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To probe into the changes and significance of serum acetylcholine receptor antibody (AchR-Ab) and citric acid extractive antibody (CAE-Ab) in patients with thymoma after thoracoscopic surgery (TS). The data of 50 patients with thymoma receiving TS in our hospital from February 2017 to February 2021 were selected for retrospective analysis. Serological testing was performed before and after surgery to determine serum AchR-Ab and CAE-Ab levels, the therapeutic effect was evaluated and the trend of serum AchR-Ab and CAE-Ab changes and their meanings were analyzed. Among 50 patients with thymoma after TS, 15 (30.0%) were in remission, 25 (50.0%) had improvement and 10 (20.0%) had no response to treatment. After treatment, the serum AchR-Ab and CAE-Ab levels of patients, which were remarkably lower than those before treatment ( P  < 0.001), were remarkably lower in the remission group than in the improvement group ( P  < 0.001) and remarkably lower in the improvement group than in the ineffective group ( P  < 0.001). The ordinal logistic regression analysis concluded that the levels of AchR-Ab and CAE-Ab were related to therapeutic effect, i.e. the lower the serum AchR-Ab and CAE-Ab levels, the better the therapeutic effect. TS can reduce the serum AchR-Ab and CAE-Ab levels in patients with thymoma, and serum AchR-Ab and CAE-Ab levels can reflect the therapeutic effect, providing reference value.

Background: No useful tumor markers have been identified for the diagnosis of thymic carcinomas. Serum cytokeratin 19 fragment, measured using the CYFRA 21-1 immunoassay, is used as a tumor marker for squamous cell carcinomas in various malignant tumors. Here, we evaluated the value of CYFRA 21-1 in diagnosing thymic carcinoma., Methods: We retrospectively reviewed 94 patients with pathological diagnoses of thymic carcinoma or thymoma (32 and 62 patients, respectively) who were referred to our departments between January 2000 and March 2019. Primary outcomes included tumor marker levels and their diagnostic accuracy., Results: Patients with thymic carcinoma were significantly more likely to be male (thymic carcinoma, 68.8%; thymoma, 40.3%; p = 0.02), have an advanced TNM stage (p < 0.01), and a significantly higher CYFRA 21-1 level than those with thymoma (thymic carcinoma: median = 4.2 ng/ml; interquartile range [IQR] = 2.1-6.1 ng/ml vs. thymoma: median = 1.2 ng/ml; IQR = 0.9-1.7 ng/ml; p < 0.01). Receiver operating characteristic curves demonstrated that the area under the curve for CYFRA 21-1 to distinguish thymic carcinoma from thymoma was 0.86 (95% confidence interval [CI]: 0.74-0.93; cutoff = 2.7 ng/ml; sensitivity = 68.8%; specificity = 95.2%). Multivariable analysis demonstrated that CYFRA 21-1 (odds ratio = 25.6; 95% CI: 4.6-141.6; p < 0.01) was an independent predictor for thymic carcinoma after adjusting for TNM stage., Conclusions: Serum CYFRA 21-1 level may help in diagnosing thymic carcinoma., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

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.)

We report a case of thymoma-associated autoimmune encephalitis with positive Titin antibodies. The patient had cognitive dysfunction, psychiatric symptoms and symptomatic epilepsy. PET-CT indicated space-occupied lesion at the thoracic entrance. The patient was diagnosed with paraneoplastic autoimmune encephalitis. After immunotherapy, his condition improved and underwent thymectomy. Pathology revealed type A thymoma. The patient recurred 10 days after the operation. Thymoma is associated with AE. And Titin antibodies may be involved in the extensive immune response to antigens which the patient's thymoma ectopically expressed. This case reflects the complexity of the immune relationship among autoimmune encephalitis, Titin antibodises and thymoma. Titin antibody may have a certain guiding significance for the treatment and prognosis of autoimmune encephalitis., (Copyright © 2021. Published by Elsevier B.V.)

Background: Thymomas are the most common primary malignant tumors of anterior mediastinal. However, there are no specific laboratory indicator for the diagnosis the diagnosis of thymoma. The aim of this study was to screen out a tumor marker for diagnosis of thymoma by mRNA microarray analysis and confirmed it., Methods: By mRNA microarray analysis of 31 thymomas and peritumoral thymic tissues, we found that the transcription level of neuronal pentraxin 1 (NPTX1) gene was up-regulated more than 4 times in thymomas. To further verify the above results, we detected the transcription and expression level of NPTX1 in 60 thymoma and 30 thymic cyst patients by quantitative Real-Time polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Furthermore, the diagnostic value of NPTX1 in thymoma by receiver operating characteristic curve (ROC) was analyzed., Results: The transcription level of NPTX1 mRNA in thymoma tissues was significantly higher than that in the thymic tissues of control group [(2.88±1.02) vs (1.35±0.47), P<0.001); The expression level of NPTX1 in thymoma tissues was significantly higher than that in the thymic tissues of control group (2 vs 1, P<0.001); The preoperative serum level of NPTX1 protein in thymoma patients were significantly higher than that in the thymic cyst patients of control group [(1,018.29±209.38) pg/mL vs (759.95±66.02) pg/mL, P<0.001]; At the threshold of 842.22 pg/mL, sensitivity and specificity of NPTX1 as a serologic marker were 85.00% and 93.33%, respectively for thymoma. ROC showed that the area the under curve (AUC) of NPTX1 was 0.902., Conclusions: NPTX1 was highly expressed in thymoma patients, and had diagnostic value for thymoma.

Objective: To improve myasthenia gravis (MG) autoantibody testing., Methods: MG serologic tests with confirmatory or refuting clinical-electrodiagnostic (EDX) testing and cancer evaluations were reviewed over 4 years (2012-2015). All patients had acetylcholine receptor-binding (AChR-Bi), modulating (AChR-Mo), and striational (STR) autoantibody testing, and negatives reflexed to muscle-specific kinase (MuSK). Thymoma and cancer occurrences were correlated with STR and reflexed glutamic acid decarboxylase 65 (GAD65), ganglionic acetylcholine receptor (α3), collapsin response mediating protein-5, and voltage-gated potassium channel complex autoantibodies., Results: Of 433 samples tested, 133 (31%) met clinical-EDX criteria for MG. Best sensitivity (90%) occurred at AChR-Bi >0.02 nmol/L, leaving 14 negative (6 ocular MG, 7 generalized MG, 1 MuSK MG) with specificity 90% (31 false-positives). Using AChR-Mo antibodies (>20% loss), specificity was better (92%, 24 false-positives), but sensitivity dropped (85%). Specificity improved (95%) by testing AChR-Mo when AChR-Bi are positive, resulting in 45% reduction of false-positives (31-17), maintaining AChR-Bi 90% sensitivity. Cutoff values recommended by area under the curve analysis did not outperform this approach. AChR-Bi and AChR-Mo values were significantly higher in true-positives. CT evaluations in 121 MG samples revealed 16 thymomas. Historical or subsequent cancers occurred in 22. STR and reflexed autoantibodies were not more common in MG with thymoma or other cancers. Full-body CT (n = 34) was performed in those with STR and reflex autoantibody positivity, but without additional cancers found., Conclusion: Accuracy of MG serologic testing is improved by reflexing AChR-Bi-positive cases to AChR-Mo. STR and other reflexed cancer evaluation autoantibodies did not provide value beyond standard CT chest imaging at the time of MG diagnosis. Diagnostic certainty is informed by AChR-Bi and AChR-Mo with higher values increasing specificity., (© 2020 American Academy of Neurology.)

Thymoma is the most common tumor of the anterior mediastinum. Routine imaging methods such as computed tomography or magnetic resonance imaging often lead to misdiagnosis between thymoma and other thymic abnormalities. Therefore, urgently needed is to develop a new diagnostic strategy. Here we identify interleukin-8 (IL-8) as a biomarker for auxiliary diagnosis of thymoma. We find that IL-8 levels in naïve T cells are markedly elevated in patients with thymoma compared to those with other thymic tumors. IL-8 levels in naive T cells are significantly decreased after surgical resection in thymoma patients, and rise again when thymoma recurs. A receiver operating characteristic curve analysis shows that IL-8 evaluation performs well in thymoma identification, with high specificities and sensitivities. We also observe significant clinical relevance between IL-8 levels in naïve T cells and clinicopathological features. In conclusion, our study suggests that IL-8 is a biomarker for thymoma identification and recurrence surveillance.

Purpose: Preoperative neutrophil count is reportedly associated with poor prognosis in cancer patients. This study aimed to investigate the clinical significance of pre-treatment peripheral blood cell counts in patients with thymic epithelial tumors (TETs)., Methods: A retrospective review of 71 patients with completely resected TETs [64 thymoma, 6 thymic carcinoma, and 1 thymic neuroendocrine tumor] between 2000 and 2018 was conducted. Associations between tumor recurrence and pre-treatment peripheral blood cell counts of leukocytes (WBC), neutrophils (Neut), lymphocytes (Lymph), monocytes (Mono), and platelets (Plt) were analyzed. Optimal cut-off points were selected using receiver operating characteristic curve analysis to predict tumor recurrence., Results: High WBC (≥ 7000), Neut (≥ 4450), and Plt (≥ 226 × 10 3 ) counts had significantly poor relapse-free survival (RFS), but high Lymph (≥ 1950) and Mono (≥ 400) did not. High Neut had the strongest correlation with recurrence (area under curve, 0.800); we focused on the analysis between high-Neut and low-Neut groups. High Neut count significantly correlated with smoking history, pre-treatment C-reactive protein level, and advanced stage; high Neut count and aggressive histology tended to show correlations. RFS was significantly poorer in the high-Neut group than in the low-Neut group (p = 0.003), with 5-year RFS rates of 63.8% and 96.8%, respectively. High Neut count was a significant adverse predictor for RFS and cumulative incidence of recurrence (p = 0.005 and p < 0.001, respectively). The risk scoring system comprising high Neut count, advanced stage, and aggressive histology demonstrated better prognostic ability than any prognostic factors alone., Conclusions: High Neut count significantly correlated with TET recurrence, suggesting a negative prognostic effect of latent inflammation in TET patients.

Extended thymectomy is employed for patients with myasthenia gravis (MG) and/or thymoma with elevated serum antiacetylcholine receptor antibody (AchR) titers. However, MG symptoms occasionally worsen in post-thymectomy patients. We explored the risk factors for exacerbation of MG symptoms after surgical therapy for patients with MG and/or thymoma with an elevated AchR titer. We retrospectively analyzed 90 patients suffering from MG and/or thymoma with an elevated AchR titer who underwent thymectomy in our institute. Patients were classified into Improved, Unchanged, and Exacerbated groups by assessing their postoperative myasthenic symptoms, amount of medication, and incidence of myasthenic crisis. Risk factors for postoperative exacerbation of myasthenic symptoms were assessed by comparing the Exacerbated with the Improved and Unchanged groups. Of the 90 patients, 29 were classified into the Improved group, 47 into the Unchanged group, and 14 into the Exacerbated group. The presence of thymoma and Masaoka stage were significantly different between the Exacerbated and Improved/Unchanged groups. Although preoperative AchR titers did not significantly differ among the groups, the perioperative AchR titers in the Exacerbated group were significantly higher than those in the other groups (P = 0.003). A multiple logistic regression analysis with stepwise forward selection showed that advanced-stage thymoma was a risk factor for postoperative exacerbation of myasthenic symptoms (P = 0.007). Patients with advanced-stage thymoma have a relative risk for exacerbation of myasthenic symptoms after surgical therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tumor growth and its chemotherapeutic regimens manifest myelosuppression, which is one of the possible causes underlying the limited success of immunotherapeutic anticancer strategies. Hence, approaches are being designed to develop safer therapeutic regimens that may have minimal damaging action on the process of myelopoiesis. 3-Bromopyruvate (3-BP) is a highly potent antimetabolic agent displaying a broad spectrum antineoplastic activity. However, 3-BP has not been investigated for its effect on the process of myelopoiesis in a tumor-bearing host. Hence, in this investigation, we studied the myelopoietic effect of in vivo administration of 3-BP to a murine host bearing a progressively growing ascitic thymoma designated as Dalton's lymphoma (DL). 3-BP administration to the DL-bearing mice resulted in a myelopotentiating action, reflected by an elevated count of bone marrow cells (BMC) accompanied by augmented proliferative ability and a declined induction of apoptosis. The BMC of 3-BP-administered mice displayed enhanced responsiveness to macrophage colony-stimulating factor for colony-forming ability of myeloid lineage along with an enhanced differentiation of F4/80 + bone marrow-derived macrophages (BMDM). BMDM differentiated from the BMC of 3-BP-administered DL-bearing mice showed an augmented response to lipopolysaccharide and interferon-γ for activation, displaying an augmented tumor cytotoxicity, expression of cytokines, reactive oxygen species, nitric oxide, CD11c, TLR-4, and HSP70. These features are indicative of the differentiation of M1 subtype of macrophages. Thus, this study demonstrates the myelopotentiating action of 3-BP, indicating its hematopoietic safety and potential for reinforcing the differentiation of macrophages in a tumor-bearing host.

Background and Purpose: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia., Methods: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2., Results: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58)., Conclusions: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG., (© 2019 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

We present the case of a 63-year-old male with pure white cell aplasia (PWCA), a rare complication of thymoma, who was successfully treated with cyclosporine A (CyA) and thymectomy. The patient presented with high fever and agranulocytosis. Complete blood count revealed a white blood cell count of 0.9 × 10 9 /L (3% neutrophils), a hemoglobin level of 15.8 g/dL, and a platelet count of 308 × 10 9 /L. Bone marrow (BM) aspiration revealed a hypocellular marrow lacking granulocytes. Computed tomography showed a large anterior mediastinal mass, and the patient was diagnosed with PWCA associated with thymoma. Thirteen days after the initiation of CyA treatment, myeloid cells appeared in the BM, and the neutrophil count in peripheral blood started to increase on day 18. Thymectomy was performed 3 months later. Although CyA treatment was discontinued after thymectomy, complete remission has been maintained for over 4 years. In vitro colony-forming unit granulocyte-macrophage (CFU-GM) assay using the patient's serum showed severe suppression of CFU-GM colonies in the presence of the patient's serum, suggesting the presence of CFU-GM inhibitor in the patient's serum. The efficacy of the immunosuppressive therapy and the CFU-GM assay suggests the potential involvement of an immunological mechanism in patients with thymoma-associated PWCA.

Rationale: An association between inflammatory myopathy and malignancy has been recognized particularly in patients positive for anti-transcription intermediary factor 1γ (TIF1γ) antibody. We report a case of anti-TIF1γ antibody positive dermatomyositis (DM) associated with thymic carcinoma which radiographically mimicked benign tumor., Patient Concerns: A 72-year-old man presented typical characteristic cutaneous manifestations and proximal muscle weakness with elevated levels of myogenic enzymes. An anterior mediastinal tumor was detected by computed tomography (CT) scan and radiographically assessed to be benign with distinct borders and little enhancement., Diagnoses: DM with anti-TIF1γ antibody and thymic carcinoma., Interventions: Thymic carcinoma was completely resected by surgery. DM was induced into remission with glucocorticoid treatment., Outcomes: The serum level of myogenic enzyme remained within normal range under low-dose glucocorticoid maintenance. No evidence of carcinoma recurrence with CT scan was observed at 1-year follow up., Lessons: The present case indicated that anti-TIF1γ antibody would play a role as the "autoimmune tumor marker" in patients with inflammatory myopathy.

Background: The introduction of the new TNM staging system for thymic epithelial malignancies produced a significant increase in the proportion of patients with stage I disease. The identification of new prognostic factors could help to select patients for adjuvant therapies based on their risk of recurrence. Neutrophil-to-lymphocyte ratio (NLR) has recently gained popularity as reliable prognostic biomarker in many different solid tumors. The aim of this study is to assess the utility of NLR evaluation as a prognostic marker in patients with surgically-treated thymoma., Methods: A retrospective analysis was conducted among patients who underwent resection for thymoma in a single center. Patients were divided in two groups, under (low-NLR-Group = 47 patients, 60%) and above (high-NLR-Group = 32 patients, 40%) a ROC-derived NLR cut-off (2.27). Associations with clinical-pathological variables were analyzed; disease-free survival (DFS) was identified as the primary endpoint., Results: Between 2007 and 2017, 79 patients had surgery for thymoma. Overall 5-year DFS was 80%. Univariate survival analysis demonstrated that NLR was significantly related to DFS when patients were stratified for TNM stage (p = 0.043). Five-year DFS in the low-NLR-Group and in the high-NLR-Group were respectively 100 and 84% in stage I-II, and 66 and 0% in stage III. TNM stage resulted as the only independent prognostic factor at multivariate analysis, with hazard ratio of 3.986 (95% CI 1.644-9.665, p = 0.002)., Conclusions: High preoperative NLR seems to be associated to a shorter DFS in patients submitted to surgery for thymoma and stratified for TNM stage.

Objective: To summarize the clinical characteristics of acquired pure red cell aplasia (PRCA) patients diagnosed in our hospital in the last 10 years., Method: The clinical features, immune state and treatment response of acquired PRCA patients diagnosed in our hospital from January 2007 to January 2017 were retrospectively analyzed., Results: The results showed that thymoma (13.21%) and parvovirus B19 (11.32%) were the most common causes for secondary PRCA. Ferritin (Fer) levels and erythropoietin (EPO) levels were increased in PRCA patients. The total CR and PR rate of immunosuppressive therapy in our studies was 68.29% and 12.20%, respectively. Patients with EPO level >400 U/L and Fer level >200 ng/ml had significantly lower CR rate than others. The patients with EPO level >400 U/L also had longer hemoglobin recovery time than patients with EPO level ≤400 U/L. Patients treated with corticosteroids (CS) + cyclosporine A (CsA) had lower relapse rate compared to the CS group (29.17% vs. 80.00%, P < .05)., Conclusion: Our data showed that patients with PRCA had high EPO and Fer levels. Thymoma and viral infections are the most common causes for secondary PRCA. The CS+ CsA group had lower relapse rate than CS group although response rate was similar. Increased EPO and Fer levels might be the negative factors for prognosis of acquired PRCA.

Thymomas are associated with autoantibody formation. The most common are anti-acetylcholine receptor antibodies, which correspond to myasthenia gravis (MG). Other autoantibodies, such as antistriational antibodies, can occur, but their relation to clinical syndromes is frequently uncertain. The etiology of antistriational antibodies is also poorly understood. In this case, a 61-year-old man with a history of thymoma was admitted with respiratory failure. The patient was positive for anti-acetylcholine receptor antibodies and antistriational antibodies. He developed cardiogenic shock and died within 2 days despite aggressive therapy. Laboratory studies revealed elevated cardiac enzymes and marked IgG elevation against Coxsackie A virus serotypes 9 and 24. Subclinical IgG elevations against additional Coxsackie A and Coxsackie B virus serotypes were also noted. Autopsy revealed lymphohistiocytic infiltrates with multinucleated giant cells in the myocardium and skeletal muscles, including the diaphragm. Giant cell polymyositis and myocarditis is a rare, lethal complication in patients with thymoma and MG. The pathogenesis is uncertain. An autoimmune process, possibly elicited by antistriational antibodies, has been suggested. The coexistence of antistriational antibodies and Coxsackie viral serologies has not been reported. This case may suggest that giant cell polymyositis and myocarditis in patients with thymoma and MG is a postviral autoimmune process.

Patients with thymoma and without clinical or electromyographical myasthenic signs may occasionally develop myasthenia several years after thymectomy. Hereby, we investigated the predictors and the evolution of this peculiar disease. We performed a retrospective analysis in 104 consecutive patients who underwent thymectomy between 1987 and 2013 for thymoma without clinical or electromyographic signs of myasthenia gravis. Predictors of post-thymectomy onset of myasthenia gravis were investigated with univariate time-to-disease analysis. Evolution of myasthenia was analyzed with time-to-regression analysis. Eight patients developed late myasthenia gravis after a median period of 33 months from thymectomy. No significant correlation was found for age, gender, Masaoka's stage, and World Health Organization histology. Only high preoperative serum acetylcholine-receptor antibodies titer (>0.3 nmol/L) was significantly associated with post-thymectomy myasthenia gravis at univariate time-to-disease (P = 0.003) analysis. Positron emission tomography was always performed in high-titer patients, and increased metabolic activity was detected in 4 of these patients. Surgical treatment through redo-sternotomy or video-assisted thoracoscopy was performed in these last cases with a remission in all patients after 12, 24, 32 and 48 months, respectively. No patient under medical treatment has yet developed a complete remission. In our study the presence of preoperative high-level serum acetylcholine receptor antibodies was the only factor significantly associated with the development of post-thymectomy myasthenia gravis. The persistence of residual islet of ectopic thymic tissue was one of the causes of the onset of myasthenia and its surgical removal was successful., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with a poor prognosis for various cancers. We evaluated the prognostic role of the preoperative NLR in patients with thymoma., Methods: We reviewed the medical records of 254 patients who underwent resection of thymic epithelial tumors at our institution. Patients were excluded if they had received steroid therapy, neoadjuvant therapy, or incomplete resection, or if they had thymic carcinoma or Good's syndrome, recurrence of thymoma, or missing data. The NLR was measured preoperatively, and outcomes of patients with a low (< 1.96) vs those with a high (≥ 1.96) NLR were compared statistically., Results: Of 159 eligible patients, 59 (37.1%) had a high NLR and 100 (62.9%) had a low NLR. Overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS), disease-related survival (DRS), and the cumulative incidence of recurrence (CIR) differed significantly between the groups. Multivariate analyses revealed that a high NLR was independently associated with disease-related survival and a cumulative incidence of recurrence. A high NLR was also associated with a higher risk of recurrence of Masaoka stage I or II thymoma., Conclusions: An elevated preoperative NLR was associated with poor outcomes after thymoma resection. Thus, the NLR may be a useful biomarker of the postoperative prognosis of thymoma.

We describe two cases of myasthenia gravis (MG) with double seropositivity for acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4) antibodies (AChR/LRP4-MG) with invasive thymoma. Both cases showed myasthenic weakness, which was restricted to the ocular muscles for >5 months from onset, and then unprovoked severe clinical deterioration supervened with predominant bulbar symptoms. The patients responded adequately to therapeutic intervention. Serum AChR antibody levels at post-intervention were markedly decreased, whereas LRP4 antibodies were almost unchanged in case 1 and slightly decreased in case 2. Although our results suggest that patients with AChR/LRP4-MG are likely to present with more severe symptoms than those with LRP4-MG, none of the previously reported cases had thymomas. Coexistence of autoantibodies may reflect breakdown of self-tolerance caused by invasive thymomas. The main cause affecting symptoms of MG in our cases was probably AChR antibodies, and anti-LRP4 antibodies might have been an exacerbating factor., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Thymoma-associated multi-organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft-versus-host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD-like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD-like erythroderma., (© 2017 Japanese Dermatological Association.)

Myasthenia gravis (MG) is generally caused by antibodies directed against the neuromuscular junction, including antibodies against the postsynaptic nicotinic acetylcholine receptor (AChR). Pathologic abnormalities of the thymus gland, including thymoma, are associated with MG. We report a 56-year-old woman who presented with double vision. Single fiber EMG confirmed myasthenia gravis. AChR, striational muscle and MuSK antibodies were absent in the serum. Chest CT demonstrated a malignant thymoma. We report the first case of seronegative myasthenia gravis associated with malignant thymoma. The case challenges the conventional wisdom that all patients with thymoma associated MG test positive for antibodies against AChR., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications., Methods: Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers)., Results: Immunoprecipitation studies identified 3 targets, including the Netrin-1 receptors DCC (deleted in colorectal carcinoma) and UNC5A (uncoordinated-5A) as well as Caspr2 (contactin-associated protein-like 2). Cell-based assays with these antigens showed that among the indicated patients, 9 had antibodies against Netrin-1 receptors (7 with additional Caspr2 antibodies) and 5 had isolated Caspr2 antibodies. Only one of the 219 controls had isolated Caspr2 antibodies with relapsing myelitis episodes. Among patients with neuromyotonia and/or myasthenia gravis, the presence of Netrin-1 receptor or Caspr2 antibodies predicted thymoma ( p < 0.05). Coexisting Caspr2 and Netrin-1 receptor antibodies were associated with concurrent thymoma, myasthenia gravis, and neuromyotonia, often with Morvan syndrome ( p = 0.009). Expression of DCC, UNC5A, and Caspr2 proteins was demonstrated in paraffin-embedded thymoma samples (3) and normal thymus., Conclusions: Antibodies against Netrin-1 receptors (DCC and UNC5a) and Caspr2 often coexist and associate with thymoma in patients with neuromyotonia and myasthenia gravis., Classification of Evidence: This study provides Class III evidence that antibodies against Netrin-1 receptors can identify patients with thymoma (sensitivity 21.4%, specificity 100%)., (© 2017 American Academy of Neurology.)

Aim: An aim of the study was to compare informative value of traditional approach (anti-AChR antibody radioimmunoassay) and evaluation of metabolic shifts by laser correlation spectroscopy in myasthenia gravis., Material and Methods: The search for the relationship between the disease severity in 77 patients, 12-80 years and the distribution pattern of subfraction serum components revealed three informative zones: 6-15, 27-67, and 127-223 nm., Results and Conclusion: In patients without disturbances of vital functions, the contribution of the first zone particles into light scatter increases and that of the third zone particles decreases. Considerable differences attaining the level of statistical significance in zones 6 and 20 nm were revealed in the spectra of serum from patients with myasthenia gravis of the same severity with and without thymoma. This opens prospects for dynamic monitoring of the efficiency of therapy.

Objective: Oxidative stress and low antioxidant status play a major role in the pathogenesis of inflammatory and autoimmune diseases. Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, and its antioxidant status is still controversial. Our study aimed to investigate the correlation between the clinical characteristics of MG and the serum antioxidant status of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine., Materials and Methods: We measured serum antioxidant molecule levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine in 380 individuals, including 166 MG and 214 healthy controls., Results: We found that MG patients had significantly lower serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine than healthy controls, whether male or female. Moreover, it was also shown in our study that uric acid, albumin and creatinine levels in patients with MG were correlated with disease activity and classifications performed by the Myasthenia Gravis Foundation of America., Conclusion: Our findings demonstrated that serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine were reduced in patients with MG. This suggested an active oxidative process in MG patients who had low antioxidant status.

Importance: Thymoma is commonly recognized in association with paraneoplastic autoimmune myasthenia gravis (MG), an IgG-mediated impairment of synaptic transmission targeting the nicotinic acetylcholine receptor of muscle. Newly identified synaptic autoantibodies may expand the serological profile of thymoma., Objective: To investigate the frequency of potentially pathogenic neural synaptic autoantibodies in patients with thymoma., Design, Setting, and Participants: We retrospectively identified patients with histopathologically confirmed thymoma and serum available to test for synaptic autoantibodies (collected 1986-2014) at the Mayo Clinic Neuroimmunology Laboratory. We identified and classified 193 patients with thymoma into 4 groups: (1) lacking neurological autoimmunity (n = 43); (2) isolated MG (n = 98); (3) MG plus additional autoimmune neurological manifestations (n = 26); and (4) neurological autoimmunity other than MG (n = 26)., Main Outcomes and Measures: Clinical presentation and serum profile of autoantibodies reactive with molecularly defined synaptic plasma membrane proteins of muscle, peripheral, and central nervous systems., Results: Of the 193 patients with thymoma, mean patient age was 52 years and did not significantly differ by sex (106 women) or group. Myasthenia gravis was the most prevalent clinical manifestation (64%) followed by dysautonomia (16 patients [8%]) and encephalopathy (15 patients [8%]); 164 patients (85%) had at least 1 synaptic autoantibody, and 63 of these patients (38%) had at least 1 more. Muscle acetylcholine receptor was most frequent (78%), followed by ganglionic acetylcholine receptor (20%), voltage-gated Kv1 potassium channel-complex (13%), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (5%). Less frequent were aquaporin-4, voltage-gated Kv1 potassium channel-complex related proteins (leucine-rich glioma-inactivated 1 and contactin-associated protein-like 2), glycine receptor, and γ-aminobutyric acid-A receptor. Synaptic autoantibodies were significantly more frequent in patients with neurological autoimmunity than in those without and were most frequent in patients with neurological manifestations other than or in addition to MG., Conclusions and Relevance: Synaptic autoantibodies, particularly those reactive with ion channels of the ligand-gated nicotinic acetylcholine receptor superfamily (namely α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, glycine, and γ-aminobutyric acid-A receptors), were prevalent in patients with thymoma. Autoantibodies of this extended spectrum may enhance autoimmune serological testing as an aid to preoperative thymoma diagnosis. Detection of currently known synaptic autoantibody specificities absent from this profile have potential algorithmic usefulness as negative predictors for thymoma (as recognized for neuronal voltage-gated calcium channel autoantibodies).

Anti-titin antibodies indicate a paraneoplastic etiology pointing towards a thymoma in myasthenia gravis (MG), but their seroprevalence and potential diagnostic value in patients with other paraneoplastic neurological syndromes (PNS) is unknown. Therefore, we screened the sera of 44 PNS patients with well-characterized onconeural antibodies (anti-Hu, Yo, Ri, CV2/CRMP5, Ma1, Ma2/Ta, or amphiphysin) for anti-titin reactivity. Two patients (4.5%) were positive for anti-titin antibodies: both patients differed regarding the PNS (sensorimotor neuropathy and subacute cerebellar degeneration vs. chorea), well-characterized onconeural antibodies (CV2/CRMP5 vs. Ri), and malignoma (small cell lung cancer vs. breast cancer). However, retrospectively, the patients neither showed any symptoms of MG nor a thymoma on a computed tomographic (CT) scan. The results of this study indicate that anti-titin antibodies without a predictive relevance for MG or thymoma may be present in a small proportion of patients with PNS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Thymic epithelial cells give rise to both thymoma and thymic carcinoma. A crucial advance in thymic epithelial tumors (TET) management may derive from the identification of novel molecular biomarkers able to improve diagnosis, prognosis and treatment planning.In a previous study, we identified microRNAs that were differentially expressed in tumor vs normal thymic tissues. Among the microRNAs resulted up-regulated in TET tissues, we evaluated miR-21-5p, miR-148a-3p, miR-141-3p, miR-34b-5p, miR-34c-5p, miR-455-5p as blood plasma circulating non-invasive biomarkers for TET management.We firstly report that the expression levels of specific onco-miRNAs, that we found upregulated in the blood plasma collected from TET patients at surgery, resulted significantly reduced in follow-up samples.This pilot study suggests that circulating miR-21-5p and miR-148a-3p could represent novel non-invasive biomarkers to evaluate the efficacy of therapy and the prognosis of TET.

Introduction: Good's syndrome is a rare cause of adult-onset immunodeficiency associated with thymoma. Good's syndrome should be considered in patients older than 40 years with the history of frequent infections. An abnormal immunoglobulin profile needs further investigation and flow cytometry which is crucial for establishing the diagno- sis of Good's syndrome., Case Report: We present a 56- year-old men with Good's syndrome diagnosed after a two-year history of recurrent infections. Examination of immune status of the patient showed decreased serum levels of all immunoglobulins. Flow cytometry of peripheral blood lym-phocyte revealed markedly reduced peripheral B cells, CD4 T-cell lymphopenia, inverted CD4/CD8 T-cell-ratio 0.37 (CD4--20.82%, CD8--70.7%). Analysis of the subpopulations of T-lymphocytes showed relative increasing γδ T cell receptor (TCR) T lymphocytes. Computed tomography scan of the chest showed a mediastinal mass compatible with thymoma of the diameter of 40 mm. After initiation of intravenous immunoglobulins the patient was in the good clinical condition and without bacterial complications. As the patient refused the operative treatment we continued to control the mediastinal tumor mass which did not increase during a 3-year follow-up., Conclusion: The presented patient had a typical immunological finding for Good's syndrome, but also the increase in γδ TCR T-lymphocyte subpopulation for which it is difficult to determine whether this is pathogenetic or secondary reactive event.

Background: miR-15b is significantly and consistently downregulated in different clinical phenotypes of myasthenia gravis (MG). However, its role in pathogenesis of MG is still not clear. This study aimed to explore the function of miR-15b in MG., Material and Methods: Blood samples from early-onset MG, late-onset MG, thymoma patients, and healthy participants were collected. The expression pattern of IL-15 and miR-15b was identified by qRT-PCR and ELISA in patient serum and mouse tissue samples. The regulative role of miR-15b on IL-15 expression was verified in an experimental autoimmune myasthenia gravis (EAMG) mice model., Results: qRT-PCR and ELISA showed that miR-15b expression was significantly lower and IL-15 expression was significantly higher in all EMG, LMG, and thymoma cases compared to healthy controls. Based on mouse model, we confirmed that miR-15b knockdown could increase IL-15 expression in healthy mice, while miR-15b overexpression could inhibit IL-15 expression in EAMG mice. Through searching in bioinformatics databases, we identified a highly conserved consequential pairing between IL-15 and miR-15b. Subsequent dual luciferase assay further verified this match., Conclusions: This study is the first to report the miR-15b-IL-15 axis can directly regulate IL15 expression, which helps to further explain the abnormal IL-15 expression in MG patients and the pathogenesis of MG.

Resistin is a pro-inflammatory cytokine involved in the pathogenesis of autoimmune diseases. To investigate serum resistin levels in patients with myasthenia gravis (MG) and determine if there are associations between resistin levels and disease severity, we measured serum resistin levels in 102 patients with anti-acetylcholine receptor antibody-positive MG (AChR-MG). We further analyzed associations between serum resistin levels and clinical variables in patients with MG. Our findings demonstrate that serum resistin levels are elevated in patients with AChR-generalized MG and AChR-MG with thymoma and are correlated with disease severity. Resistin has potential as a useful serum biomarker for inflammation in AChR-MG., (Copyright © 2015 Elsevier B.V. All rights reserved.)

No thymomatous myasthenia gravis (TMG) has been reported in patients with anti-α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor encephalitis (AMPAR-E). We described clinical presentation and autoimmune profile of the first case with both AMPAR-E and TMG. Clinical information was obtained from original medical records. Antibodies against AMPAR and confounding antigens were examined on transfected human embryonic kidney 293 cells by the indirect immunofluorescence method. In this case, anti-AMPAR antibodies and anti-acetylcholine receptor (AchR) antibodies were both positive and could explain the encephalitis and MG respectively. This report also indicated the complexity of autoimmunity network associated with thymoma. However, the relationships between thymoma, MG and AMPAR-E remained unclear., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Forkhead box P3 (FoxP3) is known as a pivotal and specific transcriptional factor of regulatory T cells, and are implicated in various immune diseases including myasthenia gravis (MG). The aim of this study was to investigate the relationships between FoxP3 expression of lymphocytes in thymoma and clinicopathological characteristics, particularly MG status in thymoma patients. We reviewed 83 thymoma specimens, including 22 from MG patients, and evaluated the FoxP3 expression of lymphocytes in thymoma using immunohistochemistry (IHC). Statistical association was evaluated using chi-square test and Fisher's exact test. Thirty-four cases (41.0%) were classified as FoxP3 positive. There were no statistical differences in sex (P=0.289), age (P=0.536), Masaoka stage (P=0.086), WHO histological classification (P=0.097), or Myasthenia Gravis Foundation of America (MGFA) Clinical Classification (P=0.117) between FoxP3 positive and negative cases. In contrast, thymoma in cases with MG showed significantly fewer FoxP3 positive lymphocytes than those in cases without MG (P=0.037). Moreover, cases with anti-acetylcholine receptor antibody titer equal to or greater than the normal limit also showed significantly fewer FoxP3 positive lymphocytes than cases within the normal limit (P<0.001). Our result indicated the possibility that the decrease of FoxP3 positive lymphocytes in thymoma may lead to the development of MG and to an increase in anti-acetylcholine receptor antibodies. In addition, FoxP3 positive lymphocytes might be a useful biomarker for evaluation of the risk of MG onset, and could open the way to more effective therapeutic strategies in thymoma patients.

A 73-year-old woman complained of right chest discomfort. Chest X-ray during the follow-up for rheumatoid arthritis showed a mediastinal tumor. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a 65-mm tumor in the right anterior mediastinum. A blood test showed high serum levels of CYFRA 21-1(29.8 ng/ml), white blood cells( WBC 10,800/µl), and C-reactive protein(CRP 16.1 mg/dl). Subsequently, inflammatory reactions improved, and the thymic tumor was resected. Histopathologically, the tumor was a type B2 thymoma with extensive coagulative necrosis. After resection, the serum CYFRA 21-1 level returned to the normal range.

Purpose: Clustering of neural autoantibodies in patients with paraneoplastic neurologic disorders may predict tumor type. A mathematical analysis of neural autoantibody clusters was performed in 78,889 patients undergoing evaluation for a suspected paraneoplastic autoimmune neurologic disorder. Tumor predictive autoantibody profiles were confirmed in sera from patients with histologically proven tonsillar cancer, thymoma, and lung cancer., Patients and Methods: Of note, 78,889 patient sera were tested for 15 defined neural autoantibodies (1.2 million tests). The observed and hypothesized frequencies of autoantibody clusters were compared and their tumor associations defined. A tumor validation study comprised serum from 368 patients with a variety of tumors (thymoma, lung, or tonsil)., Results: Informative oncological associations included (i) thymoma in 85% of patients with muscle striational, acetylcholine receptor antibodies plus CRMP5 autoantibodies; (ii) lung carcinoma in 80% with both P/Q-type and N-type calcium channel antibodies plus SOX1-IgG; and (iii) in men, prostate carcinoma frequency more than doubled when striational and muscle AChR specificities were accompanied by ganglionic AChR antibody. In women, amphiphysin-IgG alone was associated commonly with breast carcinoma, but amphiphysin-IgG, coexisting with antineuronal nuclear autoantibody-type 1 or CRMP5-IgG, was associated with lung cancer (P < 0.0001). In the validation cohorts, many tumor-associated profiles were encountered that matched the clusters identified in the screening study (e.g., 15% of thymoma patients had striational, acetylcholine receptor antibodies plus collapsin response-mediator protein-5 autoantibodies)., Conclusions: Neural autoantibodies commonly coexist in specific clusters that are identifiable by comprehensive screening. Signature autoantibody clusters may predict a patient's cancer risk and type., (©2014 American Association for Cancer Research.)

Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. While often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. The potential therapeutic value of specific neutralizing anti-cytokine autoantibodies has not been thoroughly investigated. Here we used mammalian cell display to isolate IL17A-specific antibodies from a thymoma patient with proven high-titer autoantibodies against the same. We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. These data clearly demonstrate that the human autoantibody repertoire can be mined for antibodies with high therapeutic potential for clinical development.

Several lines of evidence suggest that deficiency of eosinophils is not associated with any characteristic abnormality. Patients lacking eosinophils, in the setting of immunodeficiency or as a consequence of IgG-mediated eosinophil precursor destruction, do not display any distinguishing abnormalities related to eosinophil reduction. The observation that eosinophil-deficient mice do not display any distinctive syndrome or failure of their health is evidence that, under ordinary laboratory conditions, the eosinophil does not play a critical role in the well-being of mammals. Observations that monoclonal antibodies to interleukin-5 (IL-5) are well tolerated appear unsurprising in light of these findings. For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor α-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated. Thus, data to the present suggest that reduction of eosinophils appears to have no characteristic ill effects on normal health, and monoclonal antibodies that deplete eosinophils have the potential to be widely employed in the treatment of eosinophil-associated diseases., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We herein present a case of Good syndrome complicated by diffuse pulmonary lesions similar to diffuse panbronchiolitis (DPB). A 45-year-old Japanese man was referred to our department due to recurrent lower respiratory tract infections that had started and ameliorated nine months after thymectomy for pure red cell aplasia and myasthenia gravis. Diffuse centrilobular opacities on chest computed tomography and positivity for HLA-B54 were consistent with DPB. Additionally, hypogammaglobulinemia and a marked decrease of B-lymphocytes were observed, and therefore Good syndrome was considered. Combination therapy with azithromycin and clarithromycin alleviated the patient's respiratory symptoms and reduced the exacerbation of chronic bronchitis.

Analyzing the phenotypic characterization of the immune system cells involved in the pathogenesis of immunodeficiency with thymoma (Good's syndrome) is difficult due to the low number of studies on that subject. We describe the immunological alterations observed in a case of Good's syndrome, and we summarize the pathogenic explanations found in the literature., (Copyright © 2011 International Clinical Cytometry Society.)

Antititin antibody occurs in the serum of myasthenia gravis (MG) patients with thymoma (MGT), and is a diagnostic marker for the disease. The mechanism that triggers MGT development is, however, unclear. This study evaluated the role of the main immunogenic region (MIR) of titin in MGT pathogenesis. Titin MIR antiserum (antibody titre 1:16) was obtained and an in situ immunohistochemical study of thymomatous tissue samples was performed. Strong immunostaining for titin MIR was observed on epithelial cell membranes in MGT patients, and the degree of immunostaining was directly proportional to the number of epithelial cells in thymomatous tissue. Serum antititin antibody levels were closely related to titin MIR levels in thymoma cells; however, titin MIR levels did not appear to be related to MG severity. Antititin antibody may be a good surrogate marker for thymoma but is probably not involved in the pathogenesis of MGT.

Thymomas are often associated with various autoimmune disorders. We herein report a middle-aged female patient with thymoma and hypogammaglobulinemia (Good syndrome) who developed symptomatic normocytic anemia. Her computed tomography (CT) scans showed a cervico-mediastinal mass. The findings of a bone marrow biopsy suggested pure red cell aplasia (PRCA), and the serum levels of all immunoglobulins were extremely low. After the resection of the tumor, which was diagnosed to be Masaoka stage II and type AB thymoma, the normocytic anemia dramatically improved, but the hypogammaglobulinemia did not recover.

The aim of this study was to analyze the impact of thymectomy on kinetics of the immune reconstitution in thymoma patients. Nine consecutive patients with completely resected thymoma were enrolled. Immunophenotype analysis (total lymphocytes, CD3, CD4, CD8, CD19, NK subsets) and detection of autoantibodies at 6, 12, 18, and 24 months after thymectomy were planned. A prolonged inversion of CD4/CD8 ratio was present, due to a diminished number of CD4+ cells; CD8+ cell numbers remaining constantly normal at different time points; CD19+ cells remained for a long time understatement, achieving almost normal levels at 24 months; and NK cells always showed a normal amount. Autoantibodies against the muscle acetylcholine receptor were detected in four patients (44.4%) at the time of diagnosis, while antinuclear antibody were detected in eight patients (88.8%) at different time points during postthymectomy. A high incidence of multiple primary neoplasms was observed (66.6% of cases). Our study showed that cellular and humoral immune alterations are a common sequelae of postthymectomy. Further studies, a longer surveillance and a cooperative approach, due to the rarity of the disease, are necessary to define eventual implications of immune alterations on patient's outcome.

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.

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.