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Background and Objectives: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact., Methods: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19 + B220 high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated., Results: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19 + B220 high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy., Discussion: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: To report a patient with thymoma-associated retinopathy presenting as having a good visual prognosis., Methods: Case report and literature review., Case Report: A 42-year-old female patient was referred to our hospital for complaints of sudden visual-field defects bilaterally. Decimal corrected visual acuity (VA) was 1.5 and 1.2 in the right (RE) and left eyes (LE), respectively. Fundus autofluorescence revealed hyper-autofluorescence from the posterior pole to mid-peripheral retina in both eyes. Full-field electroretinography (ERG) amplitudes were reduced to 20-50% and 30-50% of our controls for the scotopic and photopic conditions, respectively. A systemic examination revealed the presence of thymoma, and the patient underwent thymectomy and immunosuppression therapies. Immunohistochemical analysis using the patient's serum showed immunolabeling on the photoreceptor inner segment and outer plexiform layer in the monkey retina. Two years later, VA remained at 1.5 and 1.2 in RE and LE. ERG amplitudes improved to 30-60% of the controls for the scotopic conditions. However, photopic ERG showed no remarkable change., Conclusions: To our knowledge, improvement of reduced rod-mediated ERG responses has not been described in seven previously reported patients with thymoma-associated retinopathy. The good visual prognosis of our patient may be associated with well-timed intervention.

Pure red cell aplasia (PRCA) is a rare disease characterised by anaemia and low reticulocyte count, caused by absence of erythropoiesis in the bone marrow. This report describes a case of a ring-calcified thymoma that led to the development of PRCA. Moreover, we provide an overview on the classification of thymoma and the pathophysiology and treatment of PRCA.

Purpose: To report on the implementation, validation and results of the first two proton therapy PBS treatments of limited amplitudes moving targets performed at our center., Methods and Materials: A real time optical tracking system was used to monitor the patient surface during the CT scan and treatment. This system is also able to trigger the beam during the treatment. A 4DCT (10 phases) and a Free-Breathing CT (FBCT) were used for the planning. The physician used the 4DCT for ITV delineation, while planning was performed on the FBCT. The approved plan was evaluated in two ways:The largest breathing amplitude recorded during 4DCT scan was used as gating safety threshold during treatment delivery. This planning and treatment workflow was then applied for two patients affected by thoracic thymoma., Results: The dosimetric evaluation of the plan showed no interplay effect. The second patient showed an overdosage to the coronary and Left Anterior Descending area in the worst case scenario but it was below the constraints. Duty Cycle together with number of beam interruptions gave information about the patient compliance to the treatment: the first patient breath is stable and within thresholds, whilst the second patient had more variations, causing multiple beam interruptions., Conclusion: We defined and used for two patients a protocol for the treatment of small amplitude moving targets. The planning and delivery of the treatments gave very good results in terms of coverage, OARs sparing, 4D dose evaluation of the plan and interplay effect assessment., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Routine imaging for mediastinal malignancies includes chest X-ray, CT or MRI. T1 and T2 mapping are novel MRI techniques which may have a role in expanding the assessment of internal tumour characteristics. This case report details two middle-aged women who had similar clinical presentations of mediastinal masses of comparable size and appearance when assessed with routine imaging. T1 and T2 maps were acquired on MRI to investigate whether these tumours could be further differentiated prior to surgery. T1 and T2 mapping supported suspicion for which tumour components were solid and cystic, as subsequently confirmed histologically. Furthermore, comparison between the two tumours showed native T1 values differed within the solid components by 37%, correlating to differences in proteinaceous material within the tumour types. This radiological-pathological correlation provides evidence that T1 and T2 mapping has clinical utility in the assessment and differentiation of mediastinal masses., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Rationale: Sclerosing thymoma is an extremely rare mediastinal neoplasm; it was recognized for the first time in 1994 and to date only 15 cases have been reported., Patient Concerns: The present study report a case of a 65-year-old man who was incidentally found to have an anterior mediastinal nodule, without clinical symptoms including fever, chest pain, and myasthenia gravis., Diagnoses: The chest computed tomography (CT) revealed the nodule was 4.9 × 4.2 × 3.0 cm in size. And the microscopic and immunohistochemical findings indicated that the final diagnosis was sclerosing thymoma., Interventions: The anterior mediastinal nodule was completely removed., Outcomes: No evidence of recurrence or complication was found in the second year after surgery., Lessons: The biologic behavior of the rare sclerosing thymoma is still largely mysterious; it is utmost importance to classify the sclerosing thymoma from other mediastinal tumors. Its prognosis is favorable and thymectomy is currently the mainstay of treatment.

Background: Neuroendocrine tumors are a large group of tumors with a wide spectrum of behavior, affecting mainly the digestive system and the lung. The thymus is very rarely affected., Case Presentation: A 28-year-old Arab woman presented with chronic chest pain and dyspnea. A computed tomography scan showed a huge anterior mediastinal mass invading neighboring structures. A mediastinotomy was performed with biopsies of the mass. Pathological findings were consistent with a thymic large cell neuroendocrine carcinoma., Conclusions: The occurrence of a large cell neuroendocrine carcinoma in the thymus, especially in young people, is extremely rare. In this current report, we discuss the clinicopathological issues of this rare tumor according to recent literature data.

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

A 48-year-old woman was admitted to our hospital to undergo evaluation for fatigue, severe weight loss, and nephrotic range proteinuria. Light microscopy of a renal biopsy specimen revealed class III (A) lupus nephritis, while immunofluorescence and electron microscopy only showed sparse immune deposits with findings that were not typical of lupus nephritis. Computed tomography revealed a mass in the anterior mediastinum, which was resected. The examination of the surgical specimen revealed type A noninvasive thymoma. In combination with thymomectomy, postoperative steroid therapy achieved the prompt remission of lupus nephritis. In this patient, thymoma-related autoimmunity may have contributed to the exacerbation of lupus nephritis.

Rationale: Nephropathy with concurrent invasive thymoma is a type of paraneoplastic syndrome., Patient Concerns and Diagnoses: We report a 32-year-old female with nephrotic syndrome that was first diagnosed along with invasive thymoma and treated by means of cisplatin-based chemotherapy for the thymoma. The patient initially presented with dyspnea and generalized edema. Chest radiography and computed tomography scans revealed right pleural effusion and a mass in the right middle lung field, which were confirmed by a percutaneous lung biopsy as metastatic invasive thymoma. Severe hypoalbuminemia, heavy proteinuria, hyponatremia, and hypercholesterolemia were features of the nephrotic syndrome. A kidney needle biopsy suggested focal segmental glomerulosclerosis., Interventions and Outcomes: All of the symptoms of nephrotic syndrome were resolved simultaneously during the first 2 cycles of chemotherapy. The patient was on regular follow-up with no specific treatment for nephrotic syndrome and underwent successful resection of the left pleura and anterior thymoma. The patient has shown no evidence of recurrence for 2 years., Lessons: We conclude that chemotherapy for invasive thymoma is an effective treatment for nephrotic syndrome accompanying the thymoma., Competing Interests: The authors have no funding and conflicts of interest to disclose.

A 50-year-old man presented to our hospital in 1995. Invasive thymoma was diagnosed and extended thymectomy and left upper lobe partial resection were performed. In 2013, he complained of dyspnea. Chest computed tomography showed postoperative recurrence of invasive thymoma. Several chemotherapies were administered. Severe anemia and an increase in the total bilirubin level were observed with chemotherapies. In additional, an examination showed that the direct Coombs test was positive. Cold agglutinin was also high. We herein experienced a rare case of postoperative recurrence of invasive thymoma with cold agglutinin disease and autoimmune hemolytic anemia.

We report a case of a 40-year-old woman who developed generalized muscle weakness over a period of 2 months. Physical examination revealed palpable masses in her arms and hands. Serum creatine kinase levels were elevated. Electromyography showed myopathic changes and 3 Hz repetitive nerve stimulation revealed a decremental pattern on repetitive nerve stimulation. Muscle MRI demonstrated increased signal intensity in the biceps brachii on T1-weighted images. Chest CT scan showed a mediastinal mass suggestive of thymoma. Muscle biopsy revealed giant cell polymyositis. The patient was treated with cholinesterase inhibitors and corticosteroids with improvement of strength, and subsequently underwent thymectomy followed by radiotherapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The thymus selects T cells, thus ensuring T cell tolerance. Thymoma can be associated with immune dysregulation manifesting as autoimmunity and/or immunodeficiency. Immune dysregulation in thymoma patients has only been described in case reports and small case series. The current study was a retrospective single-center study, covering the period 1/2000 to 12/2010. Clinical data were collected by chart review. We identified 29 patients with thymoma. The median age at diagnosis was 60 years (range: 23-87). Median follow-up time was 1,326 days (range: 15-3,710), and 20 patients (69%) were alive at last follow-up. Overall, in 13 of 29 patients (45%) autoimmunity and infection were observed in 7 of 29 (24%) and 3 of 29 patients (10%) infection and autoimmunity only was observed, respectively. Both opportunistic and nonopportunistic infections were recorded. Myasthenia gravis (10 of 29 patients) was the most frequent autoimmune disease. Additional entities included pemphigus, pure red cell aplasia, lichen planus, Sjögren's syndrome, systemic lupus erythematosus (n = 2 each), and cutaneous lupus erythematosus, sarcoidosis, vitiligo, polymyositis, and chronic inflammatory demyelinating polyradiculoneuropathy (n = 1 each). Six of 29 patients (21%) had more than 1 autoimmune disorder. In thymoma patients, infection, autoimmunity, and in particular a combination of both pose a challenge to treating physicians. Prospective multicenter studies are required to more precisely define the thymoma-associated immune dysregulation syndrome., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

The SOX gene family encodes a large group of transcription factors that are strongly involved in the normal human development and malignancies. Human tumors, like small cell lung carcinoma, meningioma, gastric, and pancreatic cancer, have been found to be immunogenic for SOX2 protein. In this study, we have investigated for the first time the expression and distribution of SOX2 immunoreactive cells in five normal human thymuses (2 fetal and 3 adult) and 10 thymomas bioptic specimens. Results demonstrated the presence of few positive cells in the fetal and postnatal normal human thymus with a specific distribution within thymus parenchyma compartments. On the contrary, in thymoma immunoreactivity to SOX2 increased parallel to pathological stage, and a peculiar distribution was observed in type B3 thymoma with a positive reaction in both tumor and endothelial cells.

The integrated modality positron emission tomography/computed tomography (PET/CT) with C-11 choline is an established diagnostic tool for restaging prostate cancer patients with a biochemical failure after primary treatment. Thymoma is a rare tumor originating in thymus epithelial cells, asymptomatic in one-third to one-half of patients, and often occurring in the fourth and fifth decades of life. In the present case, C-11 choline PET/CT was performed in a prostate cancer patient with a biochemical relapse, to restage the disease. In addition to the detection of local recurrent disease in prostatic fossa, an abnormal C-11 choline increased uptake in mediastinum was reported. The mediastinal finding was initially wrongly interpreted by clinicians as a lymph nodal metastasis from prostate cancer. However, histopathological analysis confirmed the presence of a thymoma. Although rare, thymoma has to be considered as differential diagnosis in case of mediastinal masses presenting C-11 choline PET/CT positive findings, to avoid inappropriate patient management.

Paraneoplastic autoimmune diseases associate occasionally with small cell lung cancers and gynecologic tumors. However, myasthenia gravis (MG) occurs in at least 30% of all patients with thymomas (usually present at MG diagnosis). These epithelial neoplasms almost always have numerous admixed maturing polyclonal T cells (thymocytes). This thymopoiesis-and export of mature CD4(+)T cells-particularly associates with MG, though there are rare/puzzling exceptions in apparently pure epithelial WHO type A thymomas. Other features potentially leading to inefficient self-tolerance induction include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatibility complex class II molecules in thymomas, absence of myoid cells, failure to generate FOXP3(+) regulatory T cells, and genetic polymorphisms affecting T-cell signaling. However, the strong focus on MG/neuromuscular targets remains unexplained and suggests some biased autoantigen expression, T-cell selection, or autoimmunization within thymomas. There must be further clues in the intriguing serological and cellular parallels in some patients with late-onset MG but without thymomas-and in others with AIRE mutations-and in the contrasts with early-onset MG, as discussed here.

Cough is one of the most common symptom for which patients seek medical attention from primary care physicians and pulmonologists. Although tuberculosis and other lung infections are common throughout the developing world, they are not among the most common causes of chronic cough. We report a case of a 23 years old male who presenting to the outpatient clinic with chronic cough not responding to regular and symptomatic treatment that was diagnosed to have thymoma. After all the common causes for chronic cough have been ruled out, unusual causes should also be considered in the differential diagnosis.

Little is known about pathogenesis -- and especially about involvement of CD8(+) T-cells -- in late-onset myasthenia gravis (LOMG). Remarkably, outstanding CD8(+) TCRVbeta-subset expansions were found in 64% and 72% of recent onset LOMG or thymoma-associated MG (vs. 16% with early-onset MG (p<0.0002); 21% in older controls (p<0.001)). In LOMG, ~25% of the expanded cells initially showed a naïve CD62L(+hi)/CD45RA(+) recent thymic emigrant (RTE)-like phenotype. These expansions associated significantly with IgG antibodies against cytomegalovirus (p<0.036), IL-12 and/ or IFN-alpha2 (p<0.03). The CD8(+) TCRVbeta expansions were stable over 5years, but RTE markers declined.

Objectives: To report a case of multifocal cortical encephalitis associated with thymoma and to establish an association of this thymoma-related paraneoplastic syndrome with voltage-gated potassium channel antibodies., Design: Case report., Setting: University hospital., Patient: A 43-year-old woman with a history of seropositive myasthenia gravis and successfully treated invasive thymoma. Four years after thymectomy, she presented with seizure and rapidly progressive confusion and aphasia. Myasthenia gravis remained in pharmacological remission. Magnetic resonance imaging of the brain showed innumerable cortically based signal abnormalities as well as extensive left mesial temporal lobe abnormality with minimal enhancement., Results: Chest computed tomography showed abnormal pleural thickening of the left lung, which proved to be recurrent metastatic thymoma. Results of serological evaluation were positive for acetylcholine receptor, striational, and voltage-gated potassium channel antibodies. She showed partial improvement in response to immunotherapy and chemotherapy but ultimately died 2 months later of tumor complications., Conclusions: Thymoma and myasthenia gravis may be associated with other autoimmune neurological disorders including paraneoplastic encephalitis. This second case of thymoma-associated multifocal cortical encephalitis demonstrates that autoimmune encephalitis can extend to cortical regions outside the limbic system. Autoimmune encephalitis should be considered in the differential diagnosis of patients with myasthenia gravis or thymoma who develop new cognitive symptoms.

The association of thymoma with myasthenia gravis has been well documented. However, the relationship between these two syndromes and Addison disease are very rarely encountered in clinical practice. We report on a 32-year-old man who underwent a resection for thymoma 48 months ago. The diagnosis of Addison disease was made followed by a diagnosis of myasthenia gravis on the basis of a high titer of acetylcholine receptor levels. The treatment of oral prednisolone 7.5 mg/day and oral prostigmine 180 mg/day was initiated. His symptoms and physical signs were improved after this treatment. To our knowledge, this is the fourth reported case of thymoma synchronously associated with myasthenia gravis and Addison disease.

Thyroid hormones play an important role in the growth of the kidney and maintenance of its functions. Prolonged hypothyroidism is known to be accompanied by changes in renal morphology such as thickening of the glomerular and tubular basement membranes as well as increased mesangial matrix. Increased transcapillary leakage of plasma proteins leading to proteinuria and generalized edema is also a known complication of hypothyroidism. In particular, autoimmune thyroiditis is associated with proteinuria. Most previous reports of autoimmune thyroiditis with nephrotic syndrome have demonstrated mixed pathological morphology marked by predominant membranous glomerulopathy. Here we present a patient whose initial presentation with profound hypothyroidism and autoimmune thyroiditis was dominated by nephrotic syndrome secondary to type 1 membranoproliferative glomerulonephritis (MPGN). The association of MPGN and autoimmune thyroiditis is very rare.

Rare associations of immunological disorders can often tell more than mice and rats about the pathogenesis of immunologically mediated human kidney disease. Cases of glomerular disease with thyroiditis and Graves' disease and of minimal change disease with lymphoepithelioma-like thymic carcinoma and lymphomatoid papulosis were recently reported in Pediatric Nephrology. These rare associations can contribute to the unraveling of the pathogenesis of membranous nephropathy (MN) and minimal change disease (MCD) and lead to the testing of novel research hypotheses. In MN, the target antigen may be thyroglobulin or another thyroid-released antigen that becomes planted in the glomerulus, but other scenarios can be envisaged, including epitope spreading, polyreactivity of pathogenic antibodies, and dysregulation of T regulatory cells, leading to the production of a variety of auto-antibodies with different specificities [immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX syndrome)]. The occurrence of MCD with hemopathies supports the role of T cells in the pathogenesis of proteinuria, although the characteristics of those T cells remain to be established and the glomerular permeability factor(s) identified.

Polymyositis revealing myasthenia gravis and malignant thymoma: a case report. The increased frequency of thymoma associated with autoimmune diseases has been well documented in the literature. However the association of polymyositis (PM) and myasthenia gravis (MG) revealing a malignant thymoma is rare. We report a case of a gentleman whose presenting symptoms were those of polymyositis.

Objective: To investigate the clinical and electrophysiological characteristics of myasthenia gravis with thymoma (MGT)., Methods: The clinical and repetitive nerve stimulation (RNS) data of 72 patients with MGT, 36 males and 36 females, and 63 patients with myasthenia gravis without thymoma (NMGT) were analyzed retrospectively., Results: The onset age of 52 of the 72 MGT patients (72.2%) was 35-59. The average onset age of the MGT patients was 39.5, older than that of the NMGT patients (29.4 yrs), and the course of the MGT patients was 13.1 months, shorter than that of the NMGT patients (29.1 months)The attack rate of the males was not significantly different than that of the females. The proportion of generalized presentation type among the MGT patients was 72.8%, higher than that among the NMGT patients (66.7%), particularly concerning the respiratory muscle (20.8% vs. 9.5%). The average time interval between the onset of symptoms and respiratory or bulbar muscle involvement of the NMGT patients were 12 and 7 months respectively, both remarkably shorter than those of the NMGT patients (26.4 and 11.6 months respectively). The abnormal RNS test yield rate of the MGT patients was 86.9%, higher than, however, not significantly that of the NMGT patients (75.0%). 97.2% of the thymoma and mediastinal abnormality could be detected through computed tomography (CT) scan on thymus. The positive rate of AchRab titer of the MGT patients was 50.0%, not significantly different from that of the NMGT patients (52.4%)., Conclusion: MGT is common in middle-aged people, both male and female. The Course is quickly progressive and generalized skeletal muscles, particularly respiratory muscles, are more involved in the MGT patients than in the NMGT patients. RNS study is a sensitive tool to identify MGT. AchRab may not be the specific antibody for recognizing MGT. CT scan is useful in differentiating thymoma preoperatively.

The aim of the study is to provide evidence that the lymphocytic infiltration of myasthenia gravis (MG) muscle do not represent a true autoimmune myositis, rather an infiltration by naive lymphocytes derived from lymphocyte-rich thymomas. Muscle biopsies from 179 patients with pure MG, 6 thymoma patients without MG and 15 patients with definite polymyositis were analyzed. In 18 patients with MG (all associated with lymphocyte-rich thymomas) and in two thymoma patients without MG, lymphocytic infiltrates were identified in muscles. By use of immunohistochemistry, we demonstrated that the lymphocytes in MG differ from those in polymyositis, being mature but in contrast to polymyositis naive CD45RA+ T lymphocytes. We suggest that the lymphocytic infiltrates in patients with MG and thymoma represent an infiltration of muscle by thymoma-derived mature but naive T cells. The finding of CD8+CD45RA+ lymphocytes in muscle may signify an underlying thymoma and should not be misdiagnosed as polymyositis.

Aim: Infiltration of the superior vena cava (SVC) due to advanced non small cell lung cancer (NSCLC) or thymoma can be treated by prosthetic replacement or tangential resection. These two technical procedures and their results are described., Methods: From 1988 to 2002, we performed 37 SVC resections: 21 replacements with polytetrafluoroethylene (PTFE) prostheses and 16 tangential exereses. Sixteen patients affected by locally advanced NSCLC (12 T4; 4 extracapsular N2) and 5 subjects with thymoma (Stage III Masaoka) underwent prosthetic replacement of the SVC. After neoadjuvant polychemotherapy, tangential resection was performed on 12 patients with extracapsular N2 NSCLC, and in 1 patient with T4 and in 3 patients with T3a disease. We performed prosthetic replacement in 18 cases using a straight prosthesis (?18-20 mm). A bridge (10-14 cm) between the innominate vein and the right atrium was created in 3 patients. The main indication for a prosthetic replacement was infiltration of more than 30% of the circumference of the SVC. There were 4 thromboembolic complications (19%), with one intraoperative death (4.8%). Tangential resection of the SVC for infiltration <20% was performed both manually and with staplers (double clamping) without any major complications., Results: Mean survival was 23 months in those patients who had undergone PTFE replacement for T4 lung cancer and for thymoma. Mean survival was 15 months in those who had undergone tangential resections for NSCLC with extracapsular N2. We performed restaging of the tumor using chest angio-CT scan in 11 patients, one year after the operation. We found 80% patency in 7 SVC prostheses and 50% patency in 4 others: the two bridges between the left innominate vein and the right atrium appeared to be partially closed but were compensated by important collateral circles., Conclusion: SVC replacement, associated with pulmonary resection or removal of mediastinal masses, can be performed in selected cases. It should not be considered as palliative treatment because of the important perioperative risks. SVC tangential resection involves fewer surgical problems. However, since this procedure is used mostly for N2 NSCLC subjects, patients have a low mean survival in spite of adjuvant therapy.

Background: Thymoma is frequently associated with paraneoplastic diseases (PDs), most commonly with myasthenia gravis (MG). This association is thought to depend on thymoma's capacity to produce and export T lymphocytes., Objective: (1) To determine the frequency and characteristics of thymoma-associated PDs other than MG; (2) to evaluate T cell maturation in thymomas with and without PDs., Methods: We studied 260 patients with thymoma (associated with MG in 228). The occurrence of PDs was monitored together with the tumor outcome. Phenotypic characterization of thymocyte subsets in 14 thymoma samples (7 with and 7 without MG) was performed by FACS., Results: A total of 47 PDs was diagnosed in 41/260 patients (15.8 %). Neurological PDs included neuromyotonia, limbic encephalitis, polymyositis, subacute hearing loss, psychosis and sleep disorders. A broad spectrum of nonneurological PDs were observed, among these, hematological and cutaneous diseases prevailed. Like MG, these disorders occurred either in the presence of the thymoma or at different times after thymomectomy; their onset often heralded a tumor recurrence. In thymomas from MG subjects, we found an increased proportion of fully mature CD4 single positive (SP) thymocytes and a reduced frequency of CD4SPCD25(+) cells; the latter finding may reflect a deficient generation of T regulatory cells, a reduced intratumorous activation of T cells, or both., Conclusions: We confirm the strong association of thymoma with PDs. These disorders often occurred in MG patients and their course in relation to thymoma was similar to that of MG. In accordance with previous observations, we found some alterations in the intratumorous production of mature CD4(+) T cells that could be involved in the pathogenesis of paraneoplastic autoimmunity.

Objective: To investigate whether excitation-contraction (E-C) coupling of muscle is impaired in patients with myasthenia gravis (MG)., Methods: In 51 patients with generalized MG and 35 normal subjects, compound muscle action potentials (CMAPs) of the abductor pollicis brevis, and movement-related potentials using an accelerometer placed at the thumb tip were simultaneously recorded after median nerve stimulation at the wrist. The E-C coupling time (ECCT) was estimated by a latency difference between CMAP and movement-related potential. Antibodies against acetylcholine receptor (AChR), ryanodine receptor (RyR), and muscle specific receptor tyrosine kinase (MuSK) were measured by immunoassays., Results: The mean ECCT was significantly longer in patients with MG (mean+/-SEM; 2.79+/-0.1 ms; p=0.002) than in normal controls (2.52+/-0.1 ms). Among MG patients, the mean ECCT was longer for patients with thymoma than for those without it (P=0.04), and was shorter for patients treated with FK506 (an immunosuppressant and also an enhancer of RyR related Ca(2+) release) than for those not receiving this treatment (p=0.04). ECCT had no significant correlation with anti-AChR, anti-RyR, or anti-MuSK antibodies., Conclusions: In MG, E-C coupling appears to be impaired, particularly in patients with thymoma, and FK506 possibly facilitates E-C coupling., Significance: The functional implication of impaired E-C coupling is not established, but it may contribute to muscle weakness in patients with MG.

Myasthenia gravis is characterized by weakness and easy fatiguability of voluntary muscles. Myasthenic patients are sensitive to non-depolarizing relaxants. Sevoflurane, as an alternative, can be used to achieve good tracheal intubation. In this report, we present our experiences.

Recently, limbic encephalitis (LE) associated with Voltage-gated potassium channel antibody (VGKC-Ab) has been postulated as a new autoimmune disorder. Most previously reported cases of VGKC-Ab-associated LE were non-paraneoplastic, and reports of a paraneoplastic type are rare. Here we describe a 59-year-old woman with paraneoplastic VGKC-Ab-associated LE preceding the recurrence of invasive thymoma. There was a close temporal relationship between the clinical course and the changes of the VGKC-Ab titer. Unlike many of the non-paraneoplastic VGKC-Ab-associated LE cases, our cases showed the more extensive high intensity lesions on MRI and the absence of seizure and hyponatremia.

Objectives: To describe two patients with myasthenia gravis (MG) and prolactinoma and analyze the associations between MG and prolactin (PRL) levels., Design: Two case reports and a case-control study of PRL levels in 192 patients with MG., Participants: The Immunological Research Laboratory, Center for Molecular Medicine, Department of Medicine and the Department of Neurology, Karolinska Institutet, Stockholm, Sweden; St Petersburg Medical Academy for Postgraduate Studies, and St Petersburg State Medical Pediatric Academy, Russia., Results: Two women with MG and thymic hyperplasia accompanied by prolactinomas are described. The levels of plasma PRL were raised in 101 women with MG, but not in 91 men. There was an association between high PRL levels and high levels of autoantibodies against the acetylcholine receptor., Conclusions: There is an association of MG with raised levels of PRL in women. PRL has stimulating effects on immune activation and the increased levels might thus be implied in the pathophysiology of MG.

Objective: Myasthenia gravis (MG) may be associated with the presence of acetylcholine receptor antibodies (AChRAb) [seropositive MG (SPMG)] or their absence [seronegative MG (SNMG)]. Along with features of MG, the presence of the AChRAb may relate to the existence of other immune-mediated diseases. We sought to determine the association of SPMG with other potential autoimmune diseases., Methods: A retrospective evaluation of prospectively identified MG patients at a tertiary care center was performed, with patients separated into SPMG and SNMG. Prevalence of other immune-mediated disorders, as well as the epidemiology, sensitivity of diagnostic testing, and thymic pathology, was contrasted between both patient groups., Results: Of the 109 MG patients identified, 66% were SPMG. SPMG was associated with a greater likelihood of significant repetitive stimulation decrement, the presence of either thymoma or thymic hyperplasia, and the presence of thyroid disease. In addition, all patients with a diagnosis of diabetes, concurrent with MG, were found to be SPMG., Conclusions: AChRAb and SPMG impart not only a distinctive clinical and electrophysiological phenotype of MG, but are also associated with the heightened presence of endocrinological disease.

Background: Juvenile myasthenia gravis (JMG) is an uncommon disease. Unlike adults, clinical characteristics and outcomes of myasthenia gravis (MG) are not well studied in children., Patients and Methods: Case records of 77 patients with MG who were 15 years of age or less at disease onset, evaluated over a period of 34 years at the National Institute of Mental Health and Neurosciences, Bangalore, India, were reviewed. Their clinical characteristics and response to therapy was compared with 290 patients with MG onset after 15 years of age., Results: Median age at onset was 8 years and mean period of follow-up was 6.2 years (range 6 months to 25 years). At presentation, 30% of patients had ocular myasthenia and the rest had generalized disease. Twenty-one patients (27%) had disease confined to ocular muscles throughout the course and three had limb girdle myasthenia. Familial myasthenia was more common than adult onset disease, 10 patients had positive family history. Unlike adults, none of the patients had associated autoimmune disease. Fifty-two patients (67%) received corticosteroids, and azathioprine was added in five patients. Thymectomy was performed in 11 patients, six below the age of 15 years. Thymic histology was normal in one and showed hyperplasia in eight and thymoma in one. Four patients had crisis. At the end of follow-up, 25 patients were asymptomatic, 28 had partial improvement, and nine remained unchanged or worsened and two died. Ten patients achieved complete stable remission., Conclusions: This study shows some distinctive characteristics of JMG, such as higher frequency of ocular myasthenia, benign course, better long-term outcome and lack of association of thymoma and other autoimmune disorders.

In thymomas associated with myasthenia gravis (MG), the authors found that perivascular infiltrates of memory lymphocytes and mature dendritic cells (DCs) were more frequent in patients with early improvement after thymectomy than in patients without response to thymectomy. Although these findings may be limited to particular types of thymoma, thymectomy may interrupt the recruitment of mature DCs in thymus and export of activated T cells to extra-thymic tissues, thereby improving the disease.

A patient with thymoma-associated neuromyotonia and voltage-gated potassium channel (Kv1.2 and Kv1.6) antibodies by immunoprecipitation and rat brain immunolabeling was treated successfully with immunoadsorption and cyclophosphamide. Curiously, glutamic acid decarboxylase antibodies, absent at onset, appeared later. Stiff-person syndrome was absent, but fast blink reflex recovery suggested enhanced brainstem excitability. The range of antibodies produced in thymoma-associated neuromyotonia is richer, and the timing of antibody appearance more complex, than previously suspected.

Chronic intestinal pseudo-obstruction can occur as a paraneoplastic disorder, and several cases have been reported in association with thymoma or small-cell lung cancer. Autoantibodies against voltage-gated potassium channels (VGKCs) are found in acquired neuromyotonia (Isaac's syndrome), and have been reported in one case of slow transit constipation without apparent neurological disease. We describe a patient with VGKC antibodies, acquired neuromyotonia and thymoma, who first presented with a severe slow-transit constipation and in whom the gastrointestinal symptoms responded well to plasmapheresis. We suggest that VGKC antibodies might be helpful in patients with possible paraneoplastic chronic intestinal pseudo-obstruction, and a positive result should stimulate the search for a thymoma or other tumour and raise the possibility of immunotherapy., (Copyright 2005 S. Karger AG, Basel.)

Aims: To study 19 cases of primary thymic carcinoma in order to define the clinicopathological features and the precise histochemical profile of this rare and heterogeneous group of tumours of the anterior mediastinum., Methods and Results: The study group consisted of 13 males and six females, with a mean age of 58.5 years (range 29-75 years). Superior vena cava syndrome and chest pain were the main presenting symptoms. Three patients were asymptomatic. No patient had myasthenia gravis. Six different histological types were identified: neuroendocrine tumours (six patients), epidermoid carcinoma (five patients), sarcomatoid carcinoma (three patients), lymphoepithelioma-like carcinoma (two patients), mucoepidermoid carcinoma, clear cell carcinoma, and undifferentiated carcinoma (one patient each). The clear cell carcinoma was associated with a thymic cyst. No association with thymoma was observed. Surgical resection, performed in 10 cases, was complete in two. Sixteen patients received thoracic radiation, and 11 received systemic chemotherapy. Follow-up information was available in 16 cases; 12 patients presented with local or metastatic relapse, and 10 patients died of their tumour. The overall 5-year survival was 14.5%., Conclusion: Primary thymic carcinoma is a very heterogeneous group of tumours of the anterior mediastinum with an aggressive clinical behaviour, and a poor overall prognosis.

Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell antigen receptor. Although alpha beta T-cell development is observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R alpha was revealed by surface staining, and increased IL-7R alpha mRNA was documented by using reverse transcriptase-polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy.

The authors present the case of a 51-year-old female with a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) due to a malignant thymoma. Laboratory examinations of the patient showed hyponatremia, plasma hypoosmolarity in the presence of concentrated urine and normal urine excretion of sodium. CT revealed a mass lesion in the mediastinum. A biopsy of the mediastinal mass was performed and the diagnosis of thymoma with SIADH was established. This is a rare description of a malignant thymoma associated with SIADH., (Copyright 2002 S. Karger AG, Basel)

Immune-mediated acquired disorders of erythropoiesis can result in pure red cell aplasia or ineffective erythropoiesis. Erythropoiesis can be suppressed or impaired by humoral or cellular mechanisms. In vitro inhibition of erythroid colony growth by humoral factors or lymphocytes is a strong argument for the immune origin of the disease. Classical aetiologies are thymoma and hematological malignancies such as chronic lymphocytic leukaemia. Clonal proliferation of T cells has also been incriminated. Recently, acquired circulating autoantibodies directed against erythropoietin have been detected in a case of pure red cell aplasia. Autoimmune mechanisms have also been suggested in two dyserythropoietic syndromes recently described.

The authors report an autopsied patient with limbic encephalitis and recurrent thymoma. The immunohistochemical study showed selective depositions of immunoglobulin G on the neurons in the limbic system and the tumor cells of the recurrent thymoma. The immunoblotting study detected two types of antibodies that react with the human brain, rat brain, and rat thymus.