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Valerie W Rusch - One of the best experts on this subject based on the ideXlab platform.
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comparison of patterns of relapse in thymic carcinoma and Thymoma
The Journal of Thoracic and Cardiovascular Surgery, 2009Co-Authors: James Huang, Manjit S Bains, Nabil P Rizk, William D Travis, Joseph Dycoco, Robert J Downey, Raja M Flores, Bernard J Park, Gregory J Riely, Valerie W RuschAbstract:Objective Thymic carcinomas are considered to be more aggressive than Thymomas and carry a worse prognosis. We reviewed our recent experience with the surgical management of thymic tumors and compared the outcomes and patterns of relapse between patients with thymic carcinoma and those with Thymoma. Methods We performed a single-institution retrospective cohort study. Data included patient demographics, stage, treatment, pathologic findings, and postoperative outcomes. Results During the period 1995–2006, 120 patients with thymic tumors underwent surgical intervention, including 23 patients with thymic carcinoma and 97 patients with Thymoma, as classified according to the World Health Organization 2004 histologic classification. The overall 5-year survival was significantly different between patients with thymic carcinoma and those with Thymoma (thymic carcinoma, 53%; Thymoma, 89%; P = .01). Data on relapse were available for 112 patients. The progression-free 5-year survival was also significantly different between patients with thymic carcinoma and those with Thymoma (thymic carcinoma, 36%; Thymoma, 75%; P P = .01). Conclusions Patterns of relapse differ significantly between patients with thymic carcinoma and those with Thymoma, with lower progression-free survival, earlier onset, and more distant relapses in patients with thymic carcinoma. Given the greater propensity for distant failures, the inclusion of systemic therapy in the treatment of thymic carcinoma might take on greater importance. Despite significantly higher rates of distant relapse, good overall survival in patients with thymic carcinoma can be achieved.
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feasibility of multimodality therapy including extended resections in stage iva Thymoma
The Journal of Thoracic and Cardiovascular Surgery, 2007Co-Authors: James Huang, Manjit S Bains, Nabil P Rizk, William D Travis, Venkatraman E Seshan, Joseph Dycoco, Robert J Downey, Raja M Flores, Bernard J Park, Valerie W RuschAbstract:Objective Extended resections for advanced-stage Thymomas are not commonly performed because of the potential morbidity in the face of unclear survival or palliative benefit. We reviewed our experience with multimodality treatment for Masaoka stage IVA Thymomas for feasibility and outcomes. Methods We conducted a retrospective review of a single-institution surgical database. Data included patient demographics, preoperative staging and treatment, perioperative events, pathologic findings, and postoperative outcomes. Results During the period from 1996 to 2006, 18 patients who had Masaoka stage IVA Thymoma underwent surgical resection. All patients received preoperative chemotherapy. Four patients with extensive pleural involvement underwent concomitant extrapleural pneumonectomy and postoperative hemithoracic radiation. Complete resection was achieved in 12 (67%) patients. There was no operative mortality. With a median follow-up of 32.2 months (range 1.4–129.9 months), 3-year, 5-year, and 10-year survivals were 91%, 78%, and 65%, respectively, and median survival has not yet been reached. Conclusion Multimodality therapy including extended surgical resection can be performed in select patients with stage IVA Thymoma with low morbidity and mortality and can result in excellent long-term survival.
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Thymoma a multivariate analysis of factors predicting survival
The Annals of Thoracic Surgery, 1995Co-Authors: David Blumberg, Jeffrey L Port, Benny Weksler, Ruby Delgado, Juan Rosai, Manjit S Bains, Robert J Ginsberg, Nael Martini, Patricia M Mccormack, Valerie W RuschAbstract:Background. Despite complete surgical excision, malignant Thymomas often recur with resultant death. We reviewed our series to determine which factors independently predict survival after surgical resection. Methods. A retrospective analysis of patients operated on for Thymoma between 1949 and 1993 at Memorial Sloan-Kettering Cancer Center was performed. Clinical data were collected from chart review. Only patients with a pathology report confirming the diagnosis of Thymoma were included in this analysis. Kaplan-Meier survival curves were generated and comparisons of survival analyzed by log rank test. Multivariate analysis was performed by the Cox proportional hazards model. Results. One hundred eighteen patients with Thymoma underwent operation. There were 86 complete resections (73%), 18 partial resections (15%), and 14 biopsies (12%). By Masaoka staging, 25 patients were stage I (21%), 41 stage II (35%), 43 stage III (36%), and 9 stage IVa (8%). Overall survival was 77% at 5 years and 55% at 10 years. Tumor recurred in 25 (29%) of 86 completely resected Thymomas. Stage of disease ( p = 0.03) was the only independent prognostic factor affecting recurrence. By multivariate analysis, stage ( p = 0.003), tumor size ( p = 0.0001), histology ( p = 0.004), and extent of surgical resection ( p = 0.0006) were independent predictors of long-term survival. Conclusions. Patients with stage I disease require no further therapy after complete surgical resection. Neoadjuvant therapy should be considered for patients with large tumors and invasive disease.
Alexander Marx - One of the best experts on this subject based on the ideXlab platform.
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the impact of Thymoma histotype on prognosis in a worldwide database
Journal of Thoracic Oncology, 2015Co-Authors: Cleo Aron Weis, Philipp Strobel, Frank C Detterbeck, Mirella Marino, Yanhong Deng, Andrew G Nicholson, James Huang, Alberto Antonicelli, Alexander MarxAbstract:Introduction The rarity of Thymomas and lack of multi-institutional studies have hampered therapeutic progress for decades. To overcome this, the members of the International Thymic Malignancy Interest Group created a worldwide retrospective database. This database was analyzed regarding the demographic and geographic distribution of Thymomas and the impact of different variables on survival and recurrence. Methods This study analyzed 4221 Thymomas diagnosed between 1983 and 2012 with World Health Organization histotype information from the International Thymic Malignancy Interest Group database. Associations to survival and recurrence were studied by univariate and multivariate analyses. Results Type B2 Thymoma is the most common (28%) and type A the least common (12%) histotypes. They are significantly more frequent in Europe and the United States than Asia. Type A and AB occur at significantly higher age than other Thymomas (64 and 57 years, respectively). There are no differences in gender distribution. Stage is lower in type A (90% in stages I–II) and AB than B1 to B3 Thymomas (38% of type B3 in stage III). In univariate analysis, recurrence is significantly less frequent among stage I/II tumors, in type A and AB (recurrence rates, 1–2%) than B1 to B3 Thymomas (2–7%). Multivariate analysis reveals an impact of age, stage, and resection status on survival and recurrence, whereas for histology there is only a significant impact on recurrence. Conclusion New findings are (1) geographic differences such as a lower incidence of type A and B2 Thymoma in Asia; and (2) impact of stage and histology, the latter partially limited to early stage disease, on recurrence.
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itmig consensus statement on the use of the who histological classification of Thymoma and thymic carcinoma refined definitions histological criteria and reporting
Journal of Thoracic Oncology, 2014Co-Authors: Alexander Marx, Philipp Strobel, Sunil S Badve, Lara Chalabreysse, John K C Chan, Gang Chen, Laurence De Leval, Frank C Detterbeck, Nicolas GirardAbstract:Introduction: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) Thymomas and thymic carcinomas (TC). Due to a morphological continuum between some Thymoma subtypes and some morphological overlap between Thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. Methods: To overcome this problem, hematoxylin-eosin–stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" Thymomas and TC ( n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. Results: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 Thymomas and the separation of B3 Thymomas from TCs. "Atypical type A Thymoma" is tentatively proposed as a new type A Thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. Conclusion: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.
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correlating genetic aberrations with world health organization defined histology and stage across the spectrum of Thymomas
Cancer Research, 2003Co-Authors: Masayoshi Inoue, Philipp Strobel, Petr Starostik, Andreas Zettl, Stephan Schwarz, F Scaravilli, Kristin Henry, Nick Willcox, H K Mullerhermelink, Alexander MarxAbstract:Thymomas are thymic epithelial tumors. Because most of them are rich in nonneoplastic T-cells, recurrent genetic aberrations have been reported only in the rare, lymphocyte-poor WHO types A, B3, and C. We have now investigated virtually the whole spectrum of Thymomas, including the commoner types AB and B2, microdissecting or culturing neoplastic cells from these lymphocyte-rich Thymomas and applying 41 microsatellite markers covering 17 loci on 10 chromosomes. In 28 cases, comparative genomic hybridization data were available. Apart from type A, there was striking heterogeneity between Thymomas. Allelic imbalances were seen in 87.3% of the 55 cases, and MSI in 9.9%. Losses of heterozygosity (LOHs) were much the commonest aberration. Overall, they were most prevalent at four regions on chromosome 6. Aberrations elsewhere, affecting mainly 8p11.21 and 7p15.3, suggested a cortical footprint because they recurred only in the thymopoietically active type AB and B Thymomas. LOHs were also seen at the adenomatous polyposis coli (APC) locus (5q21-22) in subsets of these Thymomas, whereas combined LOHs at the APC, retinoblastoma (13q14.3), and p53 (17p13.1) loci were confined to a subset of B3 Thymomas that had possibly evolved from APC-hemizygous B2 Thymomas by tumor progression; indeed, Thymomas combing B2 plus B3 features are common. Notably, some AB and B Thymomas shared LOHs despite their nonoverlapping morphology and different clinical behavior. Finally, allelic imbalances at 8p11.21 and 16q22.1 (CDH1) were significantly more frequent in stage IV metastatic Thymomas. We conclude that the WHO-defined histological Thymoma types generally segregate with characteristic genetic features, type A Thymomas being the most homogeneous. Many findings support the view that B2 and B3 Thymomas form a continuum, with evidence of tumor progression. However, other findings imply that types A and AB are biologically distinct from the others, any potential invasiveness being severely restricted by a medullary commitment in the precursor cell undergoing neoplastic transformation.
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Thymomas alter the t cell subset composition in the blood a potential mechanism for Thymoma associated autoimmune disease
Blood, 2000Co-Authors: Viola Hoffacker, A Schultz, James J Tiesinga, Ralf Gold, Berthold Schalke, Reinhard Kiefer, Hans Konrad Mullerhermelink, Alexander MarxAbstract:Thymomas are the only tumors that are proven to generate mature T cells from immature precursors. It is unknown, however, whether intratumorous thymopoiesis has an impact on the peripheral T-cell pool and might thus be related to the high frequency of Thymoma-associated myasthenia gravis. This study shows, using fluorescence-activated cell sorting-based analyses and T-cell proliferation assays, that thymopoiesis and T-cell function in Thymomas correspond with immunologic alterations in the blood. Specifically, the proportion of circulating CD45RA + CD8 + T cells is significantly increased in patients with Thymoma compared with normal controls, in accordance with intratumorous T-cell development that is abnormally skewed toward the CD8 + phenotype. Moreover, it is primarily the proportion of circulating CD45RA + CD8 + T cells that decreases after thymectomy. The results also demonstrate that T cells reactive toward recombinant autoantigens are distributed equally between Thymomas and blood, whereas T-cell responses to foreign antigen (ie, tetanus toxoid) are seen only among circulating T cells and not among Thymoma-derived T cells. These functional studies support the hypothesis that thymopoiesis occurring within Thymomas alters the peripheral T-cell repertoire. Because many Thymomas are enriched with autoantigen-specific T cells, a disturbance of circulating T-cell subset composition by export of intratumorous T cells may contribute to paraneoplastic autoimmune disease arising in patients with Thymoma.
James Huang - One of the best experts on this subject based on the ideXlab platform.
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the impact of Thymoma histotype on prognosis in a worldwide database
Journal of Thoracic Oncology, 2015Co-Authors: Cleo Aron Weis, Philipp Strobel, Frank C Detterbeck, Mirella Marino, Yanhong Deng, Andrew G Nicholson, James Huang, Alberto Antonicelli, Alexander MarxAbstract:Introduction The rarity of Thymomas and lack of multi-institutional studies have hampered therapeutic progress for decades. To overcome this, the members of the International Thymic Malignancy Interest Group created a worldwide retrospective database. This database was analyzed regarding the demographic and geographic distribution of Thymomas and the impact of different variables on survival and recurrence. Methods This study analyzed 4221 Thymomas diagnosed between 1983 and 2012 with World Health Organization histotype information from the International Thymic Malignancy Interest Group database. Associations to survival and recurrence were studied by univariate and multivariate analyses. Results Type B2 Thymoma is the most common (28%) and type A the least common (12%) histotypes. They are significantly more frequent in Europe and the United States than Asia. Type A and AB occur at significantly higher age than other Thymomas (64 and 57 years, respectively). There are no differences in gender distribution. Stage is lower in type A (90% in stages I–II) and AB than B1 to B3 Thymomas (38% of type B3 in stage III). In univariate analysis, recurrence is significantly less frequent among stage I/II tumors, in type A and AB (recurrence rates, 1–2%) than B1 to B3 Thymomas (2–7%). Multivariate analysis reveals an impact of age, stage, and resection status on survival and recurrence, whereas for histology there is only a significant impact on recurrence. Conclusion New findings are (1) geographic differences such as a lower incidence of type A and B2 Thymoma in Asia; and (2) impact of stage and histology, the latter partially limited to early stage disease, on recurrence.
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comparison of patterns of relapse in thymic carcinoma and Thymoma
The Journal of Thoracic and Cardiovascular Surgery, 2009Co-Authors: James Huang, Manjit S Bains, Nabil P Rizk, William D Travis, Joseph Dycoco, Robert J Downey, Raja M Flores, Bernard J Park, Gregory J Riely, Valerie W RuschAbstract:Objective Thymic carcinomas are considered to be more aggressive than Thymomas and carry a worse prognosis. We reviewed our recent experience with the surgical management of thymic tumors and compared the outcomes and patterns of relapse between patients with thymic carcinoma and those with Thymoma. Methods We performed a single-institution retrospective cohort study. Data included patient demographics, stage, treatment, pathologic findings, and postoperative outcomes. Results During the period 1995–2006, 120 patients with thymic tumors underwent surgical intervention, including 23 patients with thymic carcinoma and 97 patients with Thymoma, as classified according to the World Health Organization 2004 histologic classification. The overall 5-year survival was significantly different between patients with thymic carcinoma and those with Thymoma (thymic carcinoma, 53%; Thymoma, 89%; P = .01). Data on relapse were available for 112 patients. The progression-free 5-year survival was also significantly different between patients with thymic carcinoma and those with Thymoma (thymic carcinoma, 36%; Thymoma, 75%; P P = .01). Conclusions Patterns of relapse differ significantly between patients with thymic carcinoma and those with Thymoma, with lower progression-free survival, earlier onset, and more distant relapses in patients with thymic carcinoma. Given the greater propensity for distant failures, the inclusion of systemic therapy in the treatment of thymic carcinoma might take on greater importance. Despite significantly higher rates of distant relapse, good overall survival in patients with thymic carcinoma can be achieved.
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feasibility of multimodality therapy including extended resections in stage iva Thymoma
The Journal of Thoracic and Cardiovascular Surgery, 2007Co-Authors: James Huang, Manjit S Bains, Nabil P Rizk, William D Travis, Venkatraman E Seshan, Joseph Dycoco, Robert J Downey, Raja M Flores, Bernard J Park, Valerie W RuschAbstract:Objective Extended resections for advanced-stage Thymomas are not commonly performed because of the potential morbidity in the face of unclear survival or palliative benefit. We reviewed our experience with multimodality treatment for Masaoka stage IVA Thymomas for feasibility and outcomes. Methods We conducted a retrospective review of a single-institution surgical database. Data included patient demographics, preoperative staging and treatment, perioperative events, pathologic findings, and postoperative outcomes. Results During the period from 1996 to 2006, 18 patients who had Masaoka stage IVA Thymoma underwent surgical resection. All patients received preoperative chemotherapy. Four patients with extensive pleural involvement underwent concomitant extrapleural pneumonectomy and postoperative hemithoracic radiation. Complete resection was achieved in 12 (67%) patients. There was no operative mortality. With a median follow-up of 32.2 months (range 1.4–129.9 months), 3-year, 5-year, and 10-year survivals were 91%, 78%, and 65%, respectively, and median survival has not yet been reached. Conclusion Multimodality therapy including extended surgical resection can be performed in select patients with stage IVA Thymoma with low morbidity and mortality and can result in excellent long-term survival.
Frank C Detterbeck - One of the best experts on this subject based on the ideXlab platform.
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a systematic review of paraneoplastic syndromes associated with Thymoma treatment modalities recurrence and outcomes in resected cases
The Journal of Thoracic and Cardiovascular Surgery, 2020Co-Authors: Jasmine Zhao, Vikrant Bhatnagar, Li Ding, Scott M Atay, Elizabeth A David, Michael P Mcfadden, Stephanie Stamnes, Elizabeth Lechtholzzey, Sean C Wightman, Frank C DetterbeckAbstract:Abstract Objective Paraneoplastic syndromes associated with Thymomas remain incompletely understood. The objective was to examine the association between surgically resected Thymomas and paraneoplastic syndromes over the past half century. Methods A primary PubMed/MEDLINE search was used to identify published articles describing paraneoplastic syndromes associated with Thymomas from 1960 to 2019. A secondary search identified additional articles referenced in the articles found in the primary search. Kaplan–Meier and log-rank test were used for time-to-event data analyses. Results From 407 articles describing 507 patients, 123 different paraneoplastic syndromes were associated with Thymoma. The 5 most common paraneoplastic syndromes were myasthenia gravis, pure red cell aplasia, lichen planus, Good syndrome, and limbic encephalitis. Complete or partial resolution of paraneoplastic syndrome symptoms after surgery was noted in 76% of patients, of whom 21% had a relapse or new paraneoplastic syndrome onset after surgery. The most common adjunctive therapy associated with resolution of paraneoplastic syndrome was corticosteroids (30%). For all patients after surgery, Thymoma recurrence was observed in 17% of cases, whereas recurrence of paraneoplastic syndrome was observed in 34% of cases, and both were observed in approximately 11% of cases. The 5- and 10-year overall survivals were 78% and 66%, respectively. Improved overall survival was associated with patients who had total resolution from paraneoplastic syndrome. Conclusions A comprehensive assessment of publications over the past half century suggests that a multimodal treatment approach that includes surgical resection of Thymomas is able to achieve paraneoplastic syndrome resolution in a majority of patients. Onset of new paraneoplastic syndromes after surgery is associated with the recurrence of the first paraneoplastic syndrome, and resolution of paraneoplastic syndrome is associated with improved overall survival.
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the impact of Thymoma histotype on prognosis in a worldwide database
Journal of Thoracic Oncology, 2015Co-Authors: Cleo Aron Weis, Philipp Strobel, Frank C Detterbeck, Mirella Marino, Yanhong Deng, Andrew G Nicholson, James Huang, Alberto Antonicelli, Alexander MarxAbstract:Introduction The rarity of Thymomas and lack of multi-institutional studies have hampered therapeutic progress for decades. To overcome this, the members of the International Thymic Malignancy Interest Group created a worldwide retrospective database. This database was analyzed regarding the demographic and geographic distribution of Thymomas and the impact of different variables on survival and recurrence. Methods This study analyzed 4221 Thymomas diagnosed between 1983 and 2012 with World Health Organization histotype information from the International Thymic Malignancy Interest Group database. Associations to survival and recurrence were studied by univariate and multivariate analyses. Results Type B2 Thymoma is the most common (28%) and type A the least common (12%) histotypes. They are significantly more frequent in Europe and the United States than Asia. Type A and AB occur at significantly higher age than other Thymomas (64 and 57 years, respectively). There are no differences in gender distribution. Stage is lower in type A (90% in stages I–II) and AB than B1 to B3 Thymomas (38% of type B3 in stage III). In univariate analysis, recurrence is significantly less frequent among stage I/II tumors, in type A and AB (recurrence rates, 1–2%) than B1 to B3 Thymomas (2–7%). Multivariate analysis reveals an impact of age, stage, and resection status on survival and recurrence, whereas for histology there is only a significant impact on recurrence. Conclusion New findings are (1) geographic differences such as a lower incidence of type A and B2 Thymoma in Asia; and (2) impact of stage and histology, the latter partially limited to early stage disease, on recurrence.
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itmig consensus statement on the use of the who histological classification of Thymoma and thymic carcinoma refined definitions histological criteria and reporting
Journal of Thoracic Oncology, 2014Co-Authors: Alexander Marx, Philipp Strobel, Sunil S Badve, Lara Chalabreysse, John K C Chan, Gang Chen, Laurence De Leval, Frank C Detterbeck, Nicolas GirardAbstract:Introduction: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) Thymomas and thymic carcinomas (TC). Due to a morphological continuum between some Thymoma subtypes and some morphological overlap between Thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. Methods: To overcome this problem, hematoxylin-eosin–stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" Thymomas and TC ( n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. Results: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 Thymomas and the separation of B3 Thymomas from TCs. "Atypical type A Thymoma" is tentatively proposed as a new type A Thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. Conclusion: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.
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Thymoma current diagnosis and treatment
Chinese Medical Journal, 2013Co-Authors: Frank C Detterbeck, Ahmad ZeeshanAbstract:OBJECTIVE: To review the presentation, diagnosis, staging and treatment of Thymoma. DATA SOURCES: Data were obtained from papers on Thymoma published in English within the last 30 years. No formal systematic review was conducted, but an effort was made to be comprehensive. STUDY SELECTION: Studies were selected if they contained data relevant to the topic addressed in the particular section. In particular, standards adopted by the International Thymic Malignancies Interest Group through a formal process of achieving worldwide consensus are featured. Because of the limited length of this article, we have frequently referenced recent reviews that contain a comprehensive amalgamation of literature rather than the actual source papers. RESULTS: Thymomas are rare malignant tumors. They account for about half (47%) of anterior mediastinal tumors. About one third of these are associated with myasthenia gravis. Computed tomography with intravenous contrast is the standard diagnostic modality. Thymomas appear as round or oval masses in early stages but irregular shapes with calcifications occurring in later stages. They can invade surrounding structures including mediastinal fat, pleura, major blood vessels and nerves. Fine needle aspiration, core needle biopsy or open biopsy is used to obtain tissue diagnosis. Masaoka-Koga classification is currently used to stage Thymomas. All Thymomas should be considered for resection due to their malignant potential. A complete resection is a major prognostic factor and every effort should be made to achieve this even if this means resection and reconstruction of a major thoracic structure. Median sternotomy is the standard approach for Thymoma resection. A number of minimally invasive techniques are used in selective centers. While stage I and II tumors undergo primary surgery, preoperative chemotherapy appears to increase the chances of complete resection for stage III and IVa tumors. Postoperative radiation could be considered for patients with residual disease. Excellent 5 and 10-year survival rates are noted for completely resected early stage Thymomas. CONCLUSIONS: Thymic malignancies are rare tumors. Standards have recently been achieved to allow better communication and promote collaborative research. Surgical resection is the mainstay of treatment, but a multimodality approach is useful for many patients.
John K C Chan - One of the best experts on this subject based on the ideXlab platform.
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metaplastic Thymoma a distinctive thymic neoplasm characterized by yap1 maml2 gene fusions
Modern Pathology, 2020Co-Authors: Marina Vivero, John K C Chan, Phani K Davineni, Valentina Nardi, Lynette M ShollAbstract:: Metaplastic Thymomas are rare biphasic thymic tumors that are characteristically well-circumscribed, confined to the thymus, and follow a benign to indolent clinical course. Their relationship to other thymic neoplasms remains unclear, and their molecular characteristics have not been defined. We report for the first time recurrent translocation events in metaplastic Thymomas involving the Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) genes. Eight metaplastic Thymomas were retrieved from two institutions' archives over a 21-year period. Paraffin-embedded material from all cases underwent targeted DNA-based hybrid capture next-generation sequencing. Cases showing no somatic alterations subsequently underwent targeted RNA sequencing. Allele-specific real-time polymerase chain reaction was performed to detect GTF2I c.74146970T>A (p.L424H) mutations. All cases showed characteristic histologic features of metaplastic Thymoma and demonstrated no local recurrence or distant metastatic disease at 1-22 years of follow-up. Six of eight cases were successfully sequenced, all showing YAP1-MAML2 fusions; in four cases the fusions were detected by DNA sequencing and in two cases by RNA sequencing. Two distinct products were identified: 5' YAP1 exon 1 fused to 3' MAML2 exons 2-5 or 5' YAP1 exons 1-5 fused to 3' MAML2 exons 2-5. All cases underwent allele-specific real-time polymerase chain reaction and demonstrated no GTF2I L424H mutations. Metaplastic Thymoma is a distinct, clinically indolent thymic epithelial neoplasm characterized by YAP1-MAML2 fusion and lacking the GTF2I mutations found in Type A and AB Thymomas.
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itmig consensus statement on the use of the who histological classification of Thymoma and thymic carcinoma refined definitions histological criteria and reporting
Journal of Thoracic Oncology, 2014Co-Authors: Alexander Marx, Philipp Strobel, Sunil S Badve, Lara Chalabreysse, John K C Chan, Gang Chen, Laurence De Leval, Frank C Detterbeck, Nicolas GirardAbstract:Introduction: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) Thymomas and thymic carcinomas (TC). Due to a morphological continuum between some Thymoma subtypes and some morphological overlap between Thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. Methods: To overcome this problem, hematoxylin-eosin–stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" Thymomas and TC ( n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. Results: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 Thymomas and the separation of B3 Thymomas from TCs. "Atypical type A Thymoma" is tentatively proposed as a new type A Thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. Conclusion: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.
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microThymoma definition of the entity and distinction from nodular hyperplasia of the thymic epithelium so called microscopic Thymoma
The American Journal of Surgical Pathology, 2005Co-Authors: Wah Cheuk, William Y W Tsang, John K C ChanAbstract:Abstract We report 2 cases of microscopic-sized Thymoma, which probably represents the earliest phase of Thymoma development. The 2 patients presented with pure red cell aplasia and myasthenia gravis, respectively. The thymectomy specimens did not reveal tumor on gross examination, but histologically each contained small Thymomas measuring 5 mm and 7 mm in largest dimension, respectively. One of the tumors was unencapsulated and involved a single lobule only, and the other was encapsulated and comprised two lobules. The tumors consisted of ovoid epithelial cells with pale nuclei and distinct nucleoli, scattered in a background of small lymphocytes. Foci of medullary differentiation and perivascular space were identified in the 2 cases, respectively. The lymphocytes were confirmed to be immature T cells on immunohistochemical studies (CD3+, TdT+). Except for the microscopic size, the morphology of the two tumors conforms to conventional type B1/B2 and type B2 Thymoma, respectively. We propose calling such incidental small tumor "microThymoma" to distinguish it from the so-called microscopic Thymoma, which is composed of small thymic epithelial nests and probably more appropriately termed "nodular hyperplasia" of the thymic epithelium.
