Association between thymic hyperplasia and serum calcium level in Graves' disease.

BACKGROUND: Graves' disease increases bone resorption in hyperthyroidism, leading to elevated serum calcium levels and a negative bone balance. Thymic hyperplasia is observed in some Graves' disease patients. What's more, there have been a few reports of increased serum calcium and severe osteoporosis induced by Graves' disease with thymic hyperplasia. It remains unclear whether Graves' disease with thymic hyperplasia is associated with higher serum calcium levels. Our study aimed to investigate the possibility of elevated serum calcium levels and aggravated bone mobilization in Graves' disease patients with thymic hyperplasia. METHODS: Newly diagnosed and untreated patients with Graves' disease (n = 96) were enrolled. They were divided into two groups based on the incidental detection of thymic hyperplasia during imaging. Albumin, alkaline phosphatase, calcium, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, and thyrotrophin receptor antibody (TRAb) were measured, and a computerized tomography of the chest was obtained. RESULTS: Patients with Graves' disease who had thymic hyperplasia were notably younger (P=0.018) and exhibited higher serum calcium levels (P=0.001) compared to those with Graves' disease without thymic hyperplasia. In the multiple regression analysis, thymic hyperplasia, TRAb, and female gender were significant variables associated with elevated serum calcium levels in patients with Graves' disease, collectively accounting for 31.7% of the variation in serum calcium. CONCLUSIONS: Graves' disease patients with thymic hyperplasia showed higher serum calcium levels. thymic hyperplasia, TRAb, and female gender were found to be correlated with increased serum calcium levels in Graves' disease, suggesting a potential association between thymic hyperplasia and bone mobilization in Graves' disease.

Unusual onset of Graves' disease associated with thymic hyperplasia in a 5-year-old girl with congenital bilateral clinical anophthalmia: diagnostic and therapeutic challenges.

OBJECTIVES: Graves' disease (GD) is a rare auto-immune disorder in pediatric population. The association between GD and thymic hyperplasia was rarely reported in children. Diagnosis and management of GD are challenging in children. CASE PRESENTATION: This report presents the case of a 5-year-old girl with a personal history of asthma and congenital bilateral isolated clinical anophthalmia who presented with acute congestive heart failure, sinus tachycardia and atypical signs of orbitopathy with edema and erythema of the lower right eyelid and excessive tearing. The diagnosis of GD was based on detecting a suppression of serum TSH level and the presence of high titers of TRAbs. Relapse occurred after 10 months of antithyroid drugs with chief complaints of palpitations, dyspnea and dysphagia. Computed tomography showed heterogeneous anterior mediastinal mass with no invasion into the surrounding tissue. The marked shrinkage of the mass after radioiodine therapy supported the diagnosis of thymic hyperplasia associated with GD. CONCLUSIONS: The presence of clinical anophthalmia may be a confusing factor for the diagnosis of Graves' ophthalmopathy. Recognition of the association between GD and thymic hyperplasia would avoid invasive diagnostic procedures and unnecessary surgical resection. Radioiodine therapy may be used in young children with repeated relapses of GD.

Clinical Features, Treatment, and Prognostic Factors of Childhood-Onset Myasthenia Gravis in a Large Chinese Cohort.

BACKGROUND: To describe the clinical features of patients with childhood-onset myasthenia gravis (MG) (CMG) and explore predictors affecting the treatment outcomes. METHODS: A retrospective observational cohort analysis of 859 patients with CMG with disease onset before age 14 years was performed at Tongji Hospital. RESULTS: Patients in the pubertal-onset group (n = 148) had a worse disease course than those in the prepubertal group (n = 711), including a higher incidence of generalized MG (GMG) at presentation, generalization of ocular MG (OMG), and more severe Myasthenia Gravis Foundation of America (MGFA) classification. All patients were initially treated with pyridostigmine, 657 with prednisone, and 196 with immunosuppressants (ISs). However, 226 patients were resistant to prednisone treatment. Multivariate analysis revealed that thymic hyperplasia, higher MGFA class, disease duration before prednisone administration, and thymectomy before prednisone administration were independent predictors of prednisone resistance. At the last visit, 121 of the 840 patients with OMG had developed GMG after a median of 10.0 years from symptom onset and 186 patients (21.7%) achieved complete stable remission (CSR). In multivariable analysis, age at onset, thymic hyperplasia, prednisone, and IS treatment were associated with generalization, whereas age at onset, disease duration, anti-acetylcholine receptor antibodies (AChR-ab), MGFA class II, short-term prednisone treatment, and IS treatment were associated with CSR. CONCLUSIONS: The majority of patients with CMG have mild clinical symptoms and favorable outcomes, especially those with earlier onset age, shorter disease duration, and negative AChR-ab. In addition, early prednisone and ISs are shown to be effective and safe for most patients with CMG.

Combined effect of thymectomy on myasthenia gravis in patients with concomitant auto-immune diseases: a 22-year single-center experience.

Myasthenia gravis (MG) is an autoimmune disease (AD), and patients with MG often have other types of ADs. We analyzed the prognosis of patients with MG complicated by AD after thymectomy. A retrospective analysis was performed for patients with MG complicated by ADs treated surgically in our center over the past 22 years, and their general condition and follow-up data were collected and analyzed. 33 patients were included totally. 28 patients displayed improvement or even complete recovery of MG, and 23 of 36 ADs revealed improvement or even complete recovery. The prognosis of MG is significantly correlated with the duration of postoperative follow-up time (p = 0.028), and in patients with thymoma, the larger the tumor diameter, the better the prognosis of MG (p = 0.026). Thymic hyperplasia patients were predominantly female (p = 0.049) and young (p < 0.001). The most common concomitant AD in this study was a thyroid-associated AD, which was associated with thymic hyperplasia (p < 0.001), Osserman type I MG (p < 0.001), and young age (p < 0.001). Thymectomy had a good therapeutic effect on MG complicated by AD, and there was a close correlation between surgery, thymus, MG, and ADs.

Ultrahigh-performance liquid chromatography-high-resolution mass spectrometry-based plasma metabolomics study of thymoma and thymic hyperplasia.

RATIONALE: Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problems, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma. METHODS: Metabolic profiling of plasma from thymoma and thymic hyperplasia patients was performed using ultrahigh-performance liquid chromatography combined with high-resolution mass spectrometry in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental tandem mass spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence. RESULTS: A total of 47 differential metabolites were identified in thymoma. Significantly higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significantly lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG(-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma. CONCLUSIONS: Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma.

Thymic Parenchymal Hyperplasia.

Thymic hyperplasia is a rare condition generally caused by lymphoid follicular hyperplasia associated with autoimmune disorders. True thymic parenchymal hyperplasia unassociated with lymphoid follicular hyperplasia is extremely rare and may give rise to difficulties in diagnosis. We have studied 44 patients with true thymic hyperplasia (38 females and 6 males) aged 7 months to 64 years (mean, 36 years). Eighteen patients presented with symptoms of chest discomfort or shortness of breath; in 20 patients, the lesions were discovered incidentally. Imaging studies demonstrated enlargement of the mediastinum by a mass lesion suspicious for malignancy. All patients were treated with complete surgical excision. The tumors measured from 3.5 to 24 cm (median, 10 cm; mean, 10.46 cm). Histologic examination showed lobules of thymic tissue displaying well-developed corticomedullary architecture, with scattered Hassall corpuscles separated by mature adipose tissue and bounded by a thin fibrous capsule. No cases showed evidence of lymphoid follicular hyperplasia, cytologic atypia, or confluence of the lobules. Immunohistochemical studies showed a normal pattern of distribution for keratin-positive thymic epithelial cells against a background rich in CD3/TdT/CD1a+ lymphocytes. Twenty-nine cases had an initial clinical or pathological diagnosis of thymoma or thymoma vs thymic hyperplasia. Clinical follow-up in 26 cases showed that all patients were alive and well between 5 and 15 years after diagnosis (mean, 9 years). Thymic parenchymal hyperplasia causing significant enlargement of the normal thymus that is sufficient to cause symptoms or worrisome imaging findings should be considered in the differential diagnosis of anterior mediastinal masses. The criteria for distinguishing such lesions from lymphocyte-rich thymoma are presented.

Thymic Hyperplasia With Lymphoepithelial Sialadenitis-Like Features Arising in a Patient With Immunoglobulin G4-Related Disorders: A Case Report.

Thymic hyperplasia with lymphoepithelial sialadenitis-like features is characterized by thymic hyperplasia with lymphocytic infiltrates in the thymic epithelium. The lesion differs from other forms of thymic hyperplasia, including true and follicular thymic hyperplasia, in that it presents at an advanced age and has been reported to be unassociated with autoimmune diseases. We report a case of thymic hyperplasia with lymphoepithelial sialadenitis-like features in a 55-year-old male patient with a history of an immunoglobulin G4 (IgG4)-related disorder. Histologically, the resected mediastinal mass showed features consistent with those of thymic hyperplasia with lymphoepithelial sialadenitis-like features. In addition, the IgG4/IgG ratio was elevated in the polyclonal plasmacytoid infiltration. Thymic hyperplasia with lymphoepithelial sialadenitis-like features has not been reported to be associated with IgG4-related disorders; however, as shown in our report, it is crucial to include it in the differential diagnosis of a mediastinal mass in a patient with IgG4-related disorders.

Thymectomy in ocular myasthenia gravis-prognosis and risk factors analysis.

BACKGROUND: Several retrospective studies have identified risk factors associated with ocular myasthenia gravis (OMG) generalization in non-surgical patients. However, the outcomes of OMG after thymectomy have not been investigated fully. This study aimed to explore the clinical predictors of post-thymectomy OMG prognosis. METHODS: We performed a retrospective review of OMG patients who underwent thymectomy at our institution from January 2012 to December 2021. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between clinical features and prognosis. The main outcome measures were OMG conversion, complete stable remission (CSR), and clinical improvement. RESULTS: Fifty-eight patients were identified for conversion analysis. Thirteen (22.4%) developed generalized myasthenia gravis (GMG) at a median time of 12.7 (3-37.3) months from symptom onset. Repetitive nerve stimulation (RNS)-positivity was associated with increased risk of conversion to GMG (P = 0.002). Patients with histotype B2/B3 thymoma showed a higher risk of conversion (P = 0.002) than did patients with hyperplasia and AB/B1 thymoma. Fifty-two patients fulfilled the criteria for CSR and improvement. Sixteen (30.8%) achieved CSR at a median time of 28.7 (15-54) months after thymectomy. Fifteen (28.8%) showed clinical improvement at last follow up. Patients who achieved CSR showed a younger age of onset (P = 0.022), lower percentage of acetylcholine receptor antibody-seropositivity (P = 0.029). Histologically, patients with thymic hyperplasia and stage I thymoma showed a higher chance of CSR (P = 0.010) than did patients with stage II/III thymoma. Multivariate analysis revealed that RNS-positivity (hazard ratio [HR] 6.007, P = 0.021) and histotype B2/B3 thymoma (HR 4.611, P = 0.048) were associated with OMG conversion. Thymic hyperplasia and stage I thymoma (HR 0.300, P = 0.026) were associated with OMG CSR after thymectomy. CONCLUSION: For OMG patients after thymectomy, RNS-positivity and histotype B2/B3 thymoma are independent predictors of conversion to GMG. On the other hand, thymic hyperplasia and stage I thymoma independently predict CSR.

Thymic Lesions in Myasthenia Gravis: A Clinicopathological Study from India.

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.

Pathogenesis of follicular thymic hyperplasia associated with rheumatoid arthritis.

Lymphoproliferative disorders may occur in patients with rheumatoid arthritis (RA) who are treated with methotrexate. However, follicular thymic hyperplasia (FTH) associated with RA (FTH-RA) is generally not considered a lymphoproliferative disorder. To investigate the pathogenesis of FTH-RA, we examined 12 cases of FTH involving thymic enlargement, four of FTH involving RA and eight of FTH involving myasthenia gravis (MG). Increased numbers and larger germinal center (GC) size were observed in FTH-RA group. The percentage of distorted GCs was 13.3% in FTH-RA group and 3.25% in FTH associated with MG (FTH-MG) group. A greater meshwork of follicular dendritic cells was observed in the GCs of FTH-RA group. Positive indices of CD27+ cells and PD-1+ cells per GC in FTH-RA group were significantly higher than those in FTH-MG group, though positive indices of CD68+ cells and CD163+ cells were similar. Myoid cell proliferation, as evaluated by α-SMA, tenascin-C, and l-caldesmon expression, was significantly increased in the FTH-RA group compared with the FTH-MG group. These results suggest that FTH should be considered in patients with RA treated with methotrexate. The pathogenesis of FTH-RA includes GC expansion and increased numbers of memory B cells, follicular helper T cells, and myoid cells, indicating humoral immunity activation.

[Therapeutic approach to massive thymic hyperplasia associated with respiratory distress syndrome in a newborn infant living in a developing country: a case report]. / Stratégie thérapeutique devant une hyperplasie thymique massive associée à un syndrome de détresse respiratoire chez un nouveau-né dans un pays en voie de développement: à propos d'un cas.

Thymic hyperplasia is an anterior mediastinal mass with a variable clinical presentation. It causes differential diagnostic problems in the pediatric age group and there is no consensus on the therapeutic approach. We here report the case of a 1-month-old infant treated for respiratory distress syndrome. Chest CT scan revealed anterior mediastinal mass, which was excised through median sternotomy. Anatomopathological examination showed thymic hyperplasia. Clinical outcome was satisfactory. This encouraging result suggests that, contrary to what some authors propose, it would be more appropriate to opt for an aggressive therapeutic strategy when managing symptomatic thymic hyperplasia. This is even more justified in a socio-economic context characterised by difficult access to care and follow-up measures limited by patients' means.

True thymic hyperplasia causing pure red cell aplasia: a case report.

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.

Idiopathic multicentric Castleman disease with Sjögren's syndrome and secondary membranous nephropathy: a case report and review of the literature.

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.

The coexistence of hypercalcemia, osteoporosis and thymic enlargement in graves' disease: a case report.

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.

A rare association between true thymic hyperplasia and thyroid follicular tumor: a case report.

BACKGROUND: True thymic hyperplasia is a rare condition characterized by enlargement of the thymus while its normal structure is retained. True thymic hyperplasia is known to accompany Graves' disease, but no association between true thymic hyperplasia and thyroid follicular tumor has been reported so far. We report a case of true thymic hyperplasia in a patient with a thyroid follicular tumor. CASE PRESENTATION: A 52-year-old Japanese man was referred to our hospital for evaluation of a thyroid mass and a mediastinal mass. His serum thyroglobulin level was high, and hemithyroidectomy was performed to remove the thyroid mass. The resected mass was diagnosed as a follicular tumor of uncertain malignant potential. After resection of the thyroid lesion, the patient's serum thyroglobulin levels were markedly decreased. Seven months later, the patient underwent resection of the mediastinal mass. On pathological examination, the mass was found to consist of lobules, which formed a corticomedullary structure with Hassall's bodies, indicating a normal thymic mass with hyperplastic thymic tissue, less organized cellular cords, and intermingled adipose tissue. Immunostaining for cytokeratin 19 and cytokeratin 7 indicated that the lesion was consistent with thymic tissue. The lesion was diagnosed as true thymic hyperplasia, and the histological findings suggested that secondary atrophy had occurred. No evidence of recurrence was observed at 24 months after surgery. CONCLUSIONS: We present a case of a combination of true thymic hyperplasia and thyroidal follicular tumors that, to our knowledge, has not been reported previously. High serum thyroglobulin levels might play a role in hyperplasia of the thymus. Although true thymic hyperplasia is a rare disorder, it should be included in the differential diagnosis of a mediastinal mass in patients with thyroid disease.

Enfermedades del timo por exceso y por defecto / Thymus diseases by excess and default

El timo es un órgano cervicotorácico, impar y mediano, situado en la base del cuello y parte superior del mediastino. Junto a la médula ósea es uno de los dos órganos primarios del sistema inmune y ejerce su función en los neonatos y en los niños, fundamentalmente. Entra en regresión a partir de la pubertad, aunque algunos autores plantean que la involución puede comenzar un poco antes, cuando los principales tejidos linfoides están plenamente desarrollados. Interviene sinérgicamente con otras glándulas de secreción interna: tiroides, suprarrenal, hipófisis, para elaborar substancias necesarias para el desarrollo general del organismo. Es un órgano muy sensible a todo influjo. Como todos los órganos de la economía el timo presenta enfermedades producidas tanto por crecimiento exagerado, como por hipoplasias o atrofias. Dentro de las primeras las más comunes son la hiperplasia tímica y el timoma y, entre las últimas el síndrome de DiGeorge ha sido bien caracterizado en la literatura internacional desde la segunda mitad del siglo pasado. Sin embrago, en los últimos tiempos los inmunólogos hablan de la hipoplasia tímica como entidad que puede asociarse o no a estados de inmunodeficiencia. Se describen brevemente estas afecciones(AU)

The thymus is a cervicothoracic organ, odd and medium, located at the base of the neck and upper part of the mediastinum. Next to the bone marrow is one of the two primary organs of the immune system and exerts its function in neonates and children, fundamentally. It regresses after puberty, although some authors suggest that the involution can begin a little earlier, when the main lymphoid tissues are fully developed. It intervenes synergistically with other glands of internal secretion: thyroid, adrenal, pituitary gland, to develop substances necessary for the general development of the organism. It is a very sensitive organ to all influence. Like all the organs of the economy, the thymus presents diseases caused both by exaggerated growth, as by hypoplasias or atrophies. Among the former, the most common are thymic hyperplasia and thymoma and, among the latter, DiGeorge syndrome has been well characterized in international literature since the second half of the last century. However, in recent times immunologists speak of thymic hypoplasia as an entity that may or may not be associated with immunodeficiency states. These conditions are briefly described(AU)

Detection of human parvovirus B19 infection in the thymus of patients with thymic hyperplasia-associated myasthenia gravis.

OBJECTIVE: To investigate the association between myasthenia gravis (MG) and human parvovirus B19 (B19V) infection in the thymus. METHODS: 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. RESULTS: 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) (p <0.001) 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) (p <0.001). 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). CONCLUSIONS: 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.

Enfermedad de Graves-Basedow e hiperplasia tímica: una asociación que no nos debe extrañar / raves-Basedow disease and thymic hyperplasia: an association that must not surprise us

RESUMEN El aumento del tamaño del timo asociado a hiperplasia tímica (HT) es frecuente en los pacientes con enfermedad de Graves-Basedow (EGB), si bien es poco habitual detectarla en la práctica clínica diaria. Presentamos el caso de una mujer de 38 años con EGB, a quien se le detectó de manera incidental un aumento del timo. La paciente no tenía síntomas compresivos locales y la tomografía computarizada demostró engrosamiento homogéneo de mediastino anterior sugestivo de HT. Durante la evolución, se evidenció reducción del tamaño tras el control de la función tiroidea con fármacos antitiroideos. La presencia de algunas características radiológicas como aumento difuso y homogéneo de la glándula, ausencia de invasión de estructuras vecinas, calcificaciones o imágenes quísticas, sugiere la presencia de una HT. En estos casos, el tratamiento del hipertiroidismo y un control expectante son actitudes razonables. Conocer esta evolución puede evitar intervenciones diagnósticas o terapéuticas innecesarias.

ABSTRACT Thymic enlargement associated with thymic hyperplasia (TH), in patients with Graves-Basedow disease (GBD) is common, although it remains largely unrecognized in routine clinical practice. We present the case of a 38 year-old woman with GBD, to whom an incidental thymic enlargement was detected. The patient did not have local compressive symptoms and the computerized tomography showed homogenous thickening of the anterior mediastinum suggestive of TH. During evolution, a reduction in size was observed after thyroid function was controlled by anti-thyroid drugs. The presence of some radiological features such as diffuse and homogeneous gland enlargement, absence of invasion of neighboring structures, calcifications or cystic images suggests the presence of TH. In these cases treatment of hyperthyroidism and expectant management are reasonable responses. Recognizing this evolution can avoid unnecessary diagnostic or therapeutic interventions.

Thymus involvement in early-onset myasthenia gravis.

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)-ß is overexpressed in MG thymus and could orchestrate thymic changes associated with MG. Knowledge about how IFN-ß 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.