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[My paper] S Suster, C A Moran
Department of Pathology, Ohio State University, Columbus 43210, USA.
Primary thymic epithelial neoplasms have been the subject of much controversy in recent years owing to the difficulties posed by these tumors for precise histopathologic typing and prognostication. A number of classification schemes using different terminology have been proposed, none of which has satisfactorily managed to address all the problems and concerns related to these tumors. We present a proposal for a novel approach to the histologic classification of primary thymic epithelial neoplasms that is based on morphologic features of differentiation. The principle behind this classification scheme is that the determination of the cytologic degree of atypia and the identification of the organotypical features of thymic differentiation may permit accurate classification of these neoplasms into 3 simple and reproducible diagnostic categories: thymoma, atypical thymoma, and thymic carcinoma. We further reiterate the traditional concept that tumor staging, not histopathologic typing, has a more crucial role for accurate and reliable prognostication for the better differentiated forms of these tumors.

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Indiana University Melvin and Bren Simon Cancer Center, Indianapolis 46202, USA.
PURPOSE The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. PATIENTS AND METHODS We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. RESULTS From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. CONCLUSION Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma.
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Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. marchevsky@cshs.org
Information regarding prognosis of thymoma patients stratified by both World Health Organization classification and Masaoka staging system is very limited. Analyze 5-year survival data from a large number of thymoma patients stratified by both World Health Organization histologic type and Masaoka stage using meta-analysis. Perform power analysis to estimate the number of cases that would be needed to test the null hypothesis to a power of 80%. Five-year survival data from 905 thymoma patients treated with thymectomy at seven hospitals in America, Japan, Korea, India, Italy, and Germany. Survival data was reported as "dead" or "alive" to facilitate meta-analysis. Significant differences were detected only when comparing survival rates of thymoma patients in stages I to III with those of stage IV disease. Analysis by World Health Organization histologic type and stage yielded significant differences only in patients with thymomas A vs. B2 and A vs. B3 in stage III disease. No significant data heterogeneity was detected with funnel plots and Egger's regression test. Power analysis estimated that a study with 7077 patients is needed to evaluate the prognostic significance of all thymomas stratified by both World Health Organization histologic type and stage to a power of 80%. Selected World Health Organization histologic types are significantly associated with prognosis in stage III thymoma patients and may help select individuals benefiting from neoadjuvant therapy. Power analysis shows that studies with much larger number of patients are needed to exclude the possibility that histologic type may provide significant prognostic information in other stages of the disease.
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Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
HASH(0x26bbd30)
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Human Oncology and Pathogenesis Program (HOPP, Weill Medical College of Cornell University, New York, New York, USA.
PURPOSE Thymomas and thymic carcinomas are rare intrathoracic malignancies that can be invasive and refractory to conventional treatment. Because these tumors both originate from the thymus, they are often grouped together clinically. However, whether the underlying biology of these tumors warrants such clustering is unclear, and the optimum treatment of either entity is unknown. EXPERIMENTAL DESIGN All thymic tumors were profiled for mutations in genes encoding components of the EGFR and KIT signaling pathways, assessed for EGFR and KIT expression by immunohistochemistry, and analyzed by array-based comparative genomic hybridization. Previously untreated tumors were subjected to global gene expression arrays. RESULTS We analyzed 45 thymic tumors [thymoma, n = 38 (type A, n = 8; type B2, n = 22; type B3, n = 8); thymic carcinoma, n = 7]. One thymoma and one thymic carcinoma harbored KRAS mutations (G12A and G12V, respectively), and one thymoma had a G13V HRAS mutation. Three tumors displayed strong KIT staining. Two thymic carcinomas harbored somatic KIT mutations (V560del and H697Y). In cell viability assays, the V560del mutant was associated with similar sensitivities to imatinib and sunitinib, whereas the H697Y mutant displayed greater sensitivity to sunitinib. Genomic profiling revealed distinct differences between type A to B2 thymomas versus type B3 and thymic carcinomas. Moreover, array-based comparative genomic hybridization could readily distinguish squamous cell carcinomas of the thymus versus the lung, which can often present a diagnostic challenge. CONCLUSIONS Comprehensive genomic analysis suggests that thymic carcinomas are molecularly distinct from thymomas. These data have clinical, pathologic, and therapeutic implications for the treatment of thymic malignancies.
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Divisions of Medical Oncology, National Cancer Center Hospital and Research Institute, Tokyo, Japan.
OBJECTIVE To determine which computed tomographic findings are associated with high-risk thymic epithelial tumors and a poor prognosis. METHODS Computed tomographic findings of thymic epithelial neoplasms were retrospectively evaluated in 75 patients diagnosed with thymic tumor between January 1997 and October 2003. We analyzed the correlation of the computed tomographic findings, histological subtype according to the World Health Organization classification, and the prognosis. RESULTS There were 34 with type A approximately B1 tumor and 41 with type B2 approximately C tumor. On multiple regression analysis, vascular obliteration and a blunt sternum-anterior mediastinum angle were more frequent with thymic carcinoma than with thymoma. On multivariate analysis, pleural effusion and mediastinal fat infiltration on initial computed tomography had a significant impact on survival. CONCLUSIONS Vascular obliteration and a blunt sternum-anterior mediastinum angle were predictive of thymic carcinoma. Pleural effusion and mediastinal fat infiltration were predictive of a poor prognosis.
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Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. marchevsky@cshs.org
Evidence-based pathology promotes the critical evaluation of current clinical information and the development of evidence-based diagnostic and prognostic guidelines. No randomized clinical trials of patients who have thymomas or thymic carcinomas are available to evaluate the validity of the current World Health Organization (WHO) histologic classification or the widely used Masaoka staging system. A meta-analysis of over 2000 thymoma patients estimated that only three WHO histologic types of thymomas are associated with significant survival differences. Prospective randomized clinical trials and an international registry of patients who have Thymic epithelial neoplasms are needed to stratify patients who may benefit from neoadjuvant chemotherapy, postoperative radiation therapy, and other nonsurgical modalities.
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[My paper] Mark R Wick
Division of Surgical Pathology and Cytopathology, University of Virginia Medical Center, University of Virginia Health System, Charlottesville, VA 22908-0214, USA. mrw9c@virginia.edu
The prognosis of thymic epithelial tumors depends on their separation into thymoma and thymic carcinoma, as well as the extent to which they involve adjacent tissues and organs. To formalize evaluations of the latter attribute, several staging systems have been developed over the past 30 years. These include the Masaoka, Bergh, Wilkins-Castleman, Groupe d'Etudes des Tumeurs Thymiques, and tumor-nodal-metastasis schemes. The first of those formulations is most commonly employed in clinical practice, at least in the United States. The author believes that surgical-pathologic staging is the most powerful and reliable prognosticator for thymoma, as compared with histologic subtype-related prediction of behavior for that tumor type. Those topics, as well as affiliated issues concerning tissue sampling and staging techniques, are discussed in this article.
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Department of Pathology-Unit 85, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
The etiology and molecular pathogenesis of thymic tumors are unknown. However, during the last two decades there has been some progress on elucidating the genetic abnormalities present and molecular pathways altered in thymic tumors. These abnormalities, while bearing distinctions and similarities to those described in other tumors, can be organized under the "hallmarks of cancer," as proposed by Hanahan and Weinberg. These changes include self-sufficiency in growth signaling, insensitivity to antigrowth signals, ability to evade apoptosis, limitless replicative potential, ability to sustain angiogenesis, and tissue invasion and metastasis. However, this progress is still limited and has not led to better tumor classifications, prognostication of outcome, and design of molecular targeted therapy.
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Department of Cellular Pathology, Southampton University Hospitals Trust, Southampton, UK. bruce.addis@suth.swest.nhs.uk

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Department of Pathology, M D Anderson Cancer Center, Houston, TX 77030, USA. cesarmoran@mdanderson.org
AIMS To present eight cases of primary diffuse peritoneal malignant mesothelioma in children <15 years old, with a discussion of the pitfalls of this diagnosis in the paediatric age group. METHODS AND RESULTS The cases were selected based on the following criteria:(i) primary peritoneal neoplasms confined grossly or radiographically to the abdominal cavity;(ii) negative history of previous or another associated malignancy;(iii) histopathological confirmation. All patients (five female, three male) presented clinically with symptoms of abdominal pain, distention and ascites. Grossly, the tumours showed multiple, diffuse peritoneal nodules. Histologically, seven cases corresponded to epithelioid mesotheliomas and one case displayed biphasic (epithelioid and spindle) cellular proliferation. Immunohistochemical studies for cytokeratin (CK) 5/6, calretinin and low-molecular-weight CK (CAM5.2) showed strong cytoplasmic positivity in the neoplastic cells. Three patients were treated by chemotherapy. On clinical follow-up, four patients with epithelioid mesotheliomas were alive and well from 12 to 18 months after initial diagnosis; one patient with a mixed (biphasic epithelioid/sarcomatoid) mesothelioma died of tumour 24 months after diagnosis. CONCLUSIONS Peritoneal malignant mesothelioma in children is a rare condition that can introduce difficulties in histopathological diagnosis.
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Department of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. cesarmoran@mdanderson.org
AIMS To report three cases of primary carcinoma of the neck arising in multilocular thymic cysts (MTC). METHODS AND RESULTS The patients were three men aged 47, 50 and 52 years who presented with a painless neck mass of several weeks' duration. The patients had no history of previous surgical procedures or of malignancy elsewhere. The tumours in all three patients were located on the right lateral side of the neck; all patients underwent complete surgical resection of the mass. Grossly, the tumours were cystic and measured between 20 and 30 mm in greatest diameter. Histologically, the tumours showed cyst walls lined by squamous epithelium. The cyst walls contained prominent germinal centres with lymphoid hyperplasia, cholesterol cleft granulomas, and scattered keratinized structures reminiscent of Hassall's corpuscles. In addition, a neoplastic cellular proliferation composed of round to oval cells arranged in sheets and originating from the lining of the cystic structures was present. The neoplastic cells showed moderate amounts of eosinophilic cytoplasm, round nuclei, and, in some areas, prominent nucleoli. Mitotic figures were easily found, and cellular pleomorphism was present in several areas. In two cases the tumours showed features of basaloid carcinoma of the thymus, while in one case the pattern was that of squamous cell carcinoma. Immunohistochemical studies for keratin showed a strong positive reaction in the tumour cells, while leucocyte common antigen strongly stained the lymphoid background. Follow-up information obtained in two patients showed them to be alive 6 months after initial diagnosis. One patient was lost to follow-up. CONCLUSION The cases described here represent an unusual variant of carcinoma arising in multilocular thymic cyst in the neck region.
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[My paper] S Suster, C A Moran
Department of Pathology, The Ohio State University, Columbus 43210, USA.
Neuroendocrine neoplasms of the mediastinum form part of a family of tumors characterized by genotypic, immunophenotypic, and functional properties of neuroendocrine differentiation. Although rare, these tumors have been the source of much attention and controversy in the literature. Their nomenclature and classification, in particular, have continued to evolve over the years. Such tumors comprise lesions derived from neuroendocrine elements within the thymus, from paraganglionic rests, or from misplaced embryonal structures within the mediastinum. The most common neuroendocrine neoplasms of this anatomic region, however, correspond to neuroendocrine carcinomas of the thymus. The light microscopic, immunohistochemical, and ultrastructural features of these tumors are reviewed along with the advances in our understanding of these lesions and current trends in nomenclature and terminology.
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Department of Pathology, University of Alabama at Birmingham, AL 35249,USA. ccastro@path.uab.edu
AIMS We describe the clinicopathological characteristics of 15 cases of primary signet ring cell adenocarcinoma of the lung and highlight the importance of recognizing that not all adenocarcinomas with signet ring cell features represent metastatic adenocarcinomas. METHODS AND RESULTS We evaluated the clinicopathological and immunohistochemical features of 15 cases of signet ring cell adenocarcinoma of the lung. The patients were 12 men and three women, age 30-75 years (mean 52.5 years). No evidence of a primary tumour elsewhere could be found on thorough clinical examination. Nine patients underwent resection and the remainder were biopsied. The tumours ranged from 18 to 80 mm in greatest dimension. Microscopically, two distinct patterns of growth were recognized: acinar and diffuse. The tumours were characterized by the presence of >75% signet ring cells. Periodic acid-Schiff and mucicarmine showed strong intracellular positive staining. Immunohistochemical stains for TTF-1 (6/6) and CEA (9/9) showed strong positive reaction in all cases evaluated. Three out of six cases were also positive for cytokeratin 7. All the tumours (6/6) were negative for cytokeratin 20, ER, PR and GCDFP-15. Follow-up information was obtained in 11 patients; six patients died within 1 year and five patients were alive from 3 to 36 months after initial diagnosis. CONCLUSION These cases highlight an unusual histological growth pattern of primary lung adenocarcinoma that may be mistaken for a metastasis from an occult primary. The recognition of this pattern of lung tumours is important for proper treatment.
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[My paper] C A Moran, S Suster
Department of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Twenty-five cases of thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction are presented. The patients were 11 women and 14 men between the ages of 18 and 73 years (median 45.5 years). Clinically, nine patients were asymptomatic and their mediastinal tumor was discovered on routine chest radiograph. Sixteen patients presented with symptoms of chest pain and cough. All patients underwent surgical resection of their tumor. Grossly, the tumors were described as well circumscribed and encapsulated, with the exception of two that showed infiltration of pleura and pericardium. The tumors measured from 4 to 13 cm in greatest dimension. On cut surface they showed prominent cystic areas and foci of hemorrhage and necrosis. Histologically, the tumors contained solid areas showing an admixture of round to oval epithelial cells devoid of atypia admixed with small lymphocytes in varying proportions. Cystic changes with areas of necrosis, infarction, and hemorrhage were present in all cases and comprised extensive areas of the tumors. The areas of infarction showed features of ischemic necrosis and were always intimately associated with vaso-occlusive and thrombotic phenomena and with cystic and hyperplastic changes of adjacent thymic epithelium. Clinical follow-up in 14 patients showed that 11 were alive and well from 1 to 18 years after surgery (median follow-up 9 years). Three patients died: one of complications during the immediate postoperative period, one because of colonic adenocarcinoma 9 years after diagnosis of the mediastinal tumor, and one because of pneumonia 6 years later. The two patients with invasive tumors were lost to follow-up. The present study appears to indicate that areas of hemorrhage and necrosis in well encapsulated, noninvasive thymomas do not portend an adverse prognosis.
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University of Virginia Medical Center, Charlottesville, Virginia, USA. mrw9c@virginia.edu
The immunohistochemical diagnosis of atypical epithelial proliferations in pleural fluid is a challenging topic in cytopathology and surgical pathology. Mesothelioma may be simulated clinically and radiologically by several other nonneoplastic and neoplastic disorders, mandating that strict histologic, histochemical, immunohistochemical, and ultrastructural guidelines be followed for its diagnosis. Because of its availability to most laboratories, immunohistochemistry has emerged as the most commonly used procedure for the diagnosis of pleural malignancies. This review considers the current status of that investigative modality, with particular attention to lesions that are suspected to be mesothelial.
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Department of Anatomic Pathology, University of Alabama at Birmingham, Kracks Building KB726, Birmingham, AL 35294, USA.
Three cases of primary cutaneous B-cell lymphoma with prominent signet ring-cell features are presented. The patients were three men between the ages of 37 years and 74 years (average, 55.5 years). Clinically, the three patients presented with multiple skin nodules. In one patient, the nodules had been present for approximately 5 weeks, although in the two other patients, the nodules were of unknown duration. The lesions were located in the upper extremities (forearm) and measured from 2 cm to 3 cm in diameter. No evidence of lymphadenopathy was observed in any of the patients. Surgical excision of the nodules was performed. Histologically, in two cases, the superficial and deep dermis was replaced by a diffuse cellular proliferation, and in one patient, the tumor cell population adopted a nodular pattern of growth involving adnexal structures and infiltrating the subcutaneous fat. In all cases, the tumors were composed of cells showing signet ring-cell features, with striking indentation of the nuclei toward the periphery of the cell. Immunohistochemical studies using antibodies for B-cell and T-cell markers (L-26 and UCHL) as well as antibodies for leukocyte common antigen, keratin, and kappa and lambda light chains were performed in all cases. The tumor cells showed a positive reaction for leukocyte common antigen, L-26, and lambda light chain restriction. Follow-up information was only available in one patient, who has remained alive and well 2 years after diagnosis without evidence of progression of the disease. The present cases highlight the importance of recognizing this unusual morphologic type of lymphoma so as to arrive at a correct diagnosis.
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[My paper] C A Moran, S Suster
Department of Pathology, University of Alabama at Birmingham 35294, USA.
Six hundred thirty cases of thymomas were evaluated to determine morphologic heterogeneity. The thymomas were grouped in 4 categories using previous terminology. Stratification according to the number of sections available for examination revealed a marked difference in distribution by histopathologic type. A cutoff number of 5 sections appears to provide a difference in subgrouping these tumors. In addition, the proportion of invasive tumors increases with the number of sections examined. Final classification may be affected by the extent of sampling. Histopathologic classification of thymoma, although of academic interest, may have limited practical relevance for assessment of prognosis in limited biopsy tissue. Proper evaluation of histology and aggressive potential in thymoma should be based on ample sampling and assessment of capsular integrity, which is best accomplished on thoroughly sampled resection specimens rather than incomplete or limited biopsy samples.
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Department of Pathology, The University of Alabama at Birmingham, 35294, USA.
The immunohistochemical diagnosis of mesothelioma is perhaps one of the most perplexing and controversial issues in surgical pathology. A tumor that in essence is extremely rare has managed to captivate the attention not only of pulmonologists and thoracic surgeons but also of pathologists. Throughout its history, mesothelioma has emerged as one of the tumors that has evaded definitive characterization; hence, the numerous attempts at trying to establish not only histological criteria but also histochemical, immunohistochemical, and ultrastructural guidelines for its diagnosis. Perhaps as we enter an era of more sophisticated technology, molecular biology will have an opportunity to make inroads into the diagnosis and characterization of this peculiar neoplasm. Despite the many difficulties involved in the diagnosis of malignant mesothelioma, we have recently gained significant knowledge of this entity in many respects, several decades after its description. From a morphological point of view, several variations of the histological appearances that these tumors may exhibit have been described. Traditional histochemistry and electron microscopy continue to play an important role in the evaluation of these neoplasms, with ultrastructural analysis in particular representing the most reliable technique for making this diagnosis in equivocal cases. However, because of its speed, cost-effectiveness, and general availability, immunohistochemistry has emerged as the most commonly used procedure for the diagnosis of mesotheliomas. We herein present a review of the current status of immunohistochemical evaluation of malignant lesions that are suspected of having a mesothelial lineage.

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Department of Radiology, Osaka University Graduate School of Medicine, Suita-city, Osaka, 565-0871, Japan.
Thymic epithelial tumors, such as thymomas and thymic carcinomas, are the most common primary neoplasms of the mediastinum. In 1999, the World Health Organization (WHO) proposed a consensus classification of thymic epithelial tumors based on the morphology of the epithelial cells and the ratio of lymphocytes to epithelial cells, which was revised in 2004. The latest classification system stratifies thymic epithelial tumors into six categories: types A, AB, B1, B2, B3, and thymic carcinoma. This article describes the prediction of thymoma histology and stage on the basis of radiographic criteria by reviewing the following: the WHO histologic classification of thymic epithelial tumors, the clinical staging of thymomas based on prognosis, and the radiographic appearance of thymomas according to the WHO histologic classification.
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Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, Japan.
There are only a few immunohistochemical markers that are useful for differentiating thymic carcinomas from type B3 thymomas. The purpose of this study is to examine the additional markers that would be useful for differentiating between thymic carcinoma and thymoma type B3. We performed a tissue microarray analysis of surgically resected thymic tumor specimens from 12 cases of thymic carcinoma, 7 cases of type B3 thymoma, and 68 cases of other types of thymoma. Immunostaining using 49 antibodies was scored based on staining intensity and the percentage of cells that stained positive. Seven proteins that were selected by the staining scores, namely, GLUT-1 (167 vs 4), CA-IX (110 vs 15), c-kit (162 vs 44), CD5 (33 vs 0), MUC-1 (54 vs 0), CEA (42 vs 0), and CK18 (110 vs 42), were significantly higher in the thymic carcinomas than in the type B3 thymomas. The staining sensitivity and specificity of the antibodies for thymic carcinoma were GLUT-1, sensitivity 72% and specificity 100%; CA-IX, 58 and 71%; c-kit, 72 and 85%; CD5, 33 and 100%; CK18, 58 and 71%; MUC-1, 25 and 100%; and CEA, 33 and 100%. Glucose transporter 1 (GLUT-1) is the best marker for thymic carcinoma because it had the highest sensitivity and specificity. Positive immunostaining for a combination of three markers, namely, GLUT-1, CD5, and CEA, enabled differentiation of thymic carcinoma with 91.6% sensitivity and 100% specificity. In conclusion, we identified GLUT-1 as an additional marker that will be useful for differentiating thymic carcinoma from type B3 thymoma, especially in biopsy specimens that have been crushed or are otherwise difficult to examine morphologically in thymic tumors.
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Department of Pathology, Jinling Hospital Nanjing, Medical School, Nanjing University, China. yinhl1978@ yahoo.com.cn
This study retrospectively reviewed the clinicopathological features of thymic epithelial tumors in 108 patients, and evaluated World Health Organization (WHO) histologic classification of thymic tumors. Other prognostic factors, including age, gender, clinical stage, and completeness of tumor resection were also analyzed. Seven type A tumors, 19 type AB, 23 type B1, 19 type B2, 27 type B3, and 13 thymic carcinomas were studied. The 5-year and 10-year survival rates were 100% after resection of tumor types A and AB; 93% and 81% for B1; 83% and 70% for B2; and 43% and 33% for B3. The overall 5-year and 10-year survival rates were 72.0% and 63.0%, respectively. Tumor classification was highly significant in predicting survival (P .001) and also reflected the clinical behavior of tumors. The Masaoka stage was the most important independent prognostic index in thymomas. The WHO histologic subtype and completeness of resection were also important prognostic factors.
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Divisions of Medical Oncology, National Cancer Center Hospital and Research Institute, Tokyo, Japan.
OBJECTIVE To determine which computed tomographic findings are associated with high-risk thymic epithelial tumors and a poor prognosis. METHODS Computed tomographic findings of thymic epithelial neoplasms were retrospectively evaluated in 75 patients diagnosed with thymic tumor between January 1997 and October 2003. We analyzed the correlation of the computed tomographic findings, histological subtype according to the World Health Organization classification, and the prognosis. RESULTS There were 34 with type A approximately B1 tumor and 41 with type B2 approximately C tumor. On multiple regression analysis, vascular obliteration and a blunt sternum-anterior mediastinum angle were more frequent with thymic carcinoma than with thymoma. On multivariate analysis, pleural effusion and mediastinal fat infiltration on initial computed tomography had a significant impact on survival. CONCLUSIONS Vascular obliteration and a blunt sternum-anterior mediastinum angle were predictive of thymic carcinoma. Pleural effusion and mediastinal fat infiltration were predictive of a poor prognosis.
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Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. marchevsky@cshs.org
Evidence-based pathology promotes the critical evaluation of current clinical information and the development of evidence-based diagnostic and prognostic guidelines. No randomized clinical trials of patients who have thymomas or thymic carcinomas are available to evaluate the validity of the current World Health Organization (WHO) histologic classification or the widely used Masaoka staging system. A meta-analysis of over 2000 thymoma patients estimated that only three WHO histologic types of thymomas are associated with significant survival differences. Prospective randomized clinical trials and an international registry of patients who have Thymic epithelial neoplasms are needed to stratify patients who may benefit from neoadjuvant chemotherapy, postoperative radiation therapy, and other nonsurgical modalities.
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[My paper] Mark R Wick
Division of Surgical Pathology and Cytopathology, University of Virginia Medical Center, University of Virginia Health System, Charlottesville, VA 22908-0214, USA. mrw9c@virginia.edu
The prognosis of thymic epithelial tumors depends on their separation into thymoma and thymic carcinoma, as well as the extent to which they involve adjacent tissues and organs. To formalize evaluations of the latter attribute, several staging systems have been developed over the past 30 years. These include the Masaoka, Bergh, Wilkins-Castleman, Groupe d'Etudes des Tumeurs Thymiques, and tumor-nodal-metastasis schemes. The first of those formulations is most commonly employed in clinical practice, at least in the United States. The author believes that surgical-pathologic staging is the most powerful and reliable prognosticator for thymoma, as compared with histologic subtype-related prediction of behavior for that tumor type. Those topics, as well as affiliated issues concerning tissue sampling and staging techniques, are discussed in this article.
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Department of Anatomic Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Thymic carcinoma is a rare tumor that has traditionally posed a significant challenge for diagnosis to clinicians and histopathologists. No reliable histopathologic features have yet been identified that can permit reliable distinction of these tumors from a metastasis to the mediastinum. Histologically, the tumors are characterized by morphologic features that are indistinguishable from those arising from a variety of other epithelial organs. A large number of histologic variants have been described. In general, these tumors remain a diagnosis of exclusion and, as a group, represent high-grade neoplasms with a very aggressive clinical behavior and an often-ominous prognosis.
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Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA. ssuster@mcw.edu
Thymoma classification has remained for many years a troubled and contentious field. In recent years, the World Health Organization (WHO) presented a proposal for the histopathologic classification of thymic epithelial neoplasms that has been adopted as the standard by many pathologists throughout the world. Yet, controversy still exists regarding its validity, accuracy, usefulness, and reproducibility in routine clinical practice. This article reviews the basic criteria of the current WHO classification of thymoma, along with its weaknesses and limitations, and presents alternate proposals for the histopathologic approach to the classification of thymic epithelial neoplasms.
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Division of Endoscopy and Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan. m.endo@scchr.jp
PURPOSE The objective of this study was to assess the value of (18)F-FDG PET in thymic epithelial tumors according to the WHO histologic classification and to evaluate its potential for differentiating the grade of malignancy in thymic epithelial tumors. MATERIALS AND METHODS Thirty-six patients with a thymic epithelial tumor who underwent (18)F-FDG PET examination before treatment were enrolled in the present study. The T/M ratio, which is the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of mediastinum, was compared in subgroups of a simplified WHO histological classification; low-risk thymoma (Types A, AB and B1), high-risk thymoma (Types B2 and B3), and thymic carcinoma. RESULTS Tumors included 15 low-risk thymomas, 10 high-risk thymomas and 11 thymic carcinomas. Upon visual inspection, all tumors showed (18)F-FDG accumulation and the mean T/M ratio in these three subgroups was 2.64, 4.29 and 8.90, respectively. The differences between the three subgroups were statistically significant (low-risk vs. high-risk: p=0.01, high-risk vs. thymic carcinoma: p=0.01). CONCLUSION A significant relationship was seen between (18)F-FDG PET accumulation and histologic subtype in thymic epithelial tumors when they were classified into three groups. PET may be useful for predicting the grade of malignancy in thymic epithelial tumors.
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Department of General Thoracic Surgery (L5), Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan. meinosin@surgl.med.osaka-u.ac.jp
A histological classification of thymic epithelial tumors was presented by the World Health Organization (WHO) in 1999 and again in 2004 following slight modifications, in which thymic epithelial tumors were categorized as thymomas and thymic carcinomas. Whereas thymoma is defined as an organotypic (thymus-like) tumor, thymic carcinoma is a malignant epithelial neoplasm with a morphology similar to that of malignant neoplasms arising from other organs. Herein, the recent progress in research of thymic epithelial tumors is reviewed with reference to the WHO histological classification system, with the focus on thymomas. Thymomas are classified into five types--A, AB, B1, B2, B3--according to the shape and atypia of their epithelial cells as well as the abundance of lymphocytes. The invasiveness, prognosis, and genetic imbalance of thymomas have been shown to be related to this classification system. Myasthenia gravis is frequently associated with types B1 and B2. The WHO histological classification of thymomas is not only useful for treatment but reflects their biological characteristics, including genetic alterations. Advances are expected in future studies of thymomas from the standpoint of their clinical, pathological, and biological aspects.


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