Thymic Enlargement Research Articles

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

BackgroundChemotherapy 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 presentationThis 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.ConclusionsThe 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.

Protective reactive thymus hyperplasia in COVID-19 acute respiratory distress syndrome

BackgroundPatients 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.MethodsIn 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).ResultsEighty-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 < 0.0001). Thymus enlargement in COVID patients was associated with more extensive lung injury score on CT scans (4 [3–5] vs. 2 [1.5–4], p = 0.01), but a lower mortality rate (8.6% vs. 41.2%, p < 0.001). Other factors associated with mortality were age, lymphopaenia, high CRP and co-morbidities. COVID patients had higher concentrations of IL-7 (6.00 [3.72–9.25] vs. 2.17 [1.76–4.4] pg/mL; 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).ConclusionIn 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.

Eosinophilic Myocarditis as a Cause of Death: A Case Diagnosed at Autopsy

Abstract Introduction/Objective Eosinophilic (Loffler) myocarditis is a rare disease defined by the influx of eosinophils into the endocardium and myocardium. Etiologies are numerous and include drug or hypersensitivity reactions, hypereosinophilic syndrome, hematologic malignancies, and parasitic infections. It is a diagnostically challenging entity. Presenting symptoms recorded in the literature are indefinite and nonspecific; heart failure, demonstrable arrhythmia, and elevated cardiac biomarkers. This is especially the case among younger, otherwise healthy patients without classical risk factors for atherosclerotic coronary artery disease. Methods Herein we present several cases of sudden cardiac death in young adults, including a case of unknown eosinophilic myocarditis, which highlights the potential trials in the diagnosis of this disease. Results Autopsies were performed on several adults (age range, 30-40 years) thought to have died of cardiac causes. This included a 30-year-old African American female with no significant known medical history who presented with a chief complaint of palpitations. The initial clinical impression at an outside institution was of cardiac amyloidosis. But the Technetium99 scan was inconclusive. Despite clinical management, she developed ventricular arrhythmias and could not be resuscitated. There was a vague history of taking nutritional supplements from a local grocery store. Gross findings at autopsy included circumferential subepicardial erythema, thymic enlargement (60g), and congested lungs. The heart was thoroughly sampled. Microscopic examination revealed diffuse infiltration of eosinophils, mast cells, lymphocytes and macrophages with mild myocyte necrosis and interstitial edema in all sections. There were no giant cells, no interstitial deposition of amorphous acellular material and no focus of infarcted myocardium. Thymic sections were histologically normal. Acetylcholine receptor antibody panel was negative. Conclusion We conclude that eosinophilic myocarditis though rare (0.5% unsuspected and 0.1% suspected cases), is a distinctive cause of death with a specific microscopic presentation. Our case also included thymic enlargement at autopsy – a finding not previously noted.

ANTERIOR MEDIASTINAL MASS-THYROID-INDUCED PSEUDO-THYMOMA: A PURE THYMIC HYPERPLASIA

SESSION TITLE: Medical Student/Resident Disorders of the Mediastinum Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Mediastinal masses encompass a broad spectrum of histopathology among which two-thirds are benign. Anterior mediastinal masses draw more attention because 59% of them are malignant, thymoma being the most common(1). These malignant masses more often warrant biopsy and surgical intervention. True benign thymic hyperplasia (TH) is associated with thyrotoxicosis in Grave’s disease (GD). Involution of thymus after treatment with anti-thyroid drugs(2) and significant correlation between thymulin levels with Serum T4 and T3 have been reported earlier(3). However, there are only a few cases of this coexistence that are reported and management of these pseudo thymomas is still unclear to many. CASE PRESENTATION: A 53-year-old female with no significant past medical history presented with 3-week history of worsening exertional dyspnea associated with malaise, palpitations, and severe tremors. She was tachycardic and hypertensive on arrival. CTPA revealed an incidental non-discrete well-defined anterior mediastinal soft tissue mass. There were no calcifications, adjacent invasion or mediastinal lymphadenopathy noted. Labs showed a TSH < 0.01 mIU/L, FT4 > 7.77 ng/dL and total T3 625.4 ng/dL. Patient was started on steroids, betablockers and methimazole in the hospital and reported symptom improvement in the next few days. Pulmonology was consulted and invasive procedure was deferred since it was thought to be thyroid induced thymic enlargement. Patient was set up with follow up CT to assess for regression of the mass with treatment of hyperthyroidism. DISCUSSION: TH associated with Grave’s disease is known to occur in all age groups, most commonly in young adults correlating with GD incidence in the age group. Many of these earlier case reports revealed regression of the thymic mass size on follow-up CT after at least 2-6 months of anti-thyroid treatment with medications (4), radioactive iodine therapy or thyroidectomy. Decrease in thymic volume and density were also noted (5). Due to concerns of thymoma, some patients had reported resection of GD associated thymic mass but eventually histopathology suggested thymic hyperplasia(4,5). Massive thymic masses (6,7) were also associated with GD, that regressed with antithyroid treatment. Radiological features of these masses suggested benign appearance and later proved to be TH by histopathological diagnosis. CONCLUSIONS: We here present an older adult female with GD and incidentally found anterior mediastinal mass. Considering this as benign thymic hyperplasia helped us prevent biopsy and thymectomy. These masses with no malignant features can safely be monitored for size and consistency by serial CT following appropriate treatment of hyperthyroid state. An MRI, biopsy or resection is considered in cases when there is less than 50% regression in thymic volume after 6 months of euthyroid state. Reference #1: 1. Almeida PT, Heller D. Anterior Mediastinal Mass. In Treasure Island (FL); 2020. Reference #2: 4. Dalla Costa M, Mangano FA, Betterle C. Thymic hyperplasia in patients with Graves’ disease. J Endocrinol Invest 2014;37(12):1175–9 Reference #3: 5. Haider U, Richards P. Thymic Hyperplasia Associated with Graves ’ Disease: Pathophysiology and Proposed Management Algorithm. 2017;27(8):994–1000. DISCLOSURES: No relevant relationships by Dani Fribourg, source=Web Response No relevant relationships by Rathnavali Katragadda, source=Web Response

Imaging findings of spontaneous thymic hemorrhage in infancy: Case report and literature review

The authors report imaging findings of spontaneous thymic hemorrhage, which is a rare entity in infancy, in a 4-month-old boy with congenital factor VII deficiency presented with acute respiratory distress and anemia. Widening of superior mediastinum and left pleural effusion were detected on the chest radiograph. Ultrasound and computed tomography of the chest revealed diffusely enlarged thymus with heterogeneous parenchyma from poorly-defined areas of altered echogenicity or attenuation. Vascular flow was depicted within the abnormal thymus in color-mode sonography. The spontaneous involution of thymic abnormality seen on serial ultrasonography confirmed the diagnosis of thymic hemorrhage, resulting in avoidance of further unnecessary imaging or invasive procedure.

Imaging findings of spontaneous thymic hemorrhage in infancy: Case report and literature review

The authors report imaging findings of spontaneous thymic hemorrhage, which is a rare entity in infancy, in a 4-month-old boy with congenital factor VII deficiency presented with acute respiratory distress and anemia. Widening of superior mediastinum and leftpleural effusion were detected on the chest radiograph. Ultrasound and computed tomography of the chest revealed diffusely enlarged thymus with heterogeneous parenchyma from poorly-defined areas of altered echogenicity or attenuation. Vascular flow was depicted within the abnormal thymus in color-mode sonography. Thespontaneous involution of thymic abnormality seen on serial ultrasonography confirmed the diagnosis of thymic hemorrhage, resulting in avoidance of further unnecessary imaging or invasive procedure.

Histological Signs of the Thymic Enlargement

Currently, the mortality rate in pediatric population resulted from such diseases as respiratory distress syndrome, pneumonia and infections is extremely high. It cannot be ruled out that this is due to impaired functioning of the children's immune system. The thymus gland appears to be the central organ of immunopoiesis in children, that is why pediatricians pay special attention to thymic hyperplasia. To date, there is no consensus on the nature and clinical significance of the thymic enlargement. The aim of research was to study morphometric parameters of the thymus gland in children of the first year of life having thymic enlargement. Material and methods . To analyze the incidence of thymic enlargement in deceased children, the authors selected 764 autopsy protocols of children for the period from 2012 to 2017; of these, 117 were children who died in their first year of life. Autopsies were performed in Saratov Centralized Pediatric Prosectorium. The thymic enlargement in deceased children of the first year of life was detected in 34% (40 cases). Autopsy material of 32 children was selected (15 cases with and 17 cases without the thymic enlargement) for histological examination. The thymic index was calculated to specify correlation between the thymus mass and the age and body weight of a child. Morphometric studies were performed using an mVizo-103 microvisor. Results. As demonstrated, infectious diseases are a risk factor for the formation of thymomegaly in children of the first year of life. A morphological study detected that the thymic enlargement occurred mainly due to the enlargement of the cortical layer with the reduction of the lobule area. The lobule area in the studied group of children reduced by 15%, and the number of lobes bordering in the field of view increased by 50%, respectively to the similar parameters in children of the comparison group. Conclusion. Thus, infectious pathologies appear to be the most common cause of death in children with the thymic enlargement. The study results support the fact that histological signs of thymomegaly are the increased number of bordering thymic lobes in the field of view and the increased number of immature thymocytes.

The coexistence of hypercalcemia, osteoporosis and thymic enlargement in graves\u2019 disease: a case report

BackgroundHyperthyroidism-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 presentationA 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.ConclusionThis 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.

Respiratory Failure Due to a Large Mediastinal Mass in a 4-year-old Female with Blast Cell Crisis: A Case Report.

IntroductionSymptomatic leukostasis is an exceptionally atypical presentation of blast crisis; and when coupled with an enlarged neoplastic mediastinal mass in a four-year-old female, an extremely rare and challenging pediatric emergency arises.Case ReportWe present a unique case of a four-year-old female who arrived via emergency medical services in cardiopulmonary arrest with clinical and radiographic evidence suggestive of bilateral pneumothoraces, prompting bilateral chest tube placement. Further evaluation revealed a large mediastinal mass and a concurrent white blood cell count of 428,400 per milliliter (/mL) (4,400–12,900/mL), with a 96% blast differential, consistent with complications of T-cell acute lymphoblastic leukemia.ConclusionThis case highlights how pulmonary capillary hypoperfusion secondary to leukostasis, coupled with a ventilation/perfusion mismatch due to compression atelectasis by an enlarged thymus, resulted in this patient’s respiratory arrest. Furthermore, the case highlights how mediastinal masses in pediatric patients present potential diagnostic challenges for which ultrasound may prove beneficial.

A case of triple seronegative myasthenia gravis with Graves' disease ameliorated after the removal of enlarged thymus with elevated uptake in fluorine‐18 fluorodeoxyglucose positron emission tomography

AbstractWe report on a 35‐year‐old woman who complained of myasthenia in ocular, bulbar, and limb muscles, but who was negative for antibodies against acetylcholine receptor, muscle‐specific kinase, or low‐density lipoprotein receptor‐related protein 4, accompanied by the suppression of thyroid‐stimulating hormone with elevated free T3 and free T4. Administration of edrophonium significantly ameliorated blepharoptosis, and electromyography revealed 13.9% waning after 3 Hz repetitive stimulation in the left accessory nerve. Thus, she was suspected of having triple seronegative myasthenia gravis or thyrotoxic myasthenia. She was remitted after the resection of her enlarged thymus with an elevated uptake in fluorine‐18 fluorodeoxyglucose positron emission tomography, suggesting an unknown autoimmune target that escaped detection by current autoantibody screens. Consequently, thymectomy may still be effective in patients with seronegative MG plus hyperthyroidism.

Morphologic and Immunohistochemical Characterization of Spontaneous Lymphoma/Leukemia in NSG Mice.

The NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ strain (NOD scid gamma, NSG) is a severely immunodeficient inbred laboratory mouse used for preclinical studies because it is amenable to engraftment with human cells. Combining scid and Il2rgnull mutations results in severe immunodeficiency by impairing the maturation, survival, and functionality of interleukin 2-dependent immune cells, including T, B, and natural killer lymphocytes. While NSG mice are reportedly resistant to developing spontaneous lymphomas/leukemias, there are reports of hematopoietic cancers developing. In this study, we characterized the immunophenotype of spontaneous lymphoma/leukemia in 12 NSG mice (20 to 38 weeks old). The mice had a combination of grossly enlarged thymus, spleen, or lymph nodes and variable histologic involvement of the bone marrow and other tissues. All 12 lymphomas were diffusely CD3, TDT, and CD4 positive, and 11 of 12 were also positive for CD8, which together was consistent with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T-LBL). A subset of NSG tissues from all mice and neoplastic lymphocytes from 8 of 12 cases had strong immunoreactivity for retroviral p30 core protein, suggesting an association with a viral infection. These data highlight that NSG mice may develop T-cell lymphoma at low frequency, necessitating the recognition of this spontaneously arising disease when interpreting studies.

PS917 SAFE TARGETING OF T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA BY SUBUNIT SELECTIVE GAMMA-SECRETASE INHIBITION

Background: SPI1 fusion genes are recurrently found in Early Thymic Precursor cell Acute Lymphoblastic Leukemia (ETP-ALL) cases and represent a distinct subgroup with high frequency of RAS mutations and dismal prognosis. SPI1 (PU.1) is an important transcription factor in hematopoietic cells and its dysregulation contributes to several types of leukemia. Forced overexpression of SPI1 in T-cell progenitors is known to inhibit T-cell differentiation. Conversely, knock-out of TCF7, which is highly expressed in the earliest thymic progenitors, also leads to a T-cell differentiation block. However, the role of SPI1 fusions in driving and maintaining T-ALL remains unknown. Aims: In this study we aimed to elucidate the role of the TCF7-SPI1 fusion and its potential collaboration with RAS mutation in driving and maintaining T-ALL. Methods: We performed whole genome, transcriptome and nanopore sequencing on a patient sample with the TCF7-SPI1 fusion. Primary mouse pro-T cells were cultured on Dll4-coated plates in the presence of stem cell factor (Scf) and interleukin-7 (Il7). In vivo bone marrow transplant (BMT) assays were performed using hematopoietic stem and progenitor cells (HSPCs) isolated from CD2-Cre C57BL/6J mice and transduced with retroviral vectors for inducible expression of the TCF7-SPI1 fusion and/or NRAS (G12D) mutant within developing T-cells of recipient mice. Results: Combined short read and long read RNA-sequencing characterized the exon structure of the TCF7-SPI1 fusion transcript and confirmed the presence of a NRAS (G12D) mutation in the patient sample. Expression of TCF7-SPI1 and NRAS (G12D) transformed pro-T cells to Scf and interleukin-7 (Il7) independent growth. Using an inducible in vivo BMT model, conditional expression of TCF7-SPI1 and NRAS (G12D) within developing T-cells resulted in an aggressive immature acute T-ALL characterized by hyperleukocytosis (CD4-/CD8-, CD3+, CD117+), splenomegaly but no thymus enlargement. This was in contrast to either conditional TCF7-SPI1 alone that did not develop leukemia, or with NRAS (G12D) alone that developed a mature CD4+/CD8+ lymphoma with normal white blood cell count and no peripheral leukemic invasion of the bone marrow and spleen. Notably, a deletion construct of TCF7-SPI1, lacking the N-terminal beta-catenin binding domain of TCF7 lost its oncogenic properties. Summary/Conclusion: Here, we show that TCF7-SPI1 cooperates with NRAS (G12D) to drive an aggressive immature T-cell leukemia in vivo that is dependent on the N-terminal beta-catenin binding domain of TCF7.

Management of Myasthenia Gravis

AbstractMyasthenia gravis (MG) apart from Guillain–Barré syndrome is one of the most common disorders presenting as respiratory failure secondary to muscle weakness in the modern world. MG is also one of the most researched and reasonably well understood autoimmune disorder of mankind. From the description of early cases of MG to the current day understanding, the progress in the management and therapeutics has advanced significantly. Diagnosis of MG can be accurately done either with traditional tests such as the edrophonium test or by advanced nerve conduction studies. Presence of demonstrable circulating autoantibodies against the acetyl choline receptors, muscle-specific tyrosine kinase, involvement of B and T cells in the pathogenesis, and tomographic evidence of the enlarged thymus gland in certain patients have led to designing specific treatment strategies. Removal of the circulating autoantibodies as much as possible by plasmapheresis supported by anticholinesterases and immunosuppression are the mainstay of targeted therapy. The advent of newer immunosuppressant drugs such as rituximab which targets the CD20 protein present on the surface of B cells and tacrolimus which is an interleukin 2 inhibitor has improved the therapeutic armamentarium of the physician. These agents in combination with time tested medications such as steroids and antimetabolites have rendered faster remission rates and improved outcomes in MG crisis. This article outlines the basic pathophysiology, specific and supportive management strategies in patients presenting with MG with or without crisis.

SAT-603 Graves' Disease and an Anterior Mediastinal Mass

Introduction The association between Graves’ disease (GD) and an anterior mediastinal mass (AMM) due to thymic hyperplasia (TH) has been reported. The exact incidence of TH in GD is unknown as chest imaging is not routinely performed. TH in GD typically has a benign course and majority of cases resolved spontaneously with the treatment of GD. However, lack of familiarity of such association may lead to unnecessary surgical intervention. Clinical case A 33-year-old African American lady with Sjogren’s syndrome was presented with progressive shortness of breath and chest discomfort. Exam showed sinus tachycardia, with bilateral exophthalmos and a diffusely enlarged goiter. CTA chest with no pulmonary embolism, however, there was a 11x1.9 cm homogenous mass at anterior mediastinum. She has Graves’ disease, diagnosed 5-year ago with history of non-adherence to methimazole. TFT showed TSH of <0.1 uIU/ml (ref 0.34-5.6), FT4 of 5.38 ng/dl (ref 0.6-1.6), FT3 of >20 pg/ml (ref 2.3-4.2). TSI was elevated to 365% (ref <140). She had thoracoscopic partial resection of anterior mediastinal mass at outside hospital and reported as thymus hyperplasia. Discussion Differential diagnosis of AMM include retrosternal goiter, thymoma, thymic carcinoma, lymphoma and germ cell tumor. TH is the most common etiology of AMM in GD. The risk of thymic malignancy in GD appeared to be low at 3.7% in one study. In a study by Murakami et al, thyrotropin receptors were present in thymic tissue and GD patients had larger thymic size and higher thymic density than age-matched control subjects. TH in GD can be from lymphoid hyperplasia (TLH) due to increased number of lymphoid follicles with germinal centers or true thymic hyperplasia (TTH) from actual enlargement of the thymus. Thymic enlargement is more common in TTH. The mechanism of TH in GD is appeared to be thyroid hormone dependent which affect more on cortex causing TTH and immunologic process which affect more on medullary lymphoid follicles causing TLH. The degree of TH is correlated with the severity of thyrotoxicosis and the level of TSH receptor antibodies (TRAb). Treatment with anti-thyroid causes regression of TH by reducing levels of thyroid hormone and TRAb. In a literature review by Haider et al, 31 out of 47 GD-associated TH patients had an average of 62% reduction in thymic volume with the treatment of GD. The time to regression of TH under medical treatment varies considerably from 2 to 24 months, however, majority of cases showed >50% volume reduction at six months of therapy. Clinical lesson As TH in GD is a benign reversible autoimmune process, AMM in GD can be followed with repeat imaging. Thymic biopsy may be considered only if the size of the mass does not decrease with euthyroid state or patients with concerning radiological features of AMM such as cystic or necrotic changes, invasion to surrounding structure, or calcification.

SUN-571 Thymic Hyperplasia: An Unusual Manifestation of Graves’ Disease

Background: The association of Graves’ Disease with thymic hyperplasia is often underrecognized, even though it was first described more than 100 years ago. We hereby present a case of a hyperthyroidism and thymic hyperplasia where surgery could have been avoided. Clinical Case: A 43-year-old female presented with complaints of palpitations, increased sweating, tremors and fatigue for 6 months. Labs showed undetectable TSH with elevated free T4 of 2.3 ng/dl (reference range 0.82-1.77 ng/dl) and free T3 7.7 pg/ml (reference range 2 - 4.4 pg/ml). TSI antibodies were elevated at 617 (Normal <150 %). Due to a previous history of lung nodules, the patient underwent a surveillance CT scan of the chest concurrently. This CT chest showed an anterior mediastinal mass measuring 5 cm×3 cm. The mass was highly suspicious for being thymic in origin. This mass was not noticed on the CT chest done a year ago. PET scan revealed hypermetabolic activity in the thymic and thyroid regions. It was recommended to the patient that this mass likely was thymic hyperplasia in the setting of Graves’ Disease which was amenable to conservative management. However, the patient chose to undergo trans-sternal thymectomy instead of active surveillance. Pathology showed true thymic hyperplasia and no evidence of malignancy. Conclusion: This case illustrates the benign nature of thymic enlargement in Graves’ Disease. The presence of thyrotropin receptors on the thymic epithelial cells which participate in the autoimmune response, leading to hyperplasia in Graves’ disease has been implicated in the pathogenesis of thymic enlargement (1). Pathologically, two distinct features are seen in the thymus in Graves’ disease: lymphoid hyperplasia and true thymic hyperplasia (2). In both these conditions, the thymus gland appears diffusely enlarged. The treatment of thymic enlargement in this condition is the treatment of Graves’ disease, thereby avoiding the need for surgical interventions.

Managing thymic enlargement in Graves' disease.

SummaryThymic enlargement (TE) in Graves’ disease (GD) is often diagnosed incidentally when chest imaging is done for unrelated reasons. This is becoming more common as the frequency of chest imaging increases. There are currently no clear guidelines for managing TE in GD. Subject 1 is a 36-year-old female who presented with weight loss, increased thirst and passage of urine and postural symptoms. Investigations confirmed GD, non-PTH-dependent hypercalcaemia and Addison’s disease (AD). CT scans to exclude underlying malignancy showed TE but normal viscera. A diagnosis of hypercalcaemia due to GD and AD was made. Subject 2, a 52-year-old female, was investigated for recurrent chest infections, haemoptysis and weight loss. CT thorax to exclude chest malignancy, showed TE. Planned thoracotomy was postponed when investigations confirmed GD. Subject 3 is a 47-year-old female who presented with breathlessness, chest pain and shakiness. Investigations confirmed T3 toxicosis due to GD. A CT pulmonary angiogram to exclude pulmonary embolism showed TE. The CT appearances in all three subjects were consistent with benign TE. These subjects were given appropriate endocrine treatment only (without biopsy or thymectomy) as CT appearances showed the following appearances of benign TE – arrowhead shape, straight regular margins, absence of calcification and cyst formation and radiodensity equal to surrounding muscle. Furthermore, interval scans confirmed thymic regression of over 60% in 6 months after endocrine control. In subjects with CT appearances consistent with benign TE, a conservative policy with interval CT scans at 6 months after endocrine control will prevent inappropriate surgical intervention.Learning points:Chest imaging is common in modern clinical practice and incidental anterior mediastinal abnormalities are therefore diagnosed frequently.Thymic enlargement (TE) associated with Graves’ disease (GD) is occasionally seen in view of the above.There is no validated strategy to manage TE in GD at present.However, CT (or MRI) scan features of the thymus may help characterise benign TE, and such subjects do not require thymic biopsy or surgery at presentation.In them, an expectant ‘wait and see’ policy is recommended with GD treatment only, as the thymus will show significant regression 6 months after endocrine control.

THYMIC HYPERPLASIA AS A CASE OF FALSE-POSITIVE PET CT IN A FEMALE WITH LYNCH SYNDROME

SESSION TITLE: Disorders of the Mediastinum 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: Lynch syndrome is an autosomal dominant genetic condition of defective DNA mismatch repair predisposing for malignancies. Here we present a case of Lynch syndrome with endometrial cancer and a hypermetabolic superior mediastinal lymph node on positron emission tomography-computed tomography (PET- CT). CASE PRESENTATION: An Asymptomatic 59-year old female tested positive for Lynch syndrome (PMS2 mutation) during family screening prompted by the death of her son by colon cancer after being diagnosed with Lynch syndrome. She underwent a prophylactic hysterectomy and was found to have well-differentiated adenocarcinoma of the endometrium, pT1b NxM0. Screening mammogram, colonoscopy, and upper endoscopy were negative. CT chest/abdomen/pelvis showed several lung nodules, some of which were calcified suggesting granulomas. PET-CT showed an isolated nodule (1.6 x 1.1 cm) in the upper left paratracheal area with standardized uptake values (SUV) of 11.1. She underwent ultrasound-guided biopsy of the nodule. Histopathology demonstrated scant lymphoid tissue. Flow cytometry was negative for lymphoma. Due to her Lynch syndrome and high activity on PET-CT, she underwent a second ultrasound-guided biopsy the result was suggestive of benign thymic tissue. There was no evidence of metastatic carcinoma. Repeat PET CT showed persistent hypermetabolic activity. She was referred to a thoracic surgeon for mediastinoscopy. She chose conservative observation strategy and is being followed closely. DISCUSSION: Superior mediastinal masses range from benign thymic hyperplasia to malignant etiologies such as lymphoma. Patients with Lynch syndrome are at increased risk for colorectal, endometrial, ovarian, gastric, brain, and skin cancers. However, they are not associated with chest or mediastinal malignancies.The thymus is a lymphoid organ that is active in the early years of life and atrophies in adults. Thymic hyperplasia is the proliferation of cells and increase in activity and size with normal histology seen on biopsy and is seen in young adults. Rebound thymic hyperplasia has been described in young patients treated for malignancy. (1) Increased FDG uptake was previously reported, however, the SUV ranged from 1.1 to 2.2 (2). Sakasi et al (3) reported the mean SUV to be 7.2 ± 2.9 in patients with thymic cancer. Thymic hyperplasia with SUV of 11.1 has not been reported before.Our patient had two negative core biopsies for malignancy despite having a very high SUV on PET-CT, thereby confirming a false positive scan. Our patient also did not have any obvious reasons for hyperplasia and was never treated with chemotherapy, adding to the uniqueness of the case. CONCLUSIONS: Thymic malignancies are typically associated with highly elevated SUVs on PET-CT however, on occasion, hyperplasia can cause mild elevations of an SUV. Our patient had a strongly positive PET CT but benign thymic tissue on biopsy. Reference #1: Sarji A. Physiological uptake in FDG PET simulating disease. Biomed Imaging Interv J. 2006 Oct-Dec; 2(4): e59. Reference #2: Wittram C, Fischman A, Mark E, et al. Thymic Enlargement and FDG Uptake in Three Patients: CT and FDG Positron Emission Tomography Correlated with Pathology. American Journal of Roentgenology. 2003; 180: 519-522. Reference #3: Sasaki M, Kuwabara Y, Ichiya Y, et al. Differential diagnosis of thymic tumors using a combination of 11C-methionine PET and FDG PET. J Nucl Med 1999; 40:1595-1601. DISCLOSURES: No relevant relationships by Amit Diwakar, source=Web Response No relevant relationships by Ahmad JABRI, source=Web Response no disclosure on file for Jason Lane; No relevant relationships by Colin McLaughlin, source=Web Response

GPR54 deficiency reduces the Treg population and aggravates experimental autoimmune encephalomyelitis in mice.

GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system. However, flow cytometry revealed a significant reduction in the peripheral regulatory T cell population and a moderate decrease in CD4 single-positive thymocytes in prepubertal Gpr54-/- mice. These phenotypes were confirmed in chimeric mice with GPR54 deficient bone marrow-derived cells. In addition, we found elevated T cell activation in peripheral and thymic T cells in Gpr54-/- mice. When intact mice were immunized with myelin oligodendrocyte glycoprotein, a more severe experimental autoimmune encephalomyelitis (EAE) developed in the Gpr54-/- mice. Interestingly, aggravated EAE disease was also manifested in castrated and bone marrow chimeric Gpr54-/- mice compared to the respective wild-type control, suggesting a defect in self-tolerance resulting from GPR54 deletion through a mechanism that bypassed sex hormones. These findings demonstrate a novel role for GPR54 in regulating self-tolerant immunity in a sex hormone independent manner.

Thymic pathology and cardiac myxomas: Coincidence or a closer relationship?

Myxomas are the most common benign cardiac tumors and are located more frequently in the left atrium. In the literature there are cases describing the coexistence of thymic tumors and cardiac myxomas. In the case reported herein, during the resection of a cardiac myxoma, an enlarged thymus gland was encountered and resected. The histological exam revealed a thymic hyperplasia. The aim of this case study is to assess the need of conducting further studies in order to identify a common histological pathway between thymic lesions and cardiac myxomas. The diagnosis of a cardiac myxoma could justify a further workup of the anterior mediastinum in order not to overlook a lesion of thymic origin.

Risk of coronary events 55\xa0Years after Thymic irradiation in the Hempelmann cohort

BackgroundStudies of cancer survivors treated with older radiotherapy (RT) techniques (pre-1990s) strongly suggest that ionizing radiation to the chest increases the risk of coronary heart disease (CHD). Our goal was to evaluate the impact of more modern cardiac shielding techniques of RT on the magnitude and timing of CHD risk by studying a cohort exposed to similar levels of cardiac irradiation years ago.MethodsBetween 2004 and 2008, we re-established a population-based, longitudinal cohort of 2657 subjects exposed to irradiation for an enlarged thymus during infancy between 1926 and 1957 and 4388 of their non-irradiated siblings. CHD events were assessed using a mailed survey and from causes of death listed in the National Death Index. We used Poisson regression methods to compare incidence rates by irradiation status and cardiac radiation dose. Results were adjusted for the CHD risk factors of attained-age, sex, diabetes, dyslipidemia hypertension and smoking.ResultsMedian age at time of follow-up was 57.5 years (range 41.2–88.8 yrs) for irradiated and non-irradiated siblings. The mean estimated cardiac dose amongst the irradiated was 1.45 Gray (range 0.17–20.20 Gy), with 91% receiving < 3.00 Gy. During a combined 339,924 person-years of follow-up, 213 myocardial infarctions (MI) and 350 CHD events (MI, bypass surgery and angioplasty) occurred. After adjustment for attained age, gender, and other CHD risk factors, the rate ratio for MI incidence in the irradiated group was 0.98 (95%CI, 0.74–1.30), and for any CHD event was 1.07 (95%CI, 0.86–1.32). Higher radiation doses were not associated with more MIs or CHD events in this dose range, in either the crude or the adjusted analyses.ConclusionsRadiation to the heart during childhood of < 3 Gy, the exposure in most of our cohort, does not increase the lifelong risk of CHD. Reducing cardiac radiation to this amount without increasing other cardiotoxic therapies may eliminate the increased CHD risk associated with radiotherapy for childhood cancer. By extension there is unlikely to be increased CHD risk from relatively higher dose imaging techniques, such as CT, because such techniques use much smaller radiation doses than received by our cohort.