Benign lesions of the mediastinum.

Mediastinal tumours represent a heterogeneous group of entities derived from the manifold structures located in or adjacent to the mediastinum. Due to the occurrence of some of these tumours in characteristic mediastinal compartments, an anatomical subdivision of the mediastinum in the prevascular (anterior), visceral (middle), and paravertebral (posterior) is helpful for the differential diagnosis. Benign anterior mediastinal tumours linked to an enlargement of the thymic gland mainly consist of thymic cysts and several types of thymic hyperplasia: true thymic hyperplasia, rebound hyperplasia, lymphofollicular hyperplasia, and so-called thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features. Mature teratomas, ectopic (para)thyroid tissue, and benign thymic tumours such as thymolipoma or thymofibrolipoma represent further typical tumours of the anterior mediastinum. Pericardial, bronchogenic, or oesophageal duplication cysts predominate in the middle mediastinum, whereas neurogenic tumours and myelolipomas are characteristic findings in the posterior compartment. Vascular tumours, lipomas, adenomatoid tumours, Castleman disease, or mediastinitis are further examples of less frequent tumours or tumorous lesions affecting the mediastinum. This review focuses on benign mediastinal lesions with an emphasis on benign tumours of the thymus. Besides histology, characteristic epidemiological and clinical aspects prerequisite for the correct diagnosis and patient management are discussed.

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.

Clinical practices for non-neoplastic thymic lesions: Results from a multidisciplinary cohort.

BACKGROUND: Non-neoplastic thymic lesions are uncommon findings that corresponds to multiple histological and clinical entities that may be difficult to differentiate from thymic malignancies. In this study, our main objective was to describe the clinical, imaging and pathological characteristics of non-neoplastic thymic lesions in a large cohort of patients. We also aimed at understanding the key factors that led to a decision to surgically resect those lesions. METHODS AND MATERIALS: This is an observational, retrospective study. We enrolled both patients with non-neoplastic thymic lesions - normal thymus, thymic lymphoid/non-lymphoid hyperplasia, and thymic cysts - that had been pathologically-confirmed after surgical resection - , and patients with a thymic lesion that was never operated, based on imaging follow-up. RESULTS: A total of 128 patients were included, 88 of whom underwent surgical resection of the lesion (69%), and 40 patients (31%) had follow-up without surgery. Discovery of the lesion was incidental in 69 (54%) cases; thoracic magnetic resonance imaging was performed in 33 (26%) cases, 85% of which showed apparent decrease in the lesion signal intensity in phase opposition at chemical shift sequences. In the 88 operated patients, there were 34 (39%) normal thymuses, 29 (33%) lymphoid hyperplasias, 6 (7%) non-lymphoid thymic hyperplasias, and 19 (22%) thymic cysts. In the 40 non-operated patients, a major driver for the decision of follow-up was the decrease in the lesion signal intensity in phase opposition at chemical shift sequences, observed in 68% of cases; imaging follow-up of these lesions showed sustained regression in the majority of the cases. CONCLUSIONS: The management of benign thymic lesions requires multidisciplinary assessment. A strategy that integrates clinical and imaging features, including chemical-shift sequences at magnetic resonance imaging, as well as follow-up, allows a better selection of the patients for surgery.

A Developing Anterior Mediastinal Mass in a Breast Cancer Patient: Thymic Hyperplasia.

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.

[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.

CT texture analysis in evaluation of thymic tumors and thymic hyperplasia: correlation with the international thymic malignancy interest group (ITMIG) stage and WHO grade.

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.

Thymic rebound hyperplasia post-chemotherapy mistaken as disease progression in a patient with lymphoma involving mediastinum: a case report and reflection.

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.

Two polymorphic mutations in promoter region of DNA polymerase ß in relatively higher percentage of thymic hyperplasia patients.

BACKGROUND: DNA polymerase ß is one of the key enzymes involved in the repair of DNA damage, and its high or low expression is closely related to tumorigenesis. In a previous study on lung cancer, we found three genetic mutations in the promoter region of the Polb gene could be detected in the Han Chinese population. The purpose of this study was to explore the relationship between these mutations and thymic hyperplasia. METHODS: Genomic DNA was extracted from 59 thymic hyperplasia patients by the salting out method and used for amplification of the promoter region of the Polb gene. The Polb gene mutation and its frequency were analyzed systematically by comparing them with the deposited wild-type gene sequence in the NCBI database. The three typical mutated sequences in the promoter region of Polb gene, -196G > T, -168C > A and -188_-187insCGCCC, were then amplified and ligated to pGL4.10 vector, so as to get the vectors used for the infection of 293T cells to explore their transcription activities by dual-luciferase reporter system. RESULTS: Two types of mutations, -168C>A and-188_-187insCGCCC, were found in a significantly higher percentage in patients with thymic hyperplasia than in normal healthy people after sequencing analysis of 59 patients and 60 healthy controls. These results suggest that the two mutations may be closely related to thymic hyperplasia. in vitro functional experiments showed that-168C>A could significantly increase promoter activity, whereas -188_-187insCGCCC could significantly reduce promoter activity, suggesting that these two mutations may affect the expression level of the Polb gene in cells. CONCLUSIONS: Two types of mutations in the promoter region of the Polb gene, -168C>A and-188_-187insCGCCC, are associated with thymic hyperplasia and may become a new risk factor for this disease. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Genetic mutations in the Polb gene are reported to be associated with different kinds of cancers. However, their relationship with thymic hyperplasia is still unclear. WHAT THIS STUDY ADDS: For the first time, we report that two nucleotide mutations in the promoter region of the Polb gene are closely related with thymic hyperplasia after sequencing 59 patients and 60 healthy controls in the Han Chinese population.

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.

Cystic thymic degeneration with pseudoepitheliomatous hyperplasia in a Beagle puppy: an idiopathic lesion?

A 6-mo-old female Beagle dog was inappetent and depressed. The radiographic, ultrasonographic, and computed tomographic examination of the chest revealed a 10 × 7 cm multicystic mediastinal structure interpreted as altered thymus, in association with moderate pleural effusion that laboratory tests confirmed as hemothorax. No history of trauma or anticoagulant drug intoxication was reported, and no coagulation disorders were detected. Afterward, medial cranial sternotomy was performed to remove the altered tissue. Histologically, this tissue was compatible with a thymic remnant, characterized by numerous cystic lesions, mostly blood filled and lined by flattened-to-cuboidal epithelial cells, occasionally projecting into the surrounding stroma, and forming cytokeratin-positive ribbons, trabeculae, and papillae. Lymphocytes were scant, and numerous areas of congestion and hemorrhage were present throughout the samples. This case of idiopathic thymic hemorrhage with cystic degeneration of the thymus and pseudoepitheliomatous hyperplasia was an incidental finding; the dog recovered from surgery uneventfully.

A tri-modal distribution of age-of-onset in female patients with myasthenia gravis is associated with the gender-related clinical differences.

BACKGROUND: 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. METHODS: 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) and >70 years (late-onset, LOMG). RESULTS: 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. CONCLUSIONS: 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.

[An enlarged thymus associated with Graves' disease]. / Een vergrote thymus bij ziekte van Graves.

BACKGROUND: 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. CASE DESCRIPTION: 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. CONCLUSION: 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.

Occurrence of thymic pathology in two families. Is familial screening justified?

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.

PD-1 and PD-L1 expression in thymic epithelial tumours and non-neoplastic thymus.

AIMS: We explored the relationships between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression and the pathological and clinical features of thymic epithelial tumours and thymic hyperplasia. METHODS: We evaluated PD-1 and PDL-1 expressions within epithelial and microenvironmental components in thymic epithelial tumours (n=44) and thymic hyperplasias (n=8), immunohistochemically. We compared the results with demographic, clinical and histopathological features of the cases. RESULTS: We found 48% epithelial expression and 82.7% microenvironment expression for PD-1 and 11.5% epithelial expression and 34.6% microenvironment expression for PD-L1. There was no PD-1 expression, in either the epithelial or microenvironment, in the thymic hyperplasia group. PD-1 and PD-L1 positivity was more significant in thymic epithelial tumours than thymic hyperplasia. Patients with PD-1-positive microenvironments exhibited significantly shorter mean estimated survival time than their negative counterparts. CONCLUSION: These findings suggest that anti-PD-1 and anti-PD-L1 therapies may benefit patients due to high release of PD-1 and PD-L1 in thymic epithelial tumours.

Challenging the current model of early-onset myasthenia gravis pathogenesis in the light of the MGTX trial and histological heterogeneity of thymectomy specimens.

The MGTX trial provided evidence that, in general, thymectomy is beneficial in adult patients up to 60 years of age with anti-acetylcholine receptor-positive, nonthymomatous myasthenia gravis (MG). This finding supports the long-held view that the pathogenesis of this type of MG (early-onset MG (EOMG)) starts inside the thymus, results in the long-term intrathymic recruitment of autoantibody-producing B cells and plasma cells, and eventually spreads to the peripheral immune system. However, observed clinical responses to treatment in the MGTX trial were diverse. This might be due to heterogeneous epidemiological and genetic features of EOMG patients and variable durations of corticosteroid treatment before surgery, including a paucity of patients that were corticosteroid naive. Furthermore, the observed histological heterogeneity suggests that a single pathogenetic model may not fully reflect the spectrum of events that modify the course of EOMG. Here, we describe the morphology of the normal and MG-associated thymus, how to evaluate morphological changes, and the current pathogenetic model of EOMG and discuss how it could be refined by integrating MGTX-derived histological findings in thymectomy specimens and associated clinical observations.

Pathological Findings in Myasthenia Gravis Patients with Thymic Hyperplasia and Thymoma.

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.

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.

Thymic Hyperplasia Associated with Graves' Disease: Pathophysiology and Proposed Management Algorithm.

BACKGROUND: The association between Graves' disease (GD) and thymic hyperplasia (TH) was first described in 1912 and has been reported numerous times thereafter. TH associated with GD presents as an incidental mediastinal mass on chest X-ray or computed tomography (CT). The pathogenesis of TH in the setting of GD is unclear but seems to involve a complex interplay of hormonal and immunological mechanisms. SUMMARY: Here, the effect that thyroid hormones and autoimmunity have on thymic growth and size is reviewed. The authors' experience, along with a review of published case reports, reveals that general physicians may be unfamiliar with this association. This lack of familiarity may result in an aggressive management course, including surgical intervention, along with its associated risks and costs. The differential diagnosis and diagnostic workup of thymic enlargement associated with GD is discussed in light of the available clinical evidence. CONCLUSION: Recent literature confirms the generally benign nature of TH associated with GD, and supports a conservative approach for the diagnostic workup and initial management. Practical management recommendations for thymic enlargement associated with GD have been formulated and are presented here.