Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease.

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+B220high 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+B220high 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.

Improvement of reduced electroretinographic responses in thymoma-associated retinopathy: a case report and literature review.

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

A ring-calcified thymoma, mimicking pericardial cyst, precedes pure red cell aplasia for more than 10 years - A case-based overview of pathophysiology.

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

Implementation of proton therapy treatments with pencil beam scanning of targets with limited intrafraction motion.

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

Sclerosing thymoma: A rare case report and brief review of literature.

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

Novel MRI of mediastinal masses: internal differentiation of a thymoma and lymphoma with T1 and T2 mapping.

Routine imaging for mediastinal malignancies includes chest X-ray, CT or MRI. T1 and T2 mapping are novel MRI techniques which may have a role in expanding the assessment of internal tumour characteristics. This case report details two middle-aged women who had similar clinical presentations of mediastinal masses of comparable size and appearance when assessed with routine imaging. T1 and T2 maps were acquired on MRI to investigate whether these tumours could be further differentiated prior to surgery. T1 and T2 mapping supported suspicion for which tumour components were solid and cystic, as subsequently confirmed histologically. Furthermore, comparison between the two tumours showed native T1 values differed within the solid components by 37%, correlating to differences in proteinaceous material within the tumour types. This radiological-pathological correlation provides evidence that T1 and T2 mapping has clinical utility in the assessment and differentiation of mediastinal masses.

Lupus Nephritis with Thymoma Managed by Thoracoscopic Surgery and Prednisolone.

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

Thymic large cell neuroendocrine carcinoma - a rare and aggressive tumor: a case report.

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

Long-term outcomes of 307 patients after complete thymoma resection.

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

Nephrotic syndrome associated with metastatic thymoma treated with chemotherapy.

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

Postoperative Recurrence of Invasive Thymoma with Cold Agglutinin Disease and Autoimmune Hemolytic Anemia.

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

Giant cell polymyositis associated with myasthenia gravis and thymoma.

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

Sweet taste loss in myasthenia gravis: more than a coincidence?

Sweet dysgeusia, a rare taste disorder, may be encountered in severe anti-acetylcholine receptor antibody (AChRAb)-myasthenia gravis (MG). A 42 year-old man reported progressive loss of sweet taste evolving for almost 10 weeks, revealing an AChRAb-positive MG with thymoma. Improvement of sweet perception paralleled reduction of the MG composite score during the 15 months follow up period, with immunosuppressive and surgical treatments. We suggest that sweet dysgeusia is a non-motor manifestation of MG that may result from a thymoma-dependent autoimmune mechanism targeting gustducin-positive G-protein-coupled taste receptor cells, in line with recent data from MRL/MpJ-Fas lpr/ (MRL/lpr) transgenic mice with autoimmune disease.

Edema pulmonar por reexpansión tras resección de timoma gigante / Pulmonary oedema due to re-expansion after resection of a giant thymoma

Mujer de 36 años que fue sometida a una resección de timoma gigante que ocupaba gran parte del hemitórax izquierdo. Tras la resección del tumor y la insuflación del pulmón izquierdo apareció un edema pulmonar por reexpansión precoz. Se trató con diuréticos, corticoides y se mantuvo la ventilación mecánica. La paciente evolucionó favorablemente. El edema pulmonar por reexpansión es una complicación poco frecuente, pero con una alta mortalidad. Es fundamental conocer los factores implicados en su etiopatogenia. El diagnóstico y tratamiento se deben realizar de forma inmediata(AU)

A 36 year-old woman who was subjected to resection of a giant thymoma that occupied a large area of the left hemithorax. After resection of the tumour and insufflation of the left lung there was pulmonary oedema due to early re-expansion. She was treated with diuretics and corticoids and was kept on mechanical ventilation. The patient progressed favourably. Although pulmonary oedema due to re-expansion is an uncommon complication it has a high mortality. It is essential to be aware of the factors involved in its aetiopathogenesis. It should be diagnosed and treated immediately(AU)

High prevalence of infections and autoimmunity in patients with thymoma.

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

Imaging of a thymoma incidentally detected by C-11 choline PET/CT.

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

SOX2 gene expression in normal human thymus and thymoma.

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