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Thymoma and Thymic Carcinoma

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

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    MeSH term: Thymoma
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Latest Research Publications

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

Fang C, Pan H, Li Z, et al.
Invasive thymoma leading to pulmonary artery embolism during operation: A case report.
Medicine (Baltimore). 2019; 98(28):e16385 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Invasive thymoma with intraluminal tumor thrombus may cause pulmonary artery thrombus if the tumor thrombus shed off during operation. However, there is no clinical case report focused on such complication.
PATIENT CONCERNS: A 40-year-old woman presented with repeated chest pain.
DIAGNOSIS: Chest computer tomography showed huge mediastinal mass. Postoperative pathology revealed type B2 and B3 thymoma, with B3 as the main type.
INTERVENTIONS: The patient underwent tumor resection through midline sternotomy in our hospital on September 17, 2018. She received emergent pulmonary artery exploration because the tumor thrombus in superior vena cava shed off unexpectedly during operation. Postoperative pulmonary computer tomography angiography showed right pulmonary artery embolism. Then emergent right pulmonary artery embolectomy was performed through lateral thoracic incision on September 29, 2018.
OUTCOMES: The patient recovered well after surgery. D-dimer reduced rapidly and returned to normal 1 month after the second operation.
LESSONS: Intraluminal tumor thrombus in invasive thymoma patients has a risk of shedding off during operation. Prevention strategy should be made beforehand. Pulmonary artery exploration is necessary once happened.

Zhang R, Li J, Zhang H
A "coughed up" tissue diagnosed as type A thymoma in an 80-year-old man: A case report.
Medicine (Baltimore). 2019; 98(27):e16337 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Thymoma is the most common primary tumor in the anterior mediastinum. All major subtypes of thymoma can be clinically aggressive. However, type A thymoma is usually benign and rarely invasive, let alone invasive to the trachea. There are no published reports of thymoma diagnosed in a "coughed up' tissue". Here, we report an 80-year-old man who coughed up a piece of tissue which was histopathologically diagnosed as type A thymoma.
PATIENT CONCERNS: An 80-year-old man who had a history of thymoma for 8 years was admitted in our hospital with his severe cough and dyspnea and his "coughed up" something. He felt much better after coughing up the piece of tissue. He saved the tissue and sent it to the pathology department.
DIAGNOSES: The clinical diagnosis was lung cancer. But the final pathological diagnosis was type A thymoma.
INTERVENTIONS: The patient refused to get chemotherapy, or surgery, and only would like to get the traditional Chinese medicine.
OUTCOMES: The patient is stable for 19 months after he coughed up some of the tumor tissue.
LESSONS: The type A thymoma could be slowly aggressive. If left untreated, it would also invade into the trachea. When treat a patient with history of even a benign tumor, we should always bear the rare possibility in mind to avoid misdiagnosis. For an elderly patient, a "wait and see" policy may be acceptable.

Luo Q, Wu X, Huang W
Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluR2 encephalitis in a myasthenia gravis patient with complete thymectomy: a case report.
BMC Neurol. 2019; 19(1):126 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Autoimmune encephalitis (AE) is a newly recognized autoimmune disorders in which the targets are proteins or receptors involved in synaptic transmission and neuronal excitability. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain.
CASE PRESENTATION: A 50-year-old woman presented with subacute onset of memory loss and behavioral changes. High levels of serum (1:1000) and CSF (1:32) antibodies against the AMPAR GluR2 were detected. A wide range of abnormalities in 6-8 Hz low to middle slow waves was found by electroencephalographs, and high-intensity signals on fluid-attenuated inversion recovery in both the medial temporal lobe and hippocampus were identified on brain magnetic resonance images. This patient presented with myasthenia gravis and type B2 thymoma (World Health Organization Thymoma Classification) at age 48. This case was unique in that the patient initiated with the symptom of myasthenia gravis and thymoma two years prior to encephalitis, and a complete thymectomy was performed before AE onset without recurrence of the thymoma when encephalitis occurred.
CONCLUSIONS: Thymoma was reported to be associated with paraneoplastic neurological disease. This is the first time a thymectomy has been applied in a myasthenia gravis patient with thymoma two years prior to the onset of anti-AMPAR2 encephalitis. This case highlights the complexity of autoimmune encephalitis associated with thymoma.

Salem S, Saad I, Alamri R
Thymoma associated myasthenia gravis with atypical presentation of lipomatous tongue atrophy: a case report.
Pan Afr Med J. 2019; 32:38 [PubMed] Free Access to Full Article Related Publications
A 28-year-old female patient came to the outpatient dental clinic for multiple teeth extractions and full mouth rehabilitation suffer from myasthenia gravis (MG) primary presentation as tongue atrophy and facial muscles weakness and the symptoms became worries, the patient unable to speak as well and change her voice and complaining of dysphagia and dysarthria. Oral symptoms, treatment schedule and protocol, the selection, prescription and impacts of medications, and prevention of myasthenic crisis are all important; aspects should be considered by dentists and oral health care providers. Weakness of facial and oropharyngeal muscle is considered very popular at disease onset and therefore oral health providers are often the first medical professionals to observe these patients. Myasthenic patients seek particular approach and consultation in order to ensure ideal and proper dental management.

Catalano MA, Mullan CW, Rich BS, Glick RD
Pediatric thymectomy: a study of national trends in demographics, short-term outcomes, and cost.
Pediatr Surg Int. 2019; 35(7):749-757 [PubMed] Related Publications
BACKGROUND: Thymectomy in pediatric patients is an effective treatment for myasthenia gravis (MG), thymic neoplasms, and other rarer pathologies. It is an uncommon procedure in children and studies have focused on small, single-institution cohorts. We sought to better characterize its use by utilizing a national database.
METHODS: The Kids' Inpatient Database was used to identify hospital discharge records of patients ≤ 20 years old who underwent thymectomy. A retrospective cross-sectional analysis for 2003, 2006, 2009, and 2012 was performed. Trends in patient characteristics, diagnosis, surgical approach, and short-term outcomes were analyzed. Risk factors were identified using univariate and multivariate analyses.
RESULTS: There were 600 thymectomies identified. MG was the most common indication. Thoracoscopy is being used increasingly for all diagnoses except malignancy. The overall morbidity rate was 14.0%, with respiratory complications representing the largest group. No in-hospital deaths were identified. Private insurance was associated with shorter hospital stays and lower costs. Hispanic race was associated with more complications, longer stays, and higher costs. Thoracoscopic thymectomies had shorter stays than open procedures.
CONCLUSION: Thymectomy in the pediatric population is being performed safely, with low morbidity and no identified mortalities. Thoracoscopy results in reduced length of stay and is being used increasingly. Of note, socioeconomic and racial factors impact outcomes.

Van Backer JT, Cedeno-Rodriguez A, Nabagiez J
Third distant recurrence of benign thymoma in a patient with myasthenia gravis.
BMJ Case Rep. 2019; 12(4) [PubMed] Related Publications
Myasthenia gravis (MG) is an autoimmune disease where antibodies attack the presynaptic terminals at the neuromuscular junction causing progressive weakness. Associated with thymomas, resection can improve symptoms. A 29-year-old woman with MG who underwent two previous thymectomies, at ages 11 and 15 presented 14 years later with recurrent MG symptoms and an anterior mediastinal mass. Robotic-assisted thoracoscopic excision of the mediastinal mass was performed without complications. She recovered well and had improvement of her MG symptoms. Thymectomy can significantly improve symptoms in MG even for patients who do not have a thymoma. Reports of distant benign thymoma recurrence are rare. MG patients require continued monitoring and vigilance, even after thymectomy. Benign thymomas can recur even after significant time intervals, and utilisation of the robotic platform for recurrent thymoma excision is safe, even following two sternotomies. Patient symptoms improve with redo thymectomy.

Ahmed A, Soin S, Patel S
A bimodal approach to thymic carcinoma with pericardial sac invasion.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
Thymic carcinoma is a rare tumour of the thymus, representing less than 1% of thymic malignancies.

Comacchio GM, Marulli G, Mammana M, et al.
Surgical Decision Making: Thymoma and Myasthenia Gravis.
Thorac Surg Clin. 2019; 29(2):203-213 [PubMed] Related Publications
About 15% of patients with myasthenia gravis are affected by thymoma. Precise tumor staging is necessary to plan the appropriate operation. In early stages, complete surgical resection is the mainstay of treatment. Minimally invasive approaches can be safely performed by highly trained surgeons, and may be preferred in myasthenic patients because they can ensure optimal results from the oncological, neurologic, and surgical point of views, avoiding the complications of open approach. For advanced stage thymoma in myasthenic patients, a careful, multidisciplinary planning of the therapeutic approach must be undertaken, particularly for extended resections involving the lung and great vessels.

Barrios Recio J, Perez Rodriguez A, Callero A, Martinez Tadeo JA
Immunodeficiency associated with tumour pathology: Good's syndrome.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
The Good's syndrome (GS) is a low prevalence entity where thymoma often is associated with immunodeficiency. Patients may start presenting recurrent rhinosinusal infections, bronchopulmonary infections, haematological alterations and diarrhoea, secondary to immunodeficiency. They can also present respiratory symptoms and parathymic syndromes derived from the existence of thymoma, a slow-growing neoplasm located in the anterior mediastinum. We present the case of a 76-year-old man diagnosed with thymoma by image analysis, which had presented multiple episodes of pneumonia and two admissions to the hospital for diarrhoea of weeks of evolution. After finishing the study, the patient is diagnosed of GS. In this case, thymectomy prevented the appearance of parathymic syndrome, but without any effect on immunodeficiency symptoms. To decrease repeat infections, substitution therapy with immunoglobulins was started. The prognosis will depend mainly on the recurrent infectious and to a lesser extent on the thymic neoplasm.

Kaminuma Y, Tanahashi M, Yukiue H, et al.
Micronodular thymoma with lymphoid stroma diagnosed 10 years after the first operation: a case report.
J Med Case Rep. 2019; 13(1):69 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Micronodular thymoma with lymphoid stroma is a rare subtype of thymoma. Here we report a case of micronodular thymoma with lymphoid stroma that was completely resected after incomplete resection 10 years earlier.
CASE PRESENTATION: A 70-year-old Japanese woman who had undergone resection for a thymic cyst 10 years earlier was found to have a solid nodule with a multilocular lesion at the site of the previous operation. We suspected that the tumor was a malignant tumor and performed trans-sternal radical thymectomy and diagnosed the lesion as micronodular thymoma with lymphoid stroma pathologically. When we reassessed the thymic cyst that had been resected 10 years earlier, a few lesions of micronodular thymoma with lymphoid stroma were found in the cyst wall. Based on these findings, we concluded that only the cystic component of micronodular thymoma with lymphoid stroma had been removed, and that the residual lesion grew locally over the next 10 years before being completely resected by reoperation.
CONCLUSION: We experienced an unusual case of micronodular thymoma with lymphoid stroma, which is a rare subtype of thymoma. Greater care should be taken to exclude a thymoma with a cystic lesion, even if a thymic cyst is strongly suspected on computed tomography and magnetic resonance imaging.

Cui X, Wan Z, Ma Z, et al.
Occurrence of acute pulmonary embolism induced by recombinant erythropoietin during treatment of pure red cell aplasia associated with thymoma: A case report.
Medicine (Baltimore). 2019; 98(10):e14789 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Thymoma is a type of rare tumor in the thymus gland, and among patients with thymoma, less than 10% will develop pure red cell aplasia (PRCA), whereas less than 5% of patients with PRCA have a thymoma. The optimal approach for PRCA in thymoma is immunosuppressive therapy, such as steroids, cyclosporine, and human antithymocyte globulin.
PATIENT CONCERNS: A sixty-one-year-old male was diagnosed with thymoma with PRCA after he complained fatigue, tinnitus, and weakness for 1 month, he received therapy with recombinant erythropoietin (rhEPO) for 1 month after the tumor was totally resected and readmitted with pulmonary embolism and received anticoagulation therapy with enoxaparin for 3 months.
DIAGNOSES: Thymoma, pure red cell aplasia, pulmonary embolism.
INTERVENTION: He received cyclosporine A, prednisone and rhEPO treatment. Two months after the thymectomy and postoperative radiation, he was readmitted with pulmonary embolism.
OUTCOMES: Thymoma and pulmonary embolism become complete response (CR), PRCA become partial response (PR).
LESSONS: Clinicians should be alert to the possibility of the increased risk of thrombosis induced by rhEPO when it used to treat PRCA associated with thymoma. If other medication is effective for managing PRCA, rhEPO should be avoided.

Zhao T, Zhang C, Ma W, et al.
A practical approach to enrich intact tryptic N-glycopeptides through size exclusion chromatography and hydrophilicity (SELIC) using an acrylamide-agarose composite gel system.
Anal Chim Acta. 2019; 1058:107-116 [PubMed] Related Publications
Increasing researches proved that abnormal glycosylation is strongly correlated with many diseases. Specially, site-specific glycosylation and its associated heterogeneity are closely related to the function and activity of the glycoprotein. However, intact N-glycopeptide analysis still faces great challenges because the presence of highly abundant non-glycosylated peptides would suppress the ionization of lowly abundant glycopeptides. In the present study, we developed a practical intact tryptic N-glycopeptide enrichment method using acrylamide-agarose composite gel that combined the size exclusion chromatography and hydrophilic (named SELIC) effects, aimed to remove the detergent rapidly and effectively, as well as enrich intact N-glycopeptides while extracting peptides. This is a useful tool to facilitate the intact N-glycopeptides analysis of complex protein mixtures, particularly for samples that extracted from formalin-fixed and paraffin-embedded (FFPE) tissues by SDS. Using this method, we successfully identified 700 site-specific intact tryptic N-glycopeptides corresponding to 261 glycosylation sites on 191 glycoproteins from FFPE thymoma tissues.

Li S, Yuan Y, Xiao H, et al.
Discovery and validation of DNA methylation markers for overall survival prognosis in patients with thymic epithelial tumors.
Clin Epigenetics. 2019; 11(1):38 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The current prognosis of thymic epithelial tumors (TETs) is according to the World Health Organization (WHO) histologic classification and the Masaoka staging system. These methods of prognosis have certain limitations in clinical application and there is a need to seek new method for determining the prognosis of patients with TETs. To date, there have been no studies done on the use of DNA methylation biomarkers for prognosis of TETs. The present study was therefore carried out to identify DNA methylation biomarkers that can determine the overall survival in patients with TETs.
METHODS: Bioinformatic analysis of TCGA 450 K methylation array data, transcriptome sequencing data, WHO histologic classification and Masaoka staging system was performed to identify differentially expressed methylation sites between thymoma and thymic carcinoma as well as the different DNA methylation sites associated with the overall survival in patients with TETs. Using pyrosequencing, 4 different methylation sites (cg05784862, cg07154254, cg02543462, and cg06288355) were sequenced from tumor tissues of 100 Chinese patients with TETs. A prognostic model for TETs was constructed using these four methylation sites.
RESULTS: The TCGA dataset showed 5155 and 6967 hyper- and hypomethylated CpG sites in type A-B3 group and type C group, respectively, of which 3600 were located within the gene promoter regions. One hundred thirty-four genes were silenced by promoter hypermethylation and 174 mRNAs were upregulated. Analysis of univariate and multivariate Cox regression showed significant association between the methylation levels of 187 sites and the overall survival in patients with TETs. cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) were identified as independent prognostic factors for overall survival in patients with TETs after adjusting for Masaoka staging in 100 Chinese patients. The prognostic model which consists of the four abovementioned genes had higher accuracy for predicting the 5-year overall survival in patients with TETs as compared to the Masaoka clinical staging. (Time-dependent ROC analysis AUC 1.000 vs 0.742, P = 2.7 × 10
CONCLUSIONS: The methylation levels of cg05784862(KSR1), cg07154254(ELF3), cg02543462(ILRN), and cg06288355(RAG1) sites are associated with the progression of TETs and may serve as new biomarkers for predicting the overall survival in patients with TETs.

Bi Y, Meng Y, Niu Y, et al.
Genome‑wide DNA methylation profile of thymomas and potential epigenetic regulation of thymoma subtypes.
Oncol Rep. 2019; 41(5):2762-2774 [PubMed] Free Access to Full Article Related Publications
The aim of the present study was to examine the whole‑genome DNA methylation status of thymomas and identify differences in thymoma DNA methylation profiles. DNA methylation profiles of tissues (n=12) were studied using the Infinium MethylationEPIC BeadChip microarray (850K) and analyzed in relation to gene expression data. Functional annotation analysis of DNA methylation between the different groups was performed using the online tool GeneCodis3. In order to assess the diagnostic value of candidate DNA methylation markers, receiver operation characteristic (ROC) analysis was performed using the pROC package. A total of 10,014 CpGs were found to be differentially methylated (Δβ>0.2) between two thymoma types (type A and B). Combination analysis showed that 36 genes had differentially methylated CpG sites in their promoter region. 'Pathways in cancer', 'focal adhesion' and 'regulation of actin cytoskeleton' were the most enriched KEGG pathways of differentially methylated genes between tumor and controls. Among the 29 genes that were hypomethylated with a high expression, zinc finger protein 396 and Fraser extracellular matrix complex subunit 1 had the largest area under the curve. The present results may provide useful insights into the tumorigenesis of thymomas and a strong basis for future research on the molecular subtyping of epigenetic regulation in thymomas.

Massa R, Greco G, Testi M, et al.
Thymomatous myasthenia gravis: novel association with HLA DQB1*05:01 and strengthened evidence of high clinical and serological severity.
J Neurol. 2019; 266(4):982-989 [PubMed] Related Publications
BACKGROUND: The relative prevalence of myasthenia gravis (MG) subtypes is changing, and their differential features and association with HLA class II alleles are not completely understood.
METHODS: Age at onset, presence/absence of autoantibodies (Ab) and thymoma were retrospectively considered in 230 adult Italian patients. Clinical severity, assessed by MGFA scale, and the highest Ab titer were recorded. Furthermore, we performed low/high resolution typing of HLA-DRB1 and HLA-DQB1 alleles to detect associations of these loci with MG subtypes.
RESULTS: There were two peaks of incidence: under 41 years of age, with female preponderance, and over 60 years, with higher male prevalence. The former group decreased and the latter increased significantly when comparing onset period 2008-2015 to 2000-2007. Thymomatous (TMG) patients showed a higher prevalence of severe phenotype and significantly higher anti-AChR Ab titer than non-thymomatous (NTMG) patients. Among the latter, those with onset after 60 years of age (LO-NTMG) displayed significantly higher Ab titers but lower MGFA grade compared to early-onset patients (< 41 years; EO-NTMG). Significant associations were found between HLA DQB1*05:01 and TMG patients and between DQB1*05:02 and DRB1*16 alleles and LO-NTMG with anti-AChR Ab.
CONCLUSIONS: Two distinct cutoffs (< 41 and > 60 years) conveniently define EO-NTMG and LO-NTMG, with different characteristics. LO-NTMG is the most frequent disease subtype, with an increasing incidence. TMG patients reach higher clinical severity and higher antibody titers than NTMG patients. Moreover, TMG and LO-NTMG with anti-AChR Ab differ in their HLA-DQ association, providing further evidence that these two forms may have different etiologic mechanisms.

Nakamura S, Kawaguchi K, Fukui T, et al.
Multimodality therapy for thymoma patients with pleural dissemination.
Gen Thorac Cardiovasc Surg. 2019; 67(6):524-529 [PubMed] Related Publications
BACKGROUND: Although multidisciplinary treatment is recommended for patients with advanced stage and recurrent thymoma, a detailed treatment strategy remains controversial. We have performed a multimodality therapy of induction chemotherapy (CAMP therapy: cisplatin, doxorubicin, and methylprednisolone) combined with surgery for those patients. We now conducted a retrospective study for investigating the results of this multimodality therapy for thymoma patients with pleural dissemination.
PATIENTS AND METHODS: Between 2003 and 2017, 201 patients underwent surgical resection for thymomas. Twenty-six of them received induction CAMP therapy followed by surgery, and 19 of them with pleural dissemination were enrolled in this study. Those cohort were divided into 2 groups by employing surgical procedures: extrapleural pneumonectomy (EPP) group (n = 10) and resection of plural dissemination (RPD) group (n = 9).
RESULTS: The median age of all patients was 49 years. Based on the WHO classification, the histological diagnoses of those thymomas were as follows: Type B1 (n = 1), Type B2 (n = 13), and Type B3 (n = 5). Seven patients were complicated with myasthenia gravis (MG). Clinical stage of the 13 primary cases based on the Masaoka classification were stage IV, and the remaining six cases had recurrent pleural dissemination after surgery. Partial response in induction CAMP therapy was obtained in 78.9% (n = 15) of the patients. Adverse events (Grade 4) occurred in 2 patients (10.5%). Postoperative complications (Grade 4) were observed in 2 patients (10.5%). In all of the enrolled patients, the five-year overall survival rate (5Y-OS) and 5-year progression-free survival rate (5Y-PFS) were 76.7% and 55.1%, respectively. In the EPP group, 5Y-OS and 5Y-PFS were 83.3% and 83.3%, respectively, and in the RPD group, 70.0% and 29.6%, respectively.
CONCLUSIONS: Multidisciplinary treatment using induction CAMP therapy and surgical resection for thymoma patients with pleural dissemination was effective and feasible. Because of the low recurrent rate of disease, young patients with good cardiopulmonary function and well-controlled MG might be good candidates for EPP.

Kouitcheu R, Appay R, Diallo M, et al.
A case of brain metastasis of a thymic carcinoma with a review of the literature.
Neurochirurgie. 2019; 65(1):43-48 [PubMed] Related Publications
Thymic epithelial tumors (TET) are rare lesions. The brain metastases of these tumors are even rarer. We report a case of brain metastases in a known patient with a thymic carcinoma diagnosed in October 2016. She was a 73-year-old woman who presented with headache, nausea, and right hemiplegia. Brain MRI revealed five lesions (1 insular, 1 frontal and 2 left temporal, 1 right parafalcine). These lesions were initially treated using two stereotactic radiosurgery gamma knives. A macroscopically complete excision of the left frontal lesion was subsequently performed without any complications with a good evolution of the neurological symptoms postoperatively. Immunohistochemical examination was compatible with metastatic thymic carcinoma. The patient died 14 months after the initial diagnosis. A review of the literature in English has reported another 45 TET cases with brain metastases.

Lakshmaiah KC, Chaudhuri T, Babu GK, et al.
Metastatic thymic epithelial tumors: A regional cancer center experience.
Indian J Cancer. 2018 Jul-Sep; 55(3):288-291 [PubMed] Related Publications
BACKGROUND: Thymic epithelial tumors (TET) are the most common tumors of the anterior mediastinum. Patients with advanced/metastatic disease are usually treated with palliative chemotherapy (CT). Unfortunately, even though various palliative CT regimens have been used for long time, there is a real scarcity of published Indian data regarding the experience of palliative CT in metastatic TET (mTET).
MATERIALS AND METHODS: This is a retrospective analysis of mTET patients treated between January 2010 and September 2017. Patients who received at least three cycles of first-line palliative CT were included for analysis of response rates, toxicity, and survival and prognostic factors.
RESULTS: Of the 49 mTET patients, 27 (55.1%) were males. The median age at diagnosis was 52 years (range: 25-65). Eighteen patients (36.7%) had Masaoka Stage IVa disease, and the rest of the patients had IVb disease. The most common site of metastasis was pleuropericardium (n = 18), followed by lungs (n = 16) and lymph nodes (n = 9). The median progression-free survival and overall survival (OS) were 11.2 months (95% confidence interval [CI], 8.7-13.6) and 20.2 months (95% CI, 17.1-22.8), respectively, for the whole cohort (n = 49). The median OS of patients with Stage IVa disease was significantly better than that of the patients with Stage IVb disease (log-rank P = 0.000). Moreover, the "responders" to first-line CT had a significantly better median OS than the "nonresponders" (log-rank P = 0.000). Various first-line palliative CT regimens were well tolerated in our patients.
CONCLUSION: Adriamycin Cisplatin Vincristine Cyclophosphamide (ADOC), Cyclophosphamide Adriamycin Cisplatin, and paclitaxel + carboplatin all are viable first-line palliative CT options for mTET and showed a comparable survival in Indian patients. The present study suggested that "responders" to first-line CT and those with Stage IVa disease might have a better survival than "nonresponders" and those with Stage IVb disease, respectively.

Liu S, Zhou X, Song A, et al.
Surgical management of spinal metastases of thymic carcinoma: A case report and literature review.
Medicine (Baltimore). 2019; 98(3):e14198 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Metastatic thymic carcinoma in the spine is a rare disease with no standard curative managements yet. The objective of this study is to report a very rare case of spinal metastases of thymic carcinoma successfully operated by combination of instrumentation and cement augmentation together with adjuvant treatment. The management of these unique cases has yet to be well-documented.
PATIENT CONCERNS: A 57-year-old man presented with a 6-month history of continuous and progressive back pain. The patient, who had been diagnosed of thymic carcinoma (stage IV B) for 3 years, received surgical treatment of median sternotomy thymectomy, followed by 3 cycles of chemotherapy and 12 cycles of radiotherapy.
DIAGNOSIS: Magnetic resonance imaging (MRI) of spine showed spinal cord compression secondary to the epidural component of the T4 mass, with increased metastatic marrow infiltration of the left T4 vetebral body, which presented as a solid tumor. Post-operative pathology confirmed the diagnosis of spinal metastases of thymic carcinoma.
INTERVENTIONS: The patient underwent exploratory surgery, circumferential spinal cord decompression, cement augmentation and a stabilization procedure via a posterior approach.
OUTCOMES: The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 3-month follow-up visit. There were no other complications associated with the operation during the follow-up period.
LESSONS: Taken together, the lesion's clinical features, imaging results, and pathological characteristics are unique. Combined efforts of specialists from orthopedics, neurosurgery, thoracic surgery, and medical oncology led to the successful diagnosis and management of this patient. Metastatic thymic carcinoma of the spine, although rare, should be part of the differential diagnosis when the patient has a history of thymic carcinoma and presents with back pain and radiculopathy. We recommend the posterior approach for spinal decompression of the metastatic thymic carcinoma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation is also a good choice for surgical treatment.

Liu S, Zhou X, Song A, et al.
Successful treatment of malignant thymoma with sacrum metastases: A case report and review of literature.
Medicine (Baltimore). 2018; 97(51):e13796 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Malignant thymoma in the spine is a rare disease without standard curative managements so far. The objective of this article is to report a very rare case of recurrent malignant thymoma with sacrum metastases causing severe lumbosacral pain, which was presented with acute radiculopathy and treated with 2 operations combined with stabilization and cement augmentation. The management of these unique cases is not well-documented.
PATIENT CONCERNS: A 75-year-old man presented with lumbosacral pain, radiating pain and numbness of the left extremity. The patient underwent thymectomy in 2008, and posterior spinal cord decompression, tumor resection and a stabilization procedure in 2011. Pathologic results confirmed malignant thymomas of the spine. Imaging studies revealed the density of soft tissues, obvious bony destruction in the sacrum, and significant spinal cord obstruction.
DIAGNOSES: We believe this is a less-documented case of metastatic thymoma of the sacral spine presenting with back pain and radiculopathy, and presenting as a giant solid tumor.
INTERVENTIONS: The patient underwent osteoplasty via a posterior approach. Pathologic results confirmed malignant thymomas of the sacral spine.
OUTCOMES: The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 6-month and 1-year follow-up visit. There were no other complications associated with the operation during the follow-up period.
LESSONS: This article emphasizes metastatic thymoma of the spine, although rare, should be part of the differential when the patient presents with back pain and radiculopathy. We recommend the posterior approach for spinal decompression of the metastatic thymoma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation is also a good choice for surgical treatment.

Tajima Y, Yaguchi H, Mito Y
Non-motor Comorbidity of Myasthenia Gravis: Myasthenia Gravis as a Systemic Immunological Disorder Involving Non-motor Systems.
Intern Med. 2019; 58(9):1341-1347 [PubMed] Free Access to Full Article Related Publications
To explore non-motor comorbidities of myasthenia gravis (MG), we present two cases of thymoma-associated MG patients. Alopecia, pure red cell aplasia, and thymoma- associated multiorgan autoimmunity were observed in Case 1, and alopecia, thrombocytopenia, hypogammaglobulinemia and nephrotic syndrome were observed in Case 2. In both cases, autoreactive T lymphocytes inappropriately stimulated by thymus tissue may have played key roles in generating the various autoimmune-associated symptoms. Consequently, systemic immunological involvement due to the thymoma-associated breakdown of immunoregulations in both motor and non-motor systems should be considered in MG patients.

Aoki Y, Miki A, Nakano T, et al.
Thymoma with an isolated splenic metastasis eight years after extended thymectomy: a case report.
BMC Cancer. 2018; 18(1):1249 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Thymomas are typically slow-growing tumors and AB type thymomas are considered no/low risk tumors with a better prognosis. Extra-thoracic metastases are extremely rare. To the best of our knowledge, no patient with an isolated splenic metastasis from a thymoma has been reported. We report a patient who underwent laparoscopic splenectomy for a slow-growing, isolated splenic metastasis, eight years after thymectomy.
CASE PRESENTATION: The patient is a 78-year-old man. Eight years previously, the patient underwent extended thymectomy and postoperative radiation therapy for a thymoma. Five years after thymectomy, a nodule appeared in the spleen, and the lesion enlarged gradually for three years thereafter. The patient was referred for further examination and treatment. Computed tomography scan showed a sharply circumscribed 50 mm tumor slightly hypodense and heterogeneous lesion in the spleen. On T2-weighted images on Magnetic Resonance Imaging, the tumor had high intensity, equivalent to or slightly lower than that on T1-weighted images, and no decrease on diffusion-weighted images. The tumor was multinodular and showed a low-signal spoke-wheel sign in the margin, enhanced gradually in the dynamic study. Positron emission tomography-CT scan, showed relatively low accumulation. Surgical resection was undertaken, and pathological examination showed metastatic thymoma. The patient is without recurrence and has no other symptoms three years after splenectomy.
CONCLUSIONS: This is the first report of an isolated splenic metastasis from a thymoma. Further cases are needed to standardize this surgery for such lesions.

Karino K, Fujieda Y, Kawamura T, et al.
Anti-TIF1γ antibody predicted malignancy of thymic tumor with dermatomyositis as an "autoimmune tumor marker": A case report.
Medicine (Baltimore). 2018; 97(49):e13563 [PubMed] Free Access to Full Article Related Publications
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.

Kobayashi Y, Ando K, Hata T, et al.
Complete remission of pure white cell aplasia associated with thymoma after thymectomy and cyclosporine administration.
Int J Hematol. 2019; 109(3):346-350 [PubMed] Related Publications
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

Xie Y, Zhang S, Liu J, et al.
Value of CT spectral imaging in the differential diagnosis of thymoma and mediastinal lymphoma.
Br J Radiol. 2019; 92(1095):20180598 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
OBJECTIVE:: To investigate the imaging characteristics of thymoma and mediastinal lymphoma using spectral CT and evaluate whether the quantitative information can improve the differential diagnosis of these diseases.
METHODS:: This retrospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Overall, 39 patients with mediastinal tumors (24 thymomas and 15 mediastinal lymphomas) were examined with CT spectral imaging during the arterial phase (AP) and venous phase (VP). Iodine concentrations were derived from iodine-based material-decomposition CT images and normalized to the iodine concentration in the aorta. The difference in normalized iodine concentrations (NICs), HU curve slop(λ
RESULTS:: NICs during the VP and λ
CONCLUSION:: CT spectral imaging has promising potential for the diagnostic differentiation of mediastinal lymphomas and thymomas. The iodine content and λ
ADVANCES IN KNOWLEDGE:: The iodine content and λ

Boddu P, Thakral B, Alhuraiji A, et al.
Distinguishing thymoma from T-lymphoblastic leukaemia/lymphoma: a case-based evaluation.
J Clin Pathol. 2019; 72(3):251-257 [PubMed] Related Publications
T-lymphoblastic lymphoma and thymoma are distinct primary mediastinal neoplasms that can have similar clinical presentations and overlapping histological features. Microscopic distinction is occasionally difficult because the immature lymphocytes associated with thymoma may resemble T-lymphoblastic leukaemia/lymphoma cells, morphologically and immunohistochemically. An accurate diagnosis assumes particular importance since the treatment approaches for these two entities differ considerably. Multimodality diagnostic approaches incorporating histological, flow cytometry immunophenotypic' and molecular approaches are required. In this article, we describe four patients, each presenting with a mediastinal tumour in different clinicopathological settings. A detailed report of each case will follow, illustrating the challenges involved in the diagnosis in patients with these mediastinal neoplasms.

Muriana P, Carretta A, Ciriaco P, et al.
Assessment of the prognostic role of neutrophil-to-lymphocyte ratio following complete resection of thymoma.
J Cardiothorac Surg. 2018; 13(1):119 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
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.

Maeda S, Nakazato Y, Hayashi K, et al.
L-Type Amino Acid Transporter 1 Immunoreactivity as a Possible Diagnostic and Prognostic Marker of Thymic Carcinoma.
Tohoku J Exp Med. 2018; 246(3):167-174 [PubMed] Related Publications
L-type amino acid transporter 1 (LAT1) functions to transport large neutral amino acids, such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, and histidine. These amino acids are essential for cell growth and proliferation. Many studies have demonstrated LAT1 expression in various types of cancer, and its high expression level was associated with poor prognosis. However, the significance of LAT1 expression in thymic epithelial tumors is controversial. We conducted this retrospective study to investigate the LAT1 immunoreactivity in thymic epithelial tumors and its impact on prognosis. We analyzed 32 patients with thymoma and 14 patients with thymic carcinoma who underwent surgery at our institute. Immunohistochemical analysis was performed using formalin-fixed paraffin-embedded surgical tissues and an anti-LAT1 polyclonal antibody. We thus found that LAT1 immunoreactivity was undetectable in all of the thymoma specimens, regardless of the subtypes of thymoma. By contrast, LAT1 immunoreactivity was consistently detected in the cytosol of thymic carcinoma cells; namely, all 14 thymic carcinoma specimens demonstrated LAT1 immunoreactivity in the cytosol. Among these 14 thymic carcinoma specimens, four carcinoma specimens also showed LAT1 immunoreactivity in the cell membrane. Survival analysis indicated that the thymic carcinoma with the LAT1 membrane signal was associated with poor prognosis, compared with the specimens with the LAT1 cytosol signal. We therefore propose that LAT1 is expressed in the cytosol of thymic carcinoma cells, which could be a diagnostic marker of thymic carcinoma. Moreover, LAT1 expression in the cell membrane is a prognostic marker of thymic carcinoma.

Miyata R, Hamaji M, Omasa M, et al.
Survival outcomes after minimally invasive thymectomy for early-stage thymic carcinoma.
Surg Today. 2019; 49(4):357-360 [PubMed] Related Publications
Minimally invasive surgery (MIS) has occasionally been used for selected patients with thymoma, but there is little information on the MIS approach for thymic carcinoma. The aim of this study was to evaluate survival outcomes after MIS for early-stage (Masaoka stage I-II) thymic carcinoma and thymic neuroendocrine carcinoma. A retrospective chart review of the cases recorded in our multi-institutional database was performed to identify patients who underwent resection for thymic carcinoma between 1995 and 2017. MIS thymectomy was performed in 17 cases (VATS, n = 14; RATS, n = 3. male, 41%; median age, 72 years). The median follow-up period was 32.7 (range 7.4-106) months. The five-year overall survival and relapse-free survival rates were 84.4% and 77.8%, respectively. The present study demonstrated encouraging preliminary results regarding MIS for the treatment of early-stage thymic carcinoma and thymic neuroendocrine carcinoma. Further studies with a larger sample size are required to evaluate the indications for this surgery.

Wang Y, Nie J, Dai L, et al.
Efficacy and toxicities of gemcitabine and cisplatin combined with endostar in advanced thymoma and thymic carcinoma.
Thorac Cancer. 2019; 10(1):17-23 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
BACKGROUND: Thymoma and thymic carcinoma are rare thymic epithelial tumors. We investigated the efficacy of first-line gemcitabine and cisplatin (GP) chemotherapy versus gemcitabine and cisplatin chemotherapy combined with the anti-angiogenic drug endostar (GP + E) in advanced thymoma and thymic carcinoma.
METHODS: The records of 45 patients with invasive metastatic thymomas or thymic carcinomas treated with GP as first-line therapy between August 2008 and July 2017 at the Department of Respiratory Medicine, Peking University Cancer Hospital and Institute were retrospectively reviewed.
RESULTS: Eighteen patients (75%) in the GP + E group achieved a partial response and six (25%) had stable disease. In GP only group, nine (42.8%) patients achieved a partial response, 11 (52.4%) had stable disease, and one (4.8%) had progressive disease. The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression-free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively. In the GP only group, median PFS and OS were 16 and 29 months, respectively. PFS and OS were not significantly different between the groups.
CONCLUSIONS: GP has moderate efficacy and could represent a suitable first-line therapy for thymic carcinoma and thymoma. Chemotherapy combined with endostar could improve the overall response rate, but did not prolong PFS or OS.

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