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JCEM Case Reports May 2024Malignancies may induce clinical sequelae distant from the sites of the tumor. Such paraneoplastic phenomena are known to affect many organs, including the skin....
Malignancies may induce clinical sequelae distant from the sites of the tumor. Such paraneoplastic phenomena are known to affect many organs, including the skin. Vitiligo is a disorder of patchy depigmentation, appearing as white macules with distinct margins. Rarely, vitiligo has been reported as a paraneoplastic occurrence, in the settings of pituitary adenoma, thymoma, gastric carcinoma, and lymphoma. We now describe a man presenting with the abrupt onset of vitiligo on the hands coinciding with recurrence of adrenocortical carcinoma (ACC) in the abdomen. The vitiligo rapidly dissipated following resection of his cancer. We believe this to be the first report of paraneoplastic vitiligo associated with ACC. Endocrinologists typically manage ACC and should be aware of this link, as the de novo observation of vitiligo may signal the onset or recurrence of underlying tumor. Other practitioners that encounter patients with new vitiligo should add ACC to their differential diagnosis of potential underlying conditions.
PubMed: 38707658
DOI: 10.1210/jcemcr/luae070 -
EJNMMI Research May 2024Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed...
BACKGROUND
Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas.
METHODS
Patients who underwent preoperative [F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis.
RESULTS
Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004).
CONCLUSIONS
Among the [F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings.
PubMed: 38702532
DOI: 10.1186/s13550-024-01108-3 -
Biomedicines Mar 2024Programmed death-ligand 1 (PD-L1) expression in neoplastic and immune cells of the tumor microenvironment determines the efficacy of antitumor immunity, while it can be...
BACKGROUND
Programmed death-ligand 1 (PD-L1) expression in neoplastic and immune cells of the tumor microenvironment determines the efficacy of antitumor immunity, while it can be regulated at the epigenetic level by various factors, including HDACs. In this study, we aim to evaluate the expression patterns of PD-L1 in thymic epithelial tumors (TETs), while we attempt the first correlation analysis between PD-L1 and histone deacetylases (HDACs) expression.
METHODS
Immunohistochemistry was used to evaluate the expression of PD-L1 in tumor and immune cells of 91 TETs with SP263 and SP142 antibody clones, as well as the expressions of HDCA1, -2, -3, -4, -5, and -6.
RESULTS
The PD-L1 tumor proportion score (TPS) was higher, while the immune cell score (IC-score) was lower in the more aggressive TET subtypes and in more advanced Masaoka-Koga stages. A positive correlation between PD-L1 and HDAC-3, -4, and -5 cytoplasmic expression was identified.
CONCLUSIONS
Higher PD-L1 expression in neoplastic cells and lower PD-L1 expression in immune cells of TETs characterizes more aggressive and advanced neoplasms. Correlations between PD-L1 and HDAC expression unravel the impact of epigenetic regulation on the expression of immune checkpoint molecules in TETs, with possible future applications in combined therapeutic targeting.
PubMed: 38672128
DOI: 10.3390/biomedicines12040772 -
BMC Neurology Apr 2024Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed.
BACKGROUND
Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed.
METHODS
We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021.
RESULTS
Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG.
CONCLUSION
Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.
Topics: Humans; Myasthenia Gravis; Alopecia; Female; Male; Taste Disorders; Middle Aged; Adult; Aged; Japan; Registries; Thymoma; Incidence
PubMed: 38664714
DOI: 10.1186/s12883-024-03644-w -
Frontiers in Immunology 2024Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs... (Review)
Review
Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients' life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.
Topics: Adult; Humans; Thymoma; Autoimmunity; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Myasthenia Gravis; Tumor Microenvironment
PubMed: 38629065
DOI: 10.3389/fimmu.2024.1288045 -
Journal of Cardiothoracic Surgery Apr 2024The purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or...
BACKGROUND
The purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or thymic carcinoma.
METHODS
In this study, we retrospectively evaluated the clinicopathological characteristics of our surgical patients at Fukuoka University Hospital from January 1995 to December 2018.
RESULTS
There were nine cases of TNET and 16 cases of thymic carcinoma. Regarding the pathological type, the TNET group included three atypical carcinoid cases, two large cell neuroendocrine tumor cases, two small cell carcinoma cases, and two other cases. The thymic carcinoma group included 15 squamous carcinoma cases and one case of adenosquamous carcinoma. Based on the Masaoka-Koga staging system, six TNET cases and 11 thymic carcinoma cases were stage III or IV. The complete resection rate was 77% in the TNET group and 81% in the thymic carcinoma group. Additional chemotherapy and/or radiotherapy was performed in five cases of TNET and 11 cases of thymic carcinoma. The five-year survival rate and five-year disease-free survival rate were 87.5% and 75.0% in the TNET group and 58.9% and 57.1% in the thymic carcinoma group, respectively, with no significant difference between the two groups (P = 0.248 and P = 0.894, respectively). In the univariate analysis, complete resection was a statistically significant prognostic factor (P = 0.017).
CONCLUSION
In this study, no difference in prognosis was observed between TNET and thymic carcinomas. To understand the characteristics of these tumors, further case accumulation and multicenter clinical studies are needed. (243words).
Topics: Humans; Lung Neoplasms; Neoplasm Staging; Neuroendocrine Tumors; Prognosis; Retrospective Studies; Thymoma; Thymus Neoplasms
PubMed: 38627811
DOI: 10.1186/s13019-024-02723-w -
Lung Cancer (Amsterdam, Netherlands) May 2024The main objective of this report was to detail the long-term follow-up data from the REMORA study, which investigated the safety and efficacy of lenvatinib in patients...
OBJECTIVES
The main objective of this report was to detail the long-term follow-up data from the REMORA study, which investigated the safety and efficacy of lenvatinib in patients with thymic carcinoma. In addition, an exploratory analysis of the association between relative dose intensity (RDI) and the efficacy of lenvatinib is presented.
MATERIALS AND METHODS
The single-arm, open-label, phase 2 REMORA study was conducted at eight Japanese institutions. Forty-two patients received oral lenvatinib 24 mg once daily in 4-week cycles until the occurrence of intolerable adverse events or disease progression. The REMORA long-term follow-up data were evaluated, including overall survival (OS). RDI was calculated by dividing the actual dose administered to the patient by the standard recommended dose. This trial is registered on JMACCT (JMA-IIA00285) and on UMIN-CTR (UMIN000026777).
RESULTS
The updated median OS was 28.3 months (95 % confidence interval [CI]: 17.1-34.0 months), and the OS rate at 36 months was 35.7 % (95 % CI: 21.7 %-49.9 %). When grouped by RDI of lenvatinib, the median OS was 38.5 months (95 % CI: 31.2-not estimable) in patients with ≥ 75 % RDI and 17.3 months (95 % CI: 13.4-26.2 months) in patients with < 75 % RDI (hazard ratio 0.46 [95 % CI: 0.22-0.98]; P = 0.0406) at 8 weeks. Patients who maintained their lenvatinib dose over 8 weeks had a higher objective response rate than patients whose doses were reduced (75.0 % vs 29.4 %; P = 0.0379). No new safety concerns or treatment-related deaths were reported, and lenvatinib had a tolerable safety profile.
CONCLUSION
This follow-up report updated OS in patients with metastatic or recurrent thymic carcinoma. A higher RDI of lenvatinib at 8 weeks could be associated with improved outcomes.
Topics: Humans; Phenylurea Compounds; Quinolines; Male; Female; Middle Aged; Aged; Follow-Up Studies; Neoplasm Recurrence, Local; Thymoma; Adult; Antineoplastic Agents; Thymus Neoplasms; Neoplasm Metastasis; Aged, 80 and over; Treatment Outcome
PubMed: 38626709
DOI: 10.1016/j.lungcan.2024.107557 -
Cureus Mar 2024We present the case of a 57-year-old female who initially presented with a chief complaint of left-sided orbital headaches and associated left eyelid swelling. Initial...
We present the case of a 57-year-old female who initially presented with a chief complaint of left-sided orbital headaches and associated left eyelid swelling. Initial imaging work-up with CT head/orbit revealed soft tissue enhancement of the left orbital roof, concerning for neoplastic process (primary lymphoma versus extracranial primary tumor versus metastatic tumor). Further imaging studies with CT chest/abdomen/pelvis revealed an anterior mediastinal mass, concerning for possible thymoma versus lymphoma. The patient underwent further consultation with the Hematology/Oncology and Ophthalmology Departments, which recommended definitive biopsies from both sites, which showed matching histologic findings of moderately differentiated enteric-type adenocarcinoma with positive staining for CDX2, an intestinal marker. Thymic carcinomas are rare cancers that account for approximately 0.06% of all malignancies and require a high degree of clinical suspicion. Extrathoracic metastases from thymic carcinomas, especially to the orbit, is a rare occurrence and the exact incidence of this phenomenon is unknown. This case represents the diagnostic challenges associated with a rare cancer type and underscores the importance of a multidisciplinary approach to patient care.
PubMed: 38618298
DOI: 10.7759/cureus.56139 -
Cancers Mar 2024Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low... (Review)
Review
Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low tumor mutation burden, a lack of actionable genomic changes, and, especially with thymomas, defects in immune tolerance. Surgery is the mainstay of the management of resectable disease, whereas advanced, unresectable tumors are treated with platinum-based chemotherapy. Disease recurrence can occur months to years after frontline treatment. Although several options are available for conventional treatment of recurrent thymic tumors, response rates are generally low, and treatment-related toxicity can affect quality of life. A subset of patients benefit from biologic therapies, but there remains an unmet need for the development of new treatments. Immune checkpoint inhibitors are safe, clinically active, and have contributed to an improvement in survival for patients with a wide variety of cancers. However, the application of these revolutionary treatments for thymic cancers is limited to their use for the management of recurrent thymic carcinoma because of the risk of immune toxicity. In this paper, we review the current uses of immunotherapy for the management of thymic epithelial tumors and highlight potential strategies to improve safety and broaden the application of these treatments for patients with thymic cancers.
PubMed: 38611047
DOI: 10.3390/cancers16071369 -
BMC Cancer Apr 2024Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two...
PURPOSE
Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function.
METHODS
We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro.
RESULTS
In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration.
CONCLUSIONS
In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.
Topics: Humans; Acetyltransferases; Adenocarcinoma; Adenocarcinoma of Lung; Adrenal Cortex Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Chromosomal Proteins, Non-Histone; Colonic Neoplasms; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Thymus Neoplasms
PubMed: 38605349
DOI: 10.1186/s12885-024-12213-w