Search

T-lymphoblastic lymphoma (T-LBL) and thymoma are two rare primary tumors of the thymus deriving either from T-cell precursors or from thymic epithelial cells, respectively. Some thymoma subtypes (AB, B1, and B2) display numerous reactive terminal deoxynucleotidyl transferase-positive (TdT + ) T-cell precursors masking epithelial tumor cells. Therefore, the differential diagnosis between T-LBL and TdT + T-lymphocyte-rich thymoma could be challenging, especially in the case of needle biopsy. To distinguish between T-LBL and thymoma-associated lymphoid proliferations, we analyzed the global DNA methylation using two different technologies, namely MeDIP array and EPIC array, in independent samples series [17 T-LBLs compared with one TdT + lymphocyte-rich thymoma (B1 subtype) and three normal thymi, and seven lymphocyte-rich thymomas compared with 24 T-LBLs, respectively]. In unsupervised principal component analysis (PCA), T-LBL and thymoma samples clustered separately. We identified differentially methylated regions (DMRs) using MeDIP-array and EPIC-array datasets and nine overlapping genes between the two datasets considering the top 100 DMRs including ZIC1, TSHZ2, CDC42BPB, RBM24, C10orf53, and MACROD2. In order to explore the DNA methylation profiles in larger series, we defined a classifier based on these six differentially methylated gene promoters, developed an MS-MLPA assay, and demonstrated a significant differential methylation between thymomas (hypomethylated; n = 48) and T-LBLs (hypermethylated; n = 54) (methylation ratio median 0.03 versus 0.66, respectively; p < 0.0001), with MACROD2 methylation status the most discriminating. Using a machine learning strategy, we built a prediction model trained with the EPIC-array dataset and defined a cumulative score taking into account the weight of each feature. A score above or equal to 0.4 was predictive of T-LBL and conversely. Applied to the MS-MLPA dataset, this prediction model accurately predicted diagnoses of T-LBL and thymoma. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

The therapeutic approach to thymic cysts remains a subject of controversy. Predicted biomarkers for identifying thymic cysts and thymoma (THYM) are crucial. In this research, patients diagnosed with thymic cysts (MTC, n = 6) and thymoma (B1, n = 6; B3, n = 6) were enrolled. Proteins of superior quality were subjected to TMT labeling and UPLC-MS, and differentially expressed proteins (DEPs) were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactive network analyses were applied to the DEPs. Some key differentially expressed genes(DEGs) were corroborated through GEPIA 32. The pan-cancer expression levels of key DEGs remarkably linked with prognosis were determined utilizing The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). Eventually, 49 DEPs were identified in the B1 vs. MTC comparison (17 upregulated and 32 downregulated), 27 in the B3 vs. MTC comparison (8 upregulated and 19 downregulated), and 38 in the B3 vs. B1 comparison (9 upregulated and 29 downregulated). IL13RA1 (down), galectin-3 binding protein (LGALS3BP)(up), PRCSH (down), C3 (down), MXRA5 (down), TNN (down), CFHR1 (down), SUN3 (down) were jointly altered in both B1 vs. NZ and B3 vs. NZ. GEPIA validated that LGALS3BP was significantly upregulated in thymoma patients. In conclusion, LGALS3BP might be an essential biomarker to identify thymoma from the thymic cyst., (© 2024. The Author(s).)

Rationale: This study aims to present a novel surgical approach for the resection of anterior mediastinal tumors, specifically focusing on micronodular thymoma with lymphoid stroma (MNT), a rare and distinct variant of thymoma. The single subxiphoid incision technique, although reported in limited cases, offers a minimally invasive option with potential benefits. We report the case of a 76-year-old male who underwent this innovative procedure and was diagnosed with MNT, providing insight into the management and outcomes of this rare pathology., Patient Concerns: The patient presented for the excision of an anterior mediastinal tumor, with the surgery facilitated by sternal hooks to improve visualization. The rarity of MNT and its unclear prognosis underscore the need for enhanced diagnostic accuracy and tailored treatment strategies., Diagnoses: Initially diagnosed preoperatively with a thymic cyst, the patient's final diagnosis was revised to MNT following surgery, highlighting the diagnostic challenges associated with this rare tumor., Interventions: The tumor was successfully removed using minimally invasive thoracoscopic surgery through a subxiphoid single-incision, demonstrating the feasibility and potential advantages of this approach., Outcomes: The patient had a favorable postoperative course, with a swift recovery and no complications, and remained in good health without signs of relapse at the 9-month follow-up., Lessons: This case underscores the importance of recognizing the unique pathological features of MNT and the need for a cautious diagnostic approach to differentiate it from other cystic lesions. Additionally, the successful use of single-port thoracoscopy under the xiphoid process for the removal of thymic tumors suggests its potential as an effective surgical method for these challenging cases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Myasthenia gravis (MG) and idiopathic inflammatory myopathy (IIM) are autoimmune diseases of the nervous system, and their main clinical manifestation is muscle weakness. The concurrent presence of both conditions in the same patient is clinically rare and easily missed. Here, we report the case of a 74-year-old woman who went to the doctor with fluctuating weakness of the limbs and muscle pain. By analyzing the patient's history and the results of repeated frequency electrical stimulation, chest computed tomography, thigh muscle magnetic resonance imaging, serum antibody detection, lymph node biopsy, etc., she was finally diagnosed with MG-concomitant IIM with squamous cell carcinoma of the thymus. Acetylcholine receptor antibody, titin antibody, ryanodine receptor antibody, anti-JO-1 antibody, and Ro-52 antibody tests were positive. MG-concomitant IIM is often associated with thymoma. The immunopathology mechanism may be different from that of pure MG or IIM, which needs further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Dai, Liu, Zhang, Yin, Liu, Ren, Duan and Yang.)

Competing Interests: The authors report no conflicts of interest.

Background: Thymomas are thymic epithelial-derived, most common primary anterior mediastinal masses. Non-tuberculous mycobacteria (NTM) are species that do not cause leprosy and belong to species outside the Mycobacterium tuberculosis complex., Methods: With the clinical application of targeted next-generation sequencing (tNGS), we promptly confirmed a case of NTM infection combined with NTM infection after thymoma surgery, and we performed a joint literature analysis of the two diseases to improve clinicians' understanding and recognition of lung infections after thymoma surgery., Results: Chest CT of both lungs showed multiple hyperdense shadows. Sputum bacterial culture and characterization detected Neisseria Dryad and Streptococcus Grass Green. The presence of Mycobacterium abscessus infection was confirmed by alveolar lavage fluid sent for second-generation macro gene sequencing., Conclusions: The body's immune function decreases after thymoma surgery. When empirical anti-infection treatment for recurrent pneumonia in the lungs is ineffective, we should be alerted to the possibility of the presence of pulmonary non-tuberculous mycobacterial infection, and next-generation sequencing should be performed promptly to arrive quickly at a diagnosis.

Purpose: An accurate diagnosis of thymic malignancies is important, but challenging due to the broad range of differential diagnoses. This study aims to evaluate the efficacy of PET/CT and tumor markers for diagnosing thymic malignancies., Methods: Patients admitted to our department between January 2012 and December 2021 with primary anterior mediastinal tumors were retrospectively evaluated. We evaluated the relationship between the maximum standardized uptake value (SUVmax), tumor markers, and pathological diagnosis in four groups: thymic carcinoma, thymoma, lymphoma, and others., Results: In total, 139 patients were included in this study. The SUVmax was significantly higher in lymphoma, thymic carcinoma, and thymoma, in that order. The cytokeratin 19 fragment (CYFRA 21-1) was significantly higher in thymic carcinoma than in the other groups. An ROC curve analysis indicated that the optimal cut-off values of SUVmax for thymic carcinoma plus lymphoma and CYFRA 21-1 for thymic carcinoma were 7.97 (AUC = 0.934) and 2.95 (AUC = 0.768), respectively. Using a combination of cut-off values (SUVmax = 8, CYFRA 21-1 = 3), the accuracy rate for diagnosing thymic carcinoma was 91.4%., Conclusions: The SUVmax and CYFRA 21-1 levels are significant indicators for the diagnosis of thymic carcinoma. Combining these indicators resulted in a more accurate diagnosis of thymic malignancies, which could facilitate the decision-making process for determining the optimal treatment strategies., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Abstract: Intrathyroidal thymic carcinoma (ITC) is a very rare malignant epithelial tumor of the thyroid gland with thymic epithelial differentiation. Here, we are reporting the case of an eighty-year-old man who at presentation had extrathyroidal spread to the larynx and metastasis to regional lymph nodes. Though the tumor had a relatively low-grade morphology, there were areas of high mitotic activity with areas of necrosis. The classically described ivory-white gross appearance of the tumor, histomorphology of thick bands dividing the tumor into lobules, squamous cell differentiation, tight whorls of cells resembling Hassall's corpuscle, and areas showing dense lymphocytic infiltration, together with an immunoprofile of CD5, Ckit, Tumor protein 63 (p63), and B-cell lymphoma 2 gene (bcl2) positivity, helped in diagnosing this rare entity. Though classically ITC is said to have a good prognosis, cases with spread to adjacent organs and lymph node metastasis may not have an indolent course., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Background: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome., Objectives: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation., Methods: Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab., Results: Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation., Conclusion: Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare., Case Presentation: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18 F-FDG uptake on 18 F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis., Conclusion: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis., (© 2024. The Author(s).)

A young woman in her early 30s presented with a right thyroid mass and progressive hoarseness due to a right vocal cord palsy. The preoperative fine-needle aspiration cytology was classified as Bethesda V and she underwent a total thyroidectomy and neck dissection. Intraoperatively, the thyroid mass was adherent to the oesophagus, trachea and encasing the right recurrent laryngeal nerve which was sacrificed. Final histopathology diagnosed a rare subtype of thyroid cancer known as intrathyroidal thymic carcinoma (ITC). She was then sent for adjuvant radiotherapy after a multidisciplinary tumour board discussion. This case report highlights the difficulty in preoperative diagnosis of ITC and the importance of immunohistochemical staining in clinching the diagnosis. In view of its rarity, there have been no published consensus on the treatment of ITC, hence we would like to share some learning points through a comprehensive literature review., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Thymoma is a rare malignancy with usual location in the antero-superior mediastinum. Ectopic cervical thymoma (ECT) is an extremely rare tumor that originates from ectopic tissue, and is caused by the aberrant migration of the embryonic thymus. Our patient was a 56-year-old man who had a nodular lesion in the neck for several years. Computed tomography and Enhanced magnetic resonance imaging were performed. He underwent surgery, and a histological examination resulted in a diagnosis of type AB thymoma., (© 2024. The Author(s).)

Purpose: The aim of this study was to evaluate the potential role of [ 18 F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [ 18 F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUV max ), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUV max , MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUV max , TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUV max , MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [ 18 F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

Competing Interests: Competing interests: None declared.

Background: Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG)., Case Presentation: We report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies., Conclusions: Diagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention., (© 2024. The Author(s).)

Thymic imaging is challenging because the imaging appearance of a variety of benign and malignant thymic conditions are similar. CT is the most commonly used modality for mediastinal imaging, while MRI and fluorine 18 fluorodeoxyglucose (FDG) PET/CT are helpful when they are tailored to the correct indication. Each of these imaging modalities has limitations and technical pitfalls that may lead to an incorrect diagnosis and mismanagement. CT may not be sufficient for the characterization of cystic thymic processes and differentiation between thymic hyperplasia and thymic tumors. MRI can be used to overcome these limitations but is subject to other potential pitfalls such as an equivocal decrease in signal intensity at chemical shift imaging, size limitations, unusual signal intensity for cysts, subtraction artifacts, pseudonodularity on T2-weighted MR images, early imaging misinterpretation, flow and spatial resolution issues hampering assessment of local invasion, and the overlap of apparent diffusion coefficients between malignant and benign thymic entities. FDG PET/CT is not routinely indicated due to some overlap in FDG uptake between thymomas and benign thymic processes. However, it is useful for staging and follow-up of aggressive tumors (eg, thymic carcinoma), particularly for detection of occult metastatic disease. Pitfalls in imaging after treatment of thymic malignancies relate to technical challenges such as postthymectomy sternotomy streak metal artifacts, differentiation of postsurgical thymic bed changes from tumor recurrence, or human error with typical "blind spots" for identification of metastatic disease. Understanding these pitfalls enables appropriate selection of imaging modalities, improves diagnostic accuracy, and guides patient treatment. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Thymomas are benign thymic epithelial neoplasms, rarely found outside the anterior mediastinum. Although hyperthyroid states have been associated with thymic hyperplasia, only 3 thymoma cases have been previously reported in patients with Graves disease (GD), all within the anterior mediastinum. Here, we report a case of ectopic cervical thymoma in a 22-year-old female patient previously treated for GD. The patient underwent ultrasonography, computed tomography, inconclusive fine-needle aspiration, and ultimately gross dissection for diagnostic workup and definitive treatment of an anterior neck mass, producing a 2.5 × 2.3 × 1.5-cm entity consistent with Masaoka stage I and type B2 thymoma per World Health Organization classification. The patient underwent an uncomplicated subsequent clinical course, with no adjuvant radiotherapy administered. After conducting a systematic literature review, we conclude that of the 109 cases of ectopic cervical thymoma reported, this is the first to describe a case of ectopic cervical thymoma in a patient with a past medical history of GD. For GD patients in stable euthyroid remission with the persistent or recurrent presence of an anterior neck mass, the extrathyroidal origin of the mass should always be considered, including the exceptional presence of a cervical ectopic thymoma., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of investigations for the confirmation of diagnosis. Thymomas are rare mediastinal tumors that present as anterior mediastinal mass; however, thymomas presenting as pyrexia of unknown origin has rarely been reported in the literature. We report an interesting case of a middle-aged male who presented as pyrexia of unknown origin due to thymoma., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Background: Good's syndrome (GS) is a rare immune deficiency described almost 6 decades ago. Despite numerous published individual case reports and data collected in cross-sectional studies of small cohorts, the natural history and long-term outcomes of this disease remain unknown., Objective: We aimed to determine the clinical and laboratory evolution of 8 adults diagnosed with GS and consecutively evaluated between 1983 and 2023., Methods: In this prospective, longitudinal cohort study, newly diagnosed patients with GS were followed through repeated measures of clinical, immune, and hematologic changes, as well as targeted genetic screening., Results: All patients reported a healthy childhood and adolescence with symptom onset during the third or fourth decade of life. All presented to our center with recurrent bacterial sinopulmonary infections, thymoma, hypogammaglobulinemia, and absence of B cells. The median age of GS diagnosis was 57 years. During follow-up, immunoglobin replacement therapy effectively minimized sinopulmonary infections. However, the majority experienced severe and systemic viral or fungal infections, 3 developed basal cell carcinomas, and 5 had progressive bronchiectasis and persistent splenomegaly. The most notable clinical feature was opportunistic infections and in vitro evidence of cellular immune deficiency, which resulted in the death of 2 individuals. We also report a statistically significant, multidecade progressive decline in lymphocytes, platelets, hemoglobin, and red blood cells in our cohort, suggesting gradual bone marrow failure., Conclusions: Knowledge of the unique phenotype and temporal evolution of GS has allowed us to develop a more comprehensive diagnostic framework. It can be investigated as part of broader research into disease pathophysiology., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Thymic epithelial tumours show characteristic cytological features on fine-needle aspiration cytology, however the cytological features of thymoma in fluid cytology are not well described. We present the case of a 77 year-old-woman with known pleural dissemination of type B2/B3 thymoma presenting with shortness of breath and orthopnoea due to a pleural effusion. Cytological evaluation of the pleural fluid showed cellular smears composed of numerous small lymphocytes with small numbers of admixed mesothelial cells. There was no epithelial component. On immunohistochemical (IHC) staining the lymphocytes were T cells which were positive for CD3. CD1a and terminal deoxynucleotide transferase (TdT) were also positive, consistent with immature lymphocytes of thymic origin. Despite the lack of an epithelial component, this case was diagnosed as suspicious for recurrent/ metastatic thymoma. This is only the second published case of thymoma identified on pleural fluid cytology, and to our knowledge the first case describing thymoma in pleural fluid with no epithelial component, a potential pitfall with the more common differential diagnosis of a reactive lymphocytic effusion., (© 2023 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Objectives: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics., Methods: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022., Results: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence., Conclusions: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objectives: A study of tumour metabolic reprogramming has revealed disease biomarkers and avenues for therapeutic intervention. Metabolic reprogramming in thymoma is currently understudied and largely unknown. This study utilized metabolomics and isotope tracing with 13C-glucose to metabolically investigate thymomas, adjacent thymic tissue and benign thymic lesions., Methods: From 2017 to 2021, 20 patients with a suspected thymoma were recruited to this prospective Institutional Review Board approved clinical trial. At the time of surgery, 11 patients were infused with 13C-glucose, a stable, non-radioactive tracer which reports the flow of carbon through metabolic pathways. Samples were analysed by mass spectrometry to measure the abundance of >200 metabolites.13C enrichment was measured in patients who received 13C-glucose infusions., Results: Histological analysis showed that 9 patients had thymomas of diverse subtypes and 11 patients had benign cysts. In our metabolomic analysis, thymomas could be distinguished from both adjacent thymus tissue and benign lesions by metabolite abundances. Metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism were differentially expressed across these tissues.13C-glucose infusions revealed differential labelling patterns in thymoma compared to benign cysts and normal thymus tissue. The lactate/3PG labelling ratio, a metabolic marker in aggressive lung tumours correlated with lactate uptake, was increased in thymomas (1.579) compared to normal thymus (0.945) and benign masses (0.807) (thymic tissue versus tumour P = 0.021, tumour versus benign P = 0.013)., Conclusions: We report metabolic biomarkers, including differential 13C labelling of metabolites from central metabolism, that distinguish thymomas from benign tissues. Altered glucose and lactate metabolism warrant further investigation and may provide novel therapeutic targets for thymoma., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Thymomas are tumors of the mediastinum often associated with autoimmune conditions, in particular myasthenia gravis. In contrast, among the fewer than 40 reports of metaplastic thymoma, myasthenia gravis is rarely found. We describe the fourth patient, and first man, with metaplastic thymoma and myasthenia gravis. A 34-year-old had acute onset of double vision with associated dysphagia and was found to have an elevation of serum acetylcholine receptor antibodies. He underwent a transsternal thymectomy. Tissue sections showed a biphasic proliferation of keratin-positive epithelial cells with a complement of spindle cells confirming the diagnosis of metaplastic thymoma. Terminal deoxynucleotidyl transferase (TDT)-positive T lymphocytes were rare and only found in the periphery of the tumor, consistent with thymic remnant. A YAP1::MAML2 gene fusion, with an in-frame fusion between genes YAP1 Exon5 (NM&#95;001130145) and MAML2 Exon2 (NM&#95;032427) was found, supporting further the diagnosis of metaplastic thymoma (Anchored multiplex RNA sequencing [Archer Dx, Boulder, CO] assay). The patient's gender and relatively young age, the presence of an autoimmune condition, and the lack of lymphocytic infiltrate all contribute unusual features to this case and suggest avenues for further exploration., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Henry J. Kaminski, M.D., is a consultant for Roche, Cabeletta Bio, and UCB Pharmaceuticals; and is CEO and CMO of ARC Biotechnology, LLC based on US Patent 8,961,98. He is principal investigator of the Rare Disease Network for Myasthenia Gravis (MGNet) National Institute of Neurological Disorders & Stroke, U54 NS115054, Targeted Therapy for Myasthenia Gravis. R41 NS110331 to ARC Biotechnology, and co-investigator for R43NS124329 MV2C2 antibody as a new therapeutic for myasthenia gravis to Mimivax, LLC. Keith Mortman, M.D., is a consultant for Ethicon & on the advisory board for Guardant Health. We have no other potential conflicts to disclose.

Rationale: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage., Patient Concerns: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum., Diagnoses: The final diagnosis of our patient was PWCA and thymoma., Interventions: She underwent a thymectomy and cyclosporine A administration during first remission., Outcomes: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence., Lessons: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Early diagnosis remains difficult because the early symptoms of thymoma are atypical., Objectives: This study aimed to analyze the changes of serum proteins in the early stage of thymoma (stage I/II) by proteomics method and to screen and validate candidate biomarkers., Methods: Proteins were extracted from 8 sera patients with stage I/II thymoma and 9 healthy controls. The levels of serum proteins were detected by data-independent acquisition (DIA) quantitative proteomics techniques, and the differential proteins were identified. The proteomic results were verified by enzyme-linked immunosorbent assay. Additionally, differentially expressed proteins were analyzed using receiver operating characteristic curves (ROC)., Results: There were 80 differentially expressed proteins between the patients with thymoma and the healthy control group, among which 39 were up-regulated and 41 were down-regulated. Differential protein enrichment is involved in environmental information processing, signaling molecules and interactions, and in the body system and the immune system. The analysis of receptor working characteristic curves showed that the areas under the curve of CORO1A, SAA1 and LTA4H were all larger than 0.8, indicating that these proteins had good diagnostic value., Conclusion: CORO1A, SAA1 and LTA4H may be new biomarkers for early screening of thymoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations, germ cell tumours, and sarcomas. While some of these have close similarity to their counterparts in other organs, both in terms of histology and immunohistochemistry, as well as molecular features, others are unique to the thymus. The epithelial tumours, which can develop in the thymus, will be discussed in this review, with a particular emphasis on resolving differential diagnosis by means of morphology, immunohistochemical profiles, and molecular diagnostics., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Thymoma is often associated with paraneoplastic neurologic diseases. Neural autoantibody testing is an important tool aiding diagnosis of thymoma and its autoimmune neurologic complications. Autoantibodies specific for muscle striational antigens and ion channels of the ligand-gated nicotinic acetylcholine receptor superfamily are the most prevalent biomarkers. The autoimmune neurologic disorders associating most commonly with thymoma are myasthenia gravis (MG), peripheral nerve hyperexcitability (neuromyotonia and Morvan syndrome), dysautonomia, and encephalitis. Patients presenting with these neurologic disorders should be screened for thymoma at diagnosis. Although they can cause profound disability, they usually respond to immunotherapy and treatment of the thymoma. Worsening of the neurologic disorder following surgical removal of a thymoma may herald tumor recurrence. Prompt recognition of paraneoplastic neurologic disorders is critical for patient management. A multidisciplinary approach is required for optimal management of neurologic autoimmunity associated with thymoma., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: To describe cytomegalovirus retinitis in a patient with Good syndrome (hypogammaglobulinemia and thymoma), ocular progression despite treatment and fatal outcome., Methods: A 71-year-old woman with unilateral panuveitis of unknown cause and a history of thymoma resection was referred to the clinic. Visual acuity was 20/100 in her right eye and light perception in her left eye. In slit-lamp examination, the right eye had inferior, fine, pigmented keratic precipitates, 2+ anterior chamber cells, cataract, and 2+ vitreous cells, with no fundus detail and normal ocular ultrasound results. Left eye presented a white cataract, chronic hypotony, and increased choroidal thickness with calcifications. Laboratory evaluations showed normal or negative results for common causes of infection and inflammation. Prednisolone acetate eye drops were started, with improvement of AC inflammation. Cataract surgery was performed, reaching visual acuity of 20/30. Two years later, visual acuity had decreased and 2+ vitritis and retinitis were found. On clinical suspicion of masquerade syndrome, a vitrectomy biopsy was performed; pathologic assessments reported no data on ocular lymphoma. Leukopenia and lymphopenia were found: immunoglobulin levels, CD4 count, and viral load revealed systemic immunosuppression. The aqueous tap was positive for cytomegalovirus. Oral valganciclovir and intravitreal ganciclovir were initiated., Results: In a patient with previous resection of thymoma and hypogammaglobulinemia, final diagnosis was Good syndrome, with cytomegalovirus retinitis being secondary to immunosuppression. Despite treatment, cytomegalovirus retinitis progressed and systemic deterioration resulted in mortal outcome., Conclusion: Good syndrome is an extremely rare disease, and association with cytomegalovirus retinitis is uncommon. To the authors' knowledge, only 14 cases exist in the literature.

Distinguishing T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) from thymomas (especially B1 or B2 type) can be challenging particularly in limited trucut biopsy material where appreciating architecture is difficult or the background epithelial component does not provide tangible evidence for definite diagnosis. As a pathologist, it is important to accurately diagnose these neoplasms because they have entirely distinct management protocols. Recent studies have reported that LIM Domain Only 2 (LMO2) is expressed in neoplastic lymphoblasts of T-ALL/T-LBL and is absent in thymocytes of normal thymuses or thymomas. An observational study was done to test the sensitivity and specificity of LMO2 in differentiating neoplastic lymphoblasts from thymocytes of thymomas/normal thymuses. Our study showed that LMO2 had sensitivity of 70% and specificity of 100% in diagnosing LBL. None of the thymomas (B1 or B2 type) showed expression of LMO2 in the neoplastic cells. LMO2 is a reliable marker of transformed T-cell precursors and should be routinely included in immunohistochemical panel when evaluating thymic/mediastinal neoplasms.

Rationale: Patients who have myasthenia gravis or dermatomyositis show clinical signs of muscular weakening. Ocular muscle involvement is uncommon, and symmetrical proximal limb weakness is the typical presentation of dermatomyositis. However, the earliest and most noticeable sign in those with myasthenia gravis is extraocular muscular paralysis. Dermatomyositis is frequently complicated by malignancy, and the common malignancies associated with dermatomyositis vary by region and ethnicity, while thymoma is relatively rare. About 10% to 15% of people with myasthenia gravis have thymoma, which is involved in the etiology of the disease., Patient Concerns: A 68-year-old female presented with ocular muscle weakness for 10 days that manifested as bilateral blepharoptosis with the phenomenon of "light in the morning and heavy in the evening." Imaging examination showed anterior mediastinal thymic tumor with metastasis., Diagnoses: After a thorough physical examination, we discovered bilateral upper limbs with grade IV muscle strength and the typical rash of dermatomyositis. In combination with elevated serum kinase levels and electromyography suggesting myogenic damage, the patient was finally diagnosed as dermatomyositis with multiple metastases of thymoma., Interventions: The patient received oral hydroxychloroquine sulfate, topical corticosteroids, and tacrolimus ointment, but these did not work very well. Subsequently, the patient underwent surgery combined with radiotherapy for the thymoma., Outcomes: Muscle weakness in the patient improved after effective treatment of tumor, and the rash mostly disappeared., Conclusion: Ocular muscle weakness and thymoma are more common in myasthenia gravis, but we cannot ignore the possibility of dermatomyositis. To further establish the diagnosis, a thorough physical examination and laboratory findings are required. Further tumor screening should be performed for patients with dermatomyositis. Early detection and management of possible tumors are essential to the treatment of dermatomyositis linked to malignancies., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Intrathyroid thymic carcinoma (ITTC) is a rare malignancy. The current understanding of ITTC is inadequate, and there is no standard treatment for ITTC. In the present study, we aimed to explore the clinicopathological characteristics of ITTC and identify potential therapeutic targets., Methods: The clinicopathological characteristics of 22 ITTC patients at our institution were reviewed. The expression of DNA mismatch repair (MMR) proteins and PD-L1 in ITTC were assessed by immunohistochemistry (IHC)., Results: All patients underwent surgery. There were nine females and 13 males, with a slight male predominance. Their ages ranged from 42 to 79 years (average, 54. 1 years). The diameters of the neck masses ranged from 10 to 100 mm (average, 39 mm). Ipsilateral lymph node (LN) dissection was performed in 18 patients: 12 demonstrated LN metastasis, six showed no LN metastasis, and no lymph nodes were dissected in four. One patient had liver metastasis. CK5/6, P63, CD5, and CD117 were expressed in all cases. All cases were negative for TTF1, PAX8, thyroglobulin, and BRAF V600E. DNA MMR protein expression was retained in all tested tumors, and EBV-encoded small RNA (EBER) in situ hybridization was consistently negative. The Ki67 proliferation index ranged from 10 to 70 %. All patients were followed-up for 14-134 months, four died, six were lost to follow-up, and the remaining patients survived without disease. The PD-L1 combined positive score ranged from 10 to 80 (average: 40)., Conclusion: Our results confirm that CD5 and CD117 co-expression support a diagnosis of ITTC. All tumors in this cohort were DNA MMR-proficient and were not associated with Epstein-Barr virus (EBV) infection. A high CPS for PD-L1 suggests that immune checkpoint inhibitor therapy may be worthy of further exploration in patients with ITTC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Good's syndrome, an infrequent adult-onset immunodeficiency is characterized by the triad of thymoma, hypogammaglobulinemia, and increased susceptibility to recurrent infections. The clinical presentation is highly variable, with a spectrum ranging from recurrent bacterial and opportunistic infections to concomitant autoimmune diseases and, sometimes malignant pathologies. Due to heterogeneous clinical phenotypes and the lack of adequate diagnostic criteria, its recognition is often challenging, even delaying it by years. It is one of the most unusual, less studied form of the immune deficiency syndromes with a still unknown pathophysiology. It was initially considered a thymoma-associated variant of primary antibody deficiencies with a reduced or absent number of mature B cells, but it later emerged that significant defects of T cell-mediated immune functions are the underlying cause of opportunistic infections. On the basis of current evidence, Good's syndrome is evaluated as a distinct acquired form of combined immunodeficiency states and classified as a phenocopy of primary immunodeficiency diseases. Epigenetic and acquired genetic factors can play an ultimate role in its evolution., (© 2023 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Rationale and Objectives: To investigate the diagnostic value of radiomics features and dual-source dual-energy CT (DECT) based material decomposition in differentiating low-risk thymomas, high-risk thymomas, and thymic carcinomas., Materials and Methods: This retrospective study included 32 patients (16 males, mean age 66 ± 14 years) with pathologically confirmed thymic masses who underwent contrast-enhanced DECT between 10/2014 and 01/2023. Two experienced readers evaluated all patients regarding conventional radiomics features, as well as DECT-based features, including attenuation (HU), iodine density (mg/mL), and fat fraction (%). Data comparisons were performed using analysis of variance and chi-square statistic tests. Receiver operating characteristic curve analysis and Cox-regression tests were used to discriminate between low-risk/high-risk thymomas and thymic carcinomas., Results: Of the 32 thymic tumors, 12 (38%) were low-risk thymomas, 11 (34%) were high-risk thymomas, and 9 (28%) were thymic carcinomas. Values differed significantly between low-risk thymoma, high-risk thymoma, and thymic carcinoma regarding DECT-based features (p ≤ 0.023) and 30 radiomics features (p ≤ 0.037). The area under the curve to differentiate between low-risk/high-risk thymomas and thymic cancer was 0.998 (95% CI, 0.915-1.000; p < 0.001) for the combination of DECT imaging parameters and radiomics features, yielding a sensitivity of 100% and specificity of 96%. During a follow-up of 60 months (IQR, 35-60 months), the multiparametric approach including radiomics features, DECT parameters, and clinical parameters showed an excellent prognostic power to predict all-cause mortality (c-index = 0.978 [95% CI, 0.958-0.998], p = 0.003)., Conclusion: A multiparametric approach including conventional radiomics features and DECT-based features facilitates accurate, non-invasive discrimination between low-risk/high-risk thymomas and thymic carcinomas., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ibrahim Yel reports a relationship with Siemens that includes: speaking and lecture fees. Christian Booz reports a relationship with Siemens that includes: speaking and lecture fees., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is uncommon, approximately 50% of patients with thymoma have myasthenia gravis. Thymic Hodgkin lymphoma should be considered due to the multiple reported cases of patients with myasthenia gravis and Hodgkin lymphoma. In this report, we present the case of 24-year-old woman with myasthenia gravis who was incidentally found to have coexisting thymoma with thymic Hodgkin lymphoma. CASE REPORT A 24-year-old woman with a known case of vitiligo presented with a 2-year history of diplopia and incidental anterior mediastinal mass. Following investigations, myasthenia gravis was diagnosed and managed by pyridostigmine, prednisolone, and azathioprine. Regarding the anterior mediastinal mass, thymoma was suspected based on the presence of myasthenia gravis and radiological findings. She underwent extended transsternal thymectomy. The final histopathological report of the dissected thymus disclosed Hodgkin lymphoma pathology coexisting with thymoma. After the diagnosis of Hodgkin lymphoma nodular sclerosis type IIA was confirmed, 6 cycles of chemotherapy were administered. Four years of follow-up revealed no evidence of Hodgkin lymphoma. However, her symptoms of myasthenia gravis persisted despite Hodgkin lymphoma remission. CONCLUSIONS There is an unclear association between myasthenia gravies and Hodgkin lymphoma. Prior reports revealed regression of myasthenia gravies following Hodgkin lymphoma management, which suggests that myasthenia could be a complication of Hodgkin lymphoma. However, in our case, myasthenia gravis persisted after Hodgkin lymphoma management; therefore, further studies are needed to explore this association.

Background: Thymic carcinomas are rare and aggressive tumours. They constitute a heterogeneous group of tumours with various histological patterns and subtypes resembling epithelial tumours arising from other organs., Case Presentation: We hereby represent a case of primary thymic carcinoma with adenoid cystic carcinoma-like features (TCACC) which is an extremely rare variant of thymic adenocarcinoma. To date and to the best of our knowledge, there are nine reported cases in literature and ours is the tenth. Our case was treated surgically but the implementation of adjuvant chemoradiotherapy has been reported in few of the published cases., Conclusions: TCACC constitutes a rare entity of thymic adenocarcinoma with limited available literature. The current data is derived from few case reports and case series. The histological overlap of these tumours and primary ACC of salivary glands poses a diagnostic challenge. Radiological investigations, immunohistochemical phenotyping and genetic analysis are crucial in establishing the diagnosis., (© 2023. The Author(s).)

Aims: Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma., Materials and Methods: Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas., Results: All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression., Conclusion: YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma., (© 2023 John Wiley & Sons Ltd.)

A mediastinal cavernous hemangioma is difficult to distinguish from other types of mediastinal tumours. They are usually asymptomatic and incidentally discovered in an imaging study but can present with compressive symptoms or by infiltration of adjacent structures. A 64-year-old woman with a prior history of triple negative invasive carcinoma of the breast, under surveillance was referred after a Chest CT-scan showed a soft tissue 40x20 mm mediastinal mass, suggestive of a thymoma, and as such no tissue biopsy was obtained. A right-side uniportal VATS was performed, the anterior mediastinum dissected and the mass was exposed, and several anomalous veins were identified. Histopathology showed 36x31x15 mm mass, compatible with a cavernous hemangioma of the anterior mediastinum. This case, whilst not questioning the NCCN statement suggesting not doing a tissue biopsy, points to the fact that rare differential diagnosis, like a Cavernous Hemangioma do exist, and a careful and sound judgement is needed at all times.

Aims: The reliable classification of type A versus type B3 thymomas has prognostic and therapeutic relevance, but can be problematic due to considerably overlapping morphology. No immunohistochemical markers aiding in this distinction have been published so far., Methods and Results: We identified and quantified numerous differentially expressed proteins using an unbiased proteomic screen by mass spectrometry in pooled protein lysates from three type A and three type B3 thymomas. From these, candidates were validated in a larger series of paraffin-embedded type A and B3 thymomas. We identified argininosuccinate synthetase 1 (ASS1) and special AT-rich sequence binding protein 1 (SATB1) as highly discriminatory between 34 type A and 20 type B3 thymomas (94% sensitivity, 98% specificity and 96% accuracy). Although not the focus of this study, the same markers also proved helpful in the diagnosis of type AB (n = 14), B1 (n = 4) and B2 thymomas (n = 10)., Conclusions: Mutually exclusive epithelial expression of ASS1 in 100% of type B3 thymomas and ectopic nuclear expression of SATB1 in 92% of type A thymomas support the distinction between type A and type B3 thymomas with 94% sensitivity, 98% specificity and 96% accuracy., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Thymic epithelial neoplasms are the most common tumors of thymic origin but are overall rare in the general population. Their morphologic diversity, ranging from low grade to overtly malignant lesions, along with various histologic growth patterns make them a diagnostically challenging group of tumors. Very occasionally, thymomas and thymic carcinomas may develop in combination with other benign or malignant lesions of thymic origin, further complicating the diagnostic process. The focus of this review lies on the spectrum of thymic epithelial tumors that present with other thymic lesions in the same tumor mass, such as multilocular thymic cysts, neuroendocrine neoplasms, lymphomas, and germ cell tumors among others. Awareness of the existence of such unusual tumors may not only aid in their diagnosis but may also have implications for prognostic and therapeutic purposes.