Diagnosis Of Thymic Epithelial Tumors Research Articles

A diagnostic model based on 18F-FDG PET/CT parameters in improving the differential diagnosis of invasive thymic epithelial tumors and anterior mediastinal lymphomas

BackgroundAccurately distinguishing between invasive thymic epithelial tumors (TETs) and anterior mediastinal lymphoma before surgery is crucial for subsequent treatment choices. But currently, the diagnosis of invasive TET is sometimes difficult to distinguish from anterior mediastinal lymphoma.ObjectiveTo assess the application of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) in the differential diagnosis of TETs and anterior mediastinal lymphomas.Methods18F-FDG PET/CT images of 133 invasive TETs and anterior mediastinal lymphomas patients were retrospectively analyzed. In particular, the tumor’s longest diameter and maximum standardized uptake value (SUVmax) were evaluated. The SUVmax and longest diameter values of the two groups were analyzed by using the receiver operating characteristic (ROC) curve to determine the optimal threshold and diagnostic efficiency.ResultsAge, myasthenia gravis, SUVmax and tumor longest diameter differed significantly between invasive TETs and anterior mediastinal lymphomas patients. The tumor location, calcification, relationship with adjacent vessels and distant metastasis differed significantly between the groups. The ROC analysis showed an AUC for SUVmax and tumor longest diameter of 0.841 and 0.737. Respectively, the cutoff values with the best diagnostic performance were 9.65 (sensitivity: 77.78%, specificity: 81.97%) and 6.65 (sensitivity: 80.56%, specificity: 62.30%) for SUVmax and tumor longest diameter. The diagnostic model of SUVmax, calcification, relationship with surrounding blood vessels, lymph node metastasis and lung metastasis in the highest AUC of 0.935 (sensitivity: 90.16%, specificity: 88.89%). In addition, we incorporated splenic involvement and metastatic sub-diaphragmatic lymph node into Model 2 as a new predictive model 3 for differential diagnosis and found a significant improvement in the diagnostic performance of Model 3.ConclusionThe diagnostic model composed of 18F-FDG PET parameters is improving the differential diagnosis of invasive TETs and anterior mediastinal lymphomas.

Cine MR feature tracking analysis for diagnosing thymic epithelial tumors: a feasibility study

BackgroundTo assess the feasibility of the cine MR feature tracking technique for the evaluation of cardiovascular-induced morphological deformation in the diagnosis of thymic epithelial tumors (TETs).MethodsOur study population consisted of 43 patients with pathologically proven TETs including 10 low-grade thymomas, 23 high-grade thymomas, and 10 thymic carcinomas. Cine MR images were acquired using a balanced steady-state free precession sequence with short periods of breath-hold in the axial and oblique planes in the slice with the largest lesion cross-sectional area. The tumor margin was manually delineated in the diastolic phase and was automatically tracked for all other cardiac phases. The change rates of the long-to-short diameter ratio (∆LSR) and tumor area (∆area) associated with pulsation were compared between the three pathological groups using the Kruskal–Wallis H test and the Mann–Whitney U test. A receiver-operating characteristic (ROC) curve analysis was performed to assess the ability of each parameter to differentiate thymic carcinomas from thymomas.Results∆LSR and ∆area were significantly different among the three groups in the axial plane (p = 0.028 and 0.006, respectively) and in the oblique plane (p = 0.034 and 0.043, respectively). ∆LSR and ∆area values were significantly lower in thymic carcinomas than in thymomas in the axial plane (for both, p = 0.012) and in the oblique plane (p = 0.015 and 0.011, respectively). The area under the ROC curves for ∆LSR and ∆area for the diagnosis of thymic carcinoma ranged from 0.755 to 0.764.ConclusionsEvaluation of morphological deformation using cine-MR feature tracking analysis can help diagnose histopathological subtypes of TETs and identify thymic carcinomas preoperatively.

Epigenetics of Thymic Epithelial Tumors.

Thymic epithelial tumors (TETs) arise from the epithelial cells of the thymus and consist in the 1% of all adult malignancies, despite the fact that they are the most common lesions of the anterior mediastinum. TETs can be divided mainly into thymomas, thymic carcinomas, and the rarest ad aggressive neuroendocrine forms. Despite the surgical resection is quite resolving, the diagnosis of TETs is complicated by the absence of symptoms and the clinical presentation aggravated by several paraneoplastic disorders, including myasthenia gravis. Thus, the heterogeneity of TETs prompts the search for molecular biomarkers that could be helpful for tumor characterization and clinical outcomes prediction. With these aims, several researchers investigated the epigenetic profiles of TETs. In this manuscript, we narratively review the works investigating the deregulation of epigenetic mechanisms in TETs, highlighting the need for further studies combining genetic, epigenetic, and expression data to better characterize the different molecular subtypes and identify, for each of them, the most relevant epigenetic biomarkers of clinical utility.

Multiparameter diagnostic model based on 18F-FDG PET and clinical characteristics can differentiate thymic epithelial tumors from thymic lymphomas

ObjectiveTo evaluate the diagnostic performance of combined multiparametric 18F-fluorodeoxyglucose positron emission tomography (18FDG PET) with clinical characteristics in differentiating thymic epithelial tumors (TETs) from thymic lymphomas.Patients and methodsA total of 173 patients with 80 TETs and 93 thymic lymphomas who underwent 18F-FDG PET/CT before treatment were enrolled in this retrospective study. All patients were confirmed by pathology, and baseline characteristics and clinical data were also collected. The semi-parameters of 18F-FDG PET/CT, including lesion size, SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), TLG (total lesion glycolysis), MTV (metabolic tumor volume) and SUVR (tumor-to-normal liver standard uptake value ratio) were evaluated. The differential diagnostic efficacy was evaluated using the receiver operating characteristic (ROC) curve. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI), and Delong test were used to evaluate the improvement in diagnostic efficacy. The clinical efficacy was evaluated by decision curve analysis (DCA).ResultsAge, clinical symptoms, and metabolic parameters differed significantly between patients with TETs and thymic lymphomas. The ROC curve analysis of SUVR showed the highest differentiating diagnostic value (sensitivity = 0.763; specificity = 0.888; area under the curve [AUC] = 0.881). The combined diagnostics model of age, clinical symptoms and SUVR resulted in the highest AUC of 0.964 (sensitivity = 0.882, specificity = 0.963). Compared with SUVR, the diagnostic efficiency of the model was improved significantly. The DCA also confirmed the clinical efficacy of the model.ConclusionsThe multiparameter diagnosis model based on 18F-FDG PET and clinical characteristics had excellent value in the differential diagnosis of TETs and thymic lymphomas.

The value of diffusion-weighted and dynamic contrast-enhanced imaging in the diagnosis of thymic epithelial tumors.

Background: Thymic epithelial tumors (TETs) are clinically the most frequently encountered neoplasm of the prevascular mediastinum in adults. The role of chest magnetic resonance (MR) imaging has been increasingly stressed thanks to its excellent contrast resolution, freedom from ionizing radiation, and capability to provide additional information regarding tumors' cellular structure and vascularity.Methods: This study aimed to establish the relationship between the MR findings and pathological classification of TETs, focusing on diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) imaging. This retrospective cross-sectional study included 44 TET patients who underwent chest MR scanning. The tumors were classified into three groups according to the WHO classification: low-risk thymoma (LRT), high-risk thymoma (HRT), and non-thymoma (NT). Along with morphological characteristics, the apparent diffusion coefficient (ADC) value, time-intensity curve (TIC) pattern, and time to peak enhancement (TTP) of the tumors were recorded and compared between the three groups.Results: A smooth contour and complete or almost complete capsule were suggestive of LRTs. The median ADC value of the 44 tumors was 0.95 × 10-3 mm2/sec. Among the three groups, LRTs had the highest ADC values, while NTs had the lowest. The differences between the ADC values of the three groups were statistically significant (p = 0.006). Using an ADC cutoff of 0.82 × 10-3 mm2/sec to differentiate between LRTs and tumors of the two remaining groups, the area under the curve was 0.775, sensitivity was 100%, specificity was 50%, and accuracy was 65.91%. The washout (type 3) TIC pattern was the most prevalent, accounting for 45.45% of the population; this pattern was also predominantly observed in LRTs (71.43%). Although the median TTP of LRTs was lower than that of HRTs or NTs, no statistically significant differences were found between the TTPs of the three groups (p = 0.170).Conclusions: MR is a good imaging modality to preoperatively assess TETs. Morphological features, ADC value, TIC pattern, and TTP are helpful in preoperatively predicting TET pathology.

Outcomes of thymic epithelial tumors (TETs) with pleural metastases: Real-world insight from RYTHMIC.

8578 Background: TETs are rare and potentially aggressive malignancies with high associated prevalence of autoimmune disorders (AIDs). The pleura is the main metastatic site at relapse, referred as Masaoka-Koga stage (MK) IVa. The benefit of surgical management is unknown, so we have collected outcomes of patients with MK IVa TETs in a large prospective database. Methods: RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically discuss every case of TETs. The database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in RYTHMIC national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of patients (pts) with MK IVa TETs. Results: From January 2012 to December 2019, 2909 pts were included in the database, including 182 MK IVa (6.2%). The median age at diagnosis was 63.5 (range 9 to 91). 58/182 (32%) pts reported AIDs, 76% myasthenia gravis. 129/182 pts had synchronous pleural metastasis. 118/182 (65%) tumors were resected, of them 10 (8.4%) had only pericardial metastases. Thymoma (T) B2 rate was 35.6%, B3 17.8% and thymic carcinoma (TC) 13.5%. Induction chemotherapy (CT) was given in 46 (39%) T and 10 (8%) TC with response rate of 50% and 70% respectively. Thymectomy was performed in addition to pleurectomy in 44 pts (37.2%), pericardiectomy in 68 (57.6%), lung resection in 80 (67.8%) or pneumonectomy in 15 (12.7%). Node resection was performed in 57.6% (n = 67), 12 (18%) were positive. The complete resection rate assessed by surgeons was 57% with a median of 15 (0 to 28) resected pleural metastasis. Intrapleural chemotherapy was added for 19 (16%) pts. No mortality was reported 90 days after surgery procedure. Median follow-up was 36 months. Pleural recurrence was seen in 47 (72%) pts. Median disease-free survival (DFS) was 39 vs 16 months in resected vs not resected tumors (p < 0.0001), 5-years overall survival (OS) was 88 vs 66% (p = 0.28), respectively. Risk of relapse decreased by 60% with surgery (HR = 0.4, 95CI (0.25-0.62); p < 0.0001). Conclusions: The prevalence of MK IVa in our cohort was 6.2%. Surgery appears to be a safe and valid option for pts with MK IVa TET at diagnosis.

Tumores del epitelio tímico. Timoma

Thymic epithelial tumors (TET) are rare tumors with an unknown etiology and risk factors. They have a known association with paraneoplastic syndromes, especially myasthenia gravis. Various histopathological classifications have been described, the most used of which is the World Health Organization classification. A definitive diagnosis of TET is made via a biopsy. A differential diagnosis with other tumors of the anterior mediastinum is necessary. A computerized tomography (CT) scan is the test of choice for the staging of the disease. The most used staging system is the Masaoka system, which adequately correlates with survival. Treatment of TET is based on a complete tumor resection. Radiotherapy and chemotherapy can be used as induction, adjuvant, or palliative treatment. However, optimal therapy is still a subject of debate.

Prevalence of autoimmune diseases in thymic epithelial tumors (TET) insights from RYTHMIC.

9073 Background: TET are associated with autoimmune disorders (AID) in up to 30% of patients (pts). However, there have been wide variations in the reported prevalence of AID in TET pts in small single-center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. We aimed to describe the prevalence of AID in a large French population. Methods: RYTHMIC database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in French national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of pts with TET’s related AID. Results: From January 2012 to December 2019, 2909 pts were included in the database. The mean age at diagnosis of TET was 54 and 52% were male. In the overall population, Masaoka Koga stages were well balanced with 12.6% (n = 187) stage I, 8.8% (n = 131) stage IIa, 8.4% (n = 124) stage IIb, 11.1% (n = 164) stage III and 8.5% (n = 125) stage IV. There were 364 (12.5%) events of AID in 302 pts. 62 pts (17%) had more than 1 AID. Among the events, 236 were myasthenia gravis (MG) (64.8%), 19 Hypo-gammaglobulinemia syndrome (5.2%), 15 pure red cell aplasia (4.1%), 18 thyroiditis (4.9%) and 16 systemic erythematous lupus (4.4%). Diagnosis of AID was mostly done at tumor diagnosis (n = 239, 65.7%) but some patient had AID diagnosed before diagnosis (n = 67, 18.4%) or during follow up (n = 32, 8.8%). Among pts presenting AID, B2 was the most common subtype (n = 133, 36.5%). The incidence of AID per subtype was as follow: A (n = 10/81, 12.3%), AB (n = 48/225, 21.3%), B1 (n = 35/130, 26.9%), B2 (n = 133/295, 45.0%), B3 (n = 46/113, 40.7%), thymic carcinoma (n = 16/275, 5.8%). Conclusions: The prevalence of AID in pts with TET was 12.5%, > 40% in B2 and B3 subtypes. Diagnosis of AID can be delayed compared to the diagnosis of TET. Immunotherapy indication should be carefully assessed in pts with TET other than thymic carcinoma.

Pathological discrepancies in the diagnosis of thymic epithelial tumors: the Tallinn-Lyon experience.

Thymic epithelial tumors are rare thoracic tumors for which pathological diagnosis is challenging due to the definition of multiple subtypes, tumor heterogeneity, and variations in interobserver reproducibility. In this study, we aimed at analyzing the quality of pathological reporting in line with the consistency between initial diagnosis and final diagnosis after expert review through a collaboration between the largest thoracic oncology center in Estonia, and one expert center in France. Hospital electronic database and pathology databases from the Tallinn North Estonia Medical Centre were searched for thymic and mediastinal tumors from 2010 to 2017. Pathology specimens were referred to the Pathology Department of the Lyon University hospital. Overall, 55 tissue specimens from 49 patients were included. From pathology reports, tumor size, diagnosis, and invasion had been mentioned in ≥80% of cases, while resection status and staging were assessed in only 48% and 17% of cases, respectively. The initial diagnosis was consistent with that of the review in 60% of cases. Diagnostic concordance for thymoma subtypes was low (Cohen's kappa 0.34, 95% CI: 0.16-0.52). Overall, a major change in the management of 8 (16%) patients had to be made after pathological review: 3 patients had a normal thymus according to the reference centre, while thymoma B1 or B2 had been diagnosed locally; 5 additional patients had a final diagnosis of non-thymic tumor. Implementing structured pathology reports may help to decrease discrepancies in the diagnosis of thymic epithelial tumors. The development of expert networks is an opportunity to improve diagnosis and patient care, particularly in regard to rare cancers.

Cytological and immunocytochemical diagnosis of thymic epithelial tumors

Cytological and immunocytochemical diagnosis of thymic epithelial tumors

Computed Tomography Features associated With the Eighth Edition TNM Stage Classification for Thymic Epithelial Tumors.

The eighth edition of the TNM classification of malignant tumors for the first time includes an official staging system for thymic epithelial tumors (TETs) recognized by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). Staging is critical for the management of TETs, and determining stage accurately from imaging has the potential to improve clinical outcomes. We examine preoperative computed tomography (CT) characteristics of TETs associated with AJCC/UICC pathologic TNM stage. In this retrospective study, patients were included if they met all the following criteria: (1) diagnosis of TET, (2) had primary curative intent surgery performed at Stanford University, and (3) had available preoperative CT imaging for review. Tumor pathology was staged according to the eighth edition TNM classification. Fifteen CT scan features were examined from each patient case according to the International Thymic Malignancy Interest Group standard report terms in a blinded manner. A Lasso-regularized multivariate model was used to produce a weighted scoring system predictive of pathologic TNM stage. Examining the 54 patients included, the following CT characteristics were associated with higher pathologic TNM stage when using the following scoring system: elevated hemidiaphragm (score of 6), vascular endoluminal invasion (score of 6), pleural nodule (score of 2), lobulated contour (score of 2), and heterogeneous internal density (score of 1). Area under the receiver operating characteristic curve was 0.76. TETs with clearly invasive or metastatic features seen on CT are associated with having higher AJCC/UICC pathologic TNM stage, as expected. However, features of lobulated contour and heterogeneous internal density are also associated with higher stage disease. These findings need to be validated in an independent cohort.

P2.04-007 Role of F-18-Choline Petscan in Recurrence of Thymic Epithelial Tumors (TET): Topic: Thymic Malignancies Clinical and Translational

Fluorine-18-fluorodeoxyglucose (F-18-FDG) uptake in TETs is highly variable based on histology subtype. The fluorine-18-choline (F-18-choline) PET/CT scan represents an emerging important tool in the management of tumors with low glucose metabolism. There have been few case reports describing positive choline uptakes in TETs. The aim of this study is to evaluate the clinical use of choline PET/CT in TET. We conducted a retrospective analysis of patients (pts) with diagnosis of TETs who underwent an F-18- choline PET/CT exam in the course of their disease from Jan 2012 to May 2016. Pathologic and clinical data were extracted from medical records. FDG exams with a mean standardize uptake value (SUV) higher than 4.5 and choline exams with uptake more than two times the physiologic value, were considered as positive. A total of 10 pts were included for analyses. Among them, 8 pts were males; median age was 43 years [32-62], 8 pts presented an autoimmune disorder (62 % myasthenia gravis); 8 had thymoma (T) and 2 had thymic carcinoma (TC). All patients underwent choline PET/CT in order to evaluate suspected recurrence and/or progression. Positive choline scans were observed in 7 pts with a median SUV of 6.5 [4.8-7.8] with the following histology subtype distribution: B1 / B2 / TC in 2 / 3 / 2 pts respectively. Negative choline scan was observed in 3 pts with AB, B1 and B2 histology subtypes. Five patients (50%) showed disagreement between F-18-FDG and F-18-choline scans results. Among them, 3 pts with a negative FDG scan had a positive choline PET/CT, showing an isolated recurrence amenable to local treatment in two of them; disseminated progression excluded local treatment for the remaining patient. Diagnosis of mediastinal relapse was suspected for 2 pts on positive mediastinal FDG uptake but excluded based on a negative choline scan and MRI findings; both of them had history of mediastinal adjuvant radiotherapy. Agreement was seen between both modalities for 4 pts. Discordance between FDG and choline scans was observed for half of the pts. When FDG scan was negative, the addition of choline PET/CT impacted disease management in 75% of the cases. History of adjuvant mediastinal radiotherapy could constitute a frequent cause of false positive FDG scan with negative choline findings; therefore, choline scan might also represent a useful exam to exclude mediastinal relapses in this scenario.

Diagnostic reproducibility of thymic epithelial tumors using the World Health Organization classification: note for thoracic clinicians

Histopathological diagnosis of thymic epithelial tumors according to the current World Health Organization classification is not adequately reproducible; however, most thoracic clinicians are unaware of this. We illustrate this problem in practical settings to raise clinician awareness. An expert pathologist specialized in thymic pathology and a trained general pathologist independently diagnosed 158 resected thymic epithelial tumors. Assuming that the expert's diagnoses were more accurate, the two pathologists' diagnoses were judged to be concordant when tumor subtypes (thymoma) or categories (thymic carcinoma and neuroendocrine tumor) were in agreement. The concordance rates for different thymoma subtypes were 75 % (3/4), 30 % (11/37), 100 % (17/17), 80 % (39/49), and 53 % (9/17) for types A, AB, B1, B2, and B3, respectively. Discordant cases of type AB thymoma were mainly diagnosed as type B1 or B2 by the general pathologist. Discordant cases of type B2 thymoma were diagnosed as type AB, B1, or B3, and discordant cases of type B3 thymoma were diagnosed as type A, B2, or carcinoma. Discordant cases of thymic carcinoma were diagnosed as type A or B3 thymoma. Investigation of the concordant and discordant cases suggested that reasonable discrepancies can occur because of the noncommittal categorical boundaries inherent in this classification. Thoracic clinicians should consider this potential problem in daily practice.

The utility of FDG-PET in the diagnosis of thymic epithelial tumors

In this article, seven studies evaluating the utility of FDG-PET in the diagnosis of thymic epithelial tumors were reviewed and the results of an investigation conducted in Tokushima University Hospital are reported. FDG accumulation of low-risk thymoma is low, and FDG accumulation of thymic carcinoma is high. High-risk thymoma exhibits various degrees of accumulation and a definite conclusion has not yet been reached; however, overall, the higher the histological grade, the higher the FDG accumulation becomes, suggesting that this is correlated to staging. Our data also support the previous reports. FDG-PET may indicate lymph node metastasis and distant metastasis, which are sometimes difficult to detect using other modalities. When lymph node metastasis and/or distant metastasis are suspected in addition to thymic lesions, FDG-PET/CT, which allows for searching of the entire body at once, is useful. FDG-PET/CT is effective for estimating histopathological malignancy and staging in the diagnosis of thymic epithelial tumors and can be an important imaging test with high relevance to the prognosis of a patient.

Expression of Proteasome Subunit β5t in Thymic Epithelial Tumors

Recently, a proteasome β subunit expressed exclusively in thymic cortical epithelial cells was discovered in mice and humans. This subunit, designated β5t, is a component of the thymoproteasome, a specialized type of proteasome implicated in thymic positive selection. To investigate whether β5t could serve as a marker for the differential diagnosis of thymic epithelial tumors, we performed immunohistochemical analysis using anti-β5t antibody in 54 cases of thymic epithelial tumors comprising 41 cases of thymomas and 13 cases of thymic carcinomas. β5t was detected in the neoplastic epithelial cells of thymomas. Among the subtypes of thymoma, expression of β5t was observed in most cases of type B thymoma (20 of 21) but not in type A thymomas (0 of 3). In type AB thymomas, β5t expression was variable (6 of 17). Type B3 thymomas (4 cases) were positive for β5t but negative for CD5, c-kit, and glucose transporter 1 (GLUT-1), which are known as diagnostic markers for thymic carcinomas. In contrast, thymic carcinomas were negative for β5t (0 of 13) but expressed at least one and usually all of CD5, c-kit, and GLUT-1. Thus, β5t and CD5/c-kit/GLUT-1 were differentially expressed in type B3 thymoma and thymic carcinoma. We tested β5t expression in 39 cases of tumors arising from other organs, which showed the specific expression of β5t in thymic epithelial tumors. This study demonstrates that β5t is expressed in most type B and in some type AB thymomas and is a marker useful in differentiating type B3 thymomas from thymic carcinomas when used in combination with other diagnostic markers.

Policies and Reporting Guidelines for Small Biopsy Specimens of Mediastinal Masses

目前，胸腺恶性肿瘤治疗方案大多是根据术 后病理确定，然而，多数临床治疗决策需要在术前 通过活检小标本的病理报告来制定。所以，术前活 检小标本的正确获取和病理解读对治疗决策的制定 显得非常重要[1]。这些标本包括细针活检标本，带 芯穿刺活检标本和手术切取活检标本[2-7]。由于胸 腺肿瘤的病理诊断对组织的获取方法和获取量都有较高 的要求，加之对病理的描述也没有统一的标准，使得小 标本在诊断胸腺瘤方面存在诸多问题。为此，ITMIG在 病理科医生和外科医生回顾相关文献和提出初步建议的 基础上，经集体讨论制定了活检规范操作流程，提出了 对纵隔肿物小活检标本处理和病理报告的建议。旨在为 术前患者的治疗提供一个统一和具有循证医学证据的方 法；同时，将有利于全球数据之间的比较和开展合作研 究，充分利用医疗资源。