Histologic Classification of Thymoma and Its Relationship with Myasthenia Gravis and Clinical Stages of the Tumor

Objective： To investigate the relationship among the latest WHO classification of thymoma, myasthenia gravis （MG） and clinical stages. Methods： To review the pathological sections of 74 patients with thymoma from 1980-2004 using WHO classification （1999）, the statistical software was used to analyze the relationship among the WHO classification, MG and clinical stages. Results： （1） Two cases of type A, 23 cases of type AB, 4 cases of type B1, 27 cases of type B2, 16 cases of type B3 and 2 cases of type C were classified. Type B2 more likely accompanied MG （P〈0.05）, while none with MG occurred for type C. （2） One patient was in stage Ⅰ, 30 were in stage Ⅱ, 38 were in stage Ⅲ, and 5 were in stage Ⅳ. The latest histologic classification was significantly correlated with Masaoka stages （P〈0.01）. Conclusion： The latest WHO classification was correlated with occurrence of MG and finely reflected clinical stage. It can also evaluate the prognosis of patients.

Surgical approaches for stage Ⅰ and Ⅱ thymoma-associated myasthenia gravis:feasibility of complete video-assisted thoracoscopic surgery (VATS) thymectomy in comparison with trans-sternal resection

Complete resection could be achieved in virtually all myasthenic patients with Masaoka stage I and II thymoma us- ing the trans-sternal technique. Whether this is appropriate for minimally invasive approach is not yet clear. We evalu- ated the feasibility of complete video-assisted thoracoscopic surgery （VATS） thymectomy for the treatment of Ma- saoka stage I and Ⅱ thymoma-associated myasthenia gravis, compared to conventional trans-sternal thymectomy. We summarized 33 patients with Masaoka stage I and II thymoma-associated myasthenia gravis between April 2006 and September 2011. Of these, 15 patients underwent right-sided complete VATS （the VATS group） by us- ing adjuvant pneuomomediastinum, comparing with 18 patients using the trans-sternal approach （the T3b group）. No intraoperative death was found and no VATS case required conversion to median sternotomy. Significant differences between the two groups regarding duration of surgery and volume of intraoperative blood loss （P = 0.001 and P 〈 0.001, respectively） were observed. Postoperative morbidities were 26.7% and 33.3% for the VATS and T3b groups, respectively. All 33 patients were followed up for 12 to 61 months in the study. The cumulative probabilities of reaching complete stable remission and effective rate were 26.7% （4/15） and 93.3% （14/15） in the VATS group, which had a significantly higher complete stable remission and effective rate than those in the T3b group （P = 0.026 and P = 0.000, respectively）. We conclude that VATS thymectomy utilizing adjuvant pneuomo- mediastinum for the treatment of stage I and II thymoma-associated myasthenia gravis is technically feasible but deserves further investigation in a large series with long-term follow-up.

Long.term outcomes of 307 patients after complete thymoma resection

Background: Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection.Methods: We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College(Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses.Results: During follow?up(median, 86 months; range, 24–160 months), the 5? and 10?year disease?free survival(DFS) rates were 84.0% and 73.0%, respectively, and the 5? and 10?year overall survival(OS) rates were 91.0% and 74.0%, respectively. Masaoka stage(P < 0.001), World Health Organization(WHO) histological classification(P < 0.001), and postoperative radiotherapy after initial resection(P = 0.006) were associated with recurrence(52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura(25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence(41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post?recurrence survival. Patients with recurrent thymoma who underwent repeated resec?tion had increased post?recurrence survival rates compared with those who underwent therapies other than surgery(P = 0.017).Conclusions: Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post?recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

First description of cervical intradural thymoma metastasis

Thymoma and thymic carcinoma are rare epithelial tumors, which originate from the thymus gland. According to the World Health Organization there are "organotypic"(types A, AB, B1, B2, and B3) and "non-organotypic"(thymic carcinomas) thymomas. Type B3 thymomas are aggressive tumors, which can metastasize. Due to the rarity of these lesions, only 7 cases of extradural metastasis are described in the literature. We report the first and unique case of a man with cervical intradural B3 thymoma metastasis. A 46-year-old man underwent thymoma surgical removal. The year after the procedure he was treated for a parietal pleura metastasis. In 2006 he underwent cervical-dorsal extradural metastasis removal and C5-Th1 stabilization. Seven years after he came to our observation complaining left cervicobrachialgia and a reduction of strength of the left arm. He underwent a cervical spine magnetic resonance imaging, which showed a new lesion at the C5-C7 level. The patient underwent a surgery for the intradural B3 thymoma metastasis. Neurological symptoms improved although the removal was subtotal. He went through postoperative radiation therapy with further mass reduction. Spinal metastases are extremely rare. To date, only 7 cases of spinal extradural metastasis have been described in the literature. This is the first case of spinal intradural metastasis. Early individuation of these tumors and surgical treatment improve neurological outcome in patients with spinal cord compression. A multimodal treatment including neoadjuvant chemotherapy, surgery and postoperative radiation therapy seems to improve survival in patients with metastatic thymoma.

Reduction of natural regulatory T cells in thymomas accompanying myasthenia gravis and its possible association with Foxp3 and thymic stromal lymphopoietin

Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistochemistry and real-time reverse trancription polymerase chain reaction (real-time RT-PCR) techniques to determine Foxp3+ Treg counts and the expression levels of Foxp3 mRNA and TSLP mRNA in thymomas of 23 MG patients and thymuses of 4 healthy controls. Results: The CD4+ Foxp3+ nTreg (natural regulatory T cells) counts in thymomas were significantly lower than those in normal thymuses (P<0.01), and the expression levels of Foxp3 mRNA and TSLP mRNA were also lower in thymomas(P<0.01). Among the thymoma types, type B1 thymoma had the highest Foxp3+ nTreg count and standard values of Foxp3 mRNA and TSLP mRNA. There was a strong positive correlation between the mRNA transcriptional levels of Foxp3 and TSLP. Conclusion: The insufficient expression of Foxp3 in thymoma, which may be caused by decreased transcription of TSLP, may result in the reduction of Tregs and cause autoimmune disorders.

EXPRESSION OF β-CATENIN AND C-MYC IN THYMOMA AND THE ASSOCIATION WITH BIOLOGICAL FEATURES

Objective： β-catenin is closely associated with proliferation, differentiation, invasion and metastasis of tumor cells. C-myc is proved to be abnormally expressed in various kinds of malignant neoplasmas. This study is aimed to investigate the features of β-catenin and C-myc expressions in thymoma and the corresponding clinical significance. Method： Immunochemistry was used to detect the features of expressions of β-catenin and C-myc in thymoma and normal thymus. Of the 105 samples, according to Beratz classification, there were： epithelial type 34; lymphocyte type 35; mixed type 31 and shuttle cell type 5. According to Masaoka classification, there were： stage 1： 38; stage 2： 32; stage 3：20 and stage 4： 15. According to WHO classification, there were： type A 20; type AB 19; type B1 21; type B2 17; type B3 13 and type C 15. Results： Different ways of expression was revealed in different stages of thymomas. With the progress of thymoma, the expression of β-catenin on cell membrane decreased, while increased in cytoplasma and nucleus, even with nucleus shift. The expression of C-myc increased in invasive thymoma. Abnormal expression of β-catenin and C-myc increased, with significant difference（P〈0.05）. Conclusion： The different ways of expression and diversity of expression level may indicate the biological characters of thymoma, and could be used as an objective index for invasive thymoma.

Spontaneous rupture of hepatic metastasis from a thymoma: A case report

Bleeding resulting from spontaneous rupture of the liver is an infrequent but potentially life threatening complication that may be associated with an underlying liver disease. A hepatocellular carcinoma or hepatic adenoma is frequently reported is such cases. However, hemoperitoneum resulting from a hepatic metastatic thymoma is extremely rare. Here, we present a case of a 62-year-old man with hypovolemic shock induced by ruptured hepatic metastasis from a thymoma. At the first hospital admission, the patient had a 45-mm anterior mediastinal mass that was eventually diagnosed as a type A thymoma. The mass was excised, and the patient was disease-free for 6 years. He experienced sudden-onset right upper quadrant pain and was again admitted to our hospital. We noted large hemoperitoneum with a 10-cm encapsulated mass in S5/8 and a 2.3-cm nodular lesion in the right upper quadrant of the abdomen. He was diagnosed with hepatic metastasis from the thymoma, and he underwent chemotherapy and surgical excision.

NEOADJUVANT CHEMOTHERAPY AND OPERATION FOR INVASIVE MASAOKE STAGE Ⅲ AND Ⅳa THYMOMA

Objective: Evaluation the role of neoadjuvant chemotherapy in invasive thymoma. Methods: 14 patients with invasive thymoma(Masaoka stage Ⅲ in 12 and Ⅳa in 2) were treated with neoadjuvant chemotherapy by CAVP for 3-4 cycles (cyclophosphamide 600mg/m2 D1, adramycin 30mg/m2 or epi-adramycin 40mg/m2 D1, vincristine 0.6mg/m2 D1 or vindestine 3mg/m2 D1、D8, cisplatin 30mg/m2 D1、2、3)。After chemotherapy, all patients underwent operation in 1-3 months. We performed 10 sternotomies and 4 anterolateral thoracotomies. Radiotherapy was administrated with total dose 50-60Gy in all patients except for those who were pathologically complete remission. The group was followed up by 6 months to 3 years. Results :After chemotherapy, 5 patients(35.7%) had a complete remission(CR) and 9 patients(64.3%) had a partial remission(PR)。At operation, 9 patients had radical resection and 5 had partial resection. Postoperative pathological examination found only fibrosis in 5 patients with CR by chemotherapy. All patients were still alive except 2 patients died from visceral metastasis after 18 months and 2 years respectively. Conclusion: Neoadjuvant chemotherapy can increase the resectability of stage Ⅲ and Ⅳa invasive thymoma. A longer follow-up and a larger number of patients are needed to determine the impact of this treatment on long-term survival.

Effect of chemotherapy on autoimmune hepatitis in thymoma:a case report and literature review

Autoimmune hepatitis(AIH) has rarely been described as an autoimmune paraneoplastic syndrome of thymoma.This case is the seventh case of AIH revealed by cholestasis few years after the diagnosis of thymoma and the first case treated with chemotherapy alone.We report in this paper a new approach to this rare severe condition.A 29 year-old man presented with chest pain and dyspnea with a history of thymoma surgically removed 4 years ago.CT scan showed the recurrence of an anterior mediastinal mass.Biology showed elevated liver enzymes and profound cholestasis.No sign of viral or toxic hepatitis or bile duct abnormalities were observed.Autoimmune antibodies,except for the anti-nuclear antibody,were negative.Liver biopsy showed active chronic AIH.The patient was diagnosed with recurrent thymoma with AIH and underwent 6 cycles of chemotherapy.A complete response on thymoma and cholestasis was obtained after 10 months of follow-up.Steroids and immunosuppressors are the standard treatment for AIH.The effect of chemotherapy as a specific treatment of this paraneoplastic syndrome needs to be considered.

Two Ectopic Hamartomatous Thymomas of Suprasternal Region of the Neck in A Single Patient:A Case Report

Ectopic hamartomatous thymoma is a rare,generally benign neoplasm that mainly arises in the lower neck region and is yet to be completely understood.Herein,we describe a case with two separate and sequential growing neoplasms for the first time,distinguished from other reported solitary cases.A 58-year-old Chinese male presented with a 6-month history of two nontender,self-palpated masses in the suprasternal region of his neck.Physical examination revealed two masses with diameters of 5 cm and 2 cm.Ultrasound examination 2 years ago revealed a hyperechoic mass with a fat-derived possibility.These two neoplasms were clinically diagnosed as lipomas without other radiological examinations and were completely excised.Microscopically,they were well circumscribed and characterized by admixture with spindle cells,epithelial nests,and adipocytes in variable amounts,without atypia or mitotic activity.Immunohistochemical staining revealed that both neoplasms showed a biphasic pattern,with an epithelial nature with strong and diffuse positive expression of cytokeratin(CK)and myoepithelial differentiation with CK5/6 and p63 positivity in the spindle cells.There was no evidence of recurrence after a 28-month follow-up period.In this report,we present a unique case of ectopic hamartomatous thymoma to show the existence of multiple tumors in this rare disease.We hope to raise the awareness of the possibility of this disease when the tumor rises in typical lower neck regions,especially when mixed soft tissue or fat components are shown by imaging examination.

Swimming Heart: A Pleural, Pulmonary and Pericardial Disseminated Thymoma

Thymoma is the most common neoplasm of the anterior mediastinum and accounts for one quarter of all mediastinal tumours and half of all anterior mediastinal masses. Pericardial effusion may be present in approximately 20% of cases. This report presents a patient with a previously diagnosed thymoma without surgical indication and with poor response to chemotherapy and radiotherapy who had a pericardial effusion that likely resulted from the malignancy dissemination to pericardium.

Comparative analysis of postoperative outcomes of myasthenia gravis with and without thymoma

Objective: To explore the postoperative clinical characteristics and outcomes of myasthenia gravis with and without thymoma. Methods: Two hundred and forty-three patients with myasthenia gravis(MG) surgically treated in our department from 1978 to 2003 were studied retrospectively. The clinical characteristics, complication, remissions and survival rates were compared between MG with and without thymoma. Results: The patients of MG with thymoma were significantly older (P<0.01), had shorter duration of symptom(P<0.01), and higher myasthenia crisis rates after operation(P<0.01) than those without thymoma. No difference of Osserman classification was found between the 2 groups. The complete remission rates and partial remission rates of MG with thymoma were significantly lower than those without thymoma at 1 and 3 years(P=0.049, P=0.000, P=0.015, P=0.010), but no differences at 5 years(P=0.457, P=0.699). The survival rates were lower in MG with thymoma than without thymoma(Log rank=18.58,P=0.000). Conclusion: The clinical characteristics are different between MG with and without thymoma. The remission of symptom of MG with thymoma is worse than that of MG without thymoma in the near future, but similar in the long future. In a long-term, the death rate of MG with thymoma is significantly higher than that of MG without thymoma.

Autoimmune Hepatitis-Primary Biliary Cirrhosis: Overlap Syndrome Concomitant with Unexpected Myasthenia and Thymoma

The myasthenia gravis is an autoimmune disease which can be associated frequently with a thymoma and also with autoimmune pathologies. We report the case of a 64-year-old man affected an overlap syndrome corresponding to the association of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). He also presented concomitant myasthenia gravis and thymoma. The physical examination notes only a disturbed voice. The liver tests showed: alkaline phosphatase 600 U/l, alanine aminotransferase 1280 U/l, and aspartate aminotransferase 985 U/l. Viral serologies of hepatitis were all negative, as well as antinuclear, antimitochondrial and antismooth muscle antibodies. The diagnosis of an overlap syndrome was posed according to the biological and hepatic histhological results. An associated myasthenia was confirmed by the results of the EMG and the positivity of the anti-acetylcholine receptor antibody. A chest CT revealed a thymoma. The treatment consisted of ursodeoxycholic acid, prednisone, azathioprine and pyridostigmine. And the patient improved his voice and the liver function. Thymectomy was practiced without incidents.

Effect of Age on the Clinicopathological Characteristics and Survival Outcomes of Thymoma Patients

Background: Age is an important prognostic factor for thymoma;however, few studies have specifically focused on age-related survival outcomes in thymoma patients. This study explored the effect of age on the clinicopathological features and survival outcomes of thymoma patients. Methods: We reviewed the clinical data of 1984 chest thymoma patients from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. In accordance with the World Health Organization age brackets, the patients were divided into young (group A, 0 - 44-year-old);middle-aged (group B, 45 - 59-year-old);old (group C, 60 - 74-year-old);and seniors (group D 75 - 84-year-old). Single-factor and multivariate analysis were performed using the Kaplan-Meier method, and a multivariate Cox regression model was generated to assess patient prognosis. Results: In total, 1984 patients were included. The median follow-up time was 156.0 months (range: 0 - 492 months). Group C (60 - 74-year-old) had the most patients (35.1%), and Group D had the fewest patients (12.3%). Among all age groups, the proportion of white people and men with thymoma increased with age, while the proportion of black people and women showed a downward trend. Univariate and multivariate analyses showed that the overall survival rate of thymoma patients was negatively correlated with age. The overall survival times of the four groups were significantly different (p Conclusion: Age is an important prognostic factor for survival in thymoma patients, and younger patients have a survival advantage over older patients.

Expression and clinical significance of EGFR, PCNA, Bcl-2 and Bax in thymoma

Objective:To study the expressions and clinical significances of PCNA, EGFR, Bcl-2 and Bax in thymoma. Methods: The expressions of EGFR, PCNA, Bcl-2 and Bax in 46 cases of thymoma and 11 cases of normal thymus were detected with S-P immunohistochemistry. The results were analyzed with the pathologic indexes. Results: The positive rates of EGFR, Bcl-2 and Bax in normal thymus were 18. 2%, 9. 1%,and 18.2% respectively, while in thymoma were 71.7%, 41.3%, and 15.2% separately. The expression of EGFR in thymoma was significantly correlated with Masaoka staging and Levine classification. The survival rate of EGFR negative patients was significantly higher thanthat of EGFR positive patients (P＜0. 01). PCNA labelling index was significantly higher in thymoma as (4.00±1.87)% than in normal thymus, (2.68±0. 62)% , which was significantly correlated with Levine classification. The expression of Bcl-2 in thymoma was also significantly correlated with Levine classification. The survival rate of Bcl-2 negative patients was significantly higher than that of Bcl-2 positive patients (P＜0. 01). The expression of PCNA, EGFR, Bcl-2and Bax in thymoma had no correlation with histologic type and myasthenia gravis (MG) (P＞0. 05). Conclusion: The expression of EGFR may be involved in the occurrence and development of thymoma. EGFR can be regarded as a supplementary predictor for Masaoka staging so as to predict the progression accurately.The expression of Bcl-2 may contribute to the occurrence of thymic carcinoma and Bcl-2 can be used as a biomarker identifying thymic carcinoma.

Prognostic analysis of patients with thymoma after resection

Objective: To explore the prognostic factors influencing the long term survival rate of thymoma after resection. Methods: Sixty nine patients with thymoma surgically treated in our department from 1973 to 2000 were retrospectively studied. The possible prognostic factors were analyzed by univariate analysis and multivariate analysis with Kaplan Meiter method and Cox proportional hazard model respectively. Results: Overall patients survival rates were 83.3%, 67.4%, 48.3% at 5, 10, 15 years. The significant prognostic factors ( P <0 05) demonstrated by univariate analysis included age, Masaoka staging, WHO histological classification, resection method and Rosai/Levine classification. According to multivariate analysis, the independent prognostic factors included Masaoka stage ( P <0 01), resection method ( P <0 05) and age ( P <0 05). Conclusion: Complete surgical resection of thymomas helps increase the long term survival rate.

Rare Case of a Patient with Newly Diagnosed Thymoma Presenting with Paraneoplastic Systemic Lupus Erythematosus, Myasthenia Gravis, and Hypogammaglobulinemia

A Pleural mass biopsy was performed showing an invasive thymoma. Computed tomography (CT) scan of the chest performed on admission revealed a left sided pleural mass, anterior mediastinal mass, lymphadenopathy and pericardial effusion. Pleural mass biopsy showed an invasive thymoma. Due to her clinical presentation, a complete work-up was performed revealing paraneoplastic systemic lupus erythematous (SLE), myasthenia gravis (MG) and hypogammaglobulinemia. We reviewed the literature regarding thymoma and its relationship with paraneoplastic SLE, MG and hypogammaglobulinemia.

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Thymoma-associated Severe Aplastic Anemia: a Case Report

THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myastnema gravls ano pure red cell aplasia are the most common disorders, with the incidences of 40% and 5%, respectively, while the incidence of aplastic anemia is only about 0-1.4%. 1 Thymectomy is hard to perform on patients with severe aplastic anemia（SAA） due to severe pancytopenia.

Huge Congenital Thymic Cyst with Microscopic Thymoma

The congenital thymic cysts are rare. They have a congenital origin and they are benign. The differential diagnosis of acquired cysts, cystic thymoma and thymic malignancies in cystic degeneration can be particularly difficult. Rarely, they assume clinical relevance for the appearance of symptoms of compression, more typical of malignant lesions, and the association with thymoma was reported in very few cases in literature. For all these features, treatment strategy remains controversial and in particular surgical approach. We report a case of a huge symptomatic congenital thymic cyst, surgically removed with histological finding of microscopic thymoma.

Invasive Thymoma with Endobronchial Polypoid Growth

Thymomas are the most common neoplasms of the mediastinum. It is common that thymoma invades neighboring structures in the thorax, but direct polypoid tumor growth into the airway is extremely rare. We report a rare case of invasive thymoma with polypoid endobronchial growth in a 66-year-old woman. Computed tomography demonstrated an anterior mediastinal tumor which extended into the right upper lobe. Endoscopic examination revealed a polypoid tumor which occluded the right upper bronchus. A biopsy specimen obtained from the intraluminal mass was very suggestive of thymoma. The patient had no parathymic syndrome. The tumor was resected with the right upper lobe. The final post-operative tissue findings confirmed a type B2 thymoma of the World Health Organisation classification.