Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

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.

A basaloid carcinoma with multilocular thymic cyst mimicking a mediastinal teratoma.

This case report details a rare thymic basaloid carcinoma initially misinterpreted as a mediastinal teratoma, underscoring the diagnostic challenges posed by such tumors. A 71-year-old female presented with an asymptomatic anterior mediastinal tumor discovered incidentally during a routine health examination. Surgical intervention, followed by pathological and immunohistochemical analysis including CK-pan, p63, p40, and CD117 molecules, led to a definitive diagnosis of basaloid carcinoma of the thymus. This case highlights the critical importance of differential diagnosis in mediastinal lesions, especially those presenting with multilocular thymic cysts on chest CT. The subxiphoid video-assisted thoracoscopic surgery enabled complete tumor resection with minimal trauma and favorable postoperative outcomes. The patient opted against further radiotherapy or chemotherapy and she has survived for over eight months without recurrence. This case report contributes to the growing understanding of thymic basaloid carcinoma, a rare and potentially aggressive thymic carcinoma subtype. It emphasizes the necessity for precise surgical techniques and enhanced diagnostic acumen among cardiothoracic surgeons and oncologists.

Paraneoplastic autoimmune neurologic disorders associated with thymoma.

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.

International reproducibility study of thymic epithelial tumors staging: pT stage is an issue. proposals for improvement. A RYTHMIC/ITMIG study.

INTRODUCTION: Pathologists are staging thymic epithelial tumors (TET) according to the 8th UICC/AJCC TNM system. Within the French RYTHMIC network, dedicated to TET, agreement on pathologic tumor stage (pT) among the pathology panelists was difficult. The aim of our study was to determine the interobserver reproducibility of pT at an international level, to explore the source of discrepancies and potential interventions to address these. METHODS: An international panel of pathologists was recruited through the International Thymic Malignancy Interest Group (ITMIG). The study focused on invasion of mediastinal pleura, pericardium, and lung. From a cohort of cases identified as challenging within the RYTHMIC network, we chose a series of test and validation cases (n = 5 and 10, respectively). RESULTS: Reproducibility of the pT stage was also challenging at an international level as none of the 15 cases was classified as the same pT stage by all ITMIG pathologists. The agreement rose from slight (κ = 0.13) to moderate (κ = 0.48) between test and validation series. Discussion among the expert pathologists pinpointed two major reasons underlying discrepancies: 1) Thymomas growing with their "capsule" and adhering to the pleurae, pericardium, or lung were often misinterpreted as invading these structures. 2) Recognition of the mediastinal pleura was identified as challenging. CONCLUSION: Our study underlines that the evaluation of the pT stage of TET is problematic and needs to be addressed in more detail in an upcoming TNM classification. The publication of histopathologic images of landmarks, including ancillary tests could improve reproducibility for future TNM classifications.

Thymoma-associated autoimmune encephalitis with myasthenia gravis: Case series and literature review.

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.

[Clinical diagnosis and treatment analysis of 21 cases of intrathyroid thymic carcinoma].

Objective: To analyze the clinical efficacy of intrathyroid thymic carcinoma (ITTC). Methods: This study retrospectively analyzed the clinical data of 21 patients with ITTC diagnosed and treated at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2023, including 9 males and 12 females, with a median age of 52 years (40-60 years old). Results: There is a correlation between the maximum diameter of the tumor (≥40 mm) and lymph node metastasis (P=0.044). Seventeen patients received surgical treatment, and 4 patients only received chemotherapy. During the follow-up period, a total of 4 patients experienced death or progression, with a 2-year mortality or progression free survival rate of 74.8%. Conclusions: The prognosis of ITTC is good, and surgical treatment is the preferred treatment option, lymph node metastasis is significantly correlated with prognosis. The radiotherapy and chemotherapy of ITTC need to be determined based on the patient's condition.

Diagnostic utility of LMO2 immunohistochemistry in distinguishing T-lymphoblastic leukemia/lymphoma from thymoma.

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.

Good syndrome and cytomegalovirus retinitis: A literature review.

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.

Erythroderma in a Patient With Thymoma-Associated Myasthenia Gravis.

A woman in her 30s with myasthenia gravis diagnosed at age 27 years presented to the emergency department with severe erythroderma over the past 2 months. What is your diagnosis?

Pure white cell aplasia before and after thymectomy in the rare conundrum of thymoma: A case report and review of the literature.

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.

A Rare Case of Metaplastic Thymoma Presenting With Myasthenia Gravis.

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_001130145) and MAML2 Exon2 (NM_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.

Exploring Potential Biomarkers of Early Thymoma based on Serum Proteomics.

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.

A case of a shrunken multilocular mediastinal cyst that developed into thymic carcinoma with lung metastases 13 years later.

Multilocular thymic cysts (MTC) are acquired multilocular cysts caused by inflammation. The rarity of such lesions and a lack of recognition make diagnosis and treatment difficult. Herein, we present our experience with a multilocular mediastinal cyst that resulted in the development of thymic cancer with metastasis over a period of 13 years. Computed tomography findings revealed an anterior mediastinal mass that was suspected to be an MTC in a 49-year-old man. The mass shrank gradually over a period of 7 years; however, growth was observed at 10 years after initial detection. At 13 years after detection, thymic carcinoma with multiple lung metastases was diagnosed. Resection was recommended during the follow-up period, but the patient refused treatment. A multilocular wall and location are factors that indicate MTC. However, even if a definitive diagnosis is not made, resection of multilocular anterior mediastinal cysts should be considered as determining the preoperative diagnosis is difficult. Nevertheless, our case suggests that the coexistence of tumors with cysts is possible, and the potential for malignant tumor development exists.

Metabolic signatures of thymomas: potential biomarkers and treatment targets.

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.

Comprehensive study of clinicopathological and immune cell infiltration and lactate dehydrogenase expression in patients with thymic epithelial tumours.

BACKGROUND: Lactate dehydrogenase (LDH) has emerged as a promising biomarker for cancer. However, the current understanding of LDH and circulating LDH expression in thymic epithelial tumour (TET) is lacking. METHODS: A comprehensive literature review and meta-analysis were performed to evaluate the clinical significance of circulating LDH levels in patients with TET. Circulating LDH levels were measured using a laboratory analyser (Cobas8000, Roche, Basel, Switzerland). The maximum standardised uptake value (SUVmax) was determined in patients who underwent whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Multiplex immunohistochemistry (IHC) was performed using a commercially available kit (Opal 6-plex Detection Kit, Akoya Biosciences, Marlborough, MA, USA) and slide scanner (Slideview VS200, Olympus, Tokyo, Japan). All statistical analyses were performed using SPSS (IBM Corp., Armonk, NY, USA) and Prism version 9.0 (GraphPad Inc., San Diego, CA, USA). Differences with p < 0.05 were considered to be statistically significant. RESULTS: Meta-analysis revealed that elevated circulating serum levels of LDH predicted poor prognosis in patients with TET. Circulating levels of LDH were analysed in the serum of 313 patients with TET and 87 with benign mediastinal mass. The mean circulating LDH level in patients with thymic carcinoma (TC) was significantly higher than that in those with thymoma (TM) and the benign group (p < 0.001). Expression levels of circulating LDH were significantly reduced in postoperative samples compared with that in preoperative samples (p < 0.05). Receiver operating characteristic (ROC) curve analysis for diagnosing TC yielded an area under the curve of 0.74, with a sensitivity of 54 % and specificity of 86 %. Furthermore, patients with TC exhibited higher 18F-FDG PET/CT SUVmax values compared to those with TM. Correlation analysis demonstrated a positive association between SUVmax values and circulating LDH levels. In addition, the percentages of LDH-positive cells in TC and type B1 TM tissues were higher than those in other subtypes of TM, and a significant positive correlation between the percentages of LDH-positive and CD20-positive cells was detected in patients with TET (p < 0.05). CONCLUSION: Circulating serum LDH level may serve as a non-invasive biomarker for the diagnosis and prognosis of TET. The relationship between LDH expression and immune cell infiltration merits further regarding its application in companion diagnosis for immunotherapy.

Unraveling the Natural History of Good's Syndrome: A Progressive Adult Combined Immunodeficiency.

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.

Thymic epithelial tumours: histopathological classification and differential diagnosis.

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.