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Seminars in Nephrology Jan 2024End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the... (Review)
Review
End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the shortage of available organs. Although management and surveillance guidelines exist for malignancies identified in the transplant and waitlist populations, less is written about the management of premalignant lesions in this population. This review covers the less common premalignant lesions (intraductal papillary mucinous neoplasm, gastrointestinal stromal tumor, thymoma, and pancreatic neuroendocrine tumor) that can be found in the transplant candidate population. High-level evidence for the management of these rarer premalignant lesions in the transplant population is lacking, and this review extrapolates evidence from the general population and should not be a substitute for a multidisciplinary discussion with medical and surgical oncologists.
Topics: Humans; Kidney Transplantation; Precancerous Conditions; Kidney Failure, Chronic; Gastrointestinal Stromal Tumors; Thymoma; Pancreatic Neoplasms; Thymus Neoplasms
PubMed: 38490902
DOI: 10.1016/j.semnephrol.2024.151495 -
APMIS : Acta Pathologica,... Dec 2023Good's syndrome, an infrequent adult-onset immunodeficiency is characterized by the triad of thymoma, hypogammaglobulinemia, and increased susceptibility to recurrent... (Review)
Review
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.
Topics: Adult; Humans; Thymoma; Immunologic Deficiency Syndromes; Thymus Neoplasms; Primary Immunodeficiency Diseases; Opportunistic Infections
PubMed: 37729389
DOI: 10.1111/apm.13351 -
Portuguese Journal of Cardiac Thoracic... Jul 2023
Topics: Humans; Thymoma; Thymus Neoplasms; Paraneoplastic Syndromes
PubMed: 37418760
DOI: 10.48729/pjctvs.375 -
Handbook of Clinical Neurology 2024Although they are relatively rare, the diagnosis of paraneoplastic neurologic syndromes (PNS) can be aided by the identification of neural autoantibodies in patients'... (Review)
Review
Although they are relatively rare, the diagnosis of paraneoplastic neurologic syndromes (PNS) can be aided by the identification of neural autoantibodies in patients' serum and cerebrospinal fluid (CSF). They often clinically manifest as characteristic syndromes, including limbic encephalitis, opsoclonus-myoclonus syndrome, paraneoplastic cerebellar degeneration, and paraneoplastic encephalomyelitis. The antibodies are directed either toward intracellular targets, or epitopes on the cell surface. As compared to cell surface antibodies, intracellular paraneoplastic autoantibodies are more classically associated with cancer, most often lung, breast, thymoma, gynecologic, testicular, and/or neuroendocrine cancers. The malignancies themselves tend to be small and regionally contained, attesting to the strength of the immune system in cancer immunosurveillance. Typically, the intracellular antibodies are not directly pathogenic and tend to be associated with PNS that are poorly responsive to treatment. With some notable exceptions, including patients with PNS associated with testicular cancer, patients with intracellular antibodies are typically older individuals, in their 7th decade of life and beyond. Many of them are current or former smokers. Treatment strategies include tumor removal as well as immunotherapy to treat the concomitant PNS. Newer technologies and the ever-broadening use of cancer immunotherapies are contributing to the continued identification of novel intracellularly targeted autoantibodies.
Topics: Male; Humans; Female; Testicular Neoplasms; Paraneoplastic Syndromes, Nervous System; Autoantibodies; Limbic Encephalitis; Immunotherapy
PubMed: 38494288
DOI: 10.1016/B978-0-12-823912-4.00021-9 -
Frontiers in Immunology 2023Good syndrome (GS) is a rare adult-onset immunodeficiency first described in 1954. It is characterized by the coexistence of a thymoma and hypogammaglobulinemia,...
INTRODUCTION
Good syndrome (GS) is a rare adult-onset immunodeficiency first described in 1954. It is characterized by the coexistence of a thymoma and hypogammaglobulinemia, associated with an increased susceptibility to infections and autoimmunity. The classification and management of GS has been long hampered by the lack of data about the underlying immune alterations, a controversy existing on whether it is a unique diagnostic entity . a subtype of Common Variable Immune Deficiency (CVID).
METHODS
Here, we used high-sensitive flow cytometry to investigate the distribution of up to 70 different immune cell populations in blood of GS patients (n=9) compared to age-matched CVID patients (n=55) and healthy donors (n=61).
RESULTS
All 9 GS patients displayed reduced B-cell counts -down to undetectable levels (<0.1 cells/μL) in 8/9 cases-, together with decreased numbers of total CD4 T-cells, NK-cells, neutrophils, and basophils age-matched healthy donors. In contrast, they showed expanded TCRγδ T-cells (p ≤ 0.05). Except for a deeper B-cell defect, the pattern of immune cell alteration in blood was similar in GS and (age-matched) CVID patients. In depth analysis of CD4 T-cells revealed significantly decreased blood counts of naïve, central memory (CM) and transitional memory (TM) TCD4 cells and their functional compartments of T follicular helper (TFH), regulatory T cells (Tregs), T helper (Th)2, Th17, Th22, Th1/Th17 and Th1/Th2 cells. In addition, GS patients also showed decreased NK-cell, neutrophil, basophil, classical monocyte and of both CD1c and CD141 myeloid dendritic cell counts in blood, in parallel to an expansion of total and terminal effector TCRγδ T-cells. Interestingly, those GS patients who developed hypogammaglobulinemia several years after the thymoma presented with an immunological and clinical phenotype which more closely resembled a combined immune humoral and cellular defect, with poorer response to immunoglobulin replacement therapy, as compared to those in whom the thymoma and hypogammaglobulinemia were simultaneously detected.
DISCUSSION
Our findings provide a more accurate definition of the immune cell defects of GS patients and contribute to a better discrimination among GS patients between those with a pure B-cell defect . those suffering from a combined immunodeficiency with important consequences on the diagnosis and management of the disease.
Topics: Adult; Humans; Thymoma; Agammaglobulinemia; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; Thymus Neoplasms; Primary Immunodeficiency Diseases
PubMed: 38035080
DOI: 10.3389/fimmu.2023.1285088 -
Lung Cancer (Amsterdam, Netherlands) Oct 2023Trophoblastic antigen 2 (Trop2) is a cell surface glycoprotein expressed in multiple types of cancers, including breast cancer, non-small cell lung cancer, and...
BACKGROUND
Trophoblastic antigen 2 (Trop2) is a cell surface glycoprotein expressed in multiple types of cancers, including breast cancer, non-small cell lung cancer, and gastrointestinal cancers. Trop2 expression and the use of Trop2-directed therapy such as antibody-drug conjugate (ADC) have not yet been investigated in thymic epithelial tumors (TETs).
METHODS
Patients with TETs treated at MedStar Georgetown University Hospital were retrospectively identified. Of the patients for whom tumor samples and normal thymus tissue were available, immunohistochemistry (IHC) membranous staining for Trop2 and PD-L1 were performed. Positivity for Trop2 required at least 10% of the tumor cells to be stained, with an intensity scored of 1+ (weak), 2+ (moderate), and 3+ (strong). Cases with CPS ≥ 5% were considered positive for PD-L1.
RESULTS
30 TET samples from 29 patients (17 patients with thymoma and 12 patients with thymic carcinoma) were identified. One patient with thymic carcinoma had two samples from different time points. From the same set of patients, 13 samples of normal thymus tissue were available. In normal thymus tissue, eight samples (62%) showed no positivity of Trop2, while five samples (38%) showed 1 + IHC staining. In the thymoma samples, four (24%) showed 0 or 1 + IHC staining, while 13 (76%) showed 2 + or 3 + staining. Of the 13 thymic carcinoma samples, three samples (23%) showed 1 + IHC staining while seven (54%) showed 2 + staining and three (23%) showed 3 + staining. There was no statistically significant correlation found between PD-L1 expression and Trop-2 expression in thymoma or thymic carcinoma.
CONCLUSIONS
Trop2 is readily expressed in TETS with a higher degree of expression in thymic carcinoma. The expression of Trop-2 was lower in normal thymic tissue compared with TETs. The increased expression of Trop-2 in TETs suggests that Trop2 is an attractive therapeutic target for Trop-2 directed therapy.
Topics: Humans; Thymoma; B7-H1 Antigen; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Thymus Neoplasms; Neoplasms, Glandular and Epithelial
PubMed: 37573703
DOI: 10.1016/j.lungcan.2023.107324 -
Frontiers in Immunology 2023Thymic epithelial tumors (TETs) are a rare and diverse group of neoplasms characterized by distinct molecular signatures. This review delves into the complex molecular... (Review)
Review
Thymic epithelial tumors (TETs) are a rare and diverse group of neoplasms characterized by distinct molecular signatures. This review delves into the complex molecular networks of TETs, highlighting key aspects such as chromosomal abnormalities, molecular subtypes, aberrant gene mutations and expressions, structural gene rearrangements, and epigenetic changes. Additionally, the influence of the dynamic tumor microenvironment on TET behavior and therapeutic responses is examined. A thorough understanding of these facets elucidates TET pathogenesis, offering avenues for enhancing diagnostic accuracy, refining prognostic assessments, and tailoring targeted therapeutic strategies. Our review underscores the importance of deciphering TETs' unique molecular signatures to advance personalized treatment paradigms and improve patient outcomes. We also discuss future research directions and anticipated challenges in this intriguing field.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Prognosis; Tumor Microenvironment
PubMed: 37849766
DOI: 10.3389/fimmu.2023.1264325 -
BMJ Case Reports Jun 2024A 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...
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.
Topics: Humans; Female; Thyroid Neoplasms; Thymus Neoplasms; Thyroidectomy; Adult; Biopsy, Fine-Needle; Thymoma; Neck Dissection; Radiotherapy, Adjuvant; Diagnosis, Differential; Hoarseness
PubMed: 38862190
DOI: 10.1136/bcr-2024-260938 -
Myasthenic crisis in thymoma-associated myasthenia gravis: a multicenter retrospective cohort study.Neuromuscular Disorders : NMD Oct 2023Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently...
Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently associated with transient worsening of MG and even acute respiratory failure, namely myasthenic crisis (MC). However, little is known about the clinical features and outcomes of MC in thymoma-associated MG patients. We performed a retrospective cohort study in MG patients recruited from 9 independent tertiary neuromuscular centers in China from Jan 2015, through Oct 2022. Overall, 156 MC from 149 MG patients with positive anti-acetylcholine receptor (AChR) antibodies were finally analyzed. Next, these patients were divided into two subgroups: the TMG group (n = 60 MCs, 58 patients) and the non-thymoma-associated MG group (n = 96 MCs, 91 patients). Compared with non-thymoma-associated MG, TMG patients had a significantly shorter disease duration from symptom onset to the crisis (17.95±40.9 vs 51.31±60.61 months, P<0.0001), a larger proportion of MGFA IVa as the initial onset clinical classification (6.67% vs 0, P = 0.0205), and a longer hospital stay (39.24±22.09 [6-111] vs. 33.2 ± 23.42 days [7-120]; P = 0.0317) during the crisis. Within the TMG group, the hospital stay was significantly longer in patients with unresected thymoma compared to that in postoperative myasthenic crisis (POMC) (47.68±24.9 [6-111] vs. 34.21±18.87 days [12-82]; P = 0.0257). Early identification of the MG categories may provide some hints in tailoring therapeutic strategies to improve the prognosis.
Topics: Humans; Thymoma; Retrospective Studies; Thymectomy; Postoperative Complications; Myasthenia Gravis; Thymus Neoplasms; Receptors, Cholinergic; Autoantibodies
PubMed: 37783628
DOI: 10.1016/j.nmd.2023.09.005 -
Handbook of Clinical Neurology 2024Thymoma is often associated with paraneoplastic neurologic diseases. Neural autoantibody testing is an important tool aiding diagnosis of thymoma and its autoimmune... (Review)
Review
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.
Topics: Humans; Thymoma; Neoplasm Recurrence, Local; Thymus Neoplasms; Autoantibodies; Nervous System Diseases; Isaacs Syndrome
PubMed: 38494291
DOI: 10.1016/B978-0-12-823912-4.00008-6