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Paediatric heart transplant is an established treatment for end stage heart failure in children, however patients have to commit to lifelong medical surveillance and adhere to daily immunosuppressants to minimise the risk of rejection. Compliance with immunosuppressants can be burdensome with their toxic side effects and need for frequent blood monitoring especially in children. Though the incidence of early rejection episodes has significantly improved overtime, the long-term allograft health and survival is determined by Cardiac Allograft Vasculopathy (CAV) which affects a vast number of post-transplant patients. Once CAV has set in, there is no medical or surgical treatment to reverse it and graft survival is significantly compromised across all age groups. Current treatment strategies include novel immunosuppressant agents and drugs to lower blood lipid levels to address the underlying immunological pathophysiology and to manage traditional cardiac risk factors. Translational researchers are seeking novel immunological approaches that can lead to permanent acceptance of the allograft such as using regulatory T cell (Tregs) immunotherapy. Clinical trials in the setting of graft versus host disease, autoimmunity and kidney and liver transplantation using Tregs have shown the feasibility and safety of this strategy. This review will summarise current knowledge of the latest clinical therapies for CAV and pre-clinical evidence in support of Treg therapy for CAV. We will also discuss the different Treg sources and the considerations of translating this into a feasible immunotherapy in clinical practice in the paediatric population. [ABSTRACT FROM AUTHOR]

Members of the Protein kinases D (PKD) family are described as regulators of T cell responses. From the two T cell‐expressed isoforms PKD2 and PKD3, so far mainly the former was thoroughly investigated and is well understood. Recently, we have investigated also PKD3 using conventional as well as conditional T cell‐specific knockout models. These studies suggested PKD3 to be a T cell‐extrinsic regulator of the cells' fate. However, these former model systems did not take into account possible redundancies with the highly homologous PKD2. To overcome this issue and thus properly unravel PKD3's T cell‐intrinsic functions, here we additionally used a mouse model overexpressing a constitutively active isoform of PKD3 specifically in the T cell compartment. These transgenic mice showed a slightly higher proportion of central memory T cells in secondary lymphoid organs and blood. This effect could not be explained via differences upon polyclonal stimulation in vitro, however, may be connected to the observed developmental aberrances in the CD8 single positive compartment during thymic development. Lastly, the observed alterations in the CD8+ T cell compartment did not impact proper immune response upon immunization with ovalbumin or in a subcutaneous tumour model suggesting only a small to absent biological relevance. Taking together the knowledge of all our published studies on PKD3 in the T cell compartment, we now conclude that T cell‐intrinsic PKD3 is a fine‐tuner of central memory T cell as well as CD8 single positive thymocyte development. [ABSTRACT FROM AUTHOR]

Paediatric heart transplant is an established treatment for end stage heart failure in children, however patients have to commit to lifelong medical surveillance and adhere to daily immunosuppressants to minimise the risk of rejection. Compliance with immunosuppressants can be burdensome with their toxic side effects and need for frequent blood monitoring especially in children. Though the incidence of early rejection episodes has significantly improved overtime, the long-term allograft health and survival is determined by Cardiac Allograft Vasculopathy (CAV) which affects a vast number of post-transplant patients. Once CAV has set in, there is no medical or surgical treatment to reverse it and graft survival is significantly compromised across all age groups. Current treatment strategies include novel immunosuppressant agents and drugs to lower blood lipid levels to address the underlying immunological pathophysiology and to manage traditional cardiac risk factors. Translational researchers are seeking novel immunological approaches that can lead to permanent acceptance of the allograft such as using regulatory T cell (Tregs) immunotherapy. Clinical trials in the setting of graft versus host disease, autoimmunity and kidney and liver transplantation using Tregs have shown the feasibility and safety of this strategy. This review will summarise current knowledge of the latest clinical therapies for CAV and pre-clinical evidence in support of Treg therapy for CAV. We will also discuss the different Treg sources and the considerations of translating this into a feasible immunotherapy in clinical practice in the paediatric population.

Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies. Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance). The primary objective of phase 1 was to determine the maximum tolerated dose, and the primary end point for each dose-expansion cohort was the objective response rate. Results: A total of 88 patients were enrolled in phase 1 (n = 11) and dose expansion (n = 77) cohorts. Transaminitis was dose-limiting and expansion proceeded with oral vorolanib 200 mg daily combined with intravenous nivolumab 240 mg every 2 weeks. The objective response rate per cohort were as follows: NSCLC naive 33% (five of 15, 95% confidence interval [CI]: 13%–60%), NSCLC primary refractory 5.9% (one of 17, 95% CI: 0%–17.6%), NSCLC acquired resistance 11.1% (two of 18, 95% CI: 0%–27.8%); SCLC 0% (zero of 18), and thymic carcinoma 11% (one of nine, 95% CI: 0%–33%). Disease control rate ranged from 11.1% in SCLC (two of 18, 0%–27.8%) to 66.7 % in thymic carcinoma (six of nine, 95% CI: 33.3%–100%). The most common adverse events were fatigue (32%), aspartate transaminase (27%) and alanine transaminase elevation (25%), and diarrhea (19%). Transaminitis was more common in patients with thymic carcinoma than other tumors. Conclusions: Vorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment.

Introduction and Importance: Cervical thymic cysts are rare benign lesions that rarely considered in the differential diagnosis of neck cysts in children. The correct diagnosis is often made after surgical excision and though determination of the specific histopathological findings of the thymic cyst., Case Presentation: We report an observation of a cervical thymic cyst erroneously diagnosed preoperatively respectively as a cystic lymphangioma., Clinical Discussion: The diagnosis is generally rectified after surgery by identifying the specific histopathological findings of the thymic cyst. Treatment is surgical., Conclusion: This diagnosis should be considered in front of any indolent lateral cervical mass., Competing Interests: Conflict of interest statement The author(s) declare no potential conflicts of interest concerning the research, authorship, or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Members of the Protein kinases D (PKD) family are described as regulators of T cell responses. From the two T cell-expressed isoforms PKD2 and PKD3, so far mainly the former was thoroughly investigated and is well understood. Recently, we have investigated also PKD3 using conventional as well as conditional T cell-specific knockout models. These studies suggested PKD3 to be a T cell-extrinsic regulator of the cells' fate. However, these former model systems did not take into account possible redundancies with the highly homologous PKD2. To overcome this issue and thus properly unravel PKD3's T cell-intrinsic functions, here we additionally used a mouse model overexpressing a constitutively active isoform of PKD3 specifically in the T cell compartment. These transgenic mice showed a slightly higher proportion of central memory T cells in secondary lymphoid organs and blood. This effect could not be explained via differences upon polyclonal stimulation in vitro, however, may be connected to the observed developmental aberrances in the CD8 single positive compartment during thymic development. Lastly, the observed alterations in the CD8 + T cell compartment did not impact proper immune response upon immunization with ovalbumin or in a subcutaneous tumour model suggesting only a small to absent biological relevance. Taking together the knowledge of all our published studies on PKD3 in the T cell compartment, we now conclude that T cell-intrinsic PKD3 is a fine-tuner of central memory T cell as well as CD8 single positive thymocyte development., (© 2024 The Authors. Immunology published by John Wiley & Sons Ltd.)

Four cases of a distinct carcinoma of the thymic gland are presented. The patients were 4 adult males with an age range from 40 to 47 years (mean, 43.5 years). Clinically, all patients presented with non-specific respiratory symptoms. None of the patients had any prior history of head and neck neoplasm or surgery in that anatomic area. Large anterior mediastinal masses were found on diagnostic imaging with concurrent metastatic disease to pleura, lungs, regional lymph nodes and bones. Microscopically, all tumors were composed of a solid proliferation of hyperchromatic, monomorphic small cells with focal cytoplasmic clearing embedded in a fibromyxoid stroma. In one case, occasional duct-like structures were identified. Immunohistochemically, the tumors were positive for pancytokeratin, CD117 and MYB and negative for myoepithelial markers. Systemic chemotherapy was initiated in all patients. Despite therapy, clinical follow-up revealed that all 4 patients died of their disease 11–23 months after their initial diagnosis. The cases in this series highlight a tumor that is different from conventional thymic carcinoma and that has the morphological and immunohistochemical features commonly seen in adenoid cystic carcinomas with high-grade transformation. Correct diagnosis is essential for patient management. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines for patients with multiple endocrine neoplasia type 1 (MEN1) recommend a variety of surveillance options. Given progress over the past decade in this area, it is timely to evaluate their ongoing utility. MEN1 is characterized by the development of synchronous or asynchronous tumors affecting a multitude of endocrine and nonendocrine tissues, resulting in premature morbidity and mortality, such that the rationale for undertaking surveillance screening in at-risk individuals appears robust. Current guidelines recommend an intensive regimen of clinical, biochemical, and radiological surveillance commencing in early childhood for those with a clinical or genetic diagnosis of MEN1, with the aim of early tumor detection and treatment. Although it is tempting to assume that such screening results in patient benefits and improved outcomes, the lack of a strong evidence base for several aspects of MEN1 care, and the potential for iatrogenic harms related to screening tests or interventions of unproven benefit, make such assumptions potentially unsound. Furthermore, the psychological as well as economic burdens of intensive screening remain largely unstudied. Although screening undoubtedly constitutes an important component of MEN1 patient care, this perspective aims to highlight some of the current uncertainties and challenges related to existing MEN1 guidelines with a particular focus on the role of screening for presymptomatic tumors. Looking forward, a screening approach that acknowledges these limitations and uncertainties and places the patient at the heart of the decision-making process is advocated. [ABSTRACT FROM AUTHOR]

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a type of low-grade malignant B-cell lymphoma. The aim of this study was to investigate the clinicopathological characteristics of thymic MALT lymphoma. We analyzed the clinical, morphological, immunophenotypical, cytogenetic, and molecular characteristics of 11 cases of thymic MALT lymphoma. The relevant literature was also reviewed. The median age of the 11 patients was 50 (range: 33–60). There was a female predominance with a female-to-male ratio of 10:1. Three patients presented with Sjögren syndrome, autoimmune thrombocytopenia purpura, and type B1 thymoma, respectively. Microscopically, thymic MALT lymphoma was characterized by epithelium-lined cysts that were surrounded by small lymphocytes, centrocyte-like cells, and monocytoid B-cells. Plasmacytic differentiation was observed in two cases. The tumor cells expressed CD20, CD79α, and BCL2. Clonal immunoglobulin genes were detected in all 8 examined cases. Fluorescence in situ hybridization (FISH) for 18q21 was performed in 7 cases, and no translocations involving 18q21 were found. Targeted gene sequencing was performed in five cases with available DNA samples, and TNFAIP3, CARD11, IGLL5, and CCND3 mutations were identified. Thymic MALT lymphoma is a rare type of B cell malignancy with a female predominance and excellent clinical outcomes. Molecular aberrations involving the NF-κB pathway are frequent in thymic MALT lymphoma, suggesting that dysregulation of the NF-κB pathway is an important mechanism underlying the pathogenesis of thymic MALT lymphoma. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate SATB2 expression and prognostic implications in a large cohort of thoracic neuroendocrine tumors.Methods: Surgical pathology files (1995-2017) and an institutional thymic epithelial tumor database (2010-2020) were searched for resected neuroendocrine tumors. Cases were stained with SATB2 (clone EP281). Percent SATB2-positive tumor cells and expression intensity were scored.Results: In the lung, SATB2 was expressed in 5% or more of tumor cells in 29 (74.4%) of 39 small cell carcinomas and 9 (22.5%) of 40 atypical and 26 (40.6%) of 64 typical carcinoid tumors. SATB2 percent tumor cell expression and intensity were higher in small cell carcinomas than in carcinoid tumors (both P < .001, respectively). After adjusting for tumor subtype, SATB2 expression did not correlate with outcome. In the thymus, four (100%) of four atypical carcinoid tumors and one large cell neuroendocrine carcinoma but no small cell carcinoma (n = 2) expressed SATB2 in 5% or more of tumor cells.Conclusions: SATB2 (clone EP281) is expressed in a large subset of pulmonary and thymic neuroendocrine tumors and therefore does not appear to be a useful marker to identify the origin of neuroendocrine tumors. Validation studies are needed, specifically including thymic neuroendocrine tumors, as the expression pattern might be different in those tumors. [ABSTRACT FROM AUTHOR]

• Proton radiation offers unique advantage for thoracic neoplasms. • Protons can reduce toxicities with similar antitumor effect as conventional RT. • Protons permit safer dose-escalation and concomitant chemotherapy which may lead to improved disease control and survival. • Proton therapy may more safely allow for thoracic reirradiation with curative doses compared with photon therapy. Radiation therapy (RT) plays an important role in the curative treatment of a variety of thoracic malignancies. However, delivery of tumoricidal doses with conventional photon-based RT to thoracic tumors often presents unique challenges. Extraneous dose deposited along the entrance and exit paths of the photon beam increases the likelihood of significant acute and delayed toxicities in cardiac, pulmonary, and gastrointestinal structures. Furthermore, safe dose-escalation, delivery of concomitant systemic therapy, or reirradiation of a recurrent disease are frequently not feasible with photon RT. In contrast, protons have distinct physical properties that allow them to deposit a high irradiation dose in the target, while leaving a negligible exit dose in the adjacent organs at risk. Proton beam therapy (PBT), therefore, can reduce toxicities with similar antitumor effect or allow for dose escalation and enhanced antitumor effect with the same or even lower risk of adverse events, thus potentially improving the therapeutic ratio of the treatment. For thoracic malignancies, this favorable dose distribution can translate to decreases in treatment-related morbidities, provide more durable disease control, and potentially prolong survival. This review examines the evolving role of PBT in the treatment of thoracic malignancies and evaluates the data supporting its use. [ABSTRACT FROM AUTHOR]

The thymus generates cells of the T cell lineage that seed the lymphatic and blood systems. Transcription factor regulatory networks control the lineage programming and maturation of thymic precursor cells. Whether extrathymic antigenic events, such as the microbial colonization of the mucosal tract also shape the thymic T cell repertoire is unclear. We show here that intestinal microbes influence the thymic homeostasis of PLZF-expressing cells in early life. Impaired thymic development of PLZF+ innate lymphocytes in germ-free (GF) neonatal mice is restored by colonization with a human commensal, Bacteroides fragilis, but not with a polysaccharide A (PSA) deficient isogenic strain. Plasmacytoid dendritic cells influenced by microbes migrate from the colon to the thymus in early life to regulate PLZF+ cell homeostasis. Importantly, perturbations in thymic PLZF+ cells brought about by alterations in early gut microbiota persist into adulthood and are associated with increased susceptibility to experimental colitis. Our studies identify a pathway of communication between intestinal microbes and thymic lymphocytes in the neonatal period that can modulate host susceptibility to immune-mediated diseases later in life. [ABSTRACT FROM AUTHOR]

Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies., Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance). The primary objective of phase 1 was to determine the maximum tolerated dose, and the primary end point for each dose-expansion cohort was the objective response rate., Results: A total of 88 patients were enrolled in phase 1 (n = 11) and dose expansion (n = 77) cohorts. Transaminitis was dose-limiting and expansion proceeded with oral vorolanib 200 mg daily combined with intravenous nivolumab 240 mg every 2 weeks. The objective response rate per cohort were as follows: NSCLC naive 33% (five of 15, 95% confidence interval [CI]: 13%-60%), NSCLC primary refractory 5.9% (one of 17, 95% CI: 0%-17.6%), NSCLC acquired resistance 11.1% (two of 18, 95% CI: 0%-27.8%); SCLC 0% (zero of 18), and thymic carcinoma 11% (one of nine, 95% CI: 0%-33%). Disease control rate ranged from 11.1% in SCLC (two of 18, 0%-27.8%) to 66.7 % in thymic carcinoma (six of nine, 95% CI: 33.3%-100%). The most common adverse events were fatigue (32%), aspartate transaminase (27%) and alanine transaminase elevation (25%), and diarrhea (19%). Transaminitis was more common in patients with thymic carcinoma than other tumors., Conclusions: Vorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment., Competing Interests: Dr. Beckermann reports receiving institutional funding from Xcovery and Bristol-Myers Squibb for this work and Aravive, Pionyr, and ArsenalBio unrelated to the submitted work; received consulting fees from Aravive, Alpine Bioscience, Aveo, AstraZeneca, Exelixis, Bristol-Myers Squibb, Merck, Sanofi, and Seagen. Dr. Bestvina reports receiving consulting fees from AstraZeneca, Bristol-Myers Squibb, CVS, Daiichi Sankyo, EMD, Serono, Genentech, Gilead, Jazz, JNJ, Mirati, Novartis, Novocure, Pfizer, Regeneron, Sanofi, Takeda, and Tempus; and support for attending meetings from Bristol-Myers Squibb. Dr. Selvaggi is the Chief Medical Officer of Xcovery Holding, Inc. Dr. Sanborn reports receiving consulting fees from GlaxoSmithKline, AstraZeneca, Janssen Oncology, Macrogenics, Daiichi Sankyo, Sanofi Aventis, BeiGene, Gilead, Illumina, Targeted Oncology, Regeneron, G1 Therapeutics, GE HealthCare, Amgen, Abbvie, and Eli Lilly Oncology; and reports receiving payment or honoraria for presentations for EMD-Serono, GameOn!, Illumina, Binay Foundation, OncLive, and Meeting Events and Conference Coordinators, Inc. Dr. Berry reports receiving institutional funding from Xcovery. Dr. Borghaei reports receiving grants from 10.13039/100002491Bristol-Myers Squibb, Eli Lilly, and 10.13039/100002429Amgen; consulting fees from Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi, Guardant, Natera, Oncocyte, Beigene, iTEO, Jazz, Janssen, Puma, BerGenBio, Bayer, Iobiotech, and Grid Therapeutics; honoraria from Amgen, Pfizer, Daiichi, and Regeneron; support for attending meetings from Amgen, Bristol-Myers Squibb, Merck, Eli Lilly, EMD-Serono, Genentech, Regeneron, and Mirati; and participated on a Data Safety Monitoring Board or Advisory Board for the University of Pennsylvania CAR T Program, Takeda, Incyte, Novartis, and Springworks. The remaining authors declare no conflict of interest., (© 2023 The Authors.)

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. [ABSTRACT FROM AUTHOR]

Background Thymic epithelial tumours are rare cancers for which new treatment options are required. Identification of putative predictive markers is important for developing clinical trials. We studied the expression of five putative predictive biomarkers, potentially actionable by approved experimental drugs. Methods CD52, CD22, CD26, EG5, and IGF-1R expression were investigated by immunohistochemistry in formalin-fixed surgical samples of thymic epithelial tumour patients. All samples containing 10% positive epithelial tumour cells, independent of tumour cell intensity, were considered as positive. Correlation with histological subtype was performed. Results 106 surgical samples (89 thymomas, 12 thymic carcinoma, and 5 thymic neuroendocrine tumours) were evaluated. Overall, CD52, CD22, CD26, EG5 and IGF-1R expression was observed in 7%, 42%, 25%, 42% and 77% of samples, respectively. CD52 expression was more frequent in B2 and B3 thymoma. All TET subtypes stained for CD22, mainly AB thymoma (68%). CD26 expression also correlated with AB thymoma (68%), and A thymoma (50%) subtype, while IGFR1 was the most common marker expressed by thymic carcinoma samples (92%), followed by EG5 (60%). Only EG5 expression was significantly higher in thymic carcinomas than in thymomas (75% vs. 38%, p = 0.026). Conclusions Our data were consistent with a previous study of IGF-1R expression. Based on their expression, activity of agents targeting CD52, CD 22, CD26 and EG5 could be further explored in TET patients. [ABSTRACT FROM AUTHOR]

Thymic neuroendocrine carcinoma (NEC) is a rare type of cancer. Unlike other thymic epithelial tumors and carcinoids originating in other locations, thymic NEC possesses a more aggressive biological behavior, including invasion to proximal structures, local recurrence and distant hematogenous metastasis. Distant metastasis is often observed in the bones, lungs, spleen, liver and adrenal glands. However, pancreatic metastasis resulting from thymic NEC is extremely uncommon, and only a few cases of patients with this disease have been reported. The current study presents the case of a patient with pancreatic metastasis resulting from thymic NEC. The patient was admitted to hospital with an anterior mediastinal neoplasm, which was identified using chest enhanced computed tomography. The patient underwent a monobloc excision of the tumor with resection of involved structures. Subsequently, a pathological diagnosis of atypical thymic carcinoid was provided, according to the morphological characteristics observed and the expression of neuroendocrine markers, as identified by immunohistochemistry. Following surgery, the patient received adjuvant chemotherapy and radiotherapy. However, ~2 years after surgery, metastasis at the pancreatic head was identified. The patient underwent a total pancreatectomy and splenectomy, and did not receive any post-operative therapies; however, the patient succumbed to the disease 9 months following surgery. Overall, the results from the present study demonstrate the clinical features of thymic NEC, which may aid with the diagnosis of this rare disease in other patients. [ABSTRACT FROM AUTHOR]

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Background and Objective: Mediastinal thymic cysts are a relatively rare pathology. With the expansion of eligible individuals screened with cross-sectional imaging for lung cancer, it is likely that there will be an increase in the number of individuals presenting with these cysts. Understanding this rare pathology will become more important when this incidental pathology is encountered., Methods: Search of PubMed was undertaken using keywords "mediastinal", "mediastinum", "thymic", "thymus", "cyst". Relevant literature was reviewed and selected for this comprehensive narrative review, including case reports, case series, and retrospective reviews., Key Content and Findings: Thymic cysts in the mediastinum can be classified into two broad categories, congenital and inflammatory. Accurate diagnosis by imaging is challenging and the majority of patients are asymptomatic. Literature suggests that the majority of cysts are benign, however an unknown percentage may harbor neoplastic processes and over time can cause significant compressive symptoms. Definitive treatment and diagnosis is surgical, with overall excellent outcomes. The decision to pursue surgical treatment versus surveillance requires a shared decision making approach with patients., Conclusions: Given the scarcity of available high quality evidence regarding the management of mediastinal thymic cysts, this review provides practitioners a broad knowledge base to guide patients to make informed decisions., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-22-25/coif). The series “Mediastinal Cysts” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2022 Mediastinum. All rights reserved.)

Aim To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) in predicting the WHO grade of malignancy in thymic epithelial tumors (TETs). Methods A comprehensive literature search of studies published up to March 2014 was performed. Data on maximum standardized uptake value (SUV max ) in patients with low-risk thymomas (A, AB, B1), high-risk thymomas (B2, B3) and thymic carcinomas (C) according to the WHO classification were collected when reported by the retrieved articles. The comparison of mean SUV max between low-risk thymomas, high-risk thymomas and thymic carcinomas was expressed as weighted mean difference (WMD) and a pooled WMD was calculated including 95% confidence interval (95%CI). Results Eleven studies were selected for the meta-analysis. The pooled WMD of SUV max between high-risk and low-risk thymomas was 1.2 (95%CI: 0.4–2.0). The pooled WMD of SUV max between thymic carcinomas and low-risk thymomas was 4.8 (95%CI: 3.4–6.1). Finally, the pooled WMD of SUV max between thymic carcinomas and high-risk thymomas was 3.5 (95%CI: 2.7–4.3). Conclusions 18 F-FDG PET may predict the WHO grade of malignancy in TETs. In particular, we demonstrated a statistically significant difference of SUV max between the different TETs (low-grade thymomas, high-grade thymomas and thymic carcinomas). [ABSTRACT FROM AUTHOR]

Abstract: Thymic neuroendocrine tumours (TNETs) are uncommon but malignant neoplasms, usually associated with a poor prognosis. The number of cases reported is limited to a few hundreds and there are few prognostic factors available. All 28 patients (22 male, 6 female; median age 46.5 years) with thymic neuroendocrine tumour, treated at the Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden between 1985 and 2011 were studied. The overall 3, 5 and 10-year survival was 89%, 79% and 41% respectively. Ki67<10% (p =0.018) as well as surgical resection (p =0.001) and macroscopically radical primary surgery (p =0.034) was associated with increased survival. Staging & grading according to Masaoka and ENETS systems did not correlate with survival. However, a modified ENETS grading showed a positive correlation (p =0.015). Median time to progression was 20.5 months with Temozolomide and 18 months with platinum based therapy. Partial responses were noted in three patients (38%) treated with platinum based therapy and in two patients (20%) treated with Temozolomide based therapy. High proliferative rate, measured by Ki67 index, and absence of macroscopically radical primary resection as well as no surgical resection are three negative prognostic factors in patients with TNETs. Temozolomide or Platinum based chemotherapy should be considered as first-line medical therapy in patients with metastatic or non-resectable tumours. [Copyright &y& Elsevier]

Nine dogs were diagnosed with cranial mediastinal carcinomas. Based on histological and immunohistochemical analysis, four dogs were diagnosed with ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with anaplastic carcinomas. Clinical signs and physical examination findings were associated with a space-occupying mass, although one dog was diagnosed with functional hyperthyroidism. Surgical resection was attempted in eight dogs. The cranial mediastinal mass was invasive either into the heart or into the cranial vena cava in three dogs. Resection was complete in six dogs and unresectable in two dogs. All dogs survived surgery, but four dogs developed pulmonary thromboembolism and two dogs died of respiratory complications postoperatively. Adjunctive therapies included pre-operative radiation therapy ( n = 1) and postoperative chemotherapy ( n = 3). Three dogs had metastasis at the time of diagnosis, but none developed metastasis following surgery. The overall median survival time was 243 days. Local invasion, pleural effusion and metastasis did not have a negative impact on survival time in this small case series. [ABSTRACT FROM AUTHOR]

Abstract: Two common non-steroidal anti-inflammatory drugs (NSAIDs) and their nitric oxide (NO) adducts were evaluated for effects on stomach and thymus. Following 4-h duration (acute) oral dosing of fasted male Wistar rats, 1.33×10−4 mol/kg of ibuprofen caused significant visual irritation score and microscopic thinning, although an ulceration assay proved insensitive. Ibuprofen esterified with NO abolished irritation and significantly reduced thinning. Gastro-protective effects of NO-linked ibuprofen were associated with higher levels of diaphorase by optical density, an enzymatic marker of local synthesis of nitric oxide. Both indomethacin and its congener at 2×10−5 mol/kg produced microscopic signs of thinning only, not visible irritation or alteration of diaphorase staining. Results suggest that NO-linked ibuprofen can promote resistance to mucosal injury, possibly via local synthesis of NO. All NO-congeners and parent NSAIDs produced comparable reductions in the abundance of medullary nitrergic cells, those synthesising NO in thymus, without significantly lowering T-cellularity, the relative size of cortex wherein T-cells are produced. Findings indicate disturbance of T-cell tolerance, consistent with increased risk of autoimmune susceptibility. [Copyright &y& Elsevier]

Abstract: Thymomas are relatively rare tumors that have been reported in a number of rabbits. Clinical signs may be nebulous or a result of the effect of the tumor on the occupied space. Diagnosis is made by aspiration cytology or tissue biopsy and histopathology. Treatment options for thymomas in people and animals include surgery, chemotherapy, and radiation therapy. Surgery appears to offer the best chance for cure and is recommended when possible; however, radiation therapy may also be effective. Chemotherapy alone appears to have limited utility, at least in the rabbit. This article will discuss these treatment options and their use in rabbits with thymoma, both as reported in the literature and based on our experience. [Copyright &y& Elsevier]

Thymic mast cells were studied by light and transmission electron microscopy in chicken embryos during organogenesis. Mast cells made their first appearance at day 15. At days 16 and 17, there was a burst of mast cell development with a peak of 278 ± 54 cells/mm2 at day 16. Then, mast cell density decreased until hatching. During the whole embryonic period, about 80% of mast cells localized to the thymic medulla. In the cortex, they were less numerous, and some rare mast cells could be identified in the capsule and septa. Thymic mast cells could be recognized in association with hematopoietic foci, but frequently they grew independently from areas of hematopoiesis and appeared as single cells interspersed among thymocytes, thymic epithelial cells, and interdigitating cells. They were often recognized in close relationship with the scanty and delicate extracellular matrix of the developing gland. Viewed by electron microscopy, mast cells were relatively small cells, with a few secretory granules. Exocytosis was never seen, but, notably, granules emptied in a piecemeal degranulation fashion. This study demonstrates that the chicken thymus is a site of mast cell development during embryogenesis. The high mast cell density we found suggests a possible role for these cells during thymus organogenesis. [ABSTRACT FROM AUTHOR]

A randomized controlled trial of treatment with thymic humoral factor (THF) in 20 children with severe complicated acute measles infection, resulted in objective benefit as evidenced by improvement in the ESR and a fall in C-reactive protein, fewer complications and a reduced incidence of secondary herpes infection, An increased ratio of helper to suppressor T cells (OKT4/OKT8 ratio) and a greater lymphocyte transformation response to phytohaemagglutin was seen in those children receiving THF. We conclude that THF treatment helps to prevent the development of complications particularly secondary viral infections possibly by enhancing cell-mediated immune responses. [ABSTRACT FROM AUTHOR]

We demonstrated previously that isotopic and isochronic grafts of the quail bursa of Fabricius rudiment performed at 5 days of incubation (E5) into chick embryos resulted in the development of a chimeric bursa whose chick host B lymphocytes and accessory cells differentiated in a foreign, quail epithellal environment. Such animals reject their grafted bursa by the age of 2–3 weeks post-hatching (1,2). Isotopic embryonic grafts of the thymus epithellomesenchymal anlagen from the quail donor of the bursal rudiment were carried out at E4.5 (before their colonization by hemopoletic precursor cells), following partial or complete host thymectomy. The quall thymic epithelial stroma was accepted and invaded by chick hemopoietic precursor cells that further differentiated into lymphocytes and dendritic cells. Tolerance of the foreign bursa was induced in such thymobursal chimeras. This demonstrates that the thymic epithellum has the capacity to induce tolerance of xenogeneic rudiments when both grafts are implanted at early stages of embryonic development. We also report on the production of two birds in which removal of the chick host thymus was complete thus generating chimeras in which host T and B lymphocytes differentiated in a completely xenogeneic epithellal environment. [ABSTRACT FROM PUBLISHER]

Abstract: Thymic carcinoma (TC) is a rare intrathoracic malignancy that it can be invasive and refractory to conventional treatment. Comprehensive genomic analysis evidenced a molecularly distinct subset of thymic carcinoma with high prevalence of c-kit mutation, which may behave as a gastrointestinal stromal tumor (GIST). Here, we present a case report of TC with c-Kit mutation, who has relapsed after exposure to multiple lines of combination chemotherapy, but he has shown an impressive and long lasting response to sunitinib after imatinib failure. [Copyright &y& Elsevier]

The article presents a case of a 49-year-old white female with brain metastasis from thymic carcinoma in association with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and pituitary enlargement. The patient's enlarged pituitary was due to pituitary hyperplasia which is difficult to diagnose. Some causes are increase in demand like pregnancy, a hormonal change or circulating humoral factors like viral infections and paraneoplastic syndromes.

Summary: Hodgkin''s lymphoma may involve the lymph nodes, the thymus or both. It is the most frequent lymphoid proliferation in the mediastinum. Symptoms and radiological findings are non-specific. These tumors must be considered in case of thymus involvement in order to avoid a surgical treatment which could lead to many complications. We report a case of primary Hodgkin''s lymphoma of thymic origin in a 39-year-old woman, with a past medical history of a pleomorphic adenoma of the parotid, who presented with a chest pain. Simple chest radiography showed an anterosuperior mediastinal mass. Thoracic computed tomography revealed an 8-cm and heterogeneous thymic tumor with an involvement of mediastinal nodes. The suggested diagnosis was thymoma. A thymectomy with resection of the involved nodes was undergone via a left posterolateral thoracotomy. The definitive histologic study revealed a Hodgkin''s lymphoma classified as a nodular sclerosing type, which was confirmed by the immunohistochemistry. This case was stage I according to the Costwold classification. The patient received treatment based on 5 cycles of chemotherapy in association to radiotherapy. The response was total with a complete remission without recurrences after a follow up of 2 years. Thymic Hodgkin''s lymphoma must always be considered among the diagnostic options, because the prognosis is strongly dependent on correct early treatment. Treatment is based on radiotherapy and chemotherapy. The main prognostic factors are the size of the tumors, direct invasion of the lung or adjacent tissues, advanced stage, presence of constitutional symptoms and age older than 50–60 years. [Copyright &y& Elsevier]

Thymic carcinoids are extremely rare. We present an 80 year old hypertensive patient who presented as an emergency with sudden onset of severe chest and upper back pain raising the suspicion of acute aortic dissection or acute coronary syndrome. Further investigations revealed a carcinoid tumour of thymic origin. [Copyright &y& Elsevier]

High-grade and poorly differentiated thymic neuroendocrine carcinoma is the rarest entity in thymic epithelial tumours. The aim of this study is to report survival data in a multi-institutional database in comparison to data in the literature. Retrospective chart review was performed on the basis of our multi-institutional database to identify patients undergoing the resection of poorly differentiated thymic neuroendocrine carcinoma between 1991 and 2018. Relevant factors were extracted, and survival analysis was performed using the Kaplan-Meier method. Twenty-one patients were identified. Five-year overall survival and recurrence-free survival were 64.6% and 51.8%, respectively. Twelve (57.1%) patients had recurrences. Due to the scarcity of data reported in the literature, our data may be used as a standard in high-grade and poorly differentiated thymic neuroendocrine carcinoma., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Ever since the introduction of anti-tumor necrosis factor (TNF) agents, concerns have been raised regarding their potential for developing malignancy. We report the development of thymic atypical carcinoid tumor 9 months after the initiation of etanercept therapy in a patient having refractory spondylarthritis. This case indicates the need for following large cohorts of patients receiving anti-TNF agents to address the long-term effect of these agents on malignancies. [ABSTRACT FROM AUTHOR]