Differentiation between rebound thymic hyperplasia and thymic relapse after chemotherapy in pediatric Hodgkin lymphoma.

BACKGROUND: Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum. METHODS: After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated. RESULTS: After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth. CONCLUSION: Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH.

Graves' Disease with Thymic Hyperplasia: The Response of the Thyroid Function, Thyrotropin Receptor Autoantibody, and Thymic Size to Thiamazole Treatment.

We treated a 22-year-old woman suffering from Graves' disease and thymic hyperplasia. She was referred to our institution for a close investigation of thyrotoxicosis and thymic mass. Thyroid tests and magnetic resonance imaging resulted in a diagnosis of Graves' disease and thymic hyperplasia. The thyroid function and thyroid-stimulating hormone receptor antibody (TRAb) were normalized one and five months after thiamazole initiation, respectively. The thymic size began to decrease after 1 month and was further decreased after 5 months; it was normalized after 12 months. The correlation between TRAb titers and the thymic size (R2=0.99) suggested that the patient's autoimmunity might have contributed to the thymic hyperplasia.

Fat Content Quantification Using Dual-Energy CT for Differentiation of Anterior Mediastinal Lesions from Normal or Hyperplastic Thymus.

BACKGROUND: Detection of fat content in thymic lesions is crucial to differentiate thymic hyperplasia from thymic tumors or other anterior mediastinal pathologies. PURPOSE: To assess the feasibility of dual-energy CT (DECT) fat content quantification for the differentiation of anterior mediastinal lesions from benign thymic lesions and the normal spectrum of the thymus. MATERIALS AND METHODS: Chest DECT images of 465 patients (median 61 years, 63% female) were visually evaluated by two radiologists and semiquantitatively scored based on the degree of fatty degeneration ranging from completely fatty (score 0) to predominantly soft-tissue (score 3), and anterior mediastinal mass (score 4). A subset of scans (n =134 including all cases with scores 2-4 and 20 randomly-selected cases from scores 0 and 1) underwent quantitative DECT analysis (fat fraction, iodine density, and conventional CT value). DECT values were compared across the semiquantitative scores. RESULTS: Results of visual evaluation included 35 with predominantly solid thymus (score 3) and 15 with anterior mediastinal mass (score 4). The most common clinical diagnoses of the 15 masses (including 8 with pathologic confirmation) were metastases (n = 10) and lymphoma (n = 4). CT values in the abnormal thymus were significantly higher than those in score 3 (median: 69.7 HU versus 19.9 HU, P <0.001). There was no significant difference in iodine density values (median: 1.7 mg/ml versus 1 mg/ml, P = 0.09). However, the fat fraction value was significantly lower in the abnormal thymus (score 4) than in the predominantly soft-tissue attenuation thymuses (score 3) (median: 12.8% versus 38.7%, P <0.001). ROC curve analysis showed that fat fraction had an AUC of 0.96 (P <0.001), with a cutoff of <39.2% fat fraction yielding 100% sensitivity and 85% specificity. CONCLUSION: DECT fat fraction measurements of the thymus may provide additional value in distinguishing anterior mediastinal lesions from benign thymus. Use of DECT may reduce the need for subsequent imaging evaluation.

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.

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.

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 masses and mimics in adults: review of common and uncommon pathologies.

The thymus is a primary lymphoid organ that plays a key role in the immune system development. Normally, it is located in the anterior mediastinum and it changes tissue composition with progressive fatty involution with age. The spectrum of pathological processes involving the thymus include enlargement, tumour development, and cystic change. In addition, other local pathology can mimic thymic disease. Differentiating these entities can be challenging; however, recognizing key features on imaging is essential to appropriately guide further investigation and therapy. The focus of this pictorial review will be to highlight the important distinguishing features of thymic hyperplasia, thymomas, thymic cysts, thymic neuroendocrine tumours (NETs), thymolipomas, mediastinal teratomas, and other mimics of thymic disease. Knowledge of the varying imaging findings on computed tomography and magnetic resonance imaging is valuable for radiologists to appropriately classify disease, avoid misdiagnosis, and expedite therapy.

The paediatric thymus: recognising normal and ectopic thymic tissue.

The appearance of the paediatric thymus changes as the normal process of thymic involution occurs. Thymic tissue may be orthotopic within the anterior mediastinum or ectopically located along the course of its embryological development. The variable appearance of orthotopic and ectopic thymic tissue in children on imaging studies may lead to misinterpretation of the normal thymus as pathology. Recognition of normal thymic tissue can mitigate unnecessary further diagnostic testing and patient anxiety. In this review, we discuss the embryological development and anatomical variants of normal thymus, and demonstrate the multimodality imaging features of the normal thymus in children, including positron-emission tomography, and diffusion-weighted imaging and in- and opposed-phase imaging on magnetic resonance imaging. We demonstrate the normal thymus mimicking pathological processes and discuss features that distinguish normal thymus, including thymic rebound hyperplasia, from pathology.

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.

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

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

Anterior mediastinal lesions: CT and MRI features and differential diagnosis.

Anterior mediastinum is the most common location of mediastinal tumors, which include various solid and cystic lesions. The lesion location and CT and MRI features are important in the differential diagnosis. Recently, CT-based mediastinal compartment classification systems were proposed and suggested to be useful for accurate evaluation of mediastinal lesions. CT and MRI reflect the pathological findings of mediastinal lesions, and knowledge of the pathological features is important for the differential diagnosis. In this article, we review the CT and MRI features of anterior mediastinal lesions and describe important points in the differential diagnosis.

Pictorial Review of Mediastinal Masses with an Emphasis on Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) has become a crucial tool for evaluating mediastinal masses considering that several lesions that appear indeterminate on computed tomography and radiography can be differentiated on MRI. Using a three-compartment model to localize the mass and employing a basic knowledge of MRI, radiologists can easily diagnose mediastinal masses. Here, we review the use of MRI in evaluating mediastinal masses and present the images of various mediastinal masses categorized using the International Thymic Malignancy Interest Group's three-compartment classification system. These masses include thymic hyperplasia, thymic cyst, pericardial cyst, thymoma, mediastinal hemangioma, lymphoma, mature teratoma, bronchogenic cyst, esophageal duplication cyst, mediastinal thyroid carcinoma originating from ectopic thyroid tissue, mediastinal liposarcoma, mediastinal pancreatic pseudocyst, neurogenic tumor, meningocele, and plasmacytoma.

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.

Revisando un órgano olvidado: Evaluación del timo en PET-CT / Revisiting a Forgotten Organ: Thymus Evaluation in PET-CT

Resumen La pesquisa incidental de lesiones tímicas ha aumentado. Una adecuada aproximación a esas lesiones en la tomografía computada por emisión de positrones (PET-CT) es fundamental, pues se usa como parte de la mayoría de los procedimientos de planificación oncológica. Se han seleccionado casos representativos respecto de los aspectos más importantes de las imágenes de timo en PET-CT y cómo esa técnica puede contribuir a un diagnóstico preciso o a la planificación del tratamiento. Específicamente, presentamos una descripción general de las lesiones tímicas comunes y los imitadores de enfermedad, con énfasis en los hallazgos en PET-CT, incorporando también ejemplos de resonancia magnética (RM).

Abstract Incidental thymic lesion findings have increased. An adequate characterization of these lesions in positron emission computed tomography (PET-CT) is essential, since it is used as part of most oncological planning procedures. Representative cases have been selected regarding the most important aspects of thymus imaging in PET-CT and how this technique can contribute to an accurate diagnosis or treatment planning. Specifically, we present a general description of common thymic lesions and disease mimics, with an emphasis on PET-CT findings, also incorporating examples of magnetic resonance imaging.

[Rebound (reactive) thymic hyperplasia after chemotherapy in children with lymphoma]. / Hiperplasia tímica de rebote posquimioterapia en niños con linfoma.

INTRODUCTION: Thymic regrowth after chemotherapy treatment has been reported in children with lymphoma, and in order to avoid misdiagnosing these cases as relapses, physicians should become familiar with rebound (reactive) thymic hyperplasia (RTH) and remain aware of its possible occurrence. We aimed to estimate the prevalence of RTH in children with lymphoma after completion of chemotherapy and to evaluate the clinical characteristics, outcomes, and the findings of computed tomography (CT) and gallium-67 (GA-67) scans in these patients. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study by reviewing the health records of children with a lymphoma diagnosis managed at an outpatient paediatric oncology clinic in Jeddah, Saudi Arabia. RESULTS: Rebound thymic hyperplasia was detected in 51.9% of the lymphoma patients (14/27). It developed a median of 2.5 months after completion of chemotherapy (range, 2.0-4.25 months). Patients with RTH had significantly shorter treatment durations, and we found no significant differences between patients with and without RTH in sex, age at diagnosis, type of lymphoma or type of treatment received. All patients with RTH were asymptomatic, and routine laboratory tests did not detect any abnormalities in them. The findings of CT and GA-67 scans were highly suggestive of RTH. None of the patients with RTH had a recurrence, and RTH resolved spontaneously within a median of 6 months (range, 4.0-11.0). CONCLUSION: RTH was detected in ∼50% of children with lymphoma after completion of chemotherapy. A clinical evaluation and laboratory tests combined with imaging by CT and GA-67 can help identify RTH and rule out other lesions elsewhere.

Late Relapse of Ovarian Germ Cell Tumour.

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

[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.