Thymic tumors]

Thymomas and thymic carcinomas are rare and slow-growing tumors, which develop within the anterior mediastinum. Thymomas are often associated with autoimmune disorders and most particularly myasthenia gravis. The treatment of choice remains a complete surgical resection. Postoperative radiotherapy is often combined in case of invasive thymoma invading into adjacent organs. Postoperative radiotherapy in stage II with invasion into capsule has been more controversial lately. In inoperable locally advanced, or metastatic thymic tumors, neoadjuvant cisplatin-based followed by surgery and radiotherapy has given interesting results in the past years.     

Thymic epithelial neoplasia

Primary thymic epithelial neoplasms (PTENs) are uncommon tumors of anterior mediastinum with a broad range of biological characteristics. We retrospectively reviewed 58 consecutive patients with a diagnosis of PTENs that were confirmed pathologically during 28 yr. There were 58 patients, 31 males (53.4%) and 27 females (46.6%), with a mean age of 43.6 +/-13.8 yr (range, 17-73 yr). Twenty-one (36.2%) patients presented at the Masaoka stage I, 13 (22.4%) patient at stage II, 18 (31.0%) patient at stage III, and 6 (10.4%) patients at stage IV. Forty-five (77.7%) patients had myasthenia gravis, 1 (1.7%) immune deficiency, 1 (1.7%) pancytopenia, and 1 (1.7%) nephrotic syndrome. No paraneoplastic syndrome was associated in 10 (17.2%) patients. Complete resection was accomplished in 41 (70.7%) patients, while incomplete resection was performed in 8 (13.8%) patients. In nine (15.5%) patients only biopsy was carried out. Radiotherapy was administered to 19 (32.8%) patients. Eleven (19.0%) out of 58 who presented at advanced stages (at least III) received chemotherapy. Median follow-up period was 59 mo (range, 1-278 mo). During the follow-up period, 17 deaths occurred. Five patients (29.4%) died of tumor-related causes, and the remaining 12 patients died of other causes (cardiovascular diseases [n = 1, 5.9%], sepsis [n = 4, 23.5%], and MG-related respiratory insufficiency [n = 7, 41.2%]). The overall survival rates at 5 yr and 10 yr were 63.9% and 54.2%, respectively. Tumor-related survival rates at 5 yr and 10 yr were 89.0% and 83.2%, respectively. In our series, disease stage, presence or absence of myasthenia gravis, and tumor size did not affect survival (p> 0.05), either. Complete resection of the tumor seems to be the best predictive factor for long-term survival.     

Thymic Carcinoma With Glandular Differentiation Arising in a Congenital Thymic Cyst

A case of thymic carcinoma with glandular differentiation arising in congenital thymic cyst in a 50-year-old male is reported. Neoplasia in congenital thymic cyst is a rare phenomenon and is seldom associated with glandular differentiation. It is important to differentiate these neoplasms from carcinomas of die lower respiratory tract and from thymic carcinomas with secondary cystic degeneration, in view of their relatively good prognosis and die therapeutic implications. © 1994 Wiley-Liss, inc.     

Mutation Profile of Thymic Carcinoma and Thymic Neuroendocrine Tumor by Targeted Next-generation Sequencing

BackgroundThymic carcinoma is a rare mediastinal neoplasm, and little is known about its genetic variability, which has hampered the development of targeted therapies.Patients and MethodsWe tested a next-generation sequencing panel containing 50 common cancer-related genes in 48 cases of thymic carcinoma and 6 cases of thymic neuroendocrine tumor.ResultsWe detected 42 variant calls in 21 of 54 cases. There was no significant difference in mutation frequency between thymic carcinoma and thymic neuroendocrine tumors. Among these, TP53 was the most frequently mutated gene (18.5%), followed by KIT (7.4%) and PDGFRA (5.6%). According to the gene pathways and groups, the p53 pathway, including TP53 and ATM, was most frequently affected (20.4%), followed by the receptor tyrosine kinase (RTK)/RAS pathway (18.5%) and PI3K pathway (5.6%). According to the OncoKB, an expert-guided precision oncology knowledge base, 7 genes among 10 cases (18.5%) were annotated with level 1 evidence, suggesting potentially therapeutic targets. Prognostic analyses, conducted in thymic squamous cell carcinomas, revealed that tumor cases harboring gene mutations in RTKs, including KIT (7.4%), PDGFRA (5.6%) and EGFR (3.7%), were significantly associated with a worse overall survival time (P = .0481). Among clinicopathologic factors, the advanced Masaoka stage was marginally associated with a worse overall survival (P = .0757). In the subsequent multivariate analysis, neither of the factors achieved statistical significance.ConclusionsIn this preliminary next-generation sequencing study, we unexpectedly found evidence suggesting that several gene mutations might be therapeutic targets. The gene mutations in RTKs may be a valuable prognostic factor in thymic squamous cell carcinoma.     

Thymic Carcinomas—A Concise Multidisciplinary Update on Recent Developments From the Thymic Carcinoma Working Group of the International Thymic Malignancy Interest Group

Thymic carcinomas are rare malignancies that in general arise in the prevascular (anterior) mediastinum. These tumors are usually invasive, often present at advanced stages, and typically behave aggressively. Studies are hampered by the paucity of these tumors, the large variety of carcinoma subtypes, and the lack of unique morphologic and immunophenotypic features. Despite these challenges, advances in diagnostic imaging, surgical approaches, systemic therapies, and radiation therapy techniques have been made. The WHO classification of thymic epithelial tumors has been updated in 2021, and the eighth tumor nodal metastasis staging by the American Joint Committee on Cancer/Union for International Cancer Control included thymic carcinomas in 2017. Molecular alterations that provide more insight into the pathogenesis of these tumors and that potentially permit use of novel targeted therapies are increasingly being identified. New approaches to radiation therapy, chemotherapy, and immunotherapy are under evaluation. International societies, including the International Thymic Malignancy Interest Group, European Society of Thoracic Surgeons, and Japanese, Chinese, and Korean thymic associations, have been critical in organizing and conducting multi-institutional clinical studies. Herein, we review contemporary multidisciplinary perspectives in diagnosis and management of thymic carcinoma.     

Thymic Function and Output of Recent Thymic Emigrant T Cells During Intracranial Glioma Progression

One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostly confined to the T cell lineage. A deficiency in the production of naïve T cells from the thymus could contribute to the lymphopenia seen in GBM patients. In this study we asked whether thymic function and the production of recent thymic emigrant (RTE) T cells from the thymus was influenced by intracranial (i.c.) glioma progression. We found significant thymic involution in animals with progressive i.c. gliomas. Involuted thymi from animals with progressive i.c. T9.F gliomas showed dramatic losses of CD4⁺CD8⁺ (DP) thymocytes. Microscopic analysis complemented those findings by demonstrating a reversal of the typical cortico-medullary structure. Significant increases in apoptosis accompanied the rapid loss of viable thymocytes, which was prevented in part by adrenalectomy, suggesting a dominant role for endogenous glucocorticoids. This thymic involution was also associated with a significant decrease in peripheral RTE T cells, reflecting the diminished thymic function. Finally, we found that CD8⁺ RTE T cells were enriched in progressively growing T9 gliomas, which points to an immunological role for RTE's in anti-glioma immunity. Our findings may shed light on the significance of thymic function for anti-glioma immunity and the response to immunotherapeutic treatment paradigms.     

胸腺肿瘤专题前言

胸腺肿瘤是比较少见的胸部实体肿瘤,同时也是临床上最常见的前纵隔肿瘤。但自然预后及治疗后的远期生存却均好于诸如肺癌、食管癌等其他胸部恶性肿瘤。由于发病率低,现行的临床病理分期、组织学分型及诊疗指南都是基于专家意见,而缺乏有力的循证医学证据来指导胸腺肿瘤的规范化临床诊治。即使有些研究也大多为单中心回顾性病例报道和观察性研究,更无任何前瞻性随机对照的临床试验结果。