Classification Of Thymic Epithelial Tumors Research Articles

TNM Staging System in Thymoma: A Critical Appraisal?

Thymomas are rare tumors of the anterior mediastinum with peculiar clinical and pathological features. They have been deeply analyzed by pioneer authors, who strictly linked their name to the main pathological and staging classifications. Before the latest edition of the WHO classification of thymic epithelial tumors, the history of thymoma pathological classification inherited the name of the pathologists who systematically addressed the issue, from Levine-Rosai to Muller-Hermelink. Similarly, the thymoma staging system is intimately related to the name of two surgeons, Masaoka and Koga, who historically dealt with this disease. More recently, the traditional tumor-nodes-metastasis (TNM) system has been developed for the staging of this condition, in a rational attempt to put thymomas in conformity with the other solid tumors. The efforts of the International Thymic Malignancies Interest Group (ITMIG) and the Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) of the International Association for the Study of Lung Cancer (IASLC) resulted in the TNM classification of thymic tumors, which have been included in the eighth edition of the American Joint Committee on Cancer's (AJCC) Cancer Staging Manual. Herein, we report a narrative review of the evolution of the thymic epithelial tumors (TET) staging system and present a critical appraisal of the actual TNM classification compared with the historical Masaoka-Koga classification, with special focus on the proposal for the ninth edition of the TNM, expected in 2024.

Predicting the Risk of Thymic Tumors Using Texture Analysis of Contrast-Enhanced Chest Computed Tomography.

This study aimed to explore the value of contrast-enhanced computed tomography texture features for predicting the risk of malignant thymic epithelial tumor. Data of 97 patients with pathologically confirmed thymic epithelial tumors treated at in our hospital from March 2015 to October 2021 were retrospectively analyzed. Based on the World Health Organization classification of thymic epithelial tumors, patients were divided into a high-risk group (types B2, B3, and C; n = 45) and a low-risk group (types A, AB, and B1; n = 52). Texture analysis was performed using a first-order, gray-level histogram method. Six features were evaluated: mean, variance, skewness, kurtosis, energy, and entropy. The association between contrast-enhanced computed tomography texture features and the risk of malignancy in thymic epithelial tumors was analyzed. The predictive thresholds of predictive texture features were determined by receiver operating characteristics analysis. The mean, skewness, and entropy were significantly greater in the high-risk group than in the low-risk group ( P < 0.05); however, variance, kurtosis, and energy were comparable in the two groups ( P > 0.05). The area under curve of mean, skewness, and entropy was 0.670, 0.760, and 0.880, respectively. The optimal cutoff value of entropy for predicting risk of malignancy was 7.74, with sensitivity, specificity, and accuracy of 80.0%, 80.0%, and 75%, respectively. Contrast-enhanced computed tomography texture features, especially entropy, may be a useful tool to predict the risk of malignancy in thymic epithelial tumors.

Molecular pathology of thymoma and thymic carcinoma

Thymic epithelial tumors (TETs) comprise a heterogeneous group of epithelial-derived thymic neoplasms with diverse clinical behavior and underlying molecular genetic features. Owing to their rare nature, the molecular classification of TETs has only recently begun to be fully explored. The advent of advanced molecular studies, particularly the ability to sequence the DNA and RNA of tumors in a massively parallel fashion, has led to an increased understanding of the molecular underpinnings of thymic neoplasia. Thymomas, characterized by a heterogeneous group of molecular alterations, tend to have low mutational burdens and various copy number abnormalities including a characteristic loss of chromosomal material in the region of 6q25.2-p25.3, a recurrent, specific point mutation GTF2I p.L424H, and specific expression of certain microRNAs. Thymic carcinomas, in contrast, are generally characterized by increased tumor mutational burdens, multiple copy number alterations, and varied, non-recurrent, somatic mutations. Advances in molecular knowledge of TETs allow for more precise molecular classification of these tumors, and the presence of specific alterations aids in the diagnosis of borderline lesions. In the future, additional molecular studies will better delineate the molecular landscape of these tumors and may one day allow for more targeted treatment algorithms. This review aims to cover the current understanding of the molecular alterations thus far identified in thymomas and thymic carcinomas.

GOECP/SEOR radiotherapy guidelines for thymic epithelial tumours.

Thymic epithelial tumours (TET) are rare, heterogeneous neoplasms that range from resectable indolent tumours to aggressive thymic carcinomas with a strong tendency to metastasize. The pathological diagnosis is complex, in part due to the existence of several different classification systems. The evidence base for the management of TETs is scant and mainly based on non-randomised studies and retrospective series. Consequently, the clinical management of TETs tends to be highly heterogenous, which makes it difficult to improve the evidence level. The role of technological advances in the field of radiotherapy and new systemic therapies in the treatment of TETs has received little attention to date. In the present clinical guidelines, developed by the GOECP/SEOR, we review recent developments in the diagnosis and classification of TETs. We also present a consensus-based therapeutic strategy for each disease stage that takes into consideration the best available evidence. These guidelines focus primarily on the role of radiotherapy, including recent advances, in the management of TETs. The main aim of this document is to promote the standardisation of clinical practice and lay the foundations for future studies to clarify the main unresolved questions related to the optimal management of TET.

CT-Based Radiomics Signatures for Predicting the Risk Categorization of Thymic Epithelial Tumors.

ObjectivesThis study aims to assess the performance of radiomics approaches based on 3D computed tomography (CT), clinical and semantic features in predicting the pathological classification of thymic epithelial tumors (TETs).MethodsA total of 190 patients who underwent surgical resection and had pathologically confirmed TETs were enrolled in this retrospective study. All patients underwent non-contrast-enhanced CT (NECT) scans and contrast-enhanced CT (CECT) scans before treatment. A total of 396 hand-crafted radiomics features of each patient were extracted from the volume of interest in NECT and CECT images. We compared three clinical features and six semantic features (observed radiological traits) between patients with TETs. Two triple-classification radiomics models (RMs), two corresponding clinical RMs, and two corresponding clinical-semantic RMs were built to identify the types of the TETs. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were useful to evaluate the different models.ResultsOf the 190 patients, 83 had low-risk thymoma, 58 had high-risk thymoma, and 49 had thymic carcinoma. Clinical features (Age) and semantic features (mediastinal fat infiltration, mediastinal lymph node enlargement, and pleural effusion) were significantly different among the groups(P < 0.001). In the validation set, the NECT-based clinical RM (AUC = 0.770 for low-risk thymoma, 0.689 for high-risk thymoma, and 0.783 for thymic carcinoma; ACC = 0.569) performed better than the CECT-based clinical-semantic RM (AUC = 0.785 for low-risk thymoma, 0.576 for high-risk thymoma, and 0.774 for thymic carcinoma; ACC = 0.483).ConclusionsNECT-based and CECT-based RMs may provide a non-invasive method to distinguish low-risk thymoma, high-risk thymoma, and thymic carcinoma, and NECT-based RMs performed better.Advances in KnowledgeRadiomics models may be used for the preoperative prediction of the pathological classification of TETs.

Impact of expert pathologic review of thymic epithelial tumours on diagnosis and management in a real-life setting: A RYTHMIC study.

Classification of thymic epithelial tumours (TETs) is known to be challenging; however, the level of discordances at a nationwide level between initial and expert diagnosis and their clinical consequences are currently unknown. RYTHMIC is a national network dedicated to the management of TET based on initial histological diagnosis, followed by an additional expert review of all cases. Our aim was to evaluate the discordances between initial and expert diagnoses and whether they would have led to different clinical management. We conducted a retrospective analysis of the cohort of patients discussed at RYTHMIC tumour board from January 2012 to December 2016. Assessment of disagreement was made for histological typing and for staging. The discordances were classified as major or minor based on whether they would have changed or not the proposed therapeutic strategy, respectively. Follow-up of the patients with major discordances was conducted until December 2018. Four hundred sixty-seven patients were reviewed, and 183 (39%) discordances were identified either related to histological subtype (132) and/or stage (72). Major discordances were identified in 27 patients (6%). They included 16 patients with TET for whom treatment recommendation based on the central review would have been post-operative radiotherapy, whereas it had not been the case. However, follow-up did not show any progression among the 15 patients with high-grade histology and/or stage resected thymomas. On the other hand, among the remaining 11 patients including 7 with a diagnosis other than TET, the overall management or follow-up would have been completely different with the expert diagnosis. Our real-life cohort reveals a high level of discordances considering TET diagnosis and supports expert review for optimal clinical management.

Value of 18F-FDG PET/computed tomography in predicting the simplified WHO grade of malignancy in thymic epithelial tumors.

To investigate the value of 18F-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in predicting the simplified WHO grade of malignancy in thymic epithelial tumors. We retrospectively reviewed 81 patients with pathologically proven thymic epithelial tumors who underwent F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax) and SUVmax/tumor size were measured on the primary lesion. A receiver operating characteristics (ROC) curve were performed for assessing the ability of F-FDG PET/CT as a predictor of the simplified WHO classification. There were 43 male patients (53.1%) and 38 female patients (46.9%), and the mean age was 55.6 ± 11.9 years. The mean tumor size was 53.2 ± 21.4 mm. There were 24 low-risk thymomas (29.6%) (A, AB, and B1), 29 high-risk thymomas (35.8%) (B2 and B3), and 28 thymic carcinomas (34.6%). The SUVmax and SUVmax/tumor size were found to be predictive factors that were useful to distinguish thymomas and thymic carcinomas, and area under the ROC curve were 0.820 and 0.691, respectively (P < 0.05), and the cutoff value for discriminating thymomas and thymic carcinomas was 5.34. In conclusion, a significant relationship was observed between SUVmax, SUVmax/tumor size and histological WHO classification of thymic epithelial tumors. F-FDG PET/CT may be useful for predicting the grade of malignancy in thymic epithelial.

Machine-learning-based computed tomography radiomic analysis for histologic subtype classification of thymic epithelial tumours

PurposeTo evaluate the performance of machine-learning-based computed tomography (CT) radiomic analysis to differentiate high-risk thymic epithelial tumours (TETs) from low-risk TETs according to the WHO classification. MethodThis retrospective study included 155 patients with a histologic diagnosis of high-risk TET (n = 72) and low-risk TET (n = 83) who underwent unenhanced CT (UECT) and contrast-enhanced CT (CECT). The radiomic features were extracted from the UECT and CECT of each patient at the largest cross-section of the lesion. The classification performance was evaluated with a nested leave-one-out cross-validation approach combining the least absolute shrinkage and selection operator feature selection and four classifiers: generalised linear model (GLM), k-nearest neighbor (KNN), support vector machine (SVM) and random forest (RF). The receiver-operating characteristic curve (ROC) and the area under the curve (AUC) were used to evaluate the performance of the classifiers. ResultsThe combination of UECT and CECT radiomic features demonstrated the best performance to differentiate high-risk TETs from low-risk TETs for all four classifiers. Among these classifiers, the RF had the highest AUC of 0.87, followed by GLM (AUC = 0.86), KNN (AUC = 0.86) and SVM (AUC = 0.84). ConclusionsMachine learning-based CT radiomic analysis allows for the differentiation of high-risk TETs and low-risk TETs with excellent performance, representing a promising tool to assist clinical decision making in patients with TETs.

The evolution of the histopathologic classification of thymic epithelial tumors

Few topics in pathology have been as controversial as the classification of thymic epithelial tumors (TET). The lack of knowledge regarding the structure and function of the thymus has certainly contributed to this difficulty. Only in the second part of the 20 th century did a new awareness concerning the importance of the thymus emerge. Moreover, the heterogeneity of the histopathologic features and the variability of the lymphocytic content in TET contributed to an increase in the number of histologic classifications. This review covers the main classifications and points out the people who developed several classification schema and their underlying “driving” concepts. Historically, the first step regarded the need to separate TET from other tumors occurring in the mediastinum. Subsequently the discussion focused on establishing TET types or subtypes with different prognostic value. The development of histopathologic classifications of TET took also advantage of progressing advances in the knowledge of the thymus together with the adoption of new diagnostic tools which increased diagnostic accuracy and reproducibility. The ultimate goal of the diagnostic pathological process, from the very beginning, was to provide the most useful information to the clinicians (thoracic surgeons, oncologists) involved in patient management.

Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADCHS-ROI) and histogram-based approach. ADC histogram parameters included mean ADC (ADCmean), median ADC (ADCmedian), 10 and 90 percentile of ADC (ADC10 and ADC90), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADCmean, ADCmedian, ADC10, ADC90 and ADCHS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values <0.05), while no significant difference in skewness (p = 0.181) and kurtosis (p = 0.088). ADC10 showed best differentiating ability (cut-off value, ≤0.689 × 10-3 mm2 s-1; AUC, 0.957; sensitivity, 95.65%; specificity, 92.86%) for discriminating low-risk thymoma from high-risk thymoma and thymic carcinoma. Advanced Masaoka stages (Stage III and IV; n = 24) tumours showed significant lower ADC parameters and higher kurtosis than early Masaoka stage (Stage I and II; n = 13) tumours (all p-values <0.05), while no significant difference on skewness (p = 0.063). ADC10 showed best differentiating ability (cut-off value, ≤0.689 × 10-3 mm2 s-1; AUC, 0.913; sensitivity, 91.30%; specificity, 85.71%) for discriminating advanced and early Masaoka stage epithelial tumours. ADC histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

Thymomas and Thymic Carcinomas: A Review on Pathology, Presentation, Staging, Treatment, and Novel Systemic Therapies

Although thymomas and thymic carcinomas only represent 0.2–1.5% of all malignancies, they are the most common tumour found in the anterior mediastinum. Recently, the World Health Organization (WHO) classification of thymic epithelial tumours was revised and a new tumour, node, and metastasis (TNM) staging system is currently being developed. Nearly a third of patients with thymoma present with paraneoplastic syndromes, most commonly myasthenia gravis. Thymic carcinomas are rarely associated with paraneoplastic syndromes, with patients often presenting with local symptoms. Recommendations for the management of these tumours are primarily based on small prospective studies, meta-analyses, and expert guidelines. The development of novel therapies to treat thymomas and thymic carcinomas is an area of robust research.

Genomic Analysis of Thymic Epithelial Tumors Identifies Novel Subtypes Associated with Distinct Clinical Features.

Purpose: To reconcile the heterogeneity of thymic epithelial tumors (TET) and gain deeper understanding of the molecular determinants of TETs, we set out to establish a clinically relevant molecular classification system for these tumors.Experimental Design: Molecular subgrouping of TETs was performed in 120 patients from The Cancer Genome Atlas using a multidimensional approach incorporating analyses of DNA mutations, mRNA expression, and somatic copy number alterations (SCNA), and validated in two independent cohorts.Results: Four distinct molecular subtypes of TETs were identified. The most commonly identified gene mutation was a missense mutation in General Transcription Factor II-I (GTF2I group), which was present in 38% of patients. The next group was identified by unsupervised mRNA clustering of GTF2I wild-type tumors and represented TETs enriched in expression of genes associated with T-cell signaling (TS group; 33%). The remaining two groups were distinguished by their degree of chromosomal stability (CS group; 8%) or instability (CIN group; 21%) based upon SCNA analyses. Disease-free survival and overall survival were favorable in the GTF2I group and unfavorable in the CIN group. These molecular subgroups were associated with TET histology and clinical features including disease-free survival. Finally, we demonstrate high expression of PD1 mRNA and correlation of PD1 and CD8A in the TS subgroup.Conclusions: Molecular subtyping of TETs is associated with disease-free and overall survival. Classification of TETs by a molecular framework could aid in the refinement of staging and in the discovery and development of rational treatment options for patients with TETs. Clin Cancer Res; 23(16); 4855-64. ©2017 AACR.

Molecular analysis of thymic epithelial tumors (TETs): A report by The Cancer Genome Atlas (TCGA) research network.

8520 Background: Thymoma (T) and thymic carcinoma (TC) are the most common malignancies of the anterior mediastinum. Additionally, thymoma has an unique association with autoimmune disorders, notably myasthenia gravis (MG). Histologic classification of TETs has been largely based on the gross description of the epithelial cell appearance and the relative abundance of associated lymphocytes. A comprehensive molecular analysis of TETs has not heretofore been conducted. Methods: The TCGA Research Network conducted multi-platform analyses of 117 TETs (T = 105; TC = 10 and micronodular T = 2), which included whole-exome, transcriptome, methylome and targeted proteome analysis. Patient characteristics: median age = 60 years (range 17-84); M:F (%) = 52:48; Masaoka Stage (I-36, IIA-39, IIB-19; III-15; IVA-1; IVB-5); mg was present in 32 patients. No patient had prior therapy for metastatic disease, but 14 had prior chemotherapy and 39 had prior radiation therapy in adjuvant setting. WHO histologic classification (blinded review) revealed A = 10; A/B = 48, B1 = 12, B2 = 25, B3 = 10, micronodular T = 2 and TC = 10. Results: T has one of the lowest mutational loads of any tumor in the TCGA. A unique transcription factor, GTF2I, was the most commonly observed mutation in WHO Types A and A/B. All GTF2I mutations were exclusively at the amino acid 424 locus. This is the only tumor with this specific mutation within the entire TCGA database. HRAS, NRAS and TP53 mutations were less commonly noted among all TETs. Four distinct molecular-driven subtypes of TETs were identified that strongly correlated with the current WHO histologic classification. Increased aneuploidy and overexpression of muscle auto-antigens were associated with mg phenotype. Conclusions: Based on molecular analysis, four clusters were identified that correlated strongly with the current WHO Histologic Classification. Also identified was a unique mutation in GTF2I, which was associated with WHO Type A and A/B thymoma. This international effort represents the largest and most comprehensive molecular analysis of TETs conducted to date is expected to have important clinical and translational implications for this rare disease.

Evolution of Classification of Thymic Epithelial Tumors in the Era of Dr Thomas V. Colby.

-Numerous histomorphologic and staging classifications of thymic epithelial tumors (TETs) have been proposed during the last century, suggesting that the classification of these tumors is challenging and controversial. Difficulties of classifying TETs include various combinations of epithelial cells and lymphocytes and the paucity of these tumors. The prognostic significance, specifically of the histomorphologic classifications, has been debated. Early classifications were also challenged by the uncertainty of the neoplastic component(s) of the tumor. -To discuss the evolution of the histomorphologic classification and the staging system of TET. Controversies and problems of some classifications and their importance for therapeutic management and prognosis will be reviewed. Classifications that incorporated new concepts and approaches at the time or outcome studies will be highlighted. Current classifications will be discussed and the staging system that was recently proposed for the upcoming eighth American Joint Committee on Cancer staging will be described. -Search of literature database (PubMed) and current (2015) World Health Organization classification. -Histomorphologic and staging classifications of TET have evolved during the last century and especially during the era of Thomas V. Colby, MD. Evidence supports that the staging system has prognostic implications independent of and superior to the histomorphologic classification. Histomorphology appears to be important for biologic features of TET.

The Effect of Diagnostic Imaging on Surgical Treatment Planning in Diseases of the Thymus.

Accurate imaging of the thymus is essential in the diagnosis and surgical treatment of both neoplastic and nonneoplastic conditions. Imaging of the thymus is a rather complex task, which affects both initial diagnosis and further surgical treatment planning. Imaging techniques include a wide armamentary of possibilities, from the most frequently used computed tomography (CT) to 18-fluorodeoxyglucose positron emission tomography- (18-FDG-PET-) CT and chemical shift magnetic resonance imaging (CS-MRI). In cases where surgical treatment is involved diagnostic imaging is of pivotal importance, not only in distinguishing benign from malignant disease but also in making a way among subtypes of thymic conditions. The article presents a current review of the advantages and backdrops of different imaging techniques used in the diagnosis of benign and malignant thymic conditions, with emphasis on differential imaging of thymic hyperplasia (TH), ectopic thymic tissue (ETT), and thymic epithelial tumors (TETs), with special attention to the importance of MR imaging according to the new TNM classification of thymic epithelial tumors.

AB007. OS02.01. The integrated genomic landscape of thymic epithelial tumors: a report by the TCGA research network

Background: Thymoma and thymic carcinoma are the most common malignancies of the anterior mediastinum. Additionally, thymoma has a unique association with autoimmune disorders, notably myasthenia gravis (MG). Histologic classification of thymic epithelial tumors (TETs) has been largely based on the gross description of the epithelial cell appearance and the relative abundance of associated lymphocytes. A comprehensive molecular analysis of TETs has not heretofore been conducted.

Type A and AB thymomas: histological features associated with increased stage.

The current WHO classification of thymic epithelial neoplasms describes type A and type AB thymomas as behaving 'like benign neoplasms'. However, recent published data suggest that rare cases may show more aggressive behaviour. The aim of this study was to assess the frequency of atypical cases, and to determine whether atypia is associated with more advanced disease. One hundred and twenty-one thymomas (type A, n = 68; type AB, n = 53) were retrospectively reviewed for 'atypical' features (nuclear pleomorphism, mitotic activity, and necrosis). Logistic regression was used to ascertain the association with increasing Masaoka-Koga stage. Where available, follow-up data were also reviewed. There were 72 stage I, 42 stage II, five stage III and two stage IV tumours. Only the presence of necrosis showed a significant association with increased stage in univariate and multivariate analysis. Nuclear atypia and increased mitotic activity were not associated with increasing stage of disease. Our data support the concept of there being more aggressive atypical variants of both type A and type AB thymoma, and suggest that the presence of necrosis could be used to predict aggressive behaviour.

18F-fluorodeoxyglucose positron emission tomography for evaluation of thymic epithelial tumors: utility for World Health Organization classification and predicting recurrence-free survival

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in many oncological settings. In this study, we assessed the utility of (18)F-FDG-PET for predicting the histological classification, stage and survival of thymic epithelial tumors. We retrospectively analyzed 37 patients with thymic epithelial tumors who underwent PET before surgical resection and investigated the relationship between the maximum of standardized uptake value (SUVmax) of each tumor and the WHO classification, recurrence-free survival, and tumor-related gene expressions. The study included 15 males and 22 females, ranging in age from 22 to 81 years (mean 64 years). The tumor histology of 31 tumors was thymoma and that of the remaining tumors was thymic carcinoma. The Masaoka tumor stage was as follows: stage I in 18, II in 9, III in 5 and IV in 5 patients. The patients were divided into three groups according to a simplified histologic classification: low-risk thymoma (types A, AB and B1, n = 21), high-risk thymoma (types B2 and B3, n = 10) and thymic carcinoma (n = 6). The SUVmax of low-risk group (SUVmax ≤4.27) was significantly lower than that of high-risk group (p = 0.0114) and that of thymic carcinomas (SUVmax >4.27) was also significantly higher than that of thymomas (p < 0.0001). The group of high SUVmax (SUVmax >4.27) had significantly inferior recurrence-free survival to that of less value (SUVmax ≤4.27) (p = 0.0009). The SUVmax were not correlated with tumor-related gene expressions. The SUVmax of (18)F-FDG-PET reflects WHO classification of thymic epithelial tumors. High SUVmax predicts lower recurrence-free survival of the tumors.

Did the 2004 World Health Organization (WHO) histologic classification result in better prognostic categories for resected thymomas as compared to 1999 WHO classification scheme?

e18552 Background: The classification of thymic epithelial neoplasms is subject of controversy. The purpose of our investigation is to see whether the 2004 histologic classification results in better prognostic categories than that of the 1999 classification. Methods: The SEER 18 database was used to investigate incidence and overall survival/cause-specific survival (OS/CSS) of resected thymomas during 2000-2009. Incidence was examined by frequency and trend analyses. Patients diagnosed with first primary localized thymoma/thymic carcinoma were selected in two time periods (2000-2003: N=201; 2005-2009: N = 497). The median follow up is 79 months and 27 months respectively. OS/CSS in two patients group were analyzed by Kaplan-Meier estimation, log-rank tests, and multivariate proportional hazards modeling. Results: The proportion of six histology categories (A, AB, B1-B3,C) did not change significantly during the two time periods. Compared to patients diagnosed in 2000-2003, OS was not significantly different in patients diagnosed in 2005-2009 in the log rank tests or multivariate analysis after accounting for treatment, tumor factors, and patient characteristics (OS, HR=0.737, p=0.1580; CSS, HR=0.731, p=0.3711). Histology as 6 categories is a significant predictor for OS in the multivariate analysis in 2005-2009, but not in 2000-2003. However, the predictive role of histology is similar in both time periods in the multivariate analysis of CSS. Complete resection, classification C, and tumor stage are significantly linked to OS and CSS. Conclusions: Patients diagnosed after 2004 did not have better survival outcomes than earlier patients. The WHO classification of 2004 may be a better predictor of OS than that of 1999 as shown by the wide-spectrum of pathologists reporting to SEER.

Thymic epithelial tumors at University Federico II of Naples: A 30-year experience.

7603 Background: According to the 2004 WHO classification, thymic epithelial tumors (TETs) comprise different histologies, including thymomas, thymic carcinoma, typical and atypical carcinoids. Histology classification of TETs has a dramatic impact on the prognosis and therapeutic strategy. We here review all TETs treated at our Institution over the past 30 years. Methods: Eligible patients had a pathologically confirmed TET and had at least one access at our Institution. Relevant demographic and clinical data were retrieved. An exploratory analysis was conducted using a step-wise model in patients with completely resected tumors to seek for factors predictive of recurrence after radical surgery. Results: One hundred and three patients with TETs were included in this retrospective analysis. Forty-three were female, sixty were male. Median age was 43 years (range 32-58). Forty-three patients had myasthenia gravis. Four had a thymic neuroendrocrine tumor, 19 had a thymic carcinoma, while the remaining had a thymoma. Forty-seven patients were alive at the time of analysis. Median overall survival was 5.85 years (range, 2.58-9.9). In the whole sample population, seventy-six patients had a completely resected tumor with clear pathological margins. In this sub-group of 76 patients (median age: 46, 35-55; 30 females, 46 males), 12 had a thymic carcinoma and 30 patients recurred after radical surgery. At multivariate analysis, which included age, sex, adjuvant chemotherapy, adjuvant radiotherapy, maximum tumor diameter, presence of myasthenia gravis and stage, the only factor significantly predictive of recurrence was tumor histology (odds ratio: 3,8182, 95% CI: 1,03 to 14,1; p = 0.04). Conclusions: We showed that patients with thymic carcinomas are at increased risk of recurrence after radical surgery independently on adjuvant chemotherapy/radiotherapy treatment. Additional therapeutic options are required in the adjuvant setting of completely resected thymic carcinomas.