Thymoma and Thymic Carcinoma
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The thymus is a small organ located beneath the breastbone, it is part of the immune system and produces T-lymphocytes - cells which kill viruses and signal B-lymphocytes to make antibodies to fight infection. About 90 percent of tumors that start in the thymus are thymomas. Thyomas begin in the cells which line the thymus (epithelial cells) and look similar to normal thymus cells under the microscope. Thymomas range from slow growing tumors that rarely spread outside the thymus, to more aggressive tumors, which can potentially spread to nearby organs in the chest, such as the lining of the lung (the pleura). Thymic Carcinoma also starts in the cells which line the thymus, but looks different to normal thymus cells under the microscope. These are more likely to spread to other parts of the body. Thymic Carcinoids are a rarer type of tumour which start in hormone-producing cells. Thymic carcinoids are sometimes associated with a rare genetic disorder: multiple endocrine neoplasia type 1 (MEN-1) syndrome. Other rare types include Thymolipoma and primary thymic lymphoma.

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Latest Research Publications

Information Patients and the Public (8 links)


Information for Health Professionals / Researchers (8 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

El Batti S, Mercier O, Rohnean A, et al.
Recurrence of thymoma in the right atrium arising from the coronary sinus.
Ann Thorac Surg. 2013; 95(3):e71-2 [PubMed]
Invasive thymoma is a malignant tumor of the anterior mediastinum that could have intravenous affinity associated with a high recurrence rate. This report highlights the need of coronary sinus exploration when intraatrial thymoma recurrence is diagnosed. Surgical resection of invaded coronary sinus can be achieved safely with a good result.


Koezuka S, Sato F, Hata Y, et al.
Video-assisted thoracoscopic surgery for ectopic middle mediastinal thymoma in a patient with myasthenia gravis.
Ann Thorac Surg. 2013; 95(3):e67-8 [PubMed]
We present a rare case of middle mediastinal thymoma with myasthenia gravis. A 51-year-old man presented with right ptosis and muscle weakness, and received a diagnosis of generalized myasthenia gravis. Computed tomography of the chest showed a 20-mm nodule in the middle mediastinum, suggesting a possible ectopic thymoma. He underwent video-assisted thoracoscopic extended thymectomy and resection of the tumor. Histologic examination revealed an ectopic thymoma and ectopic thymic tissue around the tumor. One year after the operation, his condition remains well controlled solely with tacrolimus. Careful preoperative radiologic examination concerning possible ectopic thymoma outside the dissection area of the extended thymectomy is recommended.


Lukas RV, Rezania K, Malec M, Salgia R
Teaching Video NeuroImages: myokymia and nerve hyperexcitability as components of Morvan syndrome due to malignant thymoma.
Neurology. 2013; 80(5):e55 [PubMed]
A 50-year-old woman with a history of metastatic malignant thymoma presented with diffuse neuropathic pain involving the extremities and torso prior to chemotherapy and radiation. She also developed episodic diarrhea, diaphoresis, fevers, insomnia, and encephalopathy. Examination revealed rippling muscles (video on the Neurology® Web site at www.neurology.org). Prolonged afterdischarges were noted in motor nerve studies, suggestive for nerve hyperexcitability (figures 1 and 2). Electromyography (approximately 8 years after mediastinal radiation) revealed fasciculations, doublets, triplets, and myokymic discharges. Elevated serum antibodies for voltage-gated potassium channel (0.30 nmol/L, normal <0.02) and striational muscle (1:30,720, normal <1:60) were suggestive of paraneoplastic Morvan syndrome, which includes all of the features noted in our case.(1,2) The CNS features of Morvan syndrome differentiate it from Isaac syndrome, which is most often due to an autoimmune etiology. A substantial proportion of Morvan syndrome cases are paraneoplastic, the majority of which are due to thymomas.(1).


Butcovan D, Tinica G, Stefanescu C, Ionescu L
Pathological comparative assessment of two cases of thymic cyst and cystic thymoma and review of the literature.
Rev Med Chir Soc Med Nat Iasi. 2012 Jul-Sep; 116(3):812-6 [PubMed]
Cystic changes of the thymus are rare lesions. In addition to their appearance in non-neoplastic congenital and acquired conditions, they have been seen in association with certain malignancies of the thymus. Our aim is to highlight the possibility of confusing between benign and malignant thymus cysts having different cure approach. We report two thymic cyst cases, one congenital ectopic condition, and the other one, a cystic thymoma. Investigations included blood counts, echograms, and computed tomography. The cysts were excised by mediastinal route and examined pathologically. The final diagnosis was made only after histopathological examination of the surgery biopsy revealing two types of cystic thymic lesions: congenital and tumoral. Because thymic cysts may present malignant transformation, they represent a diagnostic challenge that is resolved only by surgical excision and histological examination. Due to cystic changes masking tumoral features in these cases, thorough sampling is required to ensure that a malignancy is not overlooked.


Kinoshita T, Yoshida J, Ishii G, et al.
Pulmonary metastasis from encapsulated cervical ectopic type a thymoma.
Ann Thorac Surg. 2012; 94(6):e141-2 [PubMed]
A 39-year-old woman underwent tumor resection for an encapsulated cervical ectopic thymoma (type A). However 7 years after complete resection, computed tomography (CT) screening detected a 9-mm pulmonary nodule, which was completely resected and was diagnosed as a metastasis from the ectopic thymoma. There have been few reports on cervical ectopic thymoma metastasizing to a distant site and, to the best of our knowledge, this is the first case report of a cervical ectopic type A thymoma with distant metastasis.


Kalhor N, Moran CA
Thymoma: current concepts.
Oncology (Williston Park). 2012; 26(10):975-81 [PubMed]
Thymomas are unusual tumors, representing no more than 1% of all malignancies. However, thymomas are the most common epithelial tumors of the anterior mediastinum. Unfortunately, there is no general agreement regarding the best parameters to use to predict clinical behavior in these tumors.This review considers the status of the different histological classifications thus far presented for thymomas and offers an analysis of the association between histology and clinical behavior. It also emphasizes the importance of proper staging of thymomas, delineating the benefits and shortcomings of different proposed staging systems and offering thoughts on a better and more accurate staging stratification for patients with these tumors. All of the different parameters are presented in relation to survival rates. Based on current information, staging with proper stratification remains the most important parameter for predicting prognosis. For tumors limited to the mediastinal compartment, surgical resection is the most effective treatment, while induction therapy is a good alternative for patients in whom surgical resection is not possible.


Weksler B, Dhupar R, Parikh V, et al.
Thymic carcinoma: a multivariate analysis of factors predictive of survival in 290 patients.
Ann Thorac Surg. 2013; 95(1):299-303 [PubMed]
BACKGROUND: Thymic carcinoma is a rare, aggressive disease with low 5-year survivals. We undertook this study to identify factors that impact prognosis and to better define the relationship between survival and surgical intervention.
METHODS: We queried the Surveillance, Epidemiology, and End Results cancer database and identified patients with thymic carcinoma. We performed univariate and multivariate analyses to identify factors prognostic for survival, focusing on demographic, tumor, and treatment variables.
RESULTS: For 290 patients with thymic carcinoma, the median survival was 48 months with 5-year survival of 30%. In multivariate analysis, type of surgical therapy (none, incomplete excision, complete thymic excision, debulking), Masaoka stage, and sex were important determinants of survival. Patients who underwent complete thymic excision had a significantly longer median survival than those who did not receive surgical therapy (105 versus 29 months; p < 0.001). In patients who underwent complete thymic excision, Masaoka stage and race were important determinants of survival in multivariate analysis.
CONCLUSIONS: Complete thymic excision is the preferred primary treatment for thymic carcinoma. Masaoka stage has significant prognostic implications for all patients, including those who undergo complete thymic excision.


Yellin A, Simansky DA, Ben-Avi R, et al.
Resection and heated pleural chemoperfusion in patients with thymic epithelial malignant disease and pleural spread: a single-institution experience.
J Thorac Cardiovasc Surg. 2013; 145(1):83-7; discussion 87-9 [PubMed]
OBJECTIVE: Our objective was to evaluate whether resection and heated pleural chemoperfusion (HPCP) is an effective treatment for de novo stage IVa thymoma (DNT) and thymic carcinoma (TC) and for thymoma with pleural relapse (TPR).
METHODS: A retrospective study was conducted of patients undergoing resection and HPCP in 1 center. HPCP with cisplatinum ± doxorubicin (adriamycin) was performed for 60 minutes using a standard roller pump and a modified heat exchanger to a maximal intrapleural temperature of 43°C. Follow-up included at least 1 annual computed tomographic scan until death or March 2012.
RESULTS: Thirty-five patients, 17 DNT, 14 TPR, and 4 TC, completed 42 intended treatments and were followed up for 4 to 202 months (median, 62 months). Seven patients had repeated HPCP at an interval of 2 to 12 years. There was no systemic toxicity. Ninety-day mortality was 2.5%. Major and minor morbidity occurred in 12% each. Five-, 10-, and 15-year overall survivals for DNT, TPR, and TC were 81%, 73%, 58% (DNT), 67%, 56%, 28% (TPR), and 0%, 0%, 0% (TC). Five- and 10-year progression-free survival was 61%, 43% for DNT and 48%, 18% for TPR. Presently, 11 of 17 DNT patients are alive (6, no evidence of disease), and 8 of 14 TPR are alive (6, no evidence of disease). Median survival for thymoma was 157 months. Overall survival was unrelated to any preoperative or intraoperative variable. Progression-free survival was improved in R0 compared with R1-2 resection (P < .001). Local control achieved in 21 (57%) of 37 procedures in thymoma patients was related only to completeness of resection (P = .015).
CONCLUSIONS: (1) Lung-sparing resection and HPCP is feasible and safe. (2) In thymoma with pleural spread it offers excellent survival despite moderate pleural control. (3) Preliminary results with stage IVa TC are disappointing.


Matsuo Y, Takama N, Yasuhara K, et al.
Long-survival case of thymic carcinoma with superior vena cava tumor thrombus.
Ann Thorac Surg. 2012; 94(5):1729-31 [PubMed]
Sarcomatoid carcinoma of the thymus is rare and responds poorly to treatment. Invasion of great vessels and metastasis are significant predictors for poor prognosis. Thymic tumors commonly cause superior vena cava (SVC) obstruction by extrinsic compression or invasion, but intraluminal permeation is the most uncommon cause. We report a rare, long-surviving case of sarcomatoid carcinoma with SVC syndrome developed by tumor thrombus. She underwent SVC replacement and extended thymectomy. The resection indicated intracaval extension without direct invasion of thymic tumor, histologically diagnosed as sarcomatoid carcinoma. After adjuvant chemotherapy, she continues to show no apparent recurrence for five years.


Lo Nigro C, Geraci G, Sciuto A, et al.
Surgical treatment of thymoma: personal experience.
G Chir. 2012; 33(10):318-23 [PubMed]
INTRODUCTION: Thymomas (THs) are rare epithelial tumors of the thymus gland. In this study we report our personal experience in the management and surgical treatment of THs.
CASE REPORTS: We report two clinical cases treated with combined therapy (surgery followed by adjuvant therapy).
RESULTS: Total transternal thymectomy was performed in both patients. The post-operative course was uneventful. The patients received adjuvant radiotherapy and chemotherapy. No relapse has been observed during follow-up.
DISCUSSION: THs are usually slowly growing tumors with similar incidence in both sexes. They occur through a wide age range, with a peak in the fifth and sixth decades. Distinctive features reminiscent of the normal thymus make the pathologic diagnosis of THs easy in most cases. Malignant behaviour is indicated by microscopic or macroscopic invasion of the tumor capsule or surrounding organs or by the presence of metastases. Although there is no standardized staging system for thymoma, the one proposed by Masaoka is commonly employed. Total thymectomy is the procedure of choice, even for encapsulated tumors, with carefully exploration of the mediastinum for evidence of ectopic thymic tissue or local invasion.
CONCLUSIONS: Despite an indolent course and a cytologically bland appearance, all thymic tumors can manifest a malignant behavior. Surgery continues to be the mainstay of treatment, and the ability to achieve complete resection seems to be the most important prognostic factor. Multimodality treatment involving postoperative chemotherapy and radiotherapy appears to increase the rate of complete resection and improves survival in advanced THs.


Weissferdt A, Moran CA
Desmoplastic spindle cell thymomas: a clinicopathologic and immunohistochemical study of 14 cases.
Hum Pathol. 2013; 44(4):623-7 [PubMed]
Fourteen cases of spindle cell thymoma with prominent desmoplastic changes are presented. The patients are 9 women and 5 men between the ages of 46 and 79 years. Clinically, the patients presented with symptoms of chest pain, shortness of breath, and dyspnea. Radiographic imaging showed the presence of an anterior mediastinal mass, and surgical resection of the tumor mass was accomplished in all of the cases. Grossly, all the tumors were described as ovoid tumor masses measuring between 4 and 9 cm in greatest dimension. At cut surface, the tumors were described as solid and light tan-brown in color. Necrosis and hemorrhage were not recorded in any of the cases. Histologically, 8 cases were invasive, and 6 were encapsulated tumors. Extensive areas of young fibrocollagen and a prominent fibroblastic proliferation characterized the tumors. Scattered areas of more conventional spindle cell thymoma were present in all cases but mitotic activity, necrosis, and/or hemorrhage were not identified. Immunohistochemical stains were performed in 9 cases, showing tumor cells positive for pancytokeratin, cytokeratin 5/6, Bcl-2, Pax8, and vimentin. Clinical follow-up in 8 patients showed that all are alive and well 1 to 8 years after diagnosis. The current growth pattern of spindle cell thymomas is unusual and should be kept in mind when evaluating mediastinoscopic biopsies.


lonescu L, Stefănescu C, Dănilă R, et al.
Myasthenia gravis associated with thymoma and toxic multinodular goiter. A case report.
Rev Med Chir Soc Med Nat Iasi. 2012 Apr-Jun; 116(2):540-4 [PubMed]
Adequate antithyroid drug treatment or surgery usually generates remission of myasthenia gravis (MG) in patients with thymus hyperplasia associated with Graves' hyperthyroidism. The case of a 46-year-old woman diagnosed with MG based on the clinical picture, anticholinesterase drug test and positive electromyography (EMG) is presented. The cervico-thoracic computer tomography revealed a compressive nodular goiter and normal antero-superior mediastinum and led to the diagnosis of MG secondary to the hyperthyroidism. An uneventful total thyroidectomy was performed, but postoperatively the MG symptoms worsened. TC99m tetrofosmin scintigraphy revealed an area of hyperfixation in the antero-inferior mediastinum, suggestive for thymoma, as confirmed by a repeated thoracic CT scan. Following a longitudinal sternotomy, a well incapsulated tumor of approximately 6/5 cm located in the antero-inferior mediastinum was found and an extensive thymomectomy was performed. The postoperative course was uneventful and the patient was discharged 9 days later with complete remission of myasthenia. The pathology report of the specimen revealed a mixt thymoma or AB thymoma after Muller-Hermelink and WHO classification, with invasive capsular foci corresponding to Masaoka II stadium. In conclusion, scintigraphy proved to be useful in the diagnosis and decision making of a thymoma.


Ryu HS, Koh JS, Park S, et al.
Classification of thymoma by fine needle aspiration biopsy according to WHO classification: a cytological algorithm for stepwise analysis in the classification of thymoma.
Acta Cytol. 2012; 56(5):487-94 [PubMed]
OBJECTIVE: To evaluate the cytological characteristics of each type of thymoma and introduce an algorithm to classify thymoma using fine needle aspiration biopsy (FNAB).
STUDY DESIGN: We retrospectively reviewed the cytological characteristics of 15 cases of thymoma with three thymic carcinoma (1 type A thymoma, 6 type AB thymomas and 8 type B thymomas), which were confirmed by histology. Three major and one minor cytomorphologic parameter were adopted for classification: (1) number of lymphocytes in the smear background; (2) nuclear characteristics of thymic cells; (3) lymphocytes and crush artifacts in thymic cell clusters, and (4) nuclear arrangement of thymic cells.
RESULTS: An abundant lymphocytic smear background indicated type B thymomas in 87.5% of cases, contrary to the few lymphocytes in the remaining thymic tumors excluding type B thymomas (90%). Thymic cells contained no vesicular nuclei and inconspicuous nucleoli in 85.7% of type A thymoma and type AB thymoma cases. Type AB thymomas and type B thymomas showed more prominent crush artifacts in cell clusters than type A thymoma and thymic carcinoma. Thymic cells of type B thymomas and thymic carcinoma were arranged without whirling architecture in clusters. The proposed algorithm demonstrated a predictive rate of 88.8% for thymoma classification.
CONCLUSIONS: The stepwise classification of thymoma with FNAB may be useful in patients for whom an invasive diagnosis approach is not feasible.


Shinohara S, Hanagiri T, So T, et al.
Results of surgical resection for patients with thymoma according to World Health Organization histology and Masaoka staging.
Asian J Surg. 2012; 35(4):144-8 [PubMed]
OBJECTIVES: Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma.
PATIENTS AND METHODS: This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006.
RESULTS: A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n=6), pericardium (n=5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease.
CONCLUSIONS: Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically.


Nakamura S, Tateyama H, Taniguchi T, et al.
Multilocular thymic cyst associated with thymoma: a clinicopathologic study of 20 cases with an emphasis on the pathogenesis of cyst formation.
Am J Surg Pathol. 2012; 36(12):1857-64 [PubMed]
Multilocular thymic cysts (MTCs) are considered to be acquired lesions associated with various inflammatory conditions and/or malignant tumors. MTCs associated with thymomas are rare, with only 11 cases having been reported. On reviewing 110 consecutive patients with thymomas, we found 20 cases of MTCs. The patients included 18 men and 2 women aged 32 to 65 years (median 52 y). Eleven of the patients were symptomatic, and 6 presented with symptoms associated with inflammation. Computed tomography images were available for 11 patients, and cystic lesions were identified in 4 patients. The histologic subtypes of thymoma observed were: 3 tumors of type AB, 4 tumors of type B1, 9 tumors of type B2, and 4 tumors of type B3. In addition, 2 tumors were in advanced stages. Multilocular cystic structures accompanied by acute and chronic inflammation were observed in the remnant thymic tissues. Immunohistochemically, CK13 was diffusely expressed in the inner surface cells lining the cysts, whereas CK5/6 and p63 were primarily expressed in the basal cells of the cysts. D2-40 was weakly expressed in a small number of basal epithelial cells. The immunohistochemical profiles of the cysts were similar to those of Hassall corpuscles of normal thymi. A clinical follow-up showed that 15 patients continued to be alive without any evidence of disease, 1 patient with tumor recurrence continued to be alive, and 3 patients had died of other diseases. Our results suggest that MTCs associated with thymomas are not as uncommon as thought and may develop from the promotion of differentiation of increased numbers of epithelial cells into Hassall corpuscles by inflammatory processes. Our data also suggest a better clinical behavior for patients with thymomas accompanied by MTCs than patients with thymomas unaccompanied by those cysts, although further investigation is needed.


Fukumoto K, Taniguchi T, Ishikawa Y, et al.
The utility of [18F]-fluorodeoxyglucose positron emission tomography-computed tomography in thymic epithelial tumours.
Eur J Cardiothorac Surg. 2012; 42(6):e152-6 [PubMed]
OBJECTIVES: Positron emission tomography using [(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG-PET) plays an important role in many oncological settings. In this study, we assessed the utility of (18)F-FDG PET-CT for predicting the histologic type and stage of thymic epithelial tumours.
METHODS: We retrospectively analyzed 58 patients with thymic epithelial tumours who underwent PET-CT before treatment and investigated the relationship between the histologic type based on the World Health Organization classification and the maximum standardized uptake value (SUV(max)) of each tumour. We also analyzed the relationship between the Masaoka tumour stage and the SUV(max).
RESULTS: The study included 31 males and 27 females, ranging in age from 25 to 80 years (median: 62 years). The tumour histology of 44 tumours was thymoma and that of the remaining tumours was thymic carcinoma, including 11 squamous cell carcinomas and 3 carcinoids. The Masaoka tumour stage was as follows: Stage I in 8, Stage II in 24, Stage III in 18 and Stage IV in 8 patients. The patients were divided into three groups according to a simplified histologic classification: low-risk thymomas (types A, AB and B1, n = 23), high-risk thymomas (types B2 and B3, n = 21) and thymic carcinomas (n = 14). The SUV(max) of the thymic carcinoma group was significantly higher than those of the low-risk thymoma and high-risk thymoma groups (P < 0.001, respectively). No significant differences between the low-risk thymoma and high-risk thymoma groups were observed (P = 0.204). The SUV(max) of Stages III and IV thymomas showed a higher trend toward Stages I and II thymomas (P = 0.060).
CONCLUSIONS: PET-CT is a useful modality for predicting the histologic type and tumour stage of thymic epithelial tumours.


Michels G, Drebber U, Pfister R
Thymoma--an important differential diagnosis of mediastinal tumours.
Acta Clin Belg. 2012 Jul-Aug; 67(4):304-5 [PubMed]
A 69-year-old man with slight dyspnoea underwent routine X-ray examination by his primary care physician. The X-ray and the CT showed a homogenous mass at the right side of the anterior mediastinum. The benignity and the origin of the tissue were still unknown. Therefore, we performed a CT-guided fine needle aspiration biopsy of the mediastinal mass. Histopathological examination finds out a spindle-cell or type A thymoma. Based on these findings we decide for a thoracoscopic resection of the thymoma. After the surgical intervention the patient was completely asymptomatic. In conclusion, because thymomas are prone to ectopic occurrence, they should be considered in the differential diagnosis of mediastinal tumors.


Cornea R, Cîmpean AM, Simu M, et al.
Clinical, morphological and immunohistochemical characterization of a recurrent B1 type thymoma.
Rom J Morphol Embryol. 2012; 53(3):639-43 [PubMed]
Type B1 thymoma is widely accepted as a tumor with a non-aggressive behavior even in advanced stage. Most of these tumors are classified as Masaoka stage I or II. They rarely relapse or metastasize and the surgical treatment is considered curative. We have investigated a case of thymoma type B1, which relapsed 13 months after the primary tumor was excised. The patient was diagnosed with a local tumor recurrence after investigations due to the worsening of clinical symptoms of myasthenia gravis (MG). The therapy management of such cases is debatable and protocols not yet approved. For this reason, we have analyzed different clinical, morphological and immunohistochemical characteristics that may be considered as prognostic factors for a more aggressive behavior of such tumors. We have identified some morphologic characteristics rarely seen in this type of thymoma but none considered of prognostic value. In addition, we investigated some possible immunohistochemical markers that are generally associated with a more aggressive clinical outcome in different malignant tumors and thymic epithelial tumors. Among these markers, only p53 was positive and may be useful to predict a more aggressive evolution. In summary, probably the more appropriate approach of the patient is the clinical follow-up together with treatment of the clinical symptoms of myasthenia gravis.


Ma Y, Li Q, Cui W, et al.
Expression of c-Jun, p73, Casp9, and N-ras in thymic epithelial tumors: relationship with the current WHO classification systems.
Diagn Pathol. 2012; 7:120 [PubMed] Free Access to Full Article
BACKGROUND: To evaluate the expression and differential significance of c-Jun, p73, Casp-9 and N-ras in thymic epithelial tumors (TETs) with the aim to provide useful information for tumor biology and prospective therapy.
METHODS: In this study, we analyzed the expression of four chromosome 1-related genes, namely c-Jun, p73, Casp-9 and N-ras, in 60 cases of thymic epithelial tumors. The tumors included 52 thymomas and 8 thymic carcinomas which were categorized according to the current WHO classification systems.
RESULTS: Compared with the normal thymus tissue, all thymic epithelial tumors demonstrated higher expression of c-Jun and p73. The expression of c-Jun and p73 in type B2, B3 thymoma and thymic carcinomas was similar, and significantly higher than that in all other subtypes of thymomas. Unlike type A thymoma, the expression of Casp-9 was relatively lower in type B thymoma and thymic carcinomas. With respect to the clinical staging systems, c-Jun was more expressed in progressive tumors harboring higher stages. In contrast to c-Jun, p73 and Casp-9, there was no significant aberration with N-ras expression irrespective of either tissue or tumor types.
CONCLUSIONS: The overexpression of c-Jun, p73 and Casp-9 in thymic epithelial tumors is closely related with the pathogenesis and biological behavior of the neoplasms. These candidate biomarkers provided useful information for prospective personalized therapy in the clinical management. VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/1521774814749726.


Liu CJ, Wang J, Kuo WH, Yen RF
High 18F-fluorothymidine uptake for invasive thymoma.
Clin Nucl Med. 2012; 37(10):991-2 [PubMed]
We report an invasive thymoma discovered incidentally by an 18F-FLT (fluorothymidine) PET study on a 48-year-old woman. The patient had equivocal breast lesions in her bilateral breasts. She entered a clinical 18F-FLT PET trial in our hospital to differentiate malignant breast tumors from benign ones. No 18F FLT-avid lesions in her breasts were revealed. But an intense 18F-FLT uptake lesion was noted in her right anterior mediastinum. However, an F-FDG PET scan showed only mild F-FDG uptake in the lesion. Video-assisted thoracic surgery thymectomy was subsequently performed, and the final pathology showed invasive thymoma.


Boubaker A, Prior JO, Willi JP, et al.
Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide.
Eur J Nucl Med Mol Imaging. 2012; 39(12):1868-75 [PubMed]
PURPOSE: The biokinetics and dosimetry of (111)In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and (111)In-DTPA-octreotide (Octreoscan™, OCTREO) were compared in the same patients.
METHODS: Seventeen patients (10 men, 7 women; mean age 60 years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100 % reference scan), 4, 24 and 48 h (17 patients) and 120 h (5 patients) after injection. In 16 patients the OCTREO scan (178 ± 15 MBq) was performed 16 ± 5 days before the NOCATE scan (108 ± 14 MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5 min to 48 h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM.
RESULTS: Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p < 0.001) and remained so over time. Whole-body activity showed similar α and β half-lives, but the β fraction of NOCATE was double that of OCTREO. Blood T (1/2)β for NOCATE was longer (19 vs. 6 h). As a result, the effective dose of NOCATE (105 μSv/MBq) exceeded that of OCTREO (52 μSv/MBq), and the latter result was similar to the ICRP 106 value of 54 μSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5 % of NOCATE and OCTREO attached to globular blood components.
CONCLUSION: NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO.


Sun QL, Fang WT, Feng J, et al.
Proteome analysis and tissue array for profiling protein markers associated with type B thymoma subclassification.
Chin Med J (Engl). 2012; 125(16):2811-8 [PubMed]
BACKGROUND: The prognostic relevance of World Health Organization (WHO) subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma.
METHODS: Proteins extracted from twelve type B thymoma tissue specimens (six type B1 and six type B2) were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues (including B1, B2 and B3) by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman's Rank Correlation Test.
RESULTS: Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi (GSTP1) were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma (Z = -2.963, P < 0.01). Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group (type B2 vs. B1: Z = -2.582, P = 0.01; type B3 vs. B1: Z = -4.012, P ≤ 0.001). The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors (Spearman's correlation coefficient: 0.633, P ≤ 0.001). Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage (Spearman's correlation coefficients, ezrin: 0.481, P < 0.05; GSTP1: 0.484, P < 0.01).
CONCLUSIONS: Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.


Gökmen-Polar Y, Sanders KL, Goswami CP, et al.
Establishment and characterization of a novel cell line derived from human thymoma AB tumor.
Lab Invest. 2012; 92(11):1564-73 [PubMed]
Thymomas are low-grade epithelial tumors of the anterior mediastinum. The complexity of the disease and the lack of in vitro and in vivo models hamper the development of better therapeutics. In this study, we report a novel cell line, designated as IU-TAB-1, which was established from a patient with stage II thymoma (World Health Organization-type AB). The IU-TAB-1 cell line was established in vitro and characterized using histological and immunohistochemical staining, fluorescence-activated cell sorting, cytogenetic analyses and functional assays including in vitro and a NOD/SCID xenograft model. A whole-genome gene expression analysis (Illumina) was performed on the IU-TAB-1 cell line and 34 thymomas to determine the clinical relevance of the cell line. The IU-TAB-1 cell line was positive for epithelial markers (pan-cytokeratin and EpCAM/CD326) including thymic epithelial (TE) surface markers (such as CD29, CD9, CD54/ICAM-1, CD58 and CD24) and p63, and negative for B- and T-cell lineage markers. Gene expression profiling demonstrated overlapping and distinct genes between IU-TAB-1 and primary thymomas including the primary tumor (from which the cell line was derived). IU-TAB-1 cells are tumorigenic when implanted in immunodeficient mice with tumors reaching a volume of 1000 mm³ at around 130 days. The established cell line represents a biologically relevant new tool to investigate the molecular pathology of thymic malignancies and to evaluate the efficacy of novel therapeutics both in vitro and in vivo.


Weissferdt A, Wistuba II, Moran CA
Molecular aspects of thymic carcinoma.
Lung Cancer. 2012; 78(2):127-32 [PubMed]
Thymic carcinomas are tumors of the anterior mediastinum derived from the epithelial cells of the thymic gland. Due to their low incidence they are often investigated in combination with thymomas under the rubric of "thymic epithelial neoplasms" and studies exclusively addressing thymic carcinomas are sparse. Thymic carcinomas are characterized by their histologic variability, often resembling tumors seen in other organ systems. This morphologic variation coupled with their rarity has prevented large scale research of these tumors and little is known about the etiology, biologic behavior or best treatment for thymic carcinoma. In recent years, attempts have been made to investigate the molecular characteristics of these tumors in the hope that molecular profiling can be used to predict the prognosis or lead to the development of new treatment strategies. Herein we provide an overview of the recent advances of the molecular analysis of thymic carcinoma with particular emphasis on the potential use for molecularly targeted therapies.


Shien K, Shien T, Soh J, et al.
Ectopic cervical thymoma: a case report with 18F-fluorodeoxyglucose positron emission tomography findings.
Acta Med Okayama. 2012; 66(4):357-61 [PubMed]
Ectopic thymoma is considered to arise from ectopic thymus tissue deposited as a result of the abnormal mislocalization of thymus tissue during the embryonic stage. An 86-year-old man visited our hospital with chief complaints of hoarseness and a mass in his anterior neck. A preoperative needle biopsy of the mass did not yield a definitive diagnosis. A positron emission tomography (PET) study revealed heterogeneous accumulation of (18)F-fluorodeoxyglucose (FDG) in the tumor. The tumor, affecting the left sternocleidomastoid muscle, the recurrent laryngeal nerve, the internal carotid vein, and the brachiocephalic vein, was resected using a combination of a collar incision in the neck and a median incision in the sternum. Immunohistochemically, the tumor was diagnosed as an ectopic thymoma of the neck. To date, only a few cases of ectopic thymoma presenting with FDG accumulation have been reported. Our experience indicates that ectopic thymoma should be kept in mind during the differential diagnosis of neck tumors with FDG accumulation appearing on PET images.


Badve S, Goswami C, Gökmen-Polar Y, et al.
Molecular analysis of thymoma.
PLoS One. 2012; 7(8):e42669 [PubMed] Free Access to Full Article
Histologic classification of thymomas has significant limitations with respect to both subtype definitions and consistency. In order to better understand the biology of the disease processes, we performed whole genome gene expression analysis. RNA was extracted from fresh frozen tumors from 34 patients with thymomas and followup data was available. Using the Illumina BeadStudio® platform and Human Ref-8 Beadchip, gene expression data was analyzed with Partek Genomics Suite®, and Ingenuity Pathways Analysis (IPA). Unsupervised clustering of gene expression data, representing one of the largest series in literature, resulted in identification of four molecular clusters of tumors (C1-C4), which correlated with histology (P = 0.002). However, neither histology nor clusters correlated with clinical outcomes. Correlation of gene expression data with clinical data showed that a number of genes were associated with either advanced stage at diagnosis or development of recurrence or metastases. The top pathways associated with metastases were amino acid metabolisms, biosynthesis of steroids and glycosphingolipids, cell cycle checkpoint proteins and Notch signaling. The differential expression of some of the top genes related to both metastases and stage was confirmed by RT-PCR in all cases of metastases and matched nonmetastatic cases. A number of potential candidates for therapeutics were also identified.


Takizawa M, Oda M, Matsumoto I, et al.
Myasthenia gravis complicated with lung cancer and middle mediastinal thymoma.
Asian Cardiovasc Thorac Ann. 2012; 20(4):486-8 [PubMed]
Myasthenia gravis complicated by lung cancer is rare, and the association between myasthenia gravis and lung cancer is unclear. Thymoma located in the middle mediastinum is very rare. We describe a case of myasthenia gravis complicated with lung cancer and middle mediastinal thymoma in a 69-year-old woman.


Yoshida Y, Ueda R, Murakawa T, et al.
Thymoma hyalinized by steroid therapy in myasthenia gravis.
Asian Cardiovasc Thorac Ann. 2012; 20(4):479-81 [PubMed]
We encountered a 72-year-old woman with myasthenia gravis and thymoma who received glucocorticoid therapy for respiratory failure before undergoing thymectomy. After the antiacetylcholine receptor antibody titer was normalized, and the thymoma shrunk with prednisolone, the patient was free from symptoms. On pathological examination, the majority of the thymoma (type B2) had been hyalinized. Preoperative steroid therapy was effective in stabilizing myasthenia gravis and in inducing apoptosis of both epithelial and lymphocytic components of the thymoma.


Wang Y, Li L, Li Q, et al.
Expression of P120 catenin, Kaiso, and metastasis tumor antigen-2 in thymomas.
Tumour Biol. 2012; 33(6):1871-9 [PubMed]
Thymomas of the same histological subtype sometimes manifest different biological behaviors. Metastasis Tumor Antigen-2 (MTA2) is targeted by the transcriptional repressor Kaiso, the distribution which is thought to be modulated by p120catenin (p120ctn). It is currently unclear if expression of p120ctn, Kaiso, and MTA2 relates to the biological behavior of thymoma. P120ctn, Kaiso, and MTA2 expression were examined in 137 cases of thymoma, three cases of thymic carcinoma, and 18 paired autologous normal thymic tissues using immunohistochemistry, and correlation of these proteins with histological subtypes and clinical stages were analyzed. In normal thymic epithelial cells, p120ctn was expressed on the cell membrane but Kaiso and MTA2 were not detected. Membranous p120ctn expression was reduced in thymoma epithelial cells, while ectopic cytoplasmic expression was observed in 76.6 % (105/137) of the cases. Cytoplasmic Kaiso was detected in 69.3 % (95/137) and nuclear MTA2 was detected in 70.8 % (97/137) of the thymomas. There were good consistencies (Kappa = 0.559, 0.512, 0.652; all P < 0.001) and correlations (r = 0.733, 0.652, 0.708; all P < 0.001) between cytoplasmic p120ctn, cytoplasmic Kaiso, and nuclear MTA2 expression in thymomas. All three protein factors correlated with histological type and clinical stage in thymoma (P < 0.05). Specifically, cytoplasmic p120ctn and Kaiso expression and nuclear MTA2 expression were higher in high-risk (types B2 and B3) thymomas and Masaoka stage III/IV thymomas than low-risk (types A, AB, and B1) and stage I/II thymomas (both P < 0.001), respectively. Cytoplasmic p120ctn, cytoplasmic Kaiso, and nuclear MTA2 expression correlated directly with histological type and Masaoka stage and may thus be used as potential biomarkers to predict biological behavior of thymoma.


Moonim MT, Breen R, Gill-Barman B, Santis G
Diagnosis and subclassification of thymoma by minimally invasive fine needle aspiration directed by endobronchial ultrasound: a review and discussion of four cases.
Cytopathology. 2012; 23(4):220-8 [PubMed]
Thymomas have been classified by the World Health Organisation (WHO) into six groups, based on the morphology of epithelial cells and the ratio between epithelial cells and lymphocytes within the tumour. Among 1458 consecutive cases of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) performed in a tertiary referral centre between February 2008 and February 2012, we have encountered four cases of thymic neoplasms. We discuss the cytomorphological features of three cases of type B thymoma (one each of B1, B2 and B3 subtypes) and one case of thymic carcinoma diagnosed on EBUS-TBNA using cell blocks, immunocytochemistry and flow cytometry which allowed preoperative chemotherapy to be carried out in two cases, diagnosis to be made after unsatisfactory surgical mediastinoscopy in the third and diagnosis of lymph node metastasis of the thymic carcinoma in the fourth. The differential diagnosis and criteria for subclassification of thymomas are discussed; although subclassification of these cases was possible in these cases, and tumours other than thymoma excluded, additional cases would be necessary to assess the potential accuracy of EBUS-TBNA. These, to the best of our knowledge, represent the first cases of thymoma that were diagnosed and subclassified according to WHO criteria using multimodality evaluation of EBUS-derived cytological aspirates.


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