Granulocytopenia Associated With Thymoma in a Domestic Shorthaired Cat
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Abstract:
A 5-year-old, spayed female cat was referred because of a mass in the cranial mediastinum noted on thoracic radiographs. A thymoma was diagnosed following ultrasound and biopsy of the mass. Treatment was initiated with coarse-fraction radiation therapy using external-beam therapy (four fractions of 5 Gy). The mass responded, but granulocytopenia developed. Bone marrow examination showed a myeloid to erythroid ratio of approximately 1:1, with a left shift within the myeloid line. These findings, as well as the lack of toxic changes within the peripheral blood neutrophils, suggested immune-mediated destruction of peripheral granulocytes. Immune suppression with prednisone and cyclosporine was instituted. After 7 weeks, the neutrophil count returned to normal. The tumor was removed, and cyclosporine was reduced and eventually discontinued 3 weeks postsurgery.Cite
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Abstract A simple procedure was developed for rapid analysis of animal bone marrow by flow cytometry using the lipophilic cationic dye 3,3′‐dihexyloxacarbocyanine iodide (DiOC 6 (3)). The batch process allows differentiation of bone marrow cells into lymphoid, erythroid, and myeloid populations and enables classification of erythroid and myeloid cells into proliferating and maturing subpopulations. From these data, myeloid:erythroid (M:E) ratios and maturation indices for erythroid and myeloid cells (EMI and MMI, respectively) can be derived. This procedure provides the opportunity to analyze bone marrow quantitatively and offers distinct advantages to current manual methods in terms of simplicity, throughput, and reproducibility. The method has been tested successfully using marrow from Wistar rats, B 6 C 3 F 1 mice, beagle dogs, and cynomolgus monkeys. This technique facilitates the evaluation of bone marrow samples taken from preclinical safety studies or from animal colonies of large size. © 1992 Wiley‐Liss, Inc.
Cytometry
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An imbalance in Th17 cells and Tregs may be an important cause of the pathogenesis of thymoma with myasthenia gravis (MG). In this study, 30 patients with simple thymoma and 30 patients with thymoma with MG were analyzed. Flow cytometry analysis of Th17 and Tregs in peripheral blood revealed that the percentages of Th17 in thymoma were lower than those in thymoma with MG, while the percentages of Tregs were higher than those in simple thymoma. Serum cytokine ELISA assays showed that IL-6 levels in simple thymoma were lower than those in MG patients. Further, Th17 and Tregs levels were detected by immunohistochemical double staining of thymoma tissue; the number of positive Th17 cells in thymoma with MG was higher than that in simple thymoma, while positive Tregs showed the opposite results. RORγt protein and mRNA expression in thymoma with MG were both higher than those in simple thymoma. FOXP3 protein and mRNA expression in the thymoma with MG group were lower than those in simple thymoma. The results of coculture of thymoma cells and CD4+ T cells showed that thymoma cells could promote the differentiation of Th17 cells and inhibit the Tregs. Overall, Th17 cells and related transcription factors and cytokines in thymoma with MG patients were higher than those in thymoma patients, whereas, Tregs showed the opposite results, the mechanism may be that thymoma can secrete IL6 and IL21. These findings indicated that imbalances in Th17/Tregs and RORγt/FOXP3 may account for the pathogeny of thymoma with MG.
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Thymomas are normally found in the superior mediastinum or the upper part of the anterior mediastinum. We report a case of thymoma arising in the inferior aspect of the anterior mediastinum. This case illustrates that thymic tissue may be found low in the anterior mediastinum and supports the practice of a median sternotomy approach for thorough mediastinal exploration in all cases of thymectomy.
Anterior mediastinum
Thymectomy
Median sternotomy
Thymus Neoplasm
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Thymus Neoplasm
Thymectomy
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Thymoma is a common anterior mediastinal mass, although thymomas have occasionally been found in the neck, pulmonary hillus, or posterior mediastinum.But a thymoma within the middle mediastinum has rarely been reported.We report a thymoma arising in the middle mediastinum with a review of the literature.
Anterior mediastinum
Mediastinal mass
Thymus Neoplasm
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Persistence (discontinuity)
Thymectomy
Thymus Neoplasm
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Objective
To investigate the clinicopathological features and prognosis in patients with thymoma and patients with thymoma and myasthenia gravis (MG).
Methods
A retrospective analysis was performed on the clinicopathological data of 161 patients pathologically diagnosed with thymoma alone or thymoma and MG from 2008 to 2014. In those patients, 128 had thymoma with MG and 33 had thymoma alone. The survival rates were calculated using the Kaplan-Meier method and analyzed using χ2 test or Fisher's exact probability test.
Results
The mean age of onset was 45.2 years for patients with thymoma and MG and 48.5 years for patients with thymoma alone. In patients with thymoma and MG, 74.2% had a tumor diameter of ≤5 cm, while 75.8% of patients with thymoma alone had a tumor diameter of ≥5 cm. According to the Masaoka staging system, 78.1% of patients with thymoma and MG had stage Ⅰ+ Ⅱ disease, while 51.1% of patients with thymoma alone had stage Ⅲ+ Ⅳ disease. There was no significant difference in the 3-year overall survival (OS) rate between the two groups (98.1% vs. 81.8%, P=1.000). The 5-year OS rate was significantly higher in patients with thymoma and MG than in patients with thymoma alone (91.1% vs. 42.9%, P=0.000). In all patients, 140 patients with complete resection had significantly higher 3-and 5-year OS rates than 21 patients with incomplete resection (97.2% vs. 58.8%, P=0.000; 92.7% vs. 25.0%, P=0.000). In patients with stage Ⅱ disease, there were no significant differences in the 3-or 5-year OS rates between patients with complete resection alone (n=25) and patients with complete resection and postoperative radiotherapy (n=25)(95% vs. 100%, P=1.000; 86% vs. 100%, P=0.467).
Conclusions
Compared with patients with thymoma alone, patients with thymoma and MG have an earlier age of onset, substantially smaller tumor diameters, and earlier Masaoka stages. MG and complete resection are positive prognostic factors for patients with thymoma. Radiotherapy after complete resection can reduce the recurrence rate in patients with stage Ⅱ disease.
Key words:
Thymoma; Myasthenia gravis; Clinicopathological features; Prognosis
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One half of cortical thymoma patients develop myasthenia gravis (MG), while 15% of MG patients have thymomas. MG is a neuromuscular junction disease caused in 85% of the cases by acetylcholine receptor (AChR) antibodies. Titin and ryanodine receptor (RyR) antibodies are found in 95% of thymoma MG and 50% of late-onset MG (MG onset ≥50 years), are associated with severe disease, and may predict thymoma MG outcome. Nonlimb symptom profile at MG onset with bulbar, ocular, neck, and respiratory symptoms should raise the suspicion about the presence of thymoma in MG. The presence of titin and RyR antibodies in an MG patient younger than 60 years strongly suggests a thymoma, while their absence at any age strongly excludes thymoma. Thymoma should be removed surgically. Prethymectomy plasmapheresis/iv-IgG should be considered before thymectomy. The pharmacological treatment does not differ from nonthymoma MG, except for tacrolimus which is an option in difficult thymoma and nonthymoma MG cases with RyR antibodies.
Thymectomy
Plasmapheresis
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Thymomas occurring in myasthenia gravis (MG) are usually of the cortical subtype and are usually treated by thymectomy. However, the factors that influence MG outcome in thymoma MG patients are not known. In a long-term study, MG severity and treatment was observed in 24 thymoma and 24 non-thymoma MG patients for up to 30 years, and the occurrence of muscle autoantibodies was assayed. The rate of complete stable remission was low and did not differ between the two groups. There was no significant difference in MG severity between thymoma and non-thymoma MG patients at any time during the study. Titin and ryanodine receptor (RyR) antibody occurrence was significantly higher in thymoma MG patients. Four thymoma (all titin and RyR antibody positive) and two non-thymoma (both titin and one RyR antibody positive) MG patients died from MG-related respiratory insufficiency. Seventy percent of thymoma and 75% of non-thymoma MG patients were treated with immunosuppressive drugs. The number of patients who received plasmapheresis did not differ in those who were treated because of acute MG deterioration, irrespective of planned surgery.This study shows equal MG severity and outcome in thymoma and non-thymoma MG, but the presence of RyR antibodies in thymoma MG and titin/RyR in non-thymoma MG indicates a less favorable prognosis.
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