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We treated a 22-year-old woman suffering from Graves' disease and thymic hyperplasia. She was referred to our institution for a close investigation of thyrotoxicosis and thymic mass. Thyroid tests and magnetic resonance imaging resulted in a diagnosis of Graves' disease and thymic hyperplasia. The thyroid function and thyroid-stimulating hormone receptor antibody (TRAb) were normalized one and five months after thiamazole initiation, respectively. The thymic size began to decrease after 1 month and was further decreased after 5 months; it was normalized after 12 months. The correlation between TRAb titers and the thymic size (R

Background and Objectives: Thymic pathology is common in Myasthenia Gravis(MG) and plays a crucial role in its pathogenesis and clinical outcome. This study aims to discuss the clinicohistopathological spectrum of thymic lesions in MG. Methods: In this retrospective study, MG patients who underwent thymectomy from 2011 to 2020 were included. Clinical, radiological, serological, and histopathological details are described. Results: Of 83 patients(F = 45; M = 38), 7(8%) had ocular myasthenia, and the remaining 76(92%) had the generalized form. At onset, the median age was 36 years(M = 44; F = 31). AChR antibody was positive in 71/79 patients. RNST showed decrement response in 68/78 patients. The histopathological study demonstrated thymoma in 44(53%), thymic hyperplasias [32(38%)], involuted thymus [5(6%)], thymic cyst (1) and thymic lipoma (1). WHO grading of thymoma: B2- 48%, AB-18%, B-18%, B3-14%, A-2.3%. In these, capsular infiltration was noted in 11/44, 9 had focal and 2 had diffuse infiltration. Active germinal centers were present in 20/32 patients with thymic hyperplasia and 4/44 with thymoma. Thymomas were predominant in males and thymic hyperplasia in females. The age of onset and antibody positivity rate was higher in thymoma patients. Conclusion: In our cohort, there is a female preponderance. Thymoma was the commonest pathology followed by hyperplasia. We observed earlier onset of myasthenia in females. AChR antibody positivity rate was more frequent in thymomas. This study indicates that clinico-radiological evaluation adequately supported by serology and histopathology can effectively recognize the type of thymic pathology that can guide these patients’ treatment planning, management, prognosis and follow-up.

Detection of fat content in thymic lesions is crucial to differentiate thymic hyperplasia from thymic tumors or other anterior mediastinal pathologies.To assess the feasibility of dual-energy CT (DECT) fat content quantification for the differentiation of anterior mediastinal lesions from benign thymic lesions and the normal spectrum of the thymus.Chest DECT images of 465 patients (median 61 years, 63% female) were visually evaluated by two radiologists and semiquantitatively scored based on the degree of fatty degeneration ranging from completely fatty (score 0) to predominantly soft-tissue (score 3), and anterior mediastinal mass (score 4). A subset of scans (n =134 including all cases with scores 2-4 and 20 randomly-selected cases from scores 0 and 1) underwent quantitative DECT analysis (fat fraction, iodine density, and conventional CT value). DECT values were compared across the semiquantitative scores.Results of visual evaluation included 35 with predominantly solid thymus (score 3) and 15 with anterior mediastinal mass (score 4). The most common clinical diagnoses of the 15 masses (including 8 with pathologic confirmation) were metastases (n = 10) and lymphoma (n = 4). CT values in the abnormal thymus were significantly higher than those in score 3 (median: 69.7 HU versus 19.9 HU, P0.001). There was no significant difference in iodine density values (median: 1.7 mg/ml versus 1 mg/ml, P = 0.09). However, the fat fraction value was significantly lower in the abnormal thymus (score 4) than in the predominantly soft-tissue attenuation thymuses (score 3) (median: 12.8% versus 38.7%, P0.001). ROC curve analysis showed that fat fraction had an AUC of 0.96 (P0.001), with a cutoff of39.2% fat fraction yielding 100% sensitivity and 85% specificity.DECT fat fraction measurements of the thymus may provide additional value in distinguishing anterior mediastinal lesions from benign thymus. Use of DECT may reduce the need for subsequent imaging evaluation.

Introduction: True thymic hyperplasia following chemotherapy has been described mostly in children. There are a few cases of thymus hyperplasia that have been reported in breast cancer patients. Diagnosis of this unusual entity is very crucial to pretend unnecessary surgery or interventional diagnostic procedures. Case Presentation: We report a case of thymus hyperplasia in a patient who was operated and treated with adjuvant chemotherapy for stage 2 breast cancer two years ago. In the follow-up CT scans, an anterior mediastinal mass was noted. Radiologic evaluation and follow-up revealed thymus enlargement. Discussion: Thymic hyperplasia following chemotherapy has been described in both children and adults, but occurs mostly in children and adolescents treated for lymphoma and several other types of tumors. Few cases are reported in literature describing thymus hyperplasia following chemotherapy in a breast cancer patient. The imaging findings of thymic hyperplasia on CT, MRI and PET CT are discussed. Conclusion: Radiologists must be aware of this unusual finding in breast cancer patients treated with chemotherapy to guide the clinicians appropriately in order to avoid unnecessary surgical intervention, additional invasive diagnostic procedures, or chemotherapy.

Background Chemotherapy can cause thymic atrophy and reduce T-cell output in cancer patients. However, the thymus in young adult patients has regenerative potential after chemotherapy, manifesting as thymic hyperplasia which can be easily mistaken as residual disease or recurrence in patients suffering lymphoma. Case presentation This study reports a case of lymphoma in a young female adult who was initially diagnosed with an anterior mediastinal mass, and was found to have soft tissue occupying the anterior mediastinum repeatedly after chemotherapy, suggesting a lymphoma residue or disease progression. From discussions by a multi-disciplinary team (MDT), the anterior mediastinal mass of the patient was considered unknown and might be thymus tissue or tumor tissue, and it was eventually identified as thymus tissue via histopathology. Conclusions The anterior mediastinal mass appearing after chemotherapy in patients with lymphoma can be considered as enlarged thymus, and such phenomenon is frequent in young adult patients who undergo chemotherapy or autologous hematopoietic stem cell transplantation. Additionally, detection of thymic output cells in peripheral blood might be a feasible approach to differentiate thymic hyperplasia from lymphoma.

Background Hyperthyroidism-induced hypercalcemia has been reported previously, but hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement in patients with hyperthyroidism is quite rare. We report the coexistence of hypercalcemia, osteoporosis and thymic enlargement in a patient with Graves’ disease. Case presentation A 22-year-old female was diagnosed as Graves’ disease with obviously elevated serum calcium and reduced parathyroid hormone levels. Dual-energy x-ray absorptiometry and chest enhanced computer tomography (CT) revealed severe osteoporosis and a significant enlargement of thymus. After the successful control of hyperthyroidism with methimazole, hypercalcemia was corrected, bone mineral density was improved and thymus also shrank obviously. Conclusion This is a very rare case of hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement induced by Graves’ disease. In clinical practice, examination of thymus and bone density should be considered when a patient with Graves’ disease was present with hypercalcemia.

Objectives: To evaluate the effectiveness of CT texture analysis (CTTA) in (1) differentiating Thymoma (THY) from thymic hyperplasia (TH) (2) low from high WHO grade, and (3) low from high Masaoka Koga (MK)/International Thymic Malignancy Interest Group (ITMIG) stages. Methods: After institute ethical clearance, this cross-sectional study analyzed 26 patients (THY-18, TH-8) who underwent dual energy CT (DECT) and surgery between January 2016 and December 2018. CTTA was performed using TexRad (Feedback Medical Ltd., Cambridge, UK- www.fbkmed.com ) by a single observer. Free hand regions of interest (ROIs) were placed over axial sections where there was maximum enhancement and homogeneity. Filtration histogram was used to generate six first-order texture parameters [mean, standard deviation (SD), mean of positive pixels (MPP), entropy, skewness, and kurtosis] at six spatial scaling factors “SSF 0, 2, 3, 4, 5, and 6”. Mann–Whitney test was applied among various categories and p value < 0.05 was considered significant. Three-step feature selection was performed to determine the best parameters among each category. Results: The best performing parameters were (1) THY vs TH- Mean at “SSF 0” (AUC: 0.8889) and MPP at “SSF 0” (AUC: 0.8889), (2) Low vs high WHO grade - no parameter showed statistical significance with good AUC, and (3) Low vs high MK/ITMIG stage- SD at “SSF 6” (AUC: 0.8052 and 0.8333 respectively]). Conclusion: CTTA revealed several parameters with excellent diagnostic performance in differentiating thymoma from thymic hyperplasia and MK/ITMIG high vs low stages. CTTA could potentially serve as a non-invasive tool for this stratification. Advances in knowledge: This study has employed texture analysis, a novel radiomics method on DECT scans to determine the best performing parameter and their corresponding cut-off values to differentiate among the above-mentioned categories. These new parameters may help add another layer of confidence to non-invasively stratify and prognosticate patients accurately which was only previously possible with a biopsy.

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved. Patients diagnosed with pure red cell aplasia should be investigated with a computerized tomographic scan to assess for thymic pathology and if present, this should be resected. Follow-up is essential to monitor for recurrence.

Introduction: Thymic regrowth after chemotherapy treatment has been reported in children with lymphoma, and in order to avoid misdiagnosing these cases as relapses, physicians should become familiar with rebound (reactive) thymic hyperplasia (RTH) and remain aware of its possible occurrence. We aimed to estimate the prevalence of RTH in children with lymphoma after completion of chemotherapy and to evaluate the clinical characteristics, outcomes, and the findings of computed tomography (CT) and gallium-67 (GA-67) scans in these patients. Patients and methods: We conducted a retrospective cross-sectional study by reviewing the health records of children with a lymphoma diagnosis managed at an outpatient paediatric oncology clinic in Jeddah, Saudi Arabia. Results: Rebound thymic hyperplasia was detected in 51.9% of the lymphoma patients (14/27). It developed a median of 2.5 months after completion of chemotherapy (range, 2.0–4.25 months). Patients with RTH had significantly shorter treatment durations, and we found no significant differences between patients with and without RTH in sex, age at diagnosis, type of lymphoma or type of treatment received. All patients with RTH were asymptomatic, and routine laboratory tests did not detect any abnormalities in them. The findings of CT and GA-67 scans were highly suggestive of RTH. None of the patients with RTH had a recurrence, and RTH resolved spontaneously within a median of 6 months (range, 4.0–11.0 months). Conclusion: RTH was detected in ∼50% of children with lymphoma after completion of chemotherapy. A clinical evaluation and laboratory tests combined with imaging by CT and GA-67 can help identify RTH and rule out other lesions elsewhere. Resumen: Introducción: Se ha descrito la regeneración del timo tras la quimioterapia en niños con linfoma y, para evitar diagnosticar incorrectamente estos casos como recurrencias, los facultativos han de familiarizarse con la hiperplasia tímica de rebote (HTR) y tener en consideración su posible ocurrencia. Nuestro objetivo fue estimar la prevalencia de HTR en niños con linfoma tras la quimioterapia y evaluar las características clínicas, evolución y hallazgos de las pruebas de imagen mediante tomografía computarizada (TC) y la gammagrafía con galio 67 (GA-67). Pacientes y métodos: Estudio retrospectivo transversal, mediante la revisión de las historias clínicas de niños diagnosticados de linfoma, realizado en la Clínica Ambulatoria de Oncología Infantil del Centro de Oncología de Yeda, Arabia Saudita. Resultados: Se detectó HTR en el 51,9% de los pacientes con linfoma (14/27 pacientes). La HTR ocurrió una mediana de 2,5 meses tras finalizarse el tratamiento (rango: 2,0-4,25 meses). Los pacientes con HTR recibieron tratamientos significativamente más cortos, y no se observaron diferencias entre pacientes con y sin HTR en cuanto al sexo, la edad al diagnóstico, el tipo de linfoma o el tipo de tratamiento recibido. Todos los pacientes con HTR se encontraban asintomáticos y las pruebas rutinarias de laboratorio no evidenciaron alteraciones. La TC y la GA-67 fueron altamente sugestivas de HTR. Ninguno de los pacientes con HTR tuvieron recurrencias y la HTR se resolvió espontáneamente en una mediana de 6 meses (rango: 4,0-11,0 meses). Conclusión: Se detectó HTR en alrededor del 50% de los niños con linfoma tras completarse el tratamiento. La evaluación clínica, pruebas de laboratorio, TC y gammagrafía con GA-67 resultan útiles para identificar la HTR y descartar otras lesiones en otras localizaciones.

Management of myasthenia gravis (MG) in the presence of comorbidities may be difficult. We report the effect of comorbidities in the outcome of MG. The patients with MG during 1991–2016 were included and evaluated including their demographic variables, clinical findings, Myasthenia Gravis Foundation of America (MGFA) score. The patients were categorized into early onset (≤ 40 years) and late onset (> 40 years) MG. The comorbidities (autoimmune and miscellaneous) and iatrogenic complications were compared between early and late onset, and in good and poor outcome groups. Out of 81 patients with MG, 48 patients had early and 33 late onset. In 71 (88%) patients, comorbidities were present and were autoimmune in 8 (10%) and miscellaneous in all the patients (88%). Iatrogenic complications were present in 54 (67%) patients. Thymectomy was done in 19 patients; 16 had thymoma and 3 thymic hyperplasia. Myasthenic crisis occurred in 28 patients; 5 (18%) had autoimmune and all had miscellaneous comorbidities. The patients with poor outcome had ≥ 2 comorbidities, myasthenic crisis, leukocytosis, elevated serum bilirubin and creatinine, and increased number of hospital admissions (P

Background Malignant ovarian germ cell tumours typically require multimodal therapy including surgery and systemic platinum-based chemotherapy. Most patients are cured, with survival rates exceeding 95%. Case This report describes an unusual case of ovarian germ cell tumour (GCT) recurring 15 years after surgery and manifesting as metastatic disease to the liver, lung, and retroperitoneal lymph nodes. Conclusion Thymic hyperplasia was a confounding finding in this case, and it should be considered in the differential diagnosis of a mediastinal mass in heavily treated patients with GCT.

Background Patients with COVID-19 (COVID) may develop acute respiratory distress syndrome with or without sepsis, coagulopathy and visceral damage. While chest CT scans are routinely performed in the initial assessment of patients with severe pulmonary forms, thymus involvement and reactivation have not been investigated so far. Methods In this observational study, we systematically scored the enlargement of the thymus and the lung involvement, using CT scans, in all adult patients admitted to the ICU for COVID or any other cause (control group) at one centre between March and April 2020. Initial biological investigations included nasal detection of SARS-CoV-2 ribonucleic acid by polymerase chain reaction (PCR). In a subgroup of 24 patients with different degrees of pulmonary involvement and thymus hypertrophy, plasma cytokine concentrations were measured and the export of mature T cells from the thymus was estimated simultaneously by PCR quantification of T cell receptor excision circles (TRECs). Results Eighty-seven patients were studied: 50 COVID patients and 37 controls. Non-atrophic or enlarged thymus was more commonly observed in COVID patients than in controls (66% vs. 24%, p p = 0.01), but a lower mortality rate (8.6% vs. 41.2%, p p = 0.04) and higher thymic production of new lymphocytes (sj/βTREC ratio = 2.88 [1.98–4.51] vs. 0.23 [0.15–0.60]; p = 0.004). Thymic production was also correlated with the CT scan thymic score (r = 0.38, p = 0.03) and inversely correlated with the number of lymphocytes (r = 0.56, p = 0.007). Conclusion In COVID patients, thymus enlargement was frequent and associated with increased T lymphocyte production, which appears to be a beneficial adaptation to virus-induced lymphopaenia. The lack of thymic activity/reactivation in older SARS-CoV-2 infected patients could contribute to a worse prognosis.

Background Idiopathic multicentric Castleman disease (iMCD) is an uncommon lymphoproliferative disorder and lacks treatment consensus. Herein, we report a case of iMCD complicated with Sjögren’s syndrome (SS) and secondary membranous nephropathy (SMN). Case presentation A 45-year-old female with dry mouth for 3 months and anasarca and proteinuria for 2 months was admitted. She also experienced chest tightness, wheezing, fever, weight loss, moderate proteinuria and hypoalbuminemia. A computed tomography (CT) scan revealed a tissue mass in the thymus area and enlarged multiple lymph nodes. Her symptoms did not improve after resection of the thymus mass. The pathological findings were “reactive hyperplasia of the mediastinal lymph nodes and thymic hyperplasia”. Lymph node biopsy findings confirmed iMCD with human herpes virus-8 (HHV-8) negativity. Based on anti-nuclear antibody (ANA) 1:320, anti-SSA and anti-SSB antibody positivity, salivary flow less than 0.1 ml/min and lip biopsy with focal lymphocytic sialadenitis, SS was diagnosed. Kidney biopsy showed secondary membranous nephropathy with endocapillary cell proliferation and infiltration of plasma cells and lymphocytes in the tubulointerstitium. Serum interleukin-6 (IL-6) levels were significantly increased, and therapy with tocilizumab (anti-IL-6 receptor antibody) worked well. The combination of cyclophosphamide (CyS) with methylprednisolone (MP) maintained satisfactory remission. Conclusions Our case of iMCD with SS and SMN is rare. There is a need for increased awareness of the disease to avoid unnecessary procedures and misdiagnoses. IL-6 was extremely high, and there was a rapid response to anti-IL-6 receptor agents. The combination of CyS with MP maintained complete remission.

Thymic hyperplasia presents as an anterior mediastinal mass and poses important diagnostic and therapeutic challenge. Two types of thymic hyperplasia are described: true hyperplasia and follicular hyperplasie. Literature data are peculiar concerning both entities. We aimed to describe the clinical and microscopic characteristics of thymic hyperplasia through a single institution experience during an 11-year-period.Thymic hyperplasia diagnosed during the period between 2009 and 2020 were included.In all, 46 thymic hyperplasias were diagnosed. The 46 patients consisted in 33 women and 13 men with a mean age of 30 years. Microscopic diagnosis concluded to a follicular hyperplasia in 12 cases and a true thymic hyperplasia in 34 cases. The diagnosis of true thymic hyperplasia posed a diagnostic challenge with an involuted thymus in 1 case and a thymolipoma in 1 case. The confrontation with the clinical data allowed retaining the diagnosis.The diagnosis of thymic hyperplasia is based on microscopic features. The confrontation with clinical data and the measurements of the thymus according to the age allow to retain the diagnosis in most challenging cases.

To clarify the efficacy of thymectomy among myasthenia gravis (MG) patients with and without thymoma. We classified MG patients who underwent thymectomy into 3 groups, such as thymic atrophy group, thymic follicular hyperplasia (TFH) group and thymoma group. We compared the data of clinical features and postoperative prognosis at very short-term, short-term, and medium-term. The clinical course of MG patients with atrophic thymus after thymectomy was even better than those of TFH or thymoma, in this retrospective study. However, we found no significant differences in the comparison of mean dose of prednisolone between the 3 groups at each time point.

The checkpoint protein programmed cell death ligand-1 protein (PD-L1) binds to its receptor (PD-1) activating the PD-L1/PD-1 pathway, an important therapeutic target. There is limited information regarding PD-L1 and PD-1 expression in thymic lesions. Sections from nonneoplastic thymi (n = 20), thymomas World Health Organization types A, AB, B1, B2, and B3 (n = 38) and thymic squamous cell carcinoma (n = 8) were stained for PD-L1 (clone SP142; Spring BioScience), PD-1 (MRQ22; Cell Marque), CD4 (clone SPO32; Cell Marque), and CD8 (JCB117; Ventana). Immunoreactivity for each antibody was classified as focal or diffuse and scored as follows: 0, negative; 1%-5%, 1+; 6%-20%, 2+; and >20%, 3+. The proportions of cases expressing PD-L1, PD-1, CD4, and C8 at score ≥1+ were compared by diagnosis, using χ2 statistics. PD-L1 was expressed in 90% of nonneoplastic thymi, 92% of thymomas, and 50% of carcinomas, with significantly higher scores (P < .01) in B2 and B3 thymomas and carcinomas than in AB and B1 thymomas; PD-L1 was diffuse in most B2 and B3 thymomas and focal in carcinomas. PD-1 was focally expressed, and mostly with scores 1+, in 55% of nonneoplastic thymi, 63% of thymomas, and 37.5% of carcinomas. CD4+ and CD8+ cells were diffusely distributed with scores 3+ in all lesions other than B3 thymomas and carcinomas. The latter showed CD4+ cells mostly at the interface between neoplastic cells and stroma. PD-L1 and PD-1 are not expressed in similar locations and cellular proportions in thymic lesions, raising a question as to whether the PD-L1/PD-1 pathway is an actionable therapeutic target in these lesions.

Myasthenia Gravis is an autoantibody-mediated, neuromuscular junction disease, and is usually associated with thymic abnormalities presented as thymic tumors (~10%) or hyperplastic thymus (~65%). The exact role of thymus in Myasthenia Gravis development is not clear, yet many patients benefit from thymectomy. The apoptotic ligand TNF-Related Apoptosis-Inducing Ligand is thought to be involved in the regulation of thymocyte counts, although conflicting results are reported. We investigated differential expression profiles of TNF-Related Apoptosis-Inducing Ligand and its transmembrane receptors, Nuclear Factor-kB activation status, and apoptotic cell counts in healthy thymic tissue and pathological thymus from Myasthenia Gravis patients. All tissues expressed TNF-Related Apoptosis-Inducing Ligand and its receptors, with hyperplastic tissue having the highest expression levels of death receptors DR4 and DR5. No detectable Nuclear Factor-kB activation, at least via the canonical Protein Kinase A-mediated p65 Ser276 phosphorylation, was evident in any of the tissues studied. Apoptotic cell counts were higher in MG-associated tissue compared to the normal thymus. Possible use of the TNF-Related Apoptosis-Inducing Ligand within the concept of an apoptotic ligand-mediated medical thymectomy in thymoma- or thymic hyperplasia-associated Myasthenia Gravis is also discussed.

A 23-year-old woman was referred to our center with hirsutism, acne, weight gain, weakness, and irregular menses. Laboratory tests revealed increased levels of cortisol and sex hormones, and reduced adrenocorticotropic hormone levels. The patient underwent a right adrenalectomy. Pathology of the resected right adrenal gland showed an adrenal carcinoma. Computed tomography 8 months after the surgery revealed a thymic mass that was not detected preoperatively. The frequency of rebound thymic hyperplasia after normalization of hypercortisolism is not known, but possibly as high as 40%. Physicians must be aware of this phenomenon to avoid unnecessary thoracic surgery.

Introduction: Some myasthenia gravis (MG) patients are refractory to conventional treatments. Methods: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. Results: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). Discussion: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019. info:eu-repo/semantics/publishedVersion

OBJECTIVES The purposes of this study were to assess the feasibility of fetal thymus measurement between 13 and 16 weeks' gestation, to evaluate the potential difference using color Doppler sonography with the thy-box technique, and to construct normal percentile ranges. METHODS This retrospective study included 287 healthy singleton pregnancies. The fetal thymus was shown in an axial plane of the upper mediastinum. Color Doppler imaging was applied to outline the thy-box: ie, the area between the brachiocephalic artery posteriorly and internal mammary arteries laterally. Measurements of the lateral and anteroposterior diameters of the thymus with and without color Doppler imaging were compared. RESULTS The thymus was shown in 95% of the cases (273 of 287) between 13 and 16 weeks' gestation. The mean lateral thymus diameter ± SD with color Doppler imaging (5.30 ± 0.7 mm) was significantly longer in comparison to the measurement without color Doppler imaging (5.06 ± 0.8 mm; P < .001), whereas the anteroposterior diameter was significantly shorter (3.19 ± 0.9 versus 3.26 ± 0.8 mm; P = .044). Normal percentiles of thymus measurements for gestational age were constructed. CONCLUSIONS The fetal thymus can be clearly and accurately shown as early as 13 weeks' gestation by using the thy-box. Measurements with color Doppler imaging were significantly different from those without and hence are preferable, as color Doppler imaging can delineate the thymus borders more accurately.

A tri-modal distribution of age-at-onset emerged among females patients with myasthenia gravis (MG) in our database. This finding may be indicative of different gender-based disease mechanisms.We retrospectively reviewed the files of 127 MG patients for the clinical, serology and thymus pathology according to their age at disease onset: ≤40 years (early-onset, EOMG), 40-70 years (intermediate-onset, IOMG) and70 years (late-onset, LOMG).EOMG was more common among females, and IOMG was more common among males. Ocular MG was more common among the male MG patients with an IOMG. Patients with EOMG had lower rates of positive anti-acetylcholine receptor (anti-AChR). IOMG females, but not IOMG males, had lower rates of positive anti-AChR. IOMG and EOMG females had high rates of thymic hyperplasia, while EOMG males had high rates of thymoma. Comorbidity with autoimmune diseases was common among females with IOMG and LOMG.The prevalence of IOMG was the reason for the trend reversal of MG prevalence between genders. The clinical features of patients with IOMG differed between genders in the rates of positive anti-AChR, follicular hyperplasia of the thymus and comorbidity with autoimmune diseases. This may suggest a different gender-based mechanism of immune intolerance towards AChR and other antigens.

Thyrotoxicosis and orbitopathy are the best-known expressions of Graves' disease. There are also rarer and less-known phenomena, such as thymic hyperplasia. Identification of these is important in order to avoid potentially unnecessary invasive interventions.In the case of two young women with lung embolisms, CT pulmonary angiography also revealed an enlarged thymus. This turned out to be caused by as of yet unknown Graves' disease. Since pathological examination of a thymus-biopsy sample was unable to rule out thymoma, thymectomy was performed on the first patient. Pathological examination of the entire thymus revealed hyperplasia. Additional FDG-PET/CT scan of the second patient revealed diffuse hyperactivity in the diffusely enlarged thymus. In this case, we opted for expectant treatment. A follow-up FDG-PET/CT scan 1 year later, revealed a non-abnormal thymus.An enlarged thymus caused by thymic hyperplasia is a less well-known manifestation of Graves' disease. In case additional abnormalities develop in patients with Graves' disease, it is important to consider that these might be related to the disease before diagnosing an additional new condition.

Rationale: Myasthenia gravis (MG) is the most common cause of acquired neuromuscular junction disorder. Thymectomy has been established as an effective therapy for MG, as it attenuates the natural course of the disease and may result in complete remission. Patient concerns: We report the case of a 22-year-old female with a 6-year history of MG presented with bilateral ptosis, diplopia, and intermittent dysphagia. She denied shortness of breath, dysarthria, and fatigue. Diagnoses: She had been diagnosed with MG 6 years previously at the Neurology Department of our hospital. A computed tomography (CT) scan revealed thymic hyperplasia Interventions: She was treated with modified unilateral VATET that minimized incision size. Outcomes: Unilateral VATET was performed using two 5-mm incisions to minimize pressure on intercostal soft tissues/nerves and reduce postoperative pain. Lessons: The lesson learnt from this case report is that this modified VATET method could be a useful approach to the management of non-thymomatous MG. The ability to achieve complete dissection with good cosmetic results may lead to wider acceptance of this technique by patients with MG and their neurologists for earlier thymectomy and improved outcomes. Additional studies are needed to determine the superiority of this approach to established methods.

Rationale: The development of rebound thymic hyperplasia (RTH) has been reported in patients who have recovered from stressful conditions such as surgery and steroid therapy. We report a case of RTH following the resolution of hypercortisolism after adrenalectomy for the treatment of adrenocortical adenoma in a patient with Cushing syndrome. Patient concerns: A 5-month-old female infant with a history of overeating, hirsutism, and excessive weight gain for the previous 2 months was referred to the hospital. The laboratory results revealed elevated 24-hour urinary free cortisol levels. An overnight dexamethasone suppression test showed no response. Abdominal imaging revealed a right-sided suprarenal mass measuring 4_3cm. Histology showed an adrenocortical adenoma. Thus, she underwent a right adrenalectomy. Diagnoses: The patient showed clinical improvement with weight loss and normal cortisol levels over the next 4 months. Six months after the operation, a chest computed tomography showed enlargement of the left thymic lobe, which was previously nonexistent. Interventions: A fine needle aspiration biopsy was performed, and histological examination revealed diffuse thymic hyperplasia. Outcomes: At the 1-year follow-up, the chest imaging studies showed resolution of the RTH. Lessions: An understanding of RTH after adrenalectomy as a treatment for cortisol-producing adrenocortical tumors is important for the prevention of unnecessary surgical intervention and therapy.

The familial occurrence of thymic pathology, even though rare, is widely reported in the literature and mainly concerns cases of familial autoimmune myasthenia gravis. Other less frequent cases of familial occurrence of thymoma, thymic carcinoid and thymic hyperplasia have been described. It seems that the familial occurrence is poorly recorded and thus its prevalence is underestimated. We report two families whose members presented different forms of thymic pathology and discuss the necessity of screening programs in family members of patients presenting a thymic lesion.

Background Myasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10–20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer. Methods We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C > T, MTR c.2756A > G, MTRR c.66A > G and TYMS TSER (a 28-bp tandem repeat in the 5′ promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR + MG patients. A total of 526 AChR + MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing. Results The frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia (P = 0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34–5.47)]. Conclusions The 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR + MG patients.

To investigate the association between myasthenia gravis (MG) and human parvovirus B19 (B19V) infection in the thymus.The presence of human B19V DNA and protein was assessed in 138 samples-including 68 thymic hyperplasias (39 with MG), 58 thymomas (23 with MG), and 12 normal thymus tissues-using a nested polymerase chain reaction, immunohistochemistry, laser capture microdissection, and sequencing in a double-blinded manner.B19V DNA was detected mainly in thymic hyperplasia, and the positivity rate (41.18%, 28/68) was significantly higher than that in thymoma (3.45%, 2/58) (p0.001) but not that in normal thymic tissues. Correspondingly, the positivity rate in thymic hyperplasia with MG (30.77%, 12/39) was significantly higher than that in thymoma with MG (4.35%, 1/23) (p=0.021). However, it was higher in thymic hyperplasia without MG (55.17%, 16/29) than in thymic hyperplasia with MG (30.77%, 12/39) (p=0.043). Cells in thymic hyperplasia positive for B19V VP1/VP2 protein (63.24%, 43/68) were identified mainly in ectopic germinal centres and thymic corpuscle epithelial cells, but were rare in thymomas (1.72%, 1/58) (p0.001). Moreover, the positivity rate was significantly higher in thymic hyperplasia with MG (74.36%, 29/39) than in thymic hyperplasia without MG (48.28%, 14/29) (p=0.027).To our knowledge, the present study is the first to show that human B19V infection is closely associated with thymic hyperplasia and thymic-hyperplasia-associated MG, but is not related to thymoma or thymoma-associated MG. The findings reveal a previously unrecognized aetiopathogenic mechanism of thymic-hyperplasia-associated MG, evoking numerous questions that require further investigation.

Seronegativemyastheniagravis(MG) presents a serious gap in MG diagnosis and understanding. We applied acellbasedassay(CBA) for the detection of muscle specific kinase (MuSK) antibodies undetectable by radioimmunoassay. We tested 633 triple-seronegative MG patients' sera from 13 countries, detecting 13% as positive.MuSKantibodies were found, at significantly lower frequencies, in 1.9% of healthy controls and 5.1% of other neuroimmune disease patients, including multiple sclerosis and neuromyelitis optica. The clinical data of the newly diagnosedMuSK-MG patients are presented. 27% of ocular seronegative patients wereMuSKantibody positive. Moreover, 23% had thymic hyperplasia suggesting that thymic abnormalities are more common than believed.

Thymic involvement by Langerhans cell histiocytosis (LCH) has been described mainly in isolated case reports. A description of the histopathologic patterns of LCH proliferations in the thymus, together with therapeutic implications, has not, to our knowledge, been previously addressed. The pathology consultation files at Children's Hospital of Pittsburgh of the University of Pennsylvania Medical Center were reviewed for cases of thymic involvement by LCH. Relevant cases in the literature were also reviewed, and the histopathology and clinical course of those cases were collected. Nine consultation cases of thymic involvement were reviewed, together with 23 cases in the literature, which provided adequate pathologic description and ancillary confirmation (n = 32), revealing 4 distinct pathologic groups. Group 1 showed microscopic collection of hyperplastic LCH-like cells in incidental thymectomies of patients without LCH disease, requiring no further treatment (n = 7; 22%). Group 2 showed solitary and/or cystic LCH of the thymus with gland disruption, and at least 3 cases resolved without systemic therapy (n = 10; 31%). Group 3 showed more variable thymic involvement in multisystemic LCH disease, with either a medullary restricted pattern or more diffuse gland involvement, requiring adjuvant therapy and having a higher mortality rate (n = 13; 41%). Group 4 showed a mixed histiocytic lesion with a concurrent LCH and juvenile xanthogranuloma-like proliferation (n = 2; 6%). Thymic involvement in LCH is quite rare. Based on our cases and those in the literature, we propose 4 distinct pathologic groups of thymic involvement in Langerhans cell proliferations with relevance for diagnosis and treatment.

Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It is characterized by the presence of noncaseating granulomas and an inflammatory process in which T lymphocytes, especially type-1 helper T (Th1) cells, macrophages and different cytokines are involved. Different studies have shown the importance of genetic background in addition to environmental exposure in explaining different clinical phenotypes and disease outcome. In addition, potential auto antigens that might lead to the disease have been identified.Here, we present a 53-year-old female patient presenting with subcutaneous nodules and mediastinal hilar lymphadenopathies refractory for corticosteroid treatment. Computed tomography of the thorax revealed a soft-tissue lesion in the thymus location.The lesions due to sarcoidosis resolved after thymectomy.The remission of skin and pulmonary sarcoidosis only after thymectomy does potentially indicate the critical role that the thymus might play in the pathogenesis of this disease in a certain group of patients.

It has long been established that the thymus plays a central role in autoimmune myasthenia gravis (MG) because of either thymoma or thymic hyperplasia of lymphoproliferative origin. In this review, we discuss thymic changes associated with thymic hyperplasia and their implications in the development of an autoimmune response against the acetylcholine receptor (AChR).The hyperplastic MG thymus displays all the characteristics of tertiary lymphoid organs (TLOs): neoangiogenic processes with high endothelial venule and lymphatic vessel development, chemokine overexpression favoring peripheral cell recruitment, and ectopic germinal center development. As thymic epithelial cells or myoid cells express AChR, a specific antigen presentation can easily occur within the thymus in the presence of recruited peripheral cells, such as B cells and T follicular helper cells. How the thymus turns into a TLO is not known, but local inflammation seems mandatory. Interferon (IFN)-β is overexpressed in MG thymus and could orchestrate thymic changes associated with MG. Knowledge about how IFN-β is induced in MG thymus and why its expression is sustained even long after disease onset would be of interest in the future to better understand the etiological and physiopathological mechanisms involved in autoimmune MG.

Myasthenia gravis (MG) is a B cell-mediated and T cell-dependent autoimmune disease. Thymic hyperplasia has great significance for MG pathogenesis and treatment. MicroRNAs (miRNAs) are a newly recognized type of gene expression regulatory factor that regulate gene expression at the post-transcriptional level. Additionally, miRNAs are involved in immune regulation of the thymus and the occurrence and development of autoimmune diseases. In this study, we found 33 miRNAs that were significantly dysregulated in thymic tissues from MG patients with thymus hyperplasia (MGH) compared with thymic tissues from normal controls using a miRNA microarray chip. We found a negative correlation between the miR-548k and CXCL13 mRNA levels in a large set of samples using quantitative real-time polymerase chain reaction (qRT-PCR). We found that the CXCL13 3'-untranslated region (UTR) was a target of miR-548k using bioinformatics analysis. Next, we obtained direct evidence that CXCL13 is a target of miR-548k using a luciferase reporter assay. Finally, we demonstrated negative regulation between mir-548k and CXCL13 in Jurkat cells. Thus, miR-548k regulates the mRNA expression of its target gene CXCL13 in the thymus of MGH patients and plays an important role in MGH pathogenesis.

The aim of this study was to investigate the influence of long-term building construction noise from refurbishment, which including vibration, on some physiological parameters and histopathological changes of organs of Wistar rats. Twenty 12 month old female rats were divided into two groups: rats group I (n = 10) were exposed to long-term construction noise and rats group II (n = 10) were kept under normal noise level. Study results revealed that long-term construction noise from building refurbishment has an influence on body weight, haematological and some serum biochemical parameters affects caecal microbiota, and causes histopathological changes in the organs of adult female Wistar rats. It was noticed that rats in group I exihibited significantly higher mean values for total protein, albumin and lower values for glucose, AST, ALT, blood urea nitrogen, haematological and caecal microbiota parameters than rats in group II. The most common pathologies were determined in the kidney, liver and lungs. Other observed pathologies were lymphadenopathy, catarrhal inflammation of the intestines, spleen hyperplasia and mammary gland adenofibroma. Single cases were subcutaneous fibroma in the thoracic region, abortus with uterine inflammation and thymus hyperplasia with formation of cysts were found.

Reactive and neoplastic thymic pathologies are the main considerations in the case of masses in the anterior and middle part of the mediastinum, while neurogenic tumors are predominant in the posterior mediastinum (which are not dealt with here). In neonates and infants, the commonest pathologies in the anterior mediastinum comprise germ cell tumors (mainly teratomas), congenital thymic cysts and true thymic hyperplasia (TTH). In toddlers, teratomas, yolk sac tumors and cysts predominate. In children over 5 years of age, lymphomas are the commonest mass lesions whereas thymomas and thymic carcinomas are rare. In addition, inflammation-linked hyperplasia in myasthenia gravis and rebound thymic hyperplasia after chemotherapy must be considered. Although rare at all ages, sarcomas must be considered in the differential diagnosis from birth onwards and throughout adolescence. Based on the report of a rare case of recurrent TTH, the differential diagnosis of this benign but potentially life-threatening condition is discussed.

Background Clinical predictors for myasthenia gravis relapse and ocular myasthenia gravis secondary generalization during the first two years after disease onset remain incompletely identified. This study attempts to investigate the clinical predictors for the prognosis of Myasthenia Gravis. Methods Eighty three patients with myasthenia gravis were concluded in this study. Baseline characteristics were analyzed as predictors. Results Relapse of myasthenia gravis developed in 26 patients (34%). Generalization developed in 34 ocular myasthenia gravis patients (85%). Other autoimmune diseases were observed more commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients with thymus hyperplasia progressed more rapidly than those with other thymus pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as ptosis or diplopia predicted early progression than concurrence of ptosis and diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine, thymectomy, IVIG, immunosuppressive drugs did not show significant difference between the relapsed and non-relapsed groups. The treatment outcome also showed no difference between the single OMG and second generalized groups. Conclusions Occurrence of associated autoimmune disease can serve as a potential predictor for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic hyperplasia can predict generalization in the first six months.

This study describes specific patterns of elevated inflammatory proteins in clinical subtypes of myasthenia gravis (MG) patients. MG is a chronic, autoimmune neuromuscular disease with antibodies most commonly targeting the acetylcholine receptors (AChRab), which causes fluctuating skeletal muscle fatigue. MG pathophysiology includes a strong component of inflammation, and a large proportion of patients with early onset MG additionally present thymus hyperplasia. Due to the fluctuating nature and heterogeneity of the disease, there is a great need for objective biomarkers as well as novel potential inflammatory targets. We examined the sera of 45 MG patients (40 AChRab seropositive and 5 AChRab seronegative), investigating 92 proteins associated with inflammation. Eleven of the analysed proteins were significantly elevated compared to healthy controls, out of which the three most significant were: matrix metalloproteinase 10 (MMP-10; p = 0.0004), transforming growth factor alpha (TGF-α; p = 0.0017) and extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) (also known as protein S100-A12; p = 0.0054). Further, levels of MMP-10, C-X-C motif ligand 1 (CXCL1) and brain derived neurotrophic factor (BDNF) differed between early and late onset MG. These novel targets provide valuable additional insight into the systemic inflammatory response in MG.

Rebound thymic hyperplasia (RTH) with increased 18 F-FGD uptake at positron emission tomography (PET) computed tomography (CT) is typical of pediatric patients after chemotherapy, although it may occasionally occur in adults. At CT, RTH usually appears as a diffusely enlarged thymus with areas of fatty attenuation. We report two cases of RTH in adults detected at follow-up: both showed unusual morphology on CT and were confirmed at PET-CT as areas of strongly increased radiopharmaceutical uptake, which suggested disease recurrence. Chemical-shift magnetic resonance imaging, however, demonstrated fat infiltration within the tissue. Such finding was consistent with the diagnosis of RTH and was paramount in preventing unnecessary invasive procedures or treatments.

Graves’ disease (GD) is commonly associated with other autoimmune conditions, and there is also a rare but well documented association between GD and thymic hyperplasia (TH). It is hard to say the real frequency of this latter association because most cases remain asymptomatic and are consequently not thoroughly investigated. We reviewed the literature on GD-related thymus enlargement and found 107 cases published to date. Thymic cancer was only documented in four patients, while the majority of cases were diagnosed as TH. The causative mechanisms behind TH associated with GD have yet to be fully elucidated. Several studies support the hypothesis of a TSH receptor antibody (TRAb) mediating thymic enlargement. We report on a female GD patient with an incidentally discovered anterior mediastinal mass. Our case is not consistent with the hypothesis of a TRAb-mediated mechanism because the thymus reached its largest volume at the onset of GD and shrank during remission of GD under medical treatment, despite persistently positive TRAb levels. We support the hypothesis that two different pathogenic mechanisms might be responsible for thymus enlargement: thymic cortical tissue expansion seems to be due to a hyperthyroid state, while lymphoid hyperplasia appears to correlate with immune abnormalities underlying GD.

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR-MG) is considered as a prototypic autoimmune disease. The thymus is important in the pathophysiology of the disease since thymus hyperplasia is a characteristic of early-onset AChR-MG and patients often improve after thymectomy. We hypothesized that thymic B cell and antibody repertoires of AChR-MG patients differ intrinsically from those of control individuals. Using immortalization with Epstein Barr Virus and Toll-like receptor 9 activation, we isolated and characterized monoclonal B cell lines from 5 MG patients and 8 controls. Only 2 of 570 immortalized B cell clones from MG patients produced antibodies against the AChR (both clones were from the same patient), suggesting that AChR-specific B cells are not enriched in the thymus. Surprisingly, many B cell lines from both AChR-MG and control thymus samples displayed reactivity against striated muscle proteins. Striational antibodies were produced by 15% of B cell clones from AChR-MG versus 6% in control thymus. The IgV(H) gene sequence analysis showed remarkable similarities, concerning V-H family gene distribution, mutation frequency and CDR3 composition, between B cells of AChR-MG patients and controls. MG patients showed clear evidence of clonal B cell expansion in contrast to controls. In this latter aspect, MG resembles multiple sclerosis and clinically isolated syndrome, but differs from systemic lupus erythemitosus. Our results support an antigen driven immune response in the MG thymus, but the paucity of AChR-specific B cells, in combination with the observed polyclonal expansions suggest a more diverse immune response than expected. (C) 2013 Elsevier Ltd. All rights reserved.

Thymectomy is often performed on the basis of computed tomography scan findings that are suspicious for thymoma. However, the final diagnosis may be a condition such as thymic hyperplasia or lymphoma for which thymectomy is not therapeutic. The present analysis was undertaken to determine the prevalence of a "nontherapeutic" thymectomy.The Nationwide Inpatient Sample from 2000 through 2009 was queried to identify patients who underwent a thymectomy. Only adult patients who underwent a total thymectomy without other associated procedures were analyzed. Patients with a diagnosis of myasthenia were excluded. A nontherapeutic thymectomy was defined as a patient who underwent thymectomy with an International Classification of Diseases, Ninth Revision diagnosis code of lymphoma, thymic hyperplasia, thymic cyst, or other benign diseases of the thymus.A total of 1,306 patients were identified. Overall, 72.2% (n = 943) of thymectomies were therapeutic and 27.8% (n = 363) were nontherapeutic. The most common diagnosis in the nontherapeutic group was thymic hyperplasia (n = 174). Mortality (0.32% versus 0%; p = 0.083) and overall complication rates (25% versus 17%; p0.001) were higher in the therapeutic group. Patients in the nontherapeutic group were younger (median age, 41 versus 56 years; p0.001) and more likely to undergo a video-assisted thoracoscopic surgery thymectomy (28% versus 19%; p = 0.085).In this study, 27.8% of thymectomies were nontherapeutic, and most patients underwent an open approach. The most common benign diagnosis was thymic hyperplasia, a condition for which magnetic resonance imaging has a high predictive value. Consequently, further studies are warranted to determine the optimal evaluation of patients undergoing thymectomy for presumed thymoma.

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was if thymectomy in non-thymomatous myasthenia gravis was of any benefit? Overall, 137 papers were found using the reported search, of which 16 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The outcome variables were similar in all of the papers, including complete stable remission (CSR), pharmacological remission, age at presentation, gender, duration of symptoms, preoperative classification (Oosterhius, Osserman or myasthenia gravis Foundation of America (MGFA)), thymic pathology, preoperative medications (steroids, immunosuppressants), mortality and morbidity. We conclude that evidence-based reviews have shown that relative rates of thymectomy patients compared with non-thymectomy patients attaining outcome indicate that the former group of patients is more likely to achieve medication-free remission, become asymptomatic and clinically improve (54%, P < 0.01), particularly patients with severe and generalized symptoms (P = 0.007). Patients with generalized myasthenia gravis showed 11% stronger association with favourable outcomes after thymectomy. Some studies show early remission rates (RRs), as early as 6 months post-thymectomy, of 44%. Overall, the reported remission rate for non-thymomatous myasthenia gravis is between 38 and 72% up to 10 years of follow-up. Among these patients, those with thymic hyperplasia show the best complete stable remission rates (42%, P < 0.04) in the majority of studies. Age showed variability across the studies and the cut-off was also different among them. Overall age < 45 years showed a higher probability of achieving complete stable remission during follow-up (81% benefit rate (BR), P < 0.02). Pharmacological improvement is reported between 6 and 42%. However, the certainty of these benefits has not been established due to factors such as the confounding differences between myasthenia gravis patients receiving and not receiving thymectomy, the non-randomized nature of class II studies and the lack of Class I evidence to support its use. There is currently a randomized trial ongoing looking at thymectomy by sternotomy vs controls and the results are eagerly awaited.

Postmenopausal osteoporosis is associated with estrogen deficiency and rapid bone loss. The mechanism by which estrogen deficiency results in bone loss has not been fully explained. Studies in mice rendered acutely estrogen deficient by ovariectomy have suggested that estrogen deficiency results in an activated T-lymphocyte phenotype and increased production of pro-osteoclastic cytokines. The aim of this study was to translate these findings from mouse models that suggest that the T lymphocyte plays an important role in the etiology of postmenopausal osteoporosis. We recruited premenopausal women who underwent ovariectomy for benign gynecologic conditions or for prophylaxis against ovarian cancer and a group of matched control women without ovariectomy (OVX). Subjects provided blood samples to characterize T-lymphocyte phenotype by flow cytometry and for T-lymphocyte culture and collection of conditioned media. Bone mineral density at the lumbar spine and left femoral neck was performed annually for 2 years, and volumetric measurements by computed tomography (CT) of the thymus were obtained during the first 6 months. We enrolled 6 patients who underwent OVX and 13 control women. The OVX subjects had a significant loss of bone mineral density at the lumbar spine and left femoral neck. The volumetric thymus measurements suggested an increase in thymus size in the OVX subjects but did not reach statistical significance owing to the small sample size. The T-lymphocyte phenotype in the OVX subjects demonstrated increased T-lymphocyte activation by flow cytometry compared to the control subjects. Our findings support the hypothesis that estrogen deficiency leads to an activated T-lymphocyte phenotype, which may contribute to the bone loss seen in estrogen deficiency. Larger clinical studies are necessary to confirm these findings.

Background and purpose: The differences in the characteristics of thymus histology, coexisting autoimmune diseases and related autoantibodies between anti-muscle-specific receptor tyrosine kinase (MuSK)-antibody (Ab)-positive myasthenia gravis (MG) patients, and anti-acetylcholine receptor (AChR)-Ab-positive MG patients are not clearly defined. Methods: The types of thymus histology, coexisting autoimmune diseases and associated Abs in 83 MuSK-Ab-positive patients nationwide were investigated and were compared with those in AChR-Ab-positive patients followed at our institute (n = 83). As for the autoantibodies associated with thymoma, titin Abs were measured. Results: Thymoma was not present in any of the MuSK-Ab-positive patients but presented in 21 patients (25.3%) amongst the AChR-Ab-positive patients. Titin Abs were absent in MuSK-Ab-positive patients but positive in 25 (30.1%) of the AChR-Ab-positive patients. Concomitant autoimmune diseases were present in eight MuSK-Ab-positive patients (9.6%) amongst whom Hashimoto's thyroiditis and rheumatoid arthritis predominated, whereas 22 AChR-Ab-positive patients (26.5%) had one or more concomitant autoimmune diseases of which Graves' disease predominated. Conclusions: Differences in frequency of thymoma and thymic hyperplasia, coexisting autoimmune diseases and autoantibody positivity between MuSK-Ab-positive and AChR-Ab-positive MG were indicated, suggesting that, in contrast with AChR-Ab-positive MG, thymus does not seem to be involved in the pathogenic mechanisms of MuSK-Ab-positive MG., European Journal of Neurology, 20(9), pp.1272-1276; 2013

A 1-day-old female Holstein–Friesian calf was presented for severe dyspnea. Physical examination revealed respiratory distress, moderate edema of the ventral neck, and swollen jugular veins. The calf died and was submitted for necropsy. A severely enlarged thymus (40 cm × 20 cm × 10 cm) weighing 1.37 kg was detected on gross examination. Histomorphology was normal but no tingible body macrophages were observed in the medullary areas. Immunohistochemistry was characterized by the lack of thymic cluster of differentiation 3 and major histocompatibility complex class II expression compared to age-matched controls. The findings were consistent with severe thymic hyperplasia, a rare congenital condition that is also described in children. Immunohistochemical findings were suggestive of impaired T-cell development and selection associated with lack of apoptosis of thymic cells (lack of tingible body macrophages). Thymic hyperplasia in juvenile animals should be considered among the differential diagnoses of mediastinal masses as a rare cause of respiratory distress in newborn calves.

Differential expressions of immune molecules have been shown in the thymi with pathological results, including myasthenia gravis (MG). CD25 is an activation marker expressed on T cells. CXCL13 mediates the homing and motility of B cells in secondary lymphoid tissues. Herein, we investigated the expressions of CD25 and CXCL13 in the thymi of thymic hyperplasia patients with MG or with non-MG. A total of 34 thymic hyperplasia patients with MG (20 generalized MG (GMG) and 14 ocular MG (OMG) and six thymic hyperplasia patients without MG were enrolled and analyzed using immunohistochemical staining and real-time polymerase chain reaction for CD25 and CXCL13. Our study demonstrated a higher expression of both CD25 and CXCL13 in hyperplastic thymi with OMG or GMG compared to those with non-MG. According to the immunohistochemical results, we observed that CD25 expression was significantly lower in atrophic thymi and non-MG hyperplastic thymi, compared with that in infant thymi (P = 0.002 and 0.005, respectively). In contrast to CD25 expression, we did not observe differential expression of CXCL13 among three control groups. And a similar CD25 mRNA expression was found in real-time polymerase chain reaction (PCR) results. We observed that both hyperplastic thymi with OMG or GMG expressed significantly higher levels of CD25 than those with non-MG (P = 0.007 and 0.001, respectively). And an increase of CD25 expression was observed in hyperplastic thymi with GMG compared to those with OMG (P = 0.030). Similarly, CXCL13 expression was significantly higher in hyperplastic thymi with GMG or with OMG than those with non-MG (P = 0.001 and 0.050, respectively). No significant CXCL13 expression difference was found between hyperplastic thymi with GMG and those with OMG (P > 0.05). The real-time PCR results showed a similar tendency of CD25 mRNA expression among the thymi of non-MG, OMG, and GMG patients, but the difference did not reach significance (P > 0.05). An obvious increased expression of CXCL13 was found in hyperplastic thymi with GMG patients, compared to those with non-MG and OMG patients (P = 0.003 and 0.071, respectively). There was no difference found between hyperplastic thymi with non-MG and with OMG. Regression analysis showed a positive correlation between thymic CD25 level and MG symptom severity (F = 28.240; P = 0.000, r = 0.523). Similarly, a positive correlation was found between thymic CXCL13 expression and MG disease severity (F = 36.093; P = 0.000, r = 0.671). Taken together, our findings suggest CD25 and CXCL13 participate in the pathogenesis of MG and may influence the clinical symptoms of MG.

Thymectomy is routinely carried out in patients with myasthenia gravis (MG) and thymomas. However, there is still a dispute as to whether MG patients with thymic hyperplasia should undergo thymectomy. We aimed to investigate the pathological findings in the thymus in patients with co-existing MG and thymic hyperplasia or thymomas treated with thymectomy, as well as effects of immunosuppression. Thirty-three patients with MG were selected and grouped accordingly: patients with no thymic abnormalities, patients with thymic hyperplasia, and patients with thymomas. All patients were treated with methylprednisolone alongside immunosuppression. A separate cohort of 24 MG patients with thymic hyperplasia or thymomas and treated with thymectomy were selected. As controls, 5 patients with thymomas or thymic carcinoma without MG were selected. Expression of CD5, extracellular regulated protein kinases1/2 mitogen activated protein kinase (ERK1/2MAPKs) and CD95 ligand (FasL) in the thymus was examined. Methylprednisolone and immunosuppressive therapy are highly effective in MG patients with normal thymus tissue and MG patients with thymic hyperplasia compared to MG patients with thymomas alone. CD5 expression was highest in MG patients with thymic hyperplasia, correlating with expression of ERK1/2MAPKs. FasL expression was similar across all groups. Thymomas may be distinguished from thymic hyperplasia by expression of CD5 and ERK1/2MAPKs. Thymectomy is the preferred treatment for MG patients with thymomas but may not be necessary in MG patients with thymic hyperplasia who are treated with immunosuppressive therapy.

The role of β2-adrenergic receptor (β2-AR) in the relapse of myasthenia gravis (MG) associated with thymus abnormality has not been fully identified.Using polymerase chain reaction and gene sequencing method, we investigated the relationship of β2-AR gene polymorphisms with different thymus pathology in MG patients. The role of β2-AR gene polymorphisms in the relapse of MG was further investigated.Age of onset (p = 0.034), the onset symptom of ocular MG (OMG; p = 0.023), the first symptom of OMG second generalization (p = 0.040) were different in MG with thymoma from those in MG with normal thymus or thymus hyperplasia. Gene polymorphisms of β2-AR on positions 16 and 27 showed no significant difference between relapsed and non-relapsed MG patients with thymus abnormality (thymus hyperplasia: position 16, p = 0.792; position 27, p = 0.664; thymoma: position 16, p = 0.226; position 27, p = 0.615). However, genotypes distribution on position 27 among MG patients with three thymus histology was significantly different (χ² = 8.153, p = 0.041). Furthermore, glucocorticoid can decrease relapse of MG with thymus hyperplasia (p = 0.021).MG patients with thymus abnormality differ from MG patients with normal thymus in age of onset, the onset symptom of OMG and the first symptom of OMG second generalization. β2-AR gene polymorphisms had no relationship with the relapse of MG with thymus abnormality. Gene polymorphism of β2-AR on position 27 was associated with different thymus histology of MG. Glucocorticoid was able to reduce the risk of relapse of MG with thymus hyperplasia.

The reasons for the abrogation of self-immunological tolerance in patients with myasthenia gravis (MG) may be different between those with concomitant thymic hyperplasia or thymoma, and those with no evidence of thymic involvement. We conducted a retrospective observational case series study to investigate the epidemiology as well as the clinical, serologic, and electromyographic (EMG) characteristics of individuals diagnosed as having MG. We found that the average age at MG onset of patients with either thymic hyperplasia or thymoma was much younger (by ~20years) than that of MG patients without thymic involvement. Thymic hyperplasia was more common in females than males. There were no differences in the rates of ocular MG vs. generalized MG among those three study groups. There were also no group differences in the rates of neuromuscular junction disfunction, as observed on EMG or by the results of serology tests for acetyl choline receptor antibody. Interestingly, only patients without thymic involvement had other autoimmune diseases, and most of them were females. The patients with other coexisting autoimmune disease had a similar age at MG onset as the other patients with no thymic involvement. These results shed light on the impact of epidemiological and clinical factors that result from different mechanisms of self-immunological tolerance breakdown that occurs in MG.