-
Pathologica Oct 2021In this study, the authors report on the activity of Juan Rosai, one of the pathologists most engaged in the definition of cells, diseases and tumors occurring in the... (Review)
Review
In this study, the authors report on the activity of Juan Rosai, one of the pathologists most engaged in the definition of cells, diseases and tumors occurring in the thymus and in the mediastinum during the last 60 years. With his morphological skills and tireless interest in clarification of disease patterns, he contributed extraordinarily to expand our knowledge of the mediastinal diseases and to improve our diagnostic approach. He determined extraordinary advances also in trasmission electron microscopy and in immunohistochemistry as powerful diagnostic tools. Moreover, he proposed and promoted, together with an international panel of Pathologists, the World Health Classification of Thymic tumors as a definite progress in our comprehension and diagnostics of thymic epithelial tumors (TET). Our purpose is to review J. Rosai's achievements in thymic normal structure, in TET and particularly in the entity now definied as "thymoma", in distinction from the thymic carcinoma. To do this, our narrative will also be based on personal memories, longstanding collaborations and/or friendship with J. Rosai.
Topics: Humans; Immunohistochemistry; Male; Mediastinum; Neoplasms, Glandular and Epithelial; Thymoma; Thymus Neoplasms
PubMed: 34837094
DOI: 10.32074/1591-951X-539 -
Cancer Reports (Hoboken, N.J.) Mar 2023Thymic epithelial tumors are rare and include thymomas and thymic carcinomas. There is scarce literature characterizing prognostic factors and long-term outcomes in... (Review)
Review
BACKGROUND
Thymic epithelial tumors are rare and include thymomas and thymic carcinomas. There is scarce literature characterizing prognostic factors and long-term outcomes in these tumors.
AIMS
This review aims to describe disease features of thymomas and thymic carcinomas and to report clinical differences among thymoma histological subtypes.
METHODS AND RESULTS
A retrospective chart review was performed at the University of Florida Shands Hospital, a tertiary care academic medical center in Gainesville, Florida, USA. The review included clinical data of adults with thymic epithelial tumors diagnosed between 2001 and 2021. Significant associations among demographics, histology, stage, and outcomes were investigated. Thymoma subgroup analysis was performed using histological subtype and sex. Forty patients with thymoma and seven patients with thymic carcinoma were included in the final analysis. Among those with thymomas, patients with subtype B1, B2, or B3 tumors were younger, had larger tumors, and presented with higher stage disease when compared to those with subtypes A or AB. Tumor recurrence was most common in subtype B2 and B3 tumors (50.0% and 16.7% vs. 0%; p < .01). However, there was no significant difference in overall survival between histologic subtypes. Compared to females, males with thymomas had superior overall survival (103.0 vs. 62.9 months; p = .021) despite presenting with larger tumors (9.8 vs. 5.8 cm; p = .041). Concomitant myasthenia gravis was associated with increased recurrence but not worsened mortality. Compared to thymomas, patients with thymic carcinoma presented with higher-stage disease and had poorer 5-year survival (50.0% vs. 93.1%; p < .01).
CONCLUSION
This study affirmed pathologic stage and resectability as prognostic factors for thymic epithelial tumors. New findings include inferior overall survival in female patients and higher recurrence rates in those with thymomas and concomitant myasthenia gravis.
Topics: Adult; Male; Humans; Female; Thymoma; Prognosis; Retrospective Studies; Neoplasm Recurrence, Local; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Myasthenia Gravis
PubMed: 36369906
DOI: 10.1002/cnr2.1750 -
World Journal of Surgical Oncology Jul 2023Thymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed...
PURPOSE
Thymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed to investigate the prognostic factors of patients with thymoma who received radical resection and establish the nomogram to predict the prognosis of these patients.
MATERIALS AND METHODS
Patients who underwent radical resection for thymoma with complete follow-up data between 2005 and 2021 were enrolled. Their clinicopathological characteristics and treatment methods were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors. According to the results of the univariate analysis in the Cox regression model, the predictive nomograms were created.
RESULTS
A total of 137 patients with thymoma were enrolled. With a median follow-up of 52 months, the 5-year and 10-year PFS rates were 79.5% and 68.1%, respectively. The 5-year and 10-year OS rates were 88.4% and 73.1%, respectively. Smoking status (P = 0.022) and tumor size (P = 0.039) were identified as independent prognostic factors for PFS. Multivariate analysis showed that a high level of neutrophils (P = 0.040) was independently associated with OS. The nomogram showed that the World Health Organization (WHO) histological classification contributed more to the risk of recurrence than other factors. Neutrophil count was the most important predictor of OS in patients with thymoma.
CONCLUSION
Smoking status and tumor size are risk factors for PFS in patients with thymoma. A high level of neutrophils is an independent prognostic factor for OS. The nomograms developed in this study accurately predict PFS and OS rates at 5 and 10 years in patients with thymoma based on individual characteristics.
Topics: Humans; Thymoma; Prognosis; Retrospective Studies; Thymus Neoplasms; World Health Organization
PubMed: 37430268
DOI: 10.1186/s12957-023-03068-9 -
ESMO Open Oct 2023Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the...
BACKGROUND
Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive genomic profiling database in a real-world setting.
METHODS
We included data from two different cohorts: Foundation Medicine Inc. (FMI) in the United States and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. Samples profiled were examined for all classes of alterations in 253 genes targeted across all assays. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.
RESULTS
A total of 794 patients were collected in our study, including 722 cases from FMI and 72 cases from C-CAT. In the FMI data, CDKN2A (39.9%), TP53 (30.2%) and CDKN2B (24.6%) were frequently altered in thymic carcinoma, versus TP53 (7.8%), DNMT3A (6.8%), and CDKN2A (5.8%) in thymoma. TMB-high (≥10 mutations/Mb) and MSI were present in 7.0% and 2.3% of thymic carcinomas, and 1.6% and 0.3% of thymomas, respectively. Within C-CAT data, CDKN2A (38.5%), TP53 (36.5%) and CDKN2B (30.8%) were also frequently altered in thymic carcinoma, while alterations of TSC1, SETD2 and LTK (20.0% each) were found in thymoma.
CONCLUSIONS
To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Genomics
PubMed: 37703595
DOI: 10.1016/j.esmoop.2023.101627 -
Thoracic Cancer Jun 2021Thymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent...
BACKGROUND
Thymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent in invasive thymomas than in noninvasive thymomas. However, the significance of calcification in thymomas remains unknown. This study aimed to evaluate the significance of calcification in thymomas on invasiveness to surrounding organs and investigate the characteristics of thymoma cases with calcification at our institution.
METHODS
We included thymoma patients treated at our institution between 2000 and 2016, and evaluated their characteristics, including demographics, calcification on CT, histology, Masaoka stage, and myasthenia gravis status. The patients were categorized into calcification (C) and noncalcification (NC) groups.
RESULTS
Among 51 included patients, 11 (21.6%) had calcification. A higher proportion of group C patients had World Health Organization histological type B2 and B3 tumors (high-risk) than type A, AB, and B1 tumors (low-risk; p = 0.0477). The number of patients with Masaoka stages III and IV were significantly higher in the C group than in the NC group (p < 0.0001). The C group patients had significantly higher rates of invasion to the mediastinal pleura, pericardium, lung, phrenic nerve, and chest wall and pleural dissemination than the NC group patients.
CONCLUSIONS
Calcification reflects invasiveness of tumors to surrounding organs and tissues, and may thus predict thymoma stage and histologically high-risk thymomas. Calcification in thymomas may also predict the pathological stage and help decide therapeutic methods and surgical approaches to treat thymomas based on the calcification status according to CT findings.
Topics: Calcinosis; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Thymoma
PubMed: 33955164
DOI: 10.1111/1759-7714.13964 -
Scientific Reports Feb 2023To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with...
To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with pathologically confirmed TETs were retrospectively reviewed. The subjects included 113 male and 81 female patients between 15 and 78 years of age, with a mean age of 53.8 years. Clinical outcomes were categorized according to whether relapse, metastasis or death occurred within 3 years after the first diagnosis. Associations between clinical outcomes and CT imaging features were determined using univariate and multivariate logistic regression analyses, while the survival status was analyzed by Cox regression. In this study, we analyzed 110 thymic carcinomas, 52 high-risk thymomas and 32 low-risk thymomas. Percentages of poor outcome and patient death in thymic carcinomas were much higher than those in patients with high-risk and low-risk thymomas. In the thymic carcinomas groups, 46 patients (41.8%) experienced tumor progression, local relapse or metastasis and were categorized as having poor outcomes; vessel invasion and pericardial mass were confirmed to be independent predictors by logistic regression analysis (p < 0.01). In the high-risk thymoma group, 11 patients (21.2%) were categorized as having poor outcomes, and the CT feature pericardial mass was confirmed to be an independent predictor (p < 0.01). In survival analysis, Cox regression showed that CT features of lung invasion, great vessel invasion, lung metastasis and distant organ metastasis were independent predictors for worse survival in the thymic carcinoma group (p < 0.01), while lung invasion and pericardial mass were independent predictors for worse survival in high-risk thymoma group. No CT features were related to poor outcome and worse survival in the low-risk thymoma group. Patients with thymic carcinoma had poorer prognosis and worse survival than those with high-risk or low-risk thymoma. CT can serve as an important tool for predicting the prognosis and survival of patients with TETs. In this cohort, CT features of vessel invasion and pericardial mass were related to poorer outcomes in those with thymic carcinoma and pericardial mass in those with high-risk thymoma. Features including lung invasion, great vessel invasion, lung metastasis and distant organ metastasis indicate worse survival in thymic carcinoma, whereas lung invasion and pericardial mass indicate worse survival in high-risk thymoma.
Topics: Humans; Male; Female; Middle Aged; Thymoma; Prognosis; Retrospective Studies; Neoplasm Recurrence, Local; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Lung Neoplasms
PubMed: 36801902
DOI: 10.1038/s41598-023-30041-z -
Interactive Cardiovascular and Thoracic... Jun 2022Thymomectomy is gaining consensus over complete thymectomy in early-stage thymoma without myasthenia gravis. This is due both to the difficulty of establishing...
OBJECTIVES
Thymomectomy is gaining consensus over complete thymectomy in early-stage thymoma without myasthenia gravis. This is due both to the difficulty of establishing prospective and randomized controlled studies and to the lack of well-defined selection criteria. This bicentric, retrospective propensity score-matched study aims at comparing oncological outcomes, measured in terms of overall survival and thymoma-related survival, in patients undergoing either thymomectomy or complete thymectomy.
METHODS
We retrospectively analysed medical records of patients with clinical early-stage (I and II) thymoma undergoing thymomectomy or complete thymectomy. Exclusion criteria were the presence of myasthenia gravis, clinical advanced tumours and thymic carcinoma. A propensity score-matching analysis was applied to reduce potential preoperative selection biases such as comorbidity (Charlson score), tumour maximal diameter and surgical approach (open versus minimal). All variables were dichotomized.
RESULTS
A total of 255 patients were enrolled from 2 different Hospitals, 126 underwent complete thymectomy and 129 a thymomectomy. Disease-free and thymoma-related survivals showed a 5-year rate of 87.7% and 96.0% and a 10-year rate of 82.2% and 91.9%, respectively. Propensity score-matching analysis selected a total of 176 patients equally divided between the 2 groups. No difference was found for both disease-free (P = 0.11) and thymoma-related (P = 0.37) survival in the 2 groups of resection. Multivariable Cox regression analysis showed that histology (P < 0.001), residual disease (P < 0.001) and adjuvant chemotherapy (P < 0.001) were the only predictors of shorter disease-free survival. Whereas there was no evidence to confirm that disease-free and thymoma-related survivals were influenced by resection extent.
CONCLUSIONS
Thymomectomy is an adequate surgical resection for non-myasthenic thymoma, achieving disease-free and thymoma-related survivals comparable to those after complete thymectomy.
Topics: Humans; Myasthenia Gravis; Neoplasm Staging; Propensity Score; Prospective Studies; Retrospective Studies; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 35723542
DOI: 10.1093/icvts/ivac167 -
Pathology Oncology Research : POR Jul 2017Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets...
Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation. Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss. Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas. Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas. Among non-clustered miRNAs, the upregulation of miR-21, miR-9-3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant. The expression of ALK, HER2, HER3, MET, phospho-mTOR, p16, PDGFRA, PDGFRB, PD-L1, PTEN and ROS1 was investigated by immunohistochemistry. PDGFRA was increased in thymic carcinomas and PD-L1 in B3 thymomas and thymic carcinomas. In summary, our results reveal genetic differences between thymomas and thymic carcinomas and suggest potential novel targets for therapy.
Topics: Biomarkers, Tumor; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; MicroRNAs; Mutation; Neoplasms, Glandular and Epithelial; Thymoma; Thymus Neoplasms
PubMed: 27844328
DOI: 10.1007/s12253-016-0144-8 -
Journal of B.U.ON. : Official Journal... 2021Thymic epithelial tumors represent 0.2-1.5% among all malignant neoplasms. They are slow-growing tumors with an overall recurrence rate around 10% and 90% of them are... (Review)
Review
Thymic epithelial tumors represent 0.2-1.5% among all malignant neoplasms. They are slow-growing tumors with an overall recurrence rate around 10% and 90% of them are located in the anterior mediastinum. In this review we focused on the classification, histopathology, molecular pathology and prognosis of thymic epithelial tumors, mainly thymoma and thymic carcinoma.
Topics: Carcinoma; Humans; Neoplasms, Glandular and Epithelial; Prognosis; Thymoma; Thymus Neoplasms
PubMed: 34564969
DOI: No ID Found -
Cancer Medicine Mar 2023Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of...
BACKGROUND
Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of immunotherapy also remains to be determined.
METHODS
The efficacy and safety of immunotherapy were analyzed in 11 thymoma patients who received PD-1 inhibitors according to a range of relevant indexes including the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immunotherapy-related adverse events.
RESULTS
The PFS and OS rates for all patients were 12.8 and 56.5 months, respectively. No difference in efficacy was detected between monotherapy and combination therapy (PFS: 12.8 vs 2.2 months, P = 0.787; OS: 73.8 vs 56.5 months, P = 0.367). The ORRs and DCRs for all patients were 27.3% and 90.9%, respectively. The incidence of adverse events was 45.5% among the 11 thymoma patients, including immune-related myocarditis (36.4%), immune-related liver damage (18.2%), and myasthenia gravis (18.2%). In the whole cohort of patients, the rate of adverse events of grade 3 or higher was 36.4%. The rates of adverse events of grade 3 or 4 in B3-type and non-B3-type thymoma patients were 0% and 62.5%, respectively.
CONCLUSIONS
Immunotherapy elicited a response in thymoma patients; however, more attention should be paid to the immune-related adverse events.
Topics: Humans; Thymoma; Thymus Neoplasms; Combined Modality Therapy; Immunotherapy
PubMed: 36394097
DOI: 10.1002/cam4.5357