to 80 years. We measured the area of the anterior mediastinum at the level of the carina and its average CT attenuation value. We evaluated the thymic area, the ratio of the thymus area to the total thoracic area, and the CT attenuation value. Additionally, we evaluated changes in the thymus area in the 0 to 13-year age group. The area of the thymus decreased from birth to the middle 20s. After the middle 20s, the area tended to increase and plateau till after 50 years of age. The ratio of the thymic area to the thoracic area decreased from age 0 to 20 years, but remained stable after 20 years of age. The CT attenuation values were stable from birth to puberty, decreased after puberty, and were stable again in the late 50s and beyond. The thymus of children showed mass formation, but the shape changed with age. No significant differences in the CT attenuation value were found across underlying conditions for the 0 to 13-year age group. The decrease in the CT attenuation values, observed with advancing age, reflects adipose degeneration of the thymus, indicating that by the late 50s, thymic tissue is replaced completely by adipose tissue. Our data suggest that adipose degeneration of the thymus begins after puberty and advances with age.

[Therapeutic approach to massive thymic hyperplasia associated with respiratory distress syndrome in a newborn infant living in a developing country: a case report]. / Stratégie thérapeutique devant une hyperplasie thymique massive associée à un syndrome de détresse respiratoire chez un nouveau-né dans un pays en voie de développement: à propos d'un cas.

Thymic hyperplasia is an anterior mediastinal mass with a variable clinical presentation. It causes differential diagnostic problems in the pediatric age group and there is no consensus on the therapeutic approach. We here report the case of a 1-month-old infant treated for respiratory distress syndrome. Chest CT scan revealed anterior mediastinal mass, which was excised through median sternotomy. Anatomopathological examination showed thymic hyperplasia. Clinical outcome was satisfactory. This encouraging result suggests that, contrary to what some authors propose, it would be more appropriate to opt for an aggressive therapeutic strategy when managing symptomatic thymic hyperplasia. This is even more justified in a socio-economic context characterised by difficult access to care and follow-up measures limited by patients' means.

Ultrasonographic evaluation of the fetal thymic-thoracic ratio and its association with conotruncal heart defects.

OBJECTIVE: To evaluate the thymic-thoracic ratio (TT ratio) on fetal ultrasound and its association with conotruncal heart defects. METHODS: A case control study was carried out to retrospectively assess the TT ratio on fetal echocardiograms performed between 19 and 39 weeks of gestation, showing congenital heart defects, from January to December 2018. The control group was comprised of fetuses with no echocardiogram evidence of congenital cardiac malformations. Cases of multiple pregnancies and patients where the TT ratio could not be established have been excluded. RESULTS: A total of 338 pregnancies have been analysed. Fifty-two pregnancies were diagnosed with fetal heart defects (15%), 17 of which showed conotruncal heart defects (32.7%). The TT ratio in normal fetuses (286 pregnancies) increased with gestational age, and had an average of 0.43 ± 0.06. Compared to the control group (normal fetuses), fetuses with conotruncal heart defects had significantly lower mean TT ratio (0.33 ± 0.07). Those that were diagnosed with nonconotruncal heart defects did not show any statistically significant difference in the TT ratios compared with the control group (0.40 ± 0.09 vs. 0.43 ± 0.06, respectively). CONCLUSION: The TT ratio was significantly lower in fetuses with conotruncal heart defects compared with both the control group (normal fetuses) and the fetuses with nonconotruncal heart defects.

Influence of Covid-19 infection on fetal thymus size after recovery.

OBJECTIVES: To investigate the long-term effects of the SARS-CoV-2 infection on the fetal immune system by fetal thymus size measurements with ultrasound (USG). METHODS: This prospective study was conducted in the Turkish Ministry of Health Ankara City Hospital between November 1, 2020 and April 1, 2021, with recovered, pregnant women, four weeks after they had been confirmed for the SARS-CoV-2 infection by real-time polymerase-chain-reaction (RT-PCR). COVID-19 recovered (CR) pregnant women compared with age-matched pregnant controls in terms of demographic features, fetal thymic-thoracic ratio (TTR), and laboratory parameters. RESULTS: There was no difference in demographic features between the two groups. TTR found significantly lower in the CR group than the control group (p=0.001). The fetal TTR showed a significant and moderate correlation with maternal monocyte counts, monocyte to lymphocyte ratio (MLR), and red cell distribution width (RDW); while it did not correlate with lymphocyte counts, c-reactive protein (CRP), and procalcitonin levels. CONCLUSIONS: The 2019 novel coronavirus disease (COVID-19) reduces fetal thymus size in pregnant women with mild or moderate symptoms after recovery from the infection.

Impact of antenatal corticosteroid exposure on thymus size in premature infants.

BACKGROUND: This study examined the effect of corticosteroids on the thymic index (TI) and the thymus/weight index (TWI) in infants exposed to antenatal corticosteroids (ACS). METHODS: This prospective study was conducted between August 2014 and October 2018. A thymus ultrasound was performed to assess thymus size on the second day of life. Thymus size was assessed as TI and TWI. RESULTS: In total, 167 neonates (≤34 weeks gestation)  constituted the study population, including 94 ACS-exposed infants and 73 untreated infants. The treatment group exhibited significantly lower birth weight and significantly shorter birth length than the ACS (-) group. Therefore, TI was smaller in the treatment group than in the untreated group (6.96 ± 4.05 cm3 vs. 5.64 ± 3.39 cm3). The TWI was 3.69 ± 1.8 cm3/kg in the ACS (-) group versus 3.32 ± 1.56 cm3/kg in the ACS (+) group. The median anteroposterior diameter of the right lobe was 1.33 cm (range, 0.45-2.40) in the ACS (-) group compared to 1.15 cm (range, 0.47-2.40) in the ACS (+) group. The median anteroposterior diameter of the left lobe was 1.40 cm (range, 0.43-2.20) in the ACS (-) group and 1.19 cm (range, 0.32-2.36) in the ACS (+) group. The median largest sagittal area was 2.64 cm2 (range, 0.5-5.46) in the ACS (-) group versus 2.20 cm2 (range, 0.55-5.90) in the ACS (+) group. CONCLUSION: We found that TWI was not significantly changed by ACS exposure in premature infants.

First trimester fetal thymus volume may predict preeclampsia.

OBJECTIVE: The immunological factors have role in the development of preeclampsia. The thymus is one of the main organs of the fetal immune system. The aim of this prospective clinical study was to investigate the association between fetal thymus volume and preeclampsia by adding the 3-dimensional measurement of thymus volume to the routine fetal ultrasound scan at 11-14 week of gestation. STUDY DESIGN: Totally 72 pregnant women in their first trimester of pregnancy were included and 3-D fetal thymus volume was measured with sonographic VOCAL programme. All women gestational period was followed. The data of women with preeclampsia (n = 10, study group) and without preeclampsia (n = 62, control group) were compared. MAIN OUTCOME MEASURES: Fetal thymus volume, preeclampsia development. RESULTS: Fetal thymus volume, mean gestational age at birth and newborn birthweight were found to be statistically lower in cases with preeclampsia compared with those without any complications. When the fetal thymus volume measured by the VOCAL programme in the study group was used as a marker for preeclampsia development, the limit value was 0.0375 cm3; sensitivity was 87.1% and specificity was 50% (AUC 85.3%, P < .001, 95% CI 0.751-0.949). As a result of binary logistic regression analysis; the low fetal thymus volume measured at 11-14 gestational weeks can be used as a predictive factor for preeclampsia (P < .001). CONCLUSIONS: According to the results of this study; the development of preeclampsia may be predicted by measuring 3-D fetal thymus volume at the first trimester.

CT texture analysis in evaluation of thymic tumors and thymic hyperplasia: correlation with the international thymic malignancy interest group (ITMIG) stage and WHO grade.

OBJECTIVES: To evaluate the effectiveness of CT texture analysis (CTTA) in (1) differentiating Thymoma (THY) from thymic hyperplasia (TH) (2) low from high WHO grade, and (3) low from high Masaoka Koga (MK)/International Thymic Malignancy Interest Group (ITMIG) stages. METHODS: After institute ethical clearance, this cross-sectional study analyzed 26 patients (THY-18, TH-8) who underwent dual energy CT (DECT) and surgery between January 2016 and December 2018. CTTA was performed using TexRad (Feedback Medical Ltd., Cambridge, UK- www.fbkmed.com) by a single observer. Free hand regions of interest (ROIs) were placed over axial sections where there was maximum enhancement and homogeneity. Filtration histogram was used to generate six first-order texture parameters [mean, standard deviation (SD), mean of positive pixels (MPP), entropy, skewness, and kurtosis] at six spatial scaling factors "SSF 0, 2, 3, 4, 5, and 6". Mann-Whitney test was applied among various categories and p value < 0.05 was considered significant. Three-step feature selection was performed to determine the best parameters among each category. RESULTS: The best performing parameters were (1) THY vs TH- Mean at "SSF 0" (AUC: 0.8889) and MPP at "SSF 0" (AUC: 0.8889), (2) Low vs high WHO grade - no parameter showed statistical significance with good AUC, and (3) Low vs high MK/ITMIG stage- SD at "SSF 6" (AUC: 0.8052 and 0.8333 respectively]). CONCLUSION: CTTA revealed several parameters with excellent diagnostic performance in differentiating thymoma from thymic hyperplasia and MK/ITMIG high vs low stages. CTTA could potentially serve as a non-invasive tool for this stratification. ADVANCES IN KNOWLEDGE: This study has employed texture analysis, a novel radiomics method on DECT scans to determine the best performing parameter and their corresponding cut-off values to differentiate among the above-mentioned categories. These new parameters may help add another layer of confidence to non-invasively stratify and prognosticate patients accurately which was only previously possible with a biopsy.

Quantitative Histogram Analysis of T2-Weighted and Diffusion-Weighted Magnetic Resonance Images for Prediction of Malignant Thymic Epithelial Tumors.

PURPOSE: To assess the value of histogram analysis for differentiating a high-risk thymic epithelial tumor (TET) from a low-risk TET using T2-weighted images and the apparent diffusion coefficient (ADC). METHODS: Forty-nine patients with histopathologically proven TET after thymectomy were enrolled in this study and retrospectively classified as having low-risk TET (low-risk thymoma) or high-risk TET (high-risk thymoma or thymic carcinoma). Twelve parameters were obtained from the quantitative histogram analysis. The histogram parameters were compared using the Mann-Whitney U test. Diagnostic efficacy was estimated by receiver-operating characteristic curve analysis. RESULTS: Twenty-five patients were classified as having low-risk TET and 24 as having high-risk TET. The mean ADC value showed diagnostic efficacy for differentiating high-risk TET from low-risk TET, with an area under the curve of 0.7, and was better than when using conventional methods alone. CONCLUSION: The ADC-based histogram analysis could help to differentiate between high-risk and low-risk TETs.

Tumor immunity is related to 18 F-FDG uptake in thymic epithelial tumor.

BACKGROUND: 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18 F-FDG) positron emission tomography (18 F-FDG-PET) is a convenient modality to assess the metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18 F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18 F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs. METHODS: A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18 F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C, and ß2 adrenergic receptor. RESULTS: High uptakes of SUVmax , SUVmean , MTV, and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%), and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS (performance status) of 1-2, thymic carcinoma, and advanced stage, and SUVmax on 18 F-FDG uptake displayed a close association with PD-L1 and PD-L2 expressions, but not with MTV and TLG. Our analysis revealed that SUVmax was identified as being significant relationship for positive PD-L1/PD-L2 expression. GLUT1, HIF-1α, and VEGFR2 were significantly associated with the expression of PD-L1/PD-L2 from the biological viewpoint. CONCLUSION: 18 F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect the glucose metabolism and hypoxia in thymic tumor cells.