Previous mediastinal surgery may be considered a contraindication to minimally invasive resection of anterior mediastinal masses. We have found video-assisted thoracoscopic resection of anterior mediastinal masses to be technically feasible after sternotomy or chamberlain procedures. Changes in positioning and port location may facilitate these procedures.

OBJECTIVE: As the number of elderly patients with myasthenia gravis (MG) has recently increased in Europe and the USA, a retrospective survey of Japanese MG patients was conducted in a single neurological centre over several decades. METHODS: The study consisted of 112 consecutive MG patients with onset of the disease from 1971 to 2006 from an area of approximately 0.8 million inhabitants in Japan. Patients were classified into three subgroups according to age at onset: young onset (39 years old), middle aged onset (40-59 years old) and elderly onset (60 years old). The trends in incidence rate and clinical features were examined: disease severity, seropositivity for antiacetylcholine receptor antibody, occurrence of other autoimmune diseases, occurrence of thymoma and therapeutic response. RESULTS: The onset adjusted age specific average annual incidence per 100,000 of the elderly onset MG patients increased 20-fold from 1981-1990 (0.06; 95% CI 0.00 to 0.36) to 2001-2006 (1.30; 95% CI 0.77 to 2.05). Clinical features of the elderly onset MG patients included low antiacetylcholine receptor antibody titres (mean 24.6 nmol/l), less frequent autoimmune overlaps (8.0%) and nearly no complete stable remission with or without thymectomy. CONCLUSION: The increasing incidence of elderly onset MG in Japanese patients similar to that reported in Caucasians has been confirmed. The clinical features suggest different immunological backgrounds between young onset and elderly onset MG patients, irrespective of the ethnic background.

BACKGROUND: The optimal treatment method for thymoma with pleural dissemination remains controversial. We analyzed our experience with a multimodality approach and evaluated the role of extrapleural pneumonectomy (EPP) in the treatment of disseminated thymoma. METHODS: Multimodality therapy was used to treat 11 consecutive patients with invasive thymoma disseminated into the pleural cavity. Disease was stage IVa in 9 and stage IVb disease with lymph node metastasis in 2. Our treatment strategy for those patients was induction chemotherapy with cisplatin, doxorubicin, and methylprednisolone (CAMP therapy), followed by thymectomy combined with resection of the visible disseminated nodules and postoperative radiotherapy. EPP was applied for 4 patients who had chemoresistant tumors or pleural refractory recurrence. RESULTS: Eight patients underwent induction chemotherapy. The response rate to CAMP was 85%. Thymectomy with or without the resection of disseminated pleural tumors was performed in 7 patients and EPP in 3. Postoperative radiotherapy was administered in 6. All patients except 1 with EPP had recurrence: pleural recurrence in 7, lung in 1, and multiple organs in 2. Nine patients were retreated with chemotherapy, radiotherapy, pulmonary metastasectomy, or pleurectomy. One underwent EPP for pleural recurrence. Consequently, among the 7 patients without EPP, only 1 was alive without disease and 4 were alive with pleural recurrence. In contrast, 3 of the 4 patients with EPP had no local failure and were alive without recurrence. CONCLUSIONS: In multimodality therapy for thymoma with pleural dissemination, EPP offers good local control and may lead to cure.

BACKGROUND AND OBJECTIVES: Allograft-prosthetic composite for reconstruction of the proximal femur after tumor excision is widely used as an alternative to megaprosthesis. To achieve greater biological fixation, we employed a long-stem prosthesis that is cemented proximally into the extracorporeally irradiated autograft and press-fit distally into the host femur without any supplementary plate fixation of the junction instead of the standard all-cemented technique. METHODS: From 1997 to 2002, 14 patients underwent proximal femur reconstruction with extracorporeally irradiated autograft-prosthetic composite using an AML extensively porous-coated long stem for reconstruction of the bone defect of tumor excisions. RESULTS: At the mean follow-up period of 65.7 months, only one patient (8.1%) developed non-union and another died of disease before union of the junction. The remaining 12 patients (85%) achieved union at a mean of 20.3 weeks (range, 14-40 weeks) without major complication. The mean functional Enneking score was 72.1% (range, 53-93%). CONCLUSIONS: These clinical results show that this reliable and satisfactory technique promotes union through compression at the host-graft junction with weight-bearing by leaving the distal portion of the femoral stem uncemented into the host bone. (c) 2009 Wiley-Liss, Inc.

BACKGROUND: Immunodeficiency with a thymoma (Good's syndrome) is a rare condition occurring in patients with adult-onset hypogammaglobulinaemia. CLINICAL REPORT: We describe the case of a 38-yr-old woman with an upper mediastinal mass and inflammatory infiltrations in the lungs. After thymectomy, the patient's condition did not improve. The HRCT scan showed bronchiectasies with parenchymal opacities. As pulmonary infection persisted despite wide spectrum antibiotic therapy, additional tests were performed to diagnose an immunodeficiency. Serum immunoglobulin levels were very low. T cell response to mitogens was normal, but to Staphylococcus aureus Cowan I was impaired. Immunophenotyping of peripheral blood and bone marrow aspirate showed a very low number of B-cell at all the stages of development (CD10+CD19+, CD5+CD20). In peripheral blood 2.5% of CD19+ lymphocytes were found. On the basis of clinical history and immunological analysis, Good's syndrome was recognized. Treatment with intravenous gammaglobulin and antibiotics improved the patient's performance. CONCLUSION: Measurement of serum immunoglobulin concentration is recommended for all patients suspected of thymoma.

Benign thymic hyperplasia (TH) is a known feature of hyperthyroidism. In most cases, thymic enlargement is minimal; however, this syndrome may occasionally appear as an appreciable anterior mediastinal mass. Recognition of the benign nature of TH and its regression following treatment of the hyperthyroidism is important to prevent unnecessary surgical procedures. We present a case of TH associated with hyperthyroidism due to Graves' disease.

Thymic lymphoepithelioma-like carcinoma is a rare subtype of thymic cancer with a poor prognosis; a few cases have been reported in the English literature. Strong clinical suspicion should be pursued in patient management decision making despite initial diagnostic studies, which sometimes mcould islead clinicians, as in our case.

BACKGROUND: Treatment of thymoma is often based on observation of only a few patients. Surgical resection is considered to be the most important step. Role of a pseudocapsula for surgery, its clinical significance and outcome compared with established prognostic parameters is discussed which has not been reported so far. METHODS: 84 patients with thymoma underwent resection and analysis was carried out for clinical features, prognostic factors and long-term survival. RESULTS: Fifteen patients were classified in WHO subgroup A, 21 in AB, 29 in B and 19 patients in C. Forty two patients were classified in Masaoka stage I, 19 stage II, 9 stage III and 14 stage IV. Encapsulated thymoma was seen in 40, incomplete or missing capsula in 44 patients. In 71 complete resections, local recurrence was 5%. 5-year survival was 88.1%. Thymomas with pseudocapsula showed a significant better survival (94.9% vs. 61.1%, respectively) (p = 0.001) and was correlated with the absence of nodal or distant metastasis (p = 0.04 and 0.001, respectively). Presence of pseudocapsula as well as the Masaoka and WHO classification, and R-status were of prognostic significance. R-status and Masaoka stage appeared to be of independent prognostic significance in multivariate analysis. CONCLUSION: Intraoperative presence of an encapsulated tumor is a good technical marker for the surgeon to evaluate resectability and estimate prognosis. Although the presence of a capsula is of strong significance in the univariate analysis, it failed in the multivariate analysis due to its correlation with clinical Masaoka stage. Masaoka stage has a stronger relevance than WHO classification to determinate long-term outcome.

BACKGROUND: For patients with a thoracic malignancy whose peripheral veins are not suitable for blood access for chemotherapy, we evaluated a totally implantable central venous access port, in which the port is implanted in the ulnar side of the arm and the catheter is introduced via the basilic vein into the superior vena cava (TIAP-BV). METHODS: Twenty-five patients (21 with lung cancer, 2 with malignant pleural mesothelioma, and 2 with thymoma) receiving TIAP-BV were included. Indications, surgical complications, and long-term complications were analyzed. RESULTS: Indications for TIAP-BV were: chemotherapy (17 patients) and chemotherapy with parenteral nutrition (8 patients). The following surgical complications occurred: arrhythmia due to misplacement of the tip of catheter (1 patient); intraoperative conversion from the left to right arm (2 patients); and hematoma at the implantation site (1 patient). Short-term problems were: death 1 week after implantation without the use of TIAP-BV (2 patients). Long-term complications were: skin ulcer at the port site (1 patient); early removal of TIAP-BV because of port site infection (1 patient); catheter occlusion (1 patient); and venous thrombosis of basilic vein (2 patients). In the 22 patients who did not die early or have the device withdrawn early, the median duration of TIAP-BV use was 7 months (range, 1 to 20 months) without any break to the port system, leakage of drugs, or catheter-related infections. CONCLUSION: TIAP-BV can be employed for long-term use for chemotherapy and parenteral nutrition. However, a patient's expected prognosis and infectious disease status at the time of implantation surgery should be considered before the surgery proceeds.

A 60-year-old woman presented with a palpable and painful nodule of her neck. Physical examination revealed that the anterior neck mass was enlarged without other positive findings. The tumor was not diagnosed with a fine needle aspiration biopsy, so that the excision of the tumor was underwent. The diagnosis at permanent section analysis revealed a non-invasive thymoma. The patient did not receive adjunctive postoperative therapy. For the duration of 6.5-year follow-up, metastasis of the left lobe of thyroid and right upper lobe of lung in twice have been sequentially detected and resected, and now she has been healthy with no known recurrence of the tumor. The recurrence of a non-invasive cervical ectopic thymoma has been reported as extremely rare, and this case indicates that the surgical control for recurrence lesion of cervical ectopic thymoma is effective when the tumor is resectable.

Along with myasthenia, other paraneoplastic neurological syndromes (PNS) may occur in thymoma. Anti-Hu antibodies and a clinical "anti-Hu syndrome" characterized by encephalitis and/or painful neuropathies have been reported in only three patients at the time of the diagnosis of thymoma. We describe a severe anti-Hu-related autonomic neuropathy with gastrointestinal paresis and intestinal pseudo-obstruction with malabsorption that occurred concomitantly with the worsening of myasthenic symptoms long after the initial diagnosis of thymoma in a young patient. The clinical anti-Hu syndrome preceded the radiological diagnosis of thymoma recurrence. Treatment with plasma exchange led to a transient improvement of neurological symptoms.

OBJECTIVE: Recurrent intrathoracic thymomas may have an unpredictable behavior. Cell-cycle protein expression has proven useful in predicting outcome in a variety of neoplasms. We investigated its potential prognostic importance in recurrent intrathoracic thymomas. METHODS: We reviewed the case histories of 25 consecutive patients operated on between 1987 and 2004 for intrathoracic recurrence (7 mediastinal, 18 nonmediastinal) after radical thymomectomy. Complete resection was performed in 14 patients. In the other 11 patients incomplete resection was followed by chemotherapy and radiotherapy. Expression of cell-cycle proteins (p53, p21, and p27) was assessed by immunohistochemistry in specimens retrieved from both initial and recurrent thymomas. Univariate and multivariate analysis for prognostic factors present at the time of the recurrence was performed. RESULTS: Eight of 14 patients who underwent complete resection had a second recurrence after a mean free interval of 20 +/- 9 months, and a new complete resection was reperformed in 4. After incomplete resection, chemotherapy and radiotherapy allowed total remission in 4 subjects and only 1 of these had a second recurrence. Survival after surgery of the recurrence was negatively influenced by incomplete recurrence resection (P = .03), first disease-free interval less than 24 months (P = .03), high p53 (P = .04), low p21 (P = .02), low p27 (P = .003) expressions, and combination of these proteins (p53 high, p21 low, p27 low expression) (P = .0001). Multivariate analysis selected the triple combination of cell-cycle protein expression as the most significant prognostic variable (P = .02, odds ratio = 11.96, 95% confidence interval = 1.39-102.63). CONCLUSIONS: Cell-cycle protein expression, and namely the combination of high p53, low p21, and low p27 expression, may have a potential prognostic importance in recurrent intrathoracic thymomas.

OBJECTIVE: Thymic carcinomas are considered to be more aggressive than thymomas and carry a worse prognosis. We reviewed our recent experience with the surgical management of thymic tumors and compared the outcomes and patterns of relapse between patients with thymic carcinoma and those with thymoma. METHODS: We performed a single-institution retrospective cohort study. Data included patient demographics, stage, treatment, pathologic findings, and postoperative outcomes. RESULTS: During the period 1995-2006, 120 patients with thymic tumors underwent surgical intervention, including 23 patients with thymic carcinoma and 97 patients with thymoma, as classified according to the World Health Organization 2004 histologic classification. The overall 5-year survival was significantly different between patients with thymic carcinoma and those with thymoma (thymic carcinoma, 53%; thymoma, 89%; P = .01). Data on relapse were available for 112 patients. The progression-free 5-year survival was also significantly different between patients with thymic carcinoma and those with thymoma (thymic carcinoma, 36%; thymoma, 75%; P < .01). Using multivariate analysis, thymic carcinoma and incomplete resection were found to be independent predictors of progression-free survival. Relapses in patients with thymic carcinoma tended to occur earlier, and occurred significantly more frequently at distant sites than in patients with thymoma (60% vs 13%, P = .01). CONCLUSIONS: Patterns of relapse differ significantly between patients with thymic carcinoma and those with thymoma, with lower progression-free survival, earlier onset, and more distant relapses in patients with thymic carcinoma. Given the greater propensity for distant failures, the inclusion of systemic therapy in the treatment of thymic carcinoma might take on greater importance. Despite significantly higher rates of distant relapse, good overall survival in patients with thymic carcinoma can be achieved.

Thymus is an important central lymphoid organ that plays a pivotal role in the generation of peripheral T-lymphocytes. Thymoma and thymus hyperplasia have been associated with various autoimmune disorders, mainly myasthenia gravis. There is no established relationship between thymus pathology and antiphospholipid syndrome; however, there are some reported cases of antiphospholipid syndrome associated with myasthenia gravis or following thymectomy. We present the case of a patient with antiphospholipid syndrome and thymic lymphoid follicular hyperplasia. We discuss the association between both entities and suggest a diagnostic approach of a patient with a radiological disorder of the thymus and antiphospholipid syndrome.

We report a very rare case of extralobar sequestration and pericardial agenesis in a 22-year-old man. A computed tomographic (CT) scan demonstrated an anterior mediastinal mass. No aberrant artery was preoperatively identified. The patient underwent surgery with an impression of thymoma. An extralobar sequestration receiving its blood supply from the left pulmonary artery, accompanied with pericardial agenesis, was noted at the time of operation. The anterior mediastinum is an unusual site for extralobar sequestions. It is recommended to include extralobar sequestration in the differential diagnosis of anterior mediastinal masses, even if the aberrant artery is not recognized on the computed tomographic scan.

We believe there has been only one ossifying thymoma reported in the English literature. We herein reported another such case with additional peculiar presentation of peripheral T-cell lymphocytosis. A 62-year-old woman was incidentally found to have an anterior mediastinal tumor during a medical check-up, which was surgically resected 42 months later and histopathologically confirmed to be a type B1 thymoma with stromal ossification. Fifty months after tumor removal, this patient remains alive and well without relapsed disease.

INTRODUCTION: Thymoma is a rare tumor for which there is little randomized evidence to guide treatment. Because of the lack of high-quality evidence, a formal consensus-based approach was used to develop recommendations on treatment. METHODS: A systematic refview of the literature was performed. Recommendations were formed from available evidence and developed through a two-round modified Delphi consensus approach. RESULTS: The treatment recommendations are summarized as follows: Stage I--complete resection of the entire thymus without neoadjuvant or adjuvant therapy. Stage II--complete resection of the entire thymus with consideration of adjuvant radiation for high-risk tumors. Stage IIIA--surgery either initially or after neoadjuvant therapy, or surgery followed by adjuvant therapy. Stage IIIB--treatment may include a combination of chemotherapy, radiation, and/or surgery, or if technically possible, surgery in combination with chemoradiotherapy (concurrent cisplatin based). For bulky tumors, consideration should be given to sequential chemotherapy followed by radiation. Stage IVA--as per stage III, with surgery only if metastases can be resected. Stage IVB--treatment on an individual case basis (no generic recommendations). Recurrent disease--consider surgery, radiation, and/or chemoradiation. Chemoradiation should be considered in all medically inoperable and technically inoperable patients. CONCLUSION: Consensus was achieved on these recommendations, which serve to provide practical guidance to the physician treating this rare disease.

Lymphomatoid papulosis (LyP) is a disease characterized by cyclic eruptions of papulonodular lesions, which undergo spontaneous healing. Lymphoid malignancies are present in 10%-15% of cases. The type AB thymoma is an epithelial neoplasm composed of both type A (lymphocyte-poor) and type B (lymphocyte-rich) areas. Chemokines are chemotactic cytokines, responsible for leukocyte motility and direct movement. Interactions between chemokines and their receptors have been correlated with homing of lymphoma cells to various tissues. We describe a patient whose type B LyP CD8 lesions completely resolved after surgical removal of type AB thymoma. The chemokine profile was similar in both tissues: thymus- and activation-regulated chemokine and CCR4 were focally positive in the thymoma. Thymus- and activation-regulated chemokine was positive in the epidermotropic cells and in the majority of the dermal lymphocytes in the LyP specimen, whereas CCR4 was focally positive in the dermal lymphocytes. Monokine induced by interferon-g (Mig) staining showed strong positivity in the dermal lymphocytes and in localized areas of the thymoma, but an immunostain for the Mig receptor (CXCR3) highlighted only a few scattered cells in both tissues (less than 3%). Both tissues were negative for regulated upon activation, normal T-cell expressed and secreted (RANTES) and CCR3. In summary, we report the association of a CD30-negative CD8-predominant LyP and a type AB thymoma, with similar chemokine profiles. The rarity of both conditions and the precise regression of LyP after removal of the thymoma argue against a coincidental observation. We recommend that a search for thymoma be included in the workup of LyP. Further chemokine profiling in other cases of LyP may assist in understanding their role in this disease.

PURPOSE: Thymectomy has been widely employed in the treatment of myasthenia gravis (MG). However, little data exist in Iran demonstrating the efficacy and morbidity of thymectomy. The aim of this study was to determine the clinical features, diagnostic approach, and therapeutic outcome in patients with MG who underwent thymectomy. METHODS: This historical cohort study was conducted in 3 university hospitals in Tehran. Preoperative and operative indices of 61 patients with MG who had been treated with thymectomy in these hospitals from September 2000 to July 2005 were reviewed. Among them, 20 patients were followed during one year after operation for determination of postoperative complications and one year mortality rate. RESULTS: The most common manifestations of MG were ptosis (77.0%) and upper limbs weakness (70.4%). CT scans of the thymus showed thymus enlargement, thymoma and thymus hyperplasia in 51.5% (22/43), 11.6% (5/43) and 2.32% (1/43) of patients, respectively. The postoperative complications were found in 13.1% of patients and one year mortality rate of thymectomy was 6.6%. CONCLUSION: Regarding to high one year mortality rate of thymectomy in patients of MG in this study, the assessment of the factors related to the mortality and outcome of patients who underwent thymectomy in Iran are necessary.

Mediastinal mass is not an unusual entity. It occurs mostly due to lymphoma, thymoma, germ cell tumours, granulomatous diseases, and so on. Tuberculosis is an uncommon cause of mediastinal mass. It is rarely suspected when it is presented in such an unusual way. We report here a case of a 35-year-old male who presented with mediastinal mass, which was later confirmed as a case of tuberculosis on histopathological examination. He was successfully treated with anti-tubercular drugs.

Chronic complete spinal cord injury (SCI) is associated with severe skeletal muscle atrophy as well several atrophy and physical-inactivity-related comorbidity factors such as diabetes, obesity, lipid disorders, and cardiovascular diseases. Intracellular mechanisms associated with chronic complete SCI-related muscle atrophy are not well understood, and thus their characterization may assist with developing strategies to reduce the risk of comorbidity factors. Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients. In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3beta (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70(s6kinase) (60%; P = 0.1) were also observed, the latter three in an Akt- and mTOR-independent manner. Reductions in atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3beta, and 4E-BP1, would reduce the ability to increase protein synthesis rates.

We report two patients with myasthenia gravis (MG) who underwent thymectomy but developed thymic carcinoma years after the initial surgery. In one patient, the initial thymic pathology was normal, whereas the other had an encapsulated benign thymoma that was found only on pathological assessment. These cases demonstrate that MG may occur as part of a "new" paraneoplastic syndrome even after thymectomy. The late appearance of metastatic thymoma raises questions about monitoring for these patients.

Sternal dehiscence is one complication after median sternotomy. We followed a patient with sternal dehiscence for 6 months after extended thymectomy via median sternotomy. His diagnosis was myasthenia gravis without thymoma and with complicating diabetes mellitus. Sixteen days after the operation chest radiography revealed that one of six sternal wires was cut, although sternal dehiscence was not apparent. Six months after the operation, chest radiography revealed that five of six wires were cut. The patient experienced sternal dehiscence, could not cough, and felt pain at the median wound site. We implemented a resuture technique of the sternum using Shirodkar tape for postoperative sternal dehiscence. After the second operation, sternal dehiscence was not apparent. He was able to cough and had no respiratory deficiency. One year after the second operation, chest computed tomography revealed no sternal dehiscence. Shirodkar tape is extremely useful and is low in price.

The patient was 54-year-old woman diagnosed as recurrent invasive thymoma (type B3; WHO classification). Although partial response was obtained by systemic chemotherapy (PAC: cisplatin, doxorubicin, cyclophosphamide), the tumor started to become enlarged after cessation of chemotherapy. Combined treatment of octreotide and prednisolone was administrated because various chemotherapies, including PAC, were not effective. After seven months, the tumor size was markedly decreased. The combination of octreotide and prednisolone should be considered as one of the choices of treatment in patients with recurrent thymoma.

Thymic epithelial tumors include thymoma and thymic carcinoma. Histologic findings and extent of disease are key determinants of prognosis and help guide postoperative management in patients with thymic epithelial tumors. Given the relative rarity of these tumors, the use of tumor guidelines and checklists can facilitate accurate and comprehensive pathologic reporting in this setting. Diagnostic nomenclature (World Health Organization, Suster-Moran classifications) and staging criteria (modified Masaoka system) are emphasized.

The actual contribution of T lymphocytes to protection against tumors is still unclear. In vitro imaging experiments show that tumor specific cytotoxic T lymphocytes (CTLs) are competent to kill target cells by conventional cytotoxic pathways. The emergence of multiphoton imaging in the past decade now allows real time in vivo imaging of CTLs. New insights are available on the behavior of antitumor T cells during the priming phase, during their traffic within the tumor tissue, and on their interactions with tumor cells during the effector phase. Recent reports suggest that direct killing of tumor cells by CTLs is a slow process, suggesting that the ratio of effector to target cells is determinant, or that additional cytotoxic contribution by other cell types is required to induce efficient tumor rejection. This review will focus on the publications that have imaged antitumor immune responses dynamically and discuss how this new information contributes to understand the implication of CTLs in tumor rejection.

Chemokines mediate the signaling and migration of T cells, but little is known about the transcriptional events involved therein. Microarray analysis of CXC chemokine ligand (CXCL) 12-treated T cells revealed that Wnt ligands are significantly up-regulated during CXCL12 treatment. Real-time polymerase chain reaction and Western blot analysis confirmed that the expression of noncanonical Wnt pathway members (eg, Wnt5A) was specifically up-regulated during CXCL12 stimulation, whereas beta-catenin and canonical Wnt family members were selectively down-regulated. Wnt5A augmented signaling through the CXCL12-CXCR4 axis via the activation of protein kinase C. Moreover, Wnt5A expression was required for CXCL12-mediated T-cell migration, and rWnt5A sensitized human T cells to CXCL12-induced migration. Furthermore, Wnt5A expression was also required for the sustained expression of CXCR4. These results were further supported in vivo using EL4 thymoma metastasis as a model of T-cell migration. Together, these data demonstrate that Wnt5A is a critical mediator of CXCL12-CXCR4 signaling and migration in human and murine T cells.

Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited neurodegenerative disorders caused by a mutant protein with an expanded polyglutamine tract. Phosphorylation of ataxin-1 (ATXN1) at serine 776 is implicated in SCA1 pathogenesis. Previous studies, utilizing transfected cell lines and a Drosophila photoreceptor model of SCA1, suggest that phosphorylating ATXN1 at S776 renders it less susceptible to degradation. This work also indicated that oncogene from AKR mouse thymoma (Akt) promotes the phosphorylation of ATXN1 at S776 and severity of neurodegeneration. Here, we examined the phosphorylation of ATXN1 at S776 in cerebellar Purkinje cells, a prominent site of pathology in SCA1. We found that while phosphorylation of S776 is associated with a stabilization of ATXN1 in Purkinje cells, inhibition of Akt either in vivo or in a cerebellar extract-based phosphorylation assay did not decrease the phosphorylation of ATXN1-S776. In contrast, immunodepletion and inhibition of cyclic AMP-dependent protein kinase decreased phosphorylation of ATXN1-S776. These results argue against Akt as the in vivo kinase that phosphorylates S776 of ATXN1 and suggest that cyclic AMP-dependent protein kinase is the active ATXN1-S776 kinase in the cerebellum.

PURPOSE OF REVIEW: Inherited lipodystrophies are rare autosomal recessive and dominant disorders characterized by selective, but variable, loss of adipose tissue. Marked hypertriglyceridemia is a common feature of these disorders and highlights the role of adipose tissue in lipid homeostasis. In the last decade, advances have been made in elucidating the molecular basis of many inherited lipodystrophies. We review the new insights in the pathophysiology and treatment of these disorders based on the current understanding of the biologic role of these lipodystrophy genes. RECENT FINDINGS: Eight different genetic loci, including 1-acylglycerol-3-phosphate-O-acyltransferase 2, Berardinelli-Seip congenital lipodystrophy 2, caveolin 1, lamin A/C, peroxisome proliferator-activated receptor gamma, v-AKT murine thymoma oncogene homolog 2, zinc metalloprotease and lipase maturation factor 1 have been described linked to different lipodystrophy syndromes. Mutations in these genes may cause fat loss and dyslipidemia through multiple mechanisms, which remain fully elucidated; however, they may involve defects in development and differentiation of adipocytes, and premature death and apoptosis of adipocytes. Hypertriglyceridemia is a consequence of increased VLDL synthesis from the liver, which is also loaded by ectopic triglyceride deposition, reduced clearance of triglyceride-rich lipoproteins or both. A recent study in mice with Agpat2 deficiency reports marked reduction in serum triglyceride upon feeding a fat-free diet, which suggests that low-fat diets are likely to be beneficial in lipodystrophic patients. Leptin replacement therapy is also a promising therapeutic option for lipodystrophic patients with hypoleptinemia. SUMMARY: Inherited lipodystrophies are an important cause for monogenic hypertriglyceridemia and serve to highlight the role of adipocytes in maintaining normolipidemia.

OBJECTIVES: Myasthenia gravis (MG) is an immune-mediated disorder associated with autoantibodies against postsynaptic nicotinic acetylcholine receptors at neuromuscular junctions. Rituximab, a monoclonal antibody specific for CD20, is used primarily to treat B-cell non-Hodgkin lymphoma. Although it has been used for treatment of a number of autoimmune diseases, there is limited experience in MG. METHODS: Three patients with refractory MG (2 with concurrent thymoma) were given rituximab. RESULTS: Symptoms stabilized and reductions in immunosuppressive medications were tolerated for extended periods, without adverse effects or infectious complications. CONCLUSIONS: These observations support the concept that rituximab may be helpful for the treatment of MG. Remissions in patients with or without thymoma are achievable with rituximab given in combination with commonly used modalities. Furthermore, rituximab is not necessarily contraindicated for the treatment of MG in patients being treated for thymoma. Controlled studies are called for to define its role in the treatment of refractory MG.

A 54-year-old male, non smoker, began to suffer from persistent dyspnoea and fever. X-ray and CT scan showed a cystic lesion located in the left anterior mediastinum. This lesion was removed instead of the initially scheduled surgical resection with video-assisted thoracoscopic surgery (VATS) preceded by fine needle aspiration (FNA). A diagnosis of thymoma arising in the wall of thymic cyst was made. Such a rare tumour should be taken into consideration in treating patients with a cystic mediastinal lesion, before VATS and FNA.

PURPOSE: By hypomethylating genes, decitabine may up-regulate factors required for chemotherapeutic cytotoxicity. Platinum-resistant cells may have reduced expression of the copper/platinum transporter CTR1. EXPERIMENTAL DESIGN: Thirty-one patients with refractory malignancies received decitabine 2.5 to 10 mg/m(2) on days 1 to 5, and 8 to 12 or 15 to 20 mg/m(2) on days 1 to 5. Tumor was assessed for DNA methylation (by LINE assays), apoptosis, necrosis, mitoses, Ki67, DNA methyltransferase (DNMT1), CTR1, and p16. RESULTS: Febrile neutropenia was dose limiting. One thymoma patient responded. Decitabine decreased tumor DNA methylation (from median 51.2% predecitabine to 43.7% postdecitabine; P = 0.01, with effects at all doses) and in peripheral blood mononuclear cells (from 65.3-56.0%). There was no correlation between tumor and peripheral blood mononuclear cells. Patients starting decitabine < or =3 versus >3 months after last prior cytotoxic or targeted therapy had lower predecitabine tumor CTR1 scores (P = 0.02), higher p16 (P = 0.04), and trends (P = 0.07) toward higher tumor methylation and apoptosis. Decitabine decreased tumor DNMT1 for scores initially >0 (P = 0.04). Decitabine increased tumor apoptosis (P < 0.05), mitoses (if initially low, P = 0.02), and CTR1 (if initially low, P = 0.025, or if < or =3 months from last prior therapy, P = 0.04). Tumor CTR1 scores correlated inversely with methylation (r = -0.41, P = 0.005), but CTR1 promoter was not hypermethylated. Only three patients had tumor p16 promoter hypermethylation. P16 scores did not increase. Higher blood pressure correlated with lower tumor necrosis (P = 0.03) and a trend toward greater DNA demethylation (P = 0.10). CONCLUSIONS: Exposure to various cytotoxic and targeted agents might generate broad pleiotropic resistance by reducing CTR1 and other transporters. Decitabine decreases DNA methylation and augments CTR1 expression through methylation-independent mechanisms.

Thymomas are the most common tumors of the mediastinum. The introduction of multimodality treatment strategies, as well as novel approaches to the diagnosis of these tumors, has led to changes in the clinical management of thymomas. Here we review the literature for current clinical practice in the diagnosis, management, and treatment of thymomas.

Thymic carcinoma (primary carcinoma of the thymic epithelium; type C thymoma) is a rare malignancy. It usually presents in middle-aged to elderly patients and can exhibit a wide variety of morphologic appearances. Thymic basaloid carcinoma (thymic BC) is a particularly rare subtype, with less than 20 cases published in the English literature, mostly in the form of individual case reports. In this study, we present the clinicopathologic and immunohistochemical features of 12 new cases of thymic BC. There were 10 (83%) men and 2 (17%) women. Ages at the time of initial diagnosis ranged from 34 to 77 years (mean 55 y). The 2 most common manners of presentation were dyspnea on exertion (3 patients) and as an incidental finding on radiographic imaging (2 patients). Tumors ranged in size from 4.4 to 17 cm (mean 10.1 cm). One of 12 cases (8.3%) was associated with a multilocular thymic cyst. Immunohistochemistry was performed in 8 cases. Pan-cytokeratin was positive in all cases. CD117 (c-kit) was positive in 6 of 8 cases (75%), p63 was positive in 7 of 8 cases (88%), p53 was positive in 7 of 8 cases (88%), ranging from <10% to 90%, CD5 was focally positive in 3 of 8 cases (38%), collagen type IV was positive in 4 of 8 cases (50%), and proliferative index, as estimated by Ki67, ranged from <1% to approximately 15%. In 1 of 2 cases with sarcomatoid differentiation, Ki67 was greater than 80% in the sarcomatoid area. Cases were negative for thyroid transcription factor-1 (0 of 8), S-100 (0 of 7), and synaptophysin (0 of 7). Long-term data was available in 8 patients with an average follow-up of 30 months. Five patients died of their disease at an average of 34 months from the time of diagnosis. Of the remaining 3 patients, 1 had a stable recurrence and died at 4 years from unrelated causes, and 2 were alive without the evidence of disease at 12 and 7 months, respectively. Thymic BC, although previously regarded as a low-grade neoplasm, has shown that it is capable of aggressive behavior and significant mortality. In this paper, we review the pertinent literature and discuss the possible relationship of thymic BC with thymic adenoid cystic carcinoma, as well as BCs and adenoid cystic carcinomas at other sites.

Metastatic thymic carcinoma is an aggressive neoplasm for which multimodal therapies are often ineffective. We describe here a heavily pretreated patient with advanced thymic carcinoma responsive to multikinases inhibitor BAY 43-9006 (Sorafenib). Of note, a hitherto unreported c-kit missense mutation on exon 17 (D820E) identified in tumor cells seems to explain the clinical response and highlight the key role of molecular analysis in predicting efficacy of targeted therapies even in thymic neoplasms.

Patients with thymoma are mostly investigated for autoimmunity but a few patients may have underlying immunodeficiency that is referred to as Good's syndrome (GS). Cardiothoracic surgeons must always consider this diagnosis when undertaking thymectomy, as immunoglobulin levels can be easily measured and is readily available. The immunodeficiency in GS can be life-threatening and more importantly, it is not reversed by thymectomy. Collaborative care with an Immunologist for these patients is strongly recommended.

Advances in the treatment of myasthenia gravis (MG) have reduced mortality rates due to the disease and improved patients' quality of life. Nowadays, attending neurologists can choose among different treatment strategies for MG patients. An exhaustive revision of published data on the efficacy of the different therapeutic options for MG indicates that there are insufficient evidence-based results. However, recommendations based on expert opinion can be provided. Thymectomy is indicated in all patients with a thymoma or for generalized acetylcholine receptor-seropositive patients aged 18 - 55 years. Steroids are the most widely used immunosuppressive drug for MG. They are recommended as the first-line drug in all patients with generalized MG without response to thymectomy, or in those patients who do not fulfill criteria for the surgery. The selection of second-line drugs may vary between protocols. We recommend to start with azathioprine if insufficient remission is achieved with steroids, followed by ciclosporin, mycophenolate and others. We use rituximab or cyclophosphamide only in severely drug-resistant patients. Finally, we recommend intravenous immunoglobulins or plasma exchange in MG crisis, or for unstable patients before thymectomy or in clinical exacerbations.

Extreme degree of cystic, haemorrhagic and necrotic changes in a thymoma is rare. A 22-year-old male presented with cough, grade 2 dyspnoea, and occasional chest pain for the past six months. Radiological investigations revealed a large cystic lesion in the anterior mediastinum. A benign cystic tumour was suspected. Surgical resection of the tumour was done. Grossly, the almost entirely cystic and haemorrhagic dumb-bell shaped encapsulated tumour showed a subcapsular residual nodule. Histopathological examination was suggestive diagnosis of benign thymoma (World Health Organization [WHO] Type A, medullary type) associated with the rare features of cells with dendritic processes containing melanin pigment seen singly scattered throughout the tumour.

Limbic encephalitis is an inflammatory disease localized to the "grand lobe limbique" defined by Broca in 1878, sometimes restricted to the hippocampus, but sometimes including extralimbic abnormalities. The main features are subacute onset, short-term memory disorders and cognitive impairment, temporal seizures, and hippocampic changes on MRI. A list of underlying causes has recently been published Infectious causes used to be frequent (mainly herpes simplex virus). Paraneoplastic limbic encephalitis is characterized by the presence of various onconeural antibodies, such as AntiHu and ANNA3 (bronchial small cell carcinoma), AntiMa2 (testicular tumor), AntiCV2 (lymphoma, thymoma,...). No such antibodies are detected in 40% of patients. The prognosis of these forms is poor. Voltage-gated potassium channel-associated limbic encephalopathies are due to antibodies targeting potassium channels. Mutations of the genes encoding the Kv11 and Kv12 subunits are responsible for several Shaker syndromes, including neuromyotonia, Morvan's disease, type I episodic ataxia, and limbic encephalitis with hyponatremia. Plasma exchanges and immunotherapy are effective. In patients without detectable antibodies, hippocampic anti-neuropil antibodies should be sought, particularly those targeting N-methyl-D-aspartate receptors. Ovarian teratoma is the usual cause of this type of encephalitis. Surgery and immunotherapy are effective. These disorders have been categorized into those associated with antibodies targeting intracellular antigens (poor-prognosis paraneoplastic encephalitis) and those associated with antibodies targeting antigens reacting with cellular membranes (potassium channelopathies and antineuropil antibodies), which respond to immunotherapy and carry a better prognosis. Limbic encephalitis can also reveal Hodgkin's disease, as in a case observed by the authors.

Although there are many reports of spontaneous regression of noninvasive thymoma, there are no reports of spontaneous regression of an invasive thymoma. Moreover, the mechanism of the spontaneous regression is still unknown. The present case concerns a 47-year-old man who presented with chest pain. Computed tomography (CT) showed a large anterior mediastinal mass with left pleural effusion that occluded the innominate vein. The tissue obtained by video-assisted thoracic surgery suggested a diagnosis of invasive thymic carcinoma. One month later CT showed prominent regression of the tumor, and the tumor was completely resected. On pathology, the diagnosis was thymoma type B3.

UL16-binding proteins (ULBPs) belong to a family of ligands for NKG2D activating receptor of human natural killer (NK) cells. We previously reported that RAET1E2, a soluble isoform of the RAET1E (ULBP4), inhibits NKG2D-mediated NK cytotoxicity. In this study, we examined whether ULBP4 could be recognized by gammadeltaT cells via TCRgammadelta. Here we show that immobilized soluble ULBP4 (rULBP4) induces the proliferation of human ovarian epithelial carcinoma- or colonic carcinoma-derived Vdelta2(+) T cells in vitro. These Vdelta2(+) T cells secrete Th1 cytokines and display a strong cytolytic activity toward ULBP4-transfected targets. We also show that ULBP4 binds to a soluble chimeric protein containing TCRgamma9/delta2 and activates TCR(-) Jurkat T cells transfected with TCRgamma9/delta2. Moreover, both TCRgammadelta and NKG2D are involved in ULBP4-induced activation and cytotoxicity of gammadeltaT cells. We found that ULBP4 is expressed not only on human tumor cells, but also on Epstein-Barr virus (EBV)-infected peripheral blood cells. Taken together, our data suggest that ULBP4 functions as a ligand for both TCRgammadelta and NKG2D and may play a key role in immune surveillance of tumor development and clearance of viral infection.

Here we report a case of a rare thymic tumors histologically diagnosed as lipofibroadenoma. The patient was a 32-year-old male who displayed an anterior mediastinal tumor on a chest computed tomography (CT) scan while being treated for pneumonia. The tumor was localized within the thymus, and the diameter was 3 cm. No significant change was observed in the tumor on a CT scan taken 6 months after the 1st scan. Suspecting a thymoma from the CT and magnetic resonance imaging (MRI) findings, we performed a thymothymectomy via a median sternotomy. The histopathological diagnosis was a lipofibroadenoma of the thymus. The findings resembled fibroadenoma of the breast. Lymphocytes were scarce within the tumor with abundant interstitial stroma, and the tumor epithelial cells displayed restiform and dendritic structures. The epithelial cells were mostly negative for Ki-67 immunohistochemical staining. A very small amount of calcification was detected within the tumor using alizarin red staining. Based on the histopathological findings, it was considered to be a benign tumor with little growth potential, and which had been present for a long period of time.

BACKGROUND: Advanced thymomas with disseminated nodules are difficult to manage, and the treatment strategy remains undefined. METHODS: A total of 28 thymoma patients with pleural and/or pericardial disseminated nodules were treated at Nagoya City University Hospital. Among them, 21 patients underwent resection of thymoma and pleural disseminated nodules. These patients were reviewed in the present study. RESULTS: Preoperative steroid pulse therapy was performed in 14 patients. Macroscopic total resection of all tumors was achieved in 15 patients. Postoperative adjuvant radiotherapy was performed for the mediastinum in 20 patients and hemithoracic irradiation (HTR) in 11 patients. The overall survival rate of operated 21 patients was 73.1% at 5 years. The patients who underwent resection showed a better prognosis than the patients without resection (p = 0.0006). Relapse was diagnosed in 14 of 21 patients who underwent resection. Disease-free survival was 67.5% at 1 year, 39.8% at 3 years, and 13.3% at 5 years. HTR alone did not improve the disease-free survival. Among the patients who underwent total resection, relapse-free survival was better than in the patients with subtotal resection (p = 0.009). Achievement of a trimodality therapy with preoperative steroid pulse, total resection, and postoperative HTR was associated with prolonged relapse-free survival in the operated patients (p = 0.027, hazard ratio 6.452). CONCLUSIONS: Pursuing total resection for thymoma and disseminated nodules may be beneficial for stage IV thymoma. The combination of preoperative steroid pulse therapy, macroscopic total resection, and postoperative HTR may prolong the interval to relapse, but it did not lead to cure.

Although thymic epithelial tumors are rare, they are relatively common among neoplasms of the anterior superior mediastinum. They usually exhibit indolent behavior, but do have the capacity to invade surrounding structures and metastasize to distant sites. Thymic carcinomas are rare, but are highly aggressive tumors that are associated with a poor prognosis. The mainstay of therapy is complete surgical resection. Locally advanced thymoma and thymic carcinoma require a multimodality treatment approach with a combination of surgery, chemotherapy, and radiation therapy to decrease the chances of recurrence and improve survival. The risk of disease recurrence lasts for a number of years after completion of primary therapy. A majority of cases of recurrent disease present as pleural recurrences. Once again, surgical resection of recurrent disease represents the cornerstone of successful therapy and is critical to long-term survival. In recent years, a better understanding of the biologic basis of thymic epithelial tumors has led to the emergence of targeted therapy directed against this malignancy.

CD226 is known to be expressed on many types of peripheral lymphoid cells and involved in T cell differentiation, activation, and cytotoxicity. In this study, we report that CD226 is also expressed on mouse thymocytes at varying developmental stages, and its expression is associated with resistance of thymocytes to apoptosis. The levels of CD226 expression appeared to be closely coupled with thymocyte development, in that it was preferentially expressed on CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes at all stages during mouse development, and was markedly increased on the cells in neonatal mice. Of the CD4(+)CD8(+) population, CD226 was predominantly expressed by the cells also positive for CD69, suggesting that CD226 expression may be induced in thymocyte-positive selection. Inhibition of CD226 by short hairpin RNA in a fetal thymus organ culture model led to reduced thymus cellularity, which was associated with enhanced apoptotic cell death. In contrast, CD226-transgenic mice displayed enlarged thymus lobes resulting from increased thymus cellularity. CD226 on thymocytes seemed to play a role in regulating the expression of survivin, as inhibition of CD226 down-regulated survivin, but overexpression of CD226 rescued thymocytes from apoptosis through up-regulation of survivin. In addition, overexpression of CD226 reduced sensitivity of EL-4 thymoma cells to apoptosis by up-regulating the expression of survivin. Taken together, these results indicate that CD226 is an antiapoptotic molecule and may play an important role in murine thymocyte development.

OBJECTIVE: A complete surgical resection is the cornerstone of therapy of thymic tumors. Unfortunately, there is no standard treatment for pleural recurrence. This article describes our overall experience with the surgical treatment of pleural implants in patients who previously underwent resection of a thymoma. MATERIAL AND METHODS: From January 1980 to June 2006, 20 patients previously operated on for a thymoma were operated on for the surgical resection of pleural implants. Patients with the initial Masaoka stage IVA were excluded from our analysis. Our sample comprised 10 male and 10 female patients (12-65 years old). The surgical approach to the resection of the thymoma was as follows: video-assissted thoracic surgery in 2 patients, sternotomy in 13 patients, thoracotomy in 2 patients, and sternothoracotomy in 3 patients. The initial Masaoka stage of the thymoma was IIA in 2 patients, IIB in 7 patients, and III in 11 patients. RESULTS: The interval between resection of the thymoma and pleural implants ranged from 11 to 156 (median 60) months. Fifteen patients had a thymus-related syndrome (in 13 patients it resulted myasthenia gravis), and in 11 patients it improved or remitted after treatment of the pleural recurrence. All the resections were performed through a posterolateral thoracotomy. Three patients underwent an iterative resection of new pleural implants. At the latest follow-up, 10 patients are still alive (8 disease-free) and 10 have died (9 of a relapse and 1 of the complications of red cell aplasia). From the pleural recurrence resection, the overall 5- and 10-year survivals are 43.1% and 25.8%, respectively. CONCLUSIONS: Repeat operation on patients with thymoma pleural recurrences is feasible and safe. It can produce satisfactory results in terms of overall survival and paraneoplastic syndrome control. Moreover, the multimodality treatment could improve the results of surgical treatment.

A case of invasive thymoma with intra-caval and intracardiac extension presenting as superior vena cava syndrome is reported. The tumor is excised on cardiopulmonary bypass, and superior vena cava is bypassed using a Dacron graft (DuPont, Wilmington, DE). Five-year follow-up of the patient showed a patent graft.

A 65-year-old man was admitted to our hospital with abdominal fullness and leg edema in April 2005. Diabetes mellitus and hypertension that had been diagnosed in 1990 were well-controlled with oral hypoglucemic drug. He presented with malignant thymoma accompanied by multiple metastases in the right thoracic space in December 2000. He was treated with total thymectomy, combined with chemotherapy (cisplatin + vinorelbin) and hyperthermia. This strategy obviously reduced the tumor mass. However, CT scans showed multiple recurrences of thymoma in December 2004 and abdominal fullness and leg edema appeared shortly thereafter. Laboratory findings revealed proteinuria (over 10 g/day), hypoalbuminemia, hyperlipidemia and renal dysfunction. A kidney biopsy revealed minor glomerular abnormality. He was diagnosed with minimal change nephrotic syndrome (MCNS) complicated with the recurrence of malignant thymoma. Corticosteroid therapy was started, but dialysis was transiently required to protect against oliguric acute renal failure. Three weeks after the initiation of steroid therapy, the proteinuria was improved to less than 1.0 g/day and renal function returned to within the normal range. Subsequent corticosteroid combined with immunosuppressive therapy resulted in good control of his nephrotic syndrome (NS) without recurrence. There have been a few case reports showing NS complicated with malignant thymoma. Among these, several cases with MCNS occurred after thymectomy for malignant thymoma. Interestingly, both the thymoma mass and high pre-treatment vascular endothelial growth factor (VEGF) levels decreased as NS improved with steroid therapy. These findings suggest that VEGF also might have been associated with the onset of NS in this patient.

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that activates multiple signaling pathways, including phosphatidylinositol-3-kinase/v-AKT murine thymoma viral oncogene homolog protein (Akt), has long been a target of novel therapies. Despite universal EGFR expression in head and neck squamous cell carcinoma (HNSCC), the majority of patients do not respond to EGFR inhibitors. This review focuses on mechanisms of resistance to these agents in HNSCC, and how these may be unique when compared with other malignancies such as non-small cell lung and colorectal cancers. Published studies and abstracts reveal that there are likely several mechanisms underlying resistance, suggesting that different strategies will be required to improve efficacy of EGFR inhibitors in HNSCC. Copyright 2009 Wiley Periodicals, Inc.

Thymic carcinoma is a very rare malignancy. In 1999, a World Health Organization committee published histologic criteria for distinct thymoma entities (labelled as type A, AB, B1, B2, B3 thymomas) and for the heterogeneous group of thymic carcinomas, collectively called type C tumour. Thymic carcinoma differs from thymoma in that it displays cytologically malignant features, extensive local invasion, and a substantial potential for metastasis. It constitutes a heterogeneous group of tumours that display different biological behaviours and prognoses. The majority of thymic carcinomas are either squamous carcinomas or lymphoepithelioma-like carcinomas. This study included three male patients aged 20, 46 and 19years respectively with histologically proven thymic carcinoma diagnosed at the author's institution. All of the patients presented a large mass of the anterior mediastinum. Histological examination of the different tumours revealed three distinct variants of thymic carcinoma, namely: epidermoid carcinoma, clear cell carcinoma and lymphoepithelioma-like carcinoma.

We subjected 23 formalin-fixed, paraffin-embedded tissue blocks (11 cases of thymic hyperplasia and 12 thymomas [3 encapsulated, 8 with capsular invasion, and 1 atypical]) to incubation with monoclonal anti-X-linked inhibitor of apoptosis protein (XIAP) (BD Biosciences, San Jose, CA) and monoclonal anti-p63 (4A4, Santa Cruz, Santa Cruz, CA). Granular or heterogeneous cytoplasmic XIAP staining and nuclear p63 staining were considered positive. We compared thymic hyperplasia with thymoma and capsulated thymoma with thymoma with capsular invasion or atypia. p63 was positive in virtually all thymic epithelial cells in hyperplasia and thymoma. XIAP was negative in all hyperplasia cases except one. Of 12 thymomas, 9 were XIAP+ with focal/weak to diffuse/strong positivity: 2 of 3 encapsulated and 7 of 8 thymomas with capsular invasion were XIAP+. One atypical thymoma was XIAP-. XIAP expression differed significantly between hyperplasia and thymoma (P = .0007) but not between capsulated and invasive thymomas (P = .3797). p63 is consistently positive in nonneoplastic and neoplastic thymic epithelium. XIAP expression in thymoma suggests a possible role in the pathogenesis of thymoma and may be helpful in differentiating thymic hyperplasia from thymoma, especially in small biopsy specimens. However, the level of expression does not correlate with capsular invasion or atypia.

Interleukin-13 (IL-13) has been proposed as a therapeutic target for bronchial asthma as it plays crucial roles in the pathogenesis of the disease. We developed an in vitro test system measuring transcriptional downregulatory activities on IL-13 as a primary screening method to select drug candidates from natural products. The promoter region of IL-13 (-2,048 to +1) was cloned into the upstream of a luciferase gene in the plasmid pGL4.14 containing the hygromycin resistance gene as a selection marker, generating pGL4.14-IL-13. The EL-4 thymoma and RBL-2H3 mast cells transiently expressing this plasmid highly produced the luciferase activities by responding to PI (PMA and ionomycin) stimulation up to 8-fold and 13-fold compared with the control, respectively, whereas cyclosporin A, a wellknown antiasthmatic agent, significantly downregulated the activities. The BF1 clone of RBL-2H3 cells constitutively expressing pGL4.14-IL-13 was established by selecting surviving cells under a constant lethal dose of hygromycin treatment. The feasibility of this system was evaluated by measuring the downregulatory activities of 354 natural products on the IL-13 promoter using the BF1 clone. An extract from Morus bombycis (named TBRC 156) significantly inhibited PI-induced luciferase activities and IL-13 mRNA expression, but not the protein expression. Fisetin (named TBRC 353) inhibited not only PI-induced luciferase activities and mRNA expression, but also the IL-13 protein secretion, whereas myricetin (named TBRC 354) could not suppress the IL-13 expression at all. Our data indicated that this in vitro test system is able to discriminate the effects on IL-13 expression, and furthermore, that it might be suitable as a simple and time-saving primary screening system to select antiasthmatic agents by measuring transcriptional activities of the IL-13 promoter.

BACKGROUND/AIMS: Autoimmune myasthenia gravis (MG) is a disorder of the neuromuscular junction caused in the majority of patients by autoantibodies directed against the postsynaptic nicotinic acetylcholine receptor (AChR). The classic clinical presentation of MG has been well characterized as fluctuating muscle weakness affecting particular muscle groups. METHODS: Selective review of the literature relating to the pathogenesis, diagnosis, and treatment of anti-AChR-positive MG. RESULTS: Approximately 85% of patients with generalized MG and 50% of patients with purely ocular MG have anti-AChR antibodies. A number of clinical MG subtypes may be identified amongst those patients with anti-AChR antibodies, comprising early-onset MG (onset < or = 40 years), late-onset MG (onset after 40 years), thymoma-associated MG, and ocular MG. 'Low-affinity' anti-AChR antibodies may be found in 66% of patients with generalized MG who are negative for anti-AChR and anti-muscle-specific receptor tyrosine kinase antibodies by conventional assays. While pathologic changes in the thymus gland (hyperplasia and neoplasia) almost certainly play a role in the development of MG in patients with early-onset disease and thymomatous MG, the pathogenic role of the thymus remains to be determined in ocular MG, late-onset MG, and generalized MG with low-affinity anti-AChR antibodies. CONCLUSION: Autoimmune MG with AChR autoantibodies encompasses several disease subtypes defined by clinical presentation and thymic pathology. Treatment options include thymectomy, cholinesterase inhibitors, immunosuppressive drugs and plasma exchange or intravenous immunoglobulin, and are tailored according to the clinical presentation. Copyright (c) 2009 S. Karger AG, Basel.

BACKGROUND: L-type amino acid transporter 1 (LAT1) has been associated with tumor growth and is highly expressed in the primary human neoplasms. We investigated the significance of LAT1 expression to evaluate malignant potential in thymic epithelial tumors. MATERIALS AND METHODS: Immunohistochemical studies of 45 surgically resected thymic epithelial tumors [15 noninvasive thymomas (NT), 22 invasive thymomas (IT), and 8 thymic carcinomas (TC)] were conducted. LAT1, Ki-67 labeling index (LI), vascular endothelial growth factor (VEGF), and microvessel density of the thymic epithelial tumors were analyzed. RESULTS: LAT1 expression for thymomas and thymic carcinomas were 0 (0%) of 37 and 6 (75%) of eight patients, respectively. Ki-67 LI for NT, IT, and TC were 7.9 +/- 2.8%, 16.1 +/- 8.5%, and 50.6 +/- 24.4%, respectively. VEGF expression in groups NT, IT, and TC was 0 (0%) of 15, 9 (41%) of 22, and 6 (75%) of eight patients, respectively. VEGF expression was statistically associated with microvessel count. The LAT1 expression was statistically associated with Ki-67 LI, VEGF, and microvessel density in thymic carcinomas. CONCLUSION: LAT1 is frequently expressed in thymic carcinomas but is absent in thymomas. Our results suggest that LAT1 expression might be an immunohistochemical marker for carcinomas, and could distinguish between thymomas and thymic carcinomas.

Neuromuscular diseases accompanying thymoma include myasthenia gravis, polymyositis, dermatomyositis, and neuromyotonia. Usually 50% of patients with thymoma develop myasthenia gravis. However, only 5% show polymyositis as an accompanying paraneoplastic phenomenon. We report the case of a patient with thymoma showing myasthenia gravis as well as polymyositis. Due to the simultaneous occurrence of these paraneoplastic diseases, the criteria for exact diagnosis (serum creatine kinase, EMG, ocular involvement) overlap. This diagnostic dilemma can appreciably complicate the therapeutic approach.

PURPOSE: We present an approach to prioritize single nucleotide polymorphisms for further follow-up in genome-wide association studies of type 2 diabetes. METHOD: The proposed method combines both the use of open data access from two type 2 diabetes-genome-wide association studies (granted by the Diabetes Genetics Initiative and the Welcome Trust Case Control Consortium) and the comprehensive analysis of candidate regions generated by the freely accessible ENDEAVOUR software. RESULTS: The algorithm prioritized all genes of the whole genome in relation to type 2 diabetes. There were six of 1096 single nucleotide polymorphisms in five genes potentially associated with type 2 diabetes: tachykinin receptor 3 (rs1384401), anaplastic lymphoma receptor tyrosine kinase (rs4319896), calcium channel, voltage-dependent, L type, alpha 1D subunit (rs12487452), FOXO1A (rs10507486 and rs7323267), and v-akt murine thymoma viral oncogene homolog 3 (rs897959). We estimated the fixed effect and P values of each single nucleotide polymorphism in the combined dataset by Mantel-Haenszel meta-analysis and we observed significant P values for all single nucleotide polymorphisms except for rs897959 at v-akt murine thymoma viral oncogene homolog 3. CONCLUSION: The proposed strategy may be used as an alternative tool for optimizing the information of the nearly 500,000 gene variants in which markers with modest significant P value for disease association are currently disregarded. Additionally, the said single nucleotide polymorphisms may be incorporated into the replication of the multistage design involved in the genome-wide association studies.

Lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) are implicated in a variety of normal and pathological processes. LAMP-2 is proposed to participate in chaperone-mediated autophagy.Autophagy regulates T-lymphocyte homeostasis by promoting both survival and proliferation. The biological importance of this process in the thymic gland and especially the involvement of LAMPs are far from being elucidated. The aim of the study was to examine the parallel expression of LAMPs and ubiquitin, a key molecule in autophagy, in normal human thymic glands and thymomas. The immunohistochemical expression of both markers was compared with that of cyclin D1--an important regulator of cell cycle progression. Novel evidence for differential expression of LAMPs and ubiquitin is presented. Most Hassal's corpuscules in thymoma were negative for LAMPs, but positive in normal thymus.Both lymphocytes and epithelial cells in pathological thymus showed higher intensity for LAMP-2 compared with LAMP-1. In thymoma, ubiquitin was more intensively positive in these cell types compared with the normal thymus, suggesting activated autophagy in the course of this pathological state. A deregulation in cyclin D1 expression in thymoma is also reported. The functional importance of these molecules in autophagy accompanying normal and pathological processes in the thymic gland is reviewed.

This report describes a 59-year-old male who developed myasthenia gravis 92 months following excision of an invasive thymoma, in the absence of tumour recurrence. This report highlights the importance of prolonged clinical surveillance in post-thymectomy patients.

Pure red cell aplasia is a syndrome characterized by a severe normocytic anemia, reticulocytopenia, and absence of erythroblasts from an otherwise normal bone marrow. Although the causes and natural course of this syndrome are variable and although the anemia in some patients can be managed by treatment of an underlying inflammatory or neoplastic disease, the pathogenesis of a large number of cases is autoimmune, including those associated with thymoma, and are best managed with immunosuppressive therapy.

BACKGROUND: The objective of this study was to clarify the usefulness of positron emission tomography (PET) using(18)F-fluorodeoxyglucose (FDG) and carbon 11-labeled acetate (AC) for predicting the histologic types and tumor invasiveness of thymoma in a multicenter study. METHODS: Forty thymomas were examined using both FDG-PET and AC-PET before surgery. The histologic types were type A in 1 thymoma, type AB in 12 thymomas, type B1 in 11 thymomas, type B2 in 7 thymomas, type B3 in 6 thymomas, and type C in 3 thymomas. Tumor invasiveness was assessed by pathologic tumor stage and was identified as stage I in 17 tumors, stage II in 17 tumors, stage III in 4 tumors, and stage IV in 2 tumors. FDG and AC uptake was measured as the maximum standard uptake value (SUV). RESULTS: The FDG-SUV in type C thymomas was significantly higher than that in the other types (A-B3; P = .001 - P = .048). The AC-SUV in type A/AB thymomas was significantly higher than that in the other tumor types (B1-C; P < .001 - P = .002). All 3 type C tumors had an FDG-SUV >or=6.3, and all 13 type A/AB tumors had an FDG-SUV <6.3 and an AC-SUV >or=5.7. All 17 thymomas that had an FDG-SUV <6.3 and an AC-SUV <5.7 were type B1, B2, or B3. Neither the FDG-SUV nor the AC-SUV differed significantly between the stages I/II tumors and stage III/IV tumors. CONCLUSIONS: Although neither the FDG-SUV nor the AC-SUV can predict the invasiveness of thymomas assessed by tumor stage, they are useful for predicting histologic types of thymoma. Thymomas with an FDG-SUV <6.3 and an AC-SUV >or=5.7 almost certainly are types A/AB, which is of considerable prognostic and management significance. (c) 2009 American Cancer Society.

We present a rare case of malignant invasive thymoma (type A) arising from the posterior mediastinum. A 17-year-old girl was referred to our clinic after detection of a mass on a chest roentgenogram. Thoracoscopy showed a lobulated, pale yellowish mass located in the posterior compartment together with several foci in the lung parenchyma. The tumor and parenchymal foci were totally resected through a left minithoracotomy. Postoperative pathology revealed malignant invasive thymoma type A.

Thymomas arising outside the anterior mediastinum are very rare. Their occurrence is likely to be related to ectopic thymus tissue. We report a case of thymoma in the middle mediastinum, right paratracheal region. There have been few reports of middle mediastinal thymoma. In the present case, (11)C-acetate positron emission tomography (PET) was useful for a preoperative suggestive diagnosis. Recently, (11)C-acetate has been reported to be a more sensitive PET tracer than (18)F-fluorodeoxyglucose and may be a promising tracer for complementing the deficiency of (18)F-fluorodeoxyglucose in PET imaging.

Tranilast (N-[3,4-dimethoxycinnamonyl]-anthranilic acid) is a drug of low toxicity that is orally administered, and has been used clinically in Japan as an antiallergic and antifibrotic agent. Its antifibrotic effect is thought to depend on the inhibition of transforming growth factor-beta (TGF-beta). It has also been shown to exert antitumor effects, but its mode of action is unclear. Here, we explored the antitumor effects of tranilast in vitro and in vivo. Tranilast inhibited the proliferation of several tumor cell lines including mouse mammary carcinoma (4T1), rat mammary carcinoma stem cell (LA7), and human breast carcinoma (MDA-MB-231 and MCF-7). Tranilast blocked cell-cycle progression in vitro. In the highly metastatic 4T1 cell line, tranilast inhibited phospho-Smad2 generation, consistent with a blockade of TGF-beta signaling. It also inhibited the activation of MAP kinases (extracellularly regulated kinase 1 and 2 and JNK), which have been linked to TGF-beta-dependent epithelial-to-mesenchymal transition and, indeed, it blocked epithelial-to-mesenchymal transition. Although tranilast only partially inhibited TGF-beta production by 4T1 tumor cells, it potently inhibited the production of TGF-beta, interferon-gamma, IL-6, IL-10, and IL-17 by lymphoid cells, suggesting a general anti-inflammatory activity. In vivo, female BALB/c mice were inoculated with syngeneic 4T1 cells in mammary fat pads and treated with tranilast by gavage. Tranilast reduced (>50%) the growth of the primary tumor. However, its effects on metastasis were more striking, with more than 90% reduction of metastases in the lungs and no metastasis in the liver. Thus, tranilast has potential activity as an antimetastatic agent in breast cancer.

Interleukin 10 (IL-10) is secreted by several hemopoietic cells and suppresses the Th1 mediated immune response, while stimulating B cell differentiation and the humoral immune response. IL-10 expression in Con A-stimulated peripheral blood mononuclear cells is related to three polymorphisms in the promoter region of the IL-10 gene; G/A at position -1082, T/C at position -819 and A/C at position -592. We analyzed the distribution of these IL-10 polymorphisms in 64 MG patients and 87 healthy blood donors to determine any influence on MG susceptibility. MG patients had a significantly higher frequency of the ACC/ACC haplotype (12.5% vs 3.4% in controls), as had the subgroups with late onset MG and thymomatous MG (20.0% and 21.4%, respectively). Early onset MG patients had a high frequency of the ATA/ATA haplotype (19.2% vs 3.4% in controls). Titin Ab-positive MG patients had high ACC/ACC (20.0%). This study indicates a direct link between IL-10 and MG pathogenesis, although the complex role of this multi-faceted cytokine in vivo is as yet not fully elucidated.

PURPOSE: We assessed the frequency and levels of onconeural antibodies in 974 patients with various types of tumours, but without apparent paraneoplastic neurological syndromes (PNS). PATIENTS AND METHODS: We included patients with the following tumours: 200 small-cell lung cancer (SCLC) patients, 253 breast cancer patients, 182 ovarian cancer patients, 266 uterine cancer patients and 73 thymoma patients, as well as 52 patients with PNS and cancer and 300 healthy blood donors. Sera were screened for amphiphysin, CRMP5, Hu, Ma2, Ri and Yo antibodies using a multi-well immunoprecipitation technique. RESULTS: The most frequently detected antibodies were Hu followed by CRMP5. Ma2, Yo, amphiphysin and Ri antibodies were less common, but each was found at similar frequencies. Onconeural antibodies were present at similar levels in sera from the PNS control group and from cancer patients. Hu antibodies were rare in cancers other than SCLC. CRMP5 was the only antibody found in patients with thymoma and this antibody was more common among patients with thymoma than in other tumour patients. With one exception, coexisting antibodies were only found in patients with SCLC. The presence of onconeural antibodies in SCLC patients was not associated with prolonged survival. CONCLUSION: Onconeural antibodies are associated with various types of tumours suggesting that all antibodies should be included in the serological screening for possible PNS. The levels of onconeural antibody are not sufficiently sensitive to discriminate between cancer patients with PNS and those without.

Thymomas are epithelial neoplasm of thymus and most common primary neoplasm of anterior and superior mediastinum affecting males and females equally. It occurs usually in the fifth to seventh decade. Approximately one-third of thymomas are invasive. Metastases to distant extrathoracic sites such as the liver, lung, lymph node, kidneys, ovary and brain occur infrequently. This is more common with invasive thymomas. Although brain has been shown to be a site of infrequent metastases, intraorbital metastases has not yet been reported. Here we report one such case of invasive thymoma of anterior superior mediastinum, which later metastasized to orbit as well as the brain.

Alzheimer's disease (AD), the major contributor to dementia in the elderly, involves accumulation in the brain of extracellular plaques containing the beta-amyloid protein (Abeta) and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. AD is also characterized by a loss of neurons, particularly those expressing nicotinic acetylcholine receptors (nAChRs), thereby leading to a reduction in nAChR numbers. The Abeta(1-42) protein, which is toxic to neurons, is critical to the onset and progression of AD. The discovery of new drug therapies for AD is likely to be accelerated by an improved understanding of the mechanisms whereby Abeta causes neuronal death. We examine the evidence for a role in Abeta(1-42) toxicity of nAChRs; paradoxically, nAChRs can also protect neurons when activated by nicotinic ligands. Abeta peptides and nicotine differentially activate several intracellular signaling pathways, including the phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog pathway, the extracellular signal-regulated kinase/mitogen-activated protein kinase, and JAK-2/STAT-3 pathways. These pathways control cell death or survival and the secretion of Abeta peptides. We propose that understanding the differential activation of these pathways by nicotine and/or Abeta(1-42) may offer the prospect of new routes to therapy for AD.

RT is an integral component of treatment in many tumors of the mediastinum. In recent years, there have been advances in RT planning and delivery, which have allowed more effective radiation delivery while sparing normal tissues. New technologies and radiation modalities may help achieve disease control more safely and effectively.

Combined modality therapy is gaining acceptance for treating stage 3 and 4A thymic tumors. Also, specific subsets of stage 2 tumors deserve particular attention. Single-center experiences demonstrate that there are some advantages in selected groups of patients. The overall relatively low complete response rate, however, imposes the search for better systemic therapy to optimize results. In fact, although thymic tumors are responsive to different cytotoxic regimens, none has been demonstrated to be the ideal one. New therapies and strategies should be designed and tested in large-scale multicenter prospective trials. Among the others, epidermal growth factor receptor inhibitors have shown some clinical response, because EGFR is overexpressed in thymoma. c-KIT is overexpressed in thymic carcinoma. Although in a recent study a clinical response to imatinib has been reported, results of a prospective study in patients who have thymic carcinoma are pending. Clinical responses have been reported also to other tyrosine kinase inhibitors, such as dasatinib. Other reports have stressed the presence of an up-regulation of COX-2 with a potential separate therapeutic pathway. Other markers, such as the expression of thymidine synthase and dihydropyrimidine dehydrogenase, which predict sensitivity to 5-fluoruracil-based chemotherapy, were not correlated with the clinicopathological characteristics in a series of thymomas. These new therapies should be incorporated in a standardized approach that goes from a careful assessment of histology, staging, and lymph node status, and a constructive and nonempiric cooperation between the oncologist, radiotherapist, pathologist, and thoracic surgeon.

Pediatric mediastinal tumors and cysts are rare disorders that share many similarities with adults, yet which have important differences unique to the child. Posterior mediastinal tumors are relatively more common in children than in adults and are also more likely to be malignant in children. CT imaging facilitates the diagnostic evaluation of mediastinal masses in children. Airway compression is always a concern with large mediastinal tumors in children given their relative softer and smaller airway.

Determination of the genetic markers by the application of new genomic methodologies has provided important insight into the pathogenesis of mediastinal disease. These new techniques have enabled scientists to uncover differential gene expression patterns between subtypes of thymomas, correlate tumor marker expression with germ cell tumors, and determine a link between the NF-kappaB and JAK/STAT pathways with Hodgkin's and non-Hodgkin's lymphoma. Despite the progress made in the understanding of genetic markers of select mediastinal tumors, significantly more investigation is required to elucidate the molecular pathways involved in the pathogenesis of these tumors.

The thymus has long been an organ of mystery. Today, it is known to be central to the construction of our immune system. I focus on the days when no one was sure what the thymus's function was. I review the Japanese literature regarding the beginnings of surgery of the thymus, especially the surgery for thymoma and thymectomy, which was performed as a treatment for myasthenia gravis.

We investigated an association of the HLA-A locus in 78 French Caucasian patients with autoimmune myasthenia gravis (MG) and thymic epithelial tumours. The largest effect was a protection associated with HLA-A02 in MG patients with a B2 type thymoma (OR=0.323, 95% CI: 0.113-0.756, P=0.00041). The frequency of HLA-A25 was also increased in the whole group of patients (OR=3.62, 95% CI: 1.62-7.08, P=0.0041). Our findings emphasise the interest of the histological classification in the genetic study of thymomas.

Myasthenia gravis (MG) is an autoimmune neuromuscular transmission disorder where well-defined autoantibodies against muscle and muscle cell membrane molecules are directly pathogenetic. All MG patients should be defined for subtype, as such a subclassification has treatment consequences. Ocular MG, early-onset MG, late-onset MG, MG with thymoma, MG with anti-muscle-specific tyrosine kinase antibodies and MG with no defined antibodies constitute the six MG categories. The MG diagnostic process includes neurophysiology, neuroimmunology, neuropharmacology and imaging. In addition to symptomatic therapy with acetylcholine esterase inhibitors, most patients need thymectomy and/or immunosuppressive drugs. Today's treatment is not immunospecific and far from antigen-specific, even if the pathogenesis is known in detail. Strategies for acetylcholine receptor tolerance induction, manipulating acetylcholine receptor antigen presentation or suppressing acetylcholine receptor-specific B-cells or plasma cells work in experimental MG, but have not yet been attempted properly for the human disease, or they do not work. Apart from the 10-15% of patients with paraneoplastic MG, the cause of the disease is not known. Until curative or antigen-specific therapy become available, the well-established treatment gives good-to-excellent results in most patients, with acceptable quality of life and no increased mortality. Acute and intensive care treatment during MG exacerbation is a cornerstone in the treatment.

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.

AIMS AND BACKGROUND: Advanced chemorefractory epithelial thymic tumors are still a challenge in clinical oncology. A therapeutic approach targeting a key molecular pathway could be the ideal solution in a neoplasm that can overexpress epidermal growth factor receptor (EGFR) in the epithelial component. METHODS: A patient with metastatic heavily pretreated thymic carcinoma was evaluated for EGFR expression in the primary tumor. RESULTS: Strong EGFR expression was revealed by immunohistochemistry. The patient received erlotinib therapy but had obtained no response after four months of treatment. CONCLUSION: This preliminary experience suggests that erlotinib may not be a useful therapeutic choice in advanced pretreated thymic carcinomas.

Morvan's syndrome is a rare disease characterized by peripheral nerve hyperexcitability, associated with CNS and autonomic systems involvement. High serum voltage-gated potassium channel (VGKC) antibody titers have been reported, and, till now, Morvan's syndrome has been considered as a VGKC antibody associated disease. We describe a patient with Morvan's syndrome associated with myasthenia gravis and a thymoma in his previous history, with surprisingly undetectable levels of VGKC antibodies. The clinical course is similar to those cases of Morvan's syndrome with VGKC-Ab, except for the lack of response to plasma exchange, previously considered as the first choice treatment. Nevertheless, the good response to corticosteroids therapy and the association with myasthenia confirm an autoimmune origin of the disease.

Myasthenia gravis (MG) is a well-known acquired autoimmune neuromuscular disorder. Patients with MG have a higher incidence of autoimmune disease than the normal population. MG is frequently associated with autoimmune thyroid disease, the most common of which is thyrotoxicosis. Associated hypothyroidism is not common, and the central (pituitary) origin, to our knowledge, has not yet been reported. We report an MG patient with thymoma that coexisted with central hypothyroidism, the correction of which is mandatory and significant to achieve remission.

CASE REPORT: The authors report on a 55-year-old female patient after R1 resection of a malignant thymoma with spindle type epithelial cells (WHO type A, Masaoka stage III) referred for further therapy of an ulcerative colitis. At that time, both adjuvant radiation and cytostatic therapy were not applicable due to severe activity of the ulcerative colitis. Under immunosuppressive treatment with azathioprine and steroids, the patient developed cytomegalovirus (CMV) enteritis which was triggered by therapy-induced leukopenia. After a switch from azathioprine to mycophenolatmofetil (MMF) treatment and administration of cidofovir because of nonresponse to ganciclovir and incompatibility of foscarnet sodium (Foscavir), the patient clinically improved. In addition, the patient was treated with immunoglobulins every 3-4 weeks because of antibody deficiency. At present, 3.5 years after R1 resection, the patient still has no clues of a remaining tumor mass under current immunosuppressive therapy. Ulcerative colitis is also in complete remission stage. CONCLUSION: This case indicates the very rare features of a syndrome with thymoma and antibody deficiency which was first described by Robert Good. Furthermore, the impact of immunosuppressive therapy and management of opportunistic infections on the course of this disease is obvious.

The authors describe 2 cases in which thymoma spontaneously regressed. The first patient was a 49-year-old woman with myasthenia gravis. A chest radiograph on admission showed an anterior mediastinal mass that spontaneously decreased in size as shown on a radiograph obtained 2 weeks later. Surgical removal of the mass was performed and the histopathologic examination showed a type B2 thymoma with marked coagulation necrosis in the central area. The second patient was a 46-year-old woman who was hospitalized due to chest and back pain. A chest radiograph on admission showed an anterior mediastinal mass and bilateral pleural effusion. The mass decreased in size and the effusion disappeared as shown on a chest radiograph obtained 2 months later. Computed tomography-guided biopsy was performed, and histopathologic examination revealed thymoma with marked necrosis. In both cases, dynamic contrast-enhanced magnetic resonance images showed peripheral ringlike enhancement of the mass. The clinical and radiologic features of spontaneously regressed thymoma may be different from those of common thymoma.

We describe the clinical case of a thymoma, surgically removed after diagnosis, staging, and preoperative assessment performed by means of cardiac electrocardiogram-gated multidetector computed tomography. This technique allowed a very accurate assessment of the mass, proving superior to conventional computed tomography thanks to the possibility of identifying the relationships of the mass with the mediastinal structures, including the large vessels and coronary arteries. It also established the origin of the arterial vascularization from a tributary branch of the left internal mammary artery, visualizing the pathway and the relationship of the vessel with the mass and the point where it is penetrated. Finally, we analyzed the anatomy and patency of the coronary arteries, essential data in this patient with a high risk of coronary artery disease.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant neoplasm that occurs in the thyroid gland, or head and neck. This tumor arises from either ectopic thymus tissue or remnants of branchial pouches, which retain the potential to differentiate along the thymus line. Clinical presentation and imaging can be consistent with a malignant lesion such as thyroid cancer or thymic carcinoma. Immunohistochemical staining with CD5 can differentiate CASTLE from other malignant thyroid neoplasms. A 54-year-old male had initially presented with a painless, left neck mass for 3 months. He underwent left thyroid lobectomy via a median sternotomy approach. Carcinoma showing thymus-like differentiation was the final histopathologic diagnosis. After 36 months of follow-up, no evidence of recurrence was observed. A median sternotomy is an excellent approach for CASTLE with anterior mediastinum involvement. Complete resection is important to improve the long-term survival rate and the locoregional recurrence rate.

The purpose of the treatment of autoimmune myasthenia gravis is to directly improve neuromuscular transmission, and also to reduce the production or presence of the nicotinic acetylcholine receptor (achR). Acetylcholinesterase inhibitors are the first line treatment with the rapid onset of effect, for all types of myasthenia gravis (ocular, generalized myasthenia gravis, seronegative or seropositive patients). Plasmapheresis or intravenous immunoglobulin (IVIg) is the treatment for exacerbations. Their main advantage is the rapid onset of the effect. Three to five plasma exchanges or IVIg infusions (1.2 to 2 g/b.w administered over 2-5 days) are usually recommended. In case of suspected thymoma, thymectomy should be always performed. The option of thymectomy is discussed in young patients less than 50 years old with unstable myasthenia gravis, even if thymoma lesions are not suspected. Corticosteroids and/or immunosuppressive agents are used in severe forms of the disease. A few randomized studies have shown the efficacy of the therapeutic agents. Corticosteroids are considered a major treatment of myasthenia gravis but the doses and periods of time are still being debated. The combination of corticosteroids and immunosuppressive agents are recommended early to spare corticosteroids. The treatment of myasthenia gravis should be modulated regularly (minimal doses for example).

Primary thymic carcinoma-mucoepidermoid cell (MEC) type is rare and only one report describing the cytologic features of this neoplasm in the metastatic site is described. We describe the cytological features of poorly differentiated carcinoma possibly MEC in a 54-year-old man who presented with cough, weight loss, and puffiness of face for 3 months. The significance of this infrequently encountered neoplasm lies in its potential confusion of origin of the tumor-thymus or metastases from a primary bronchial MEC. Immunocytochemical profile was suggestive of a thymic carcinoma of the MEC type. (c) 2009 Wiley-Liss, Inc.

INTRODUCTION: Thymoma is a rare tumor which represents about 20% of mediastinal tumors. It is associated with several parathymic conditions. A second cancer frequently occurs during long term follow up. CASE REPORT: We report the case of a 59 year-old woman who presented with a two month history of a dry cough. Thoracic imaging revealed a soft tissue mass in the anterior mediastinum with associated bilateral pleural effusion and mediastinal lymphadenopathy. Fibreoptic bronchoscopy was normal. CT guided-biopsy was not contributive. A diagnostic mediastinoscopy was carried out. Histological examination confirmed the diagnosis of thymoma. The patient was treated with 4 cycles of chemotherapy which led to a partial regression of the mass. The course was marked by the occurrence of a pure red cell aplasia requiring corticosteroid therapy which caused the disappearance of the anemia. However, bluish nodules appeared on the patients legs which when biopsied were found to represent Kaposi's sarcoma. The patient was treated with chemotherapy (vinblastine) without any improvement of the cutaneous lesions. CONCLUSION: Our case describes the association of a thymoma, pure red cell aplasia and Kaposi's sarcoma. Immunologic disorders seem to be in the origin of this association.