Mediastinum (Hong Kong, China)最新文献

Background and objective: Rare thoracic cancers (RTCs) comprise a heterogeneous group of malignancies characterized by low incidence, high histological diversity, and significant clinical challenges. Their rarity often results in delayed diagnoses, lack of standardized therapeutic approaches, and limited prospective clinical trials. The absence of robust data is compounded by the fragmentation of expertise across institutions, underscoring the need for centralized, multidisciplinary management and international collaboration. This article aims to provide an overview of three representative RTC models, highlighting their unique clinical, pathological, and therapeutic features, and to discuss strategies for optimizing clinical care.

Methods: A narrative review was conducted based on a targeted search of PubMed, MEDLINE, and major conference proceedings up to January 2025. The search focused on selected RTCs highlighted during the 2024 ITMIG annual meeting, using terms such as "SMARCA4-deficient undifferentiated tumors", "thymic neuroendocrine neoplasms", and "mediastinal germ cell tumors". Eligible sources included case reports, retrospective series, and narrative reviews. Only English-language publications were considered.

Key content and findings: We focus on SMARCA4-deficient undifferentiated tumors as examples of rare entities newly defined by molecular profiling; thymic neuroendocrine neoplasms as ultra-rare and biologically aggressive neoplasms; and mediastinal germ cell tumors, which share biological traits with their gonadal counterparts but exhibit unique clinical behaviors. Through these models, we highlight common themes in RTCs management, including diagnostic uncertainty, limited therapeutic options, and emerging directions.

Conclusions: We discuss the strengths and limitations of current evidence and future perspectives aimed at enhancing outcomes through dedicated registries and tailored therapeutic strategies.

Thymic epithelial tumors (TETs) are rare but represent the most common neoplasms in the adult mediastinum. They are primarily classified into thymomas and thymic carcinomas, with thymic squamous cell carcinoma (SCC) being the most prevalent subtype of thymic carcinoma. Distinguishing thymomas from thymic carcinoma is critical, as it directly influences treatment strategies. However, considerable interobserver variability remains, and differentiating type A and type B3 thymomas-characterized by scattered or absent immature T cells-from thymic SCC continues to pose a diagnostic challenge. Notably, thymomas and thymic carcinomas are biologically distinct entities. Typical thymic SCC more prominently exhibits phenotypes of medullary thymic epithelial cells (mTECs) than thymomas. For example, we have demonstrated that thymic SCC frequently shows characteristics resembling tuft cells, a subset of mTECs. Moreover, these tuft cell-like phenotypes are strongly associated with KIT expression, a well-established marker of thymic SCC, which likely activates signaling pathways characteristic of this carcinoma subtype. The mTEC-like properties of thymic SCC may support the notion that it can partially mimic the cytoarchitecture of the thymus, a feature generally associated with thymoma. Therefore, immunophenotypic profiling may enhance diagnostic accuracy in distinguishing thymomas from thymic SCC. This review presents this perspective through discussion of various TET cases, focusing on type A thymoma, type B3 thymoma, and thymic SCC. Rather than asserting a definitive viewpoint, we aim to encourage constructive discussion toward a diagnostic consensus for TETs.

The finding of a mediastinal mass often poses a diagnostic challenge for clinicians. A correct diagnosis on the nature of a mediastinal tumor is important prior to initiating any treatment. Therefore, good knowledge is needed on mediastinal anatomy and its different compartments as well as on the differential diagnosis of a wide variety of benign and malignant mediastinal lesions. A complete history of the symptoms and a full clinical examination together with imaging and laboratory tests can guide the clinician towards a final diagnosis at presentation. Pretreatment tissue biopsy of a mediastinal tumor is not always required in case the clinical diagnosis is highly probable based on the above findings and when the tumor looks well encapsulated and of non-invasive nature amenable to upfront complete surgical resection as judged by the thoracic surgeon. Tissue diagnosis is recommended for a clinically and radiographically for cancer suspected, locally advanced or unresectable mediastinal mass in order to confirm the diagnosis and to guide induction therapy or definitive systemic treatment. An ultrasound or computed tomography (CT)-guided core needle biopsy may result in sufficient tissue for definitive cytopathological diagnosis. Otherwise, a minimally invasive procedure by video-assisted thoracoscopy (VATS) or robot-assisted thoracoscopy (RATS) or occasionally an open surgical biopsy may be necessary to obtain more tissue for pathological examination and molecular testing. Depending on the location of the mediastinal mass in any of the mediastinal compartments, various surgical approaches can be chosen to biopsy. A frozen section is helpful to check the quality of the biopsy but is less effective for a precise diagnosis. The definitive pathological report needs to be awaited prior to initiating any treatment except in case of a life-threatening condition such as critical airway compression or superior vena cava syndrome.

Background: World Health Organization (WHO) classification defines subdivision of type B group (B1, B2, and B3) based on proportion of neoplastic epithelial cells and non-neoplastic lymphocytes, and a number of studies have demonstrated correlation between the subtype and prognosis, with type B3 being unfavorable. Type A and AB tumors share similar clinico-pathological features, with generally indolent behavior, and both are characterized by GTF2I mutation. A subset of type A and AB tumors shows atypical features such as increased mitotic activity, cytologic atypia and necrosis, and the term atypical type A has been proposed; however, the atypical category is not well-defined. Aim of the study is to establish criteria for atypical type A thymoma.

Methods: A total of 252 thymomas resected from 247 patients were retrieved and reviewed. A variety of clinical and histopathologic parameters were recorded and analyzed, and prognostic factors in type A and AB group were investigated in order to better define the atypical category.

Results: Median age was 63 years (range, 14-84 years), equal male:female ratio (121:129), median tumor size 65 mm (range, 10-300 mm). There were 46 tumors (type A), 105 (AB), 22 (B1), 47 (B2), and 32 (B3). The majority of patients with A/AB subtypes were above 63 years old, whereas the majority of patients with B group were below 63 years old. Type B group was more often of advanced stage compared to A/AB. Vascular invasion was shown more often in subtype A and necrosis in subtype B1. AB group included larger tumors than the other subtypes. Paraneoplastic syndromes were reported in 71 (28.4%) patients and were more frequently seen in subtypes B2 and B3. In A/AB group, multivariate Cox proportional hazard models demonstrated that mitotic count was the only independent prognostic factor as continuous variable [hazard ratio (HR) 1.15, 95% confidence interval (CI): 1.07-1.24, P<0.001]. A/AB cases were further classified by mitotic count in 4 groups (1-4, 5-9, 10-19 and ≥20 mitotic figures per 2 mm²). Patients with mitotic count 1-4, 5-9 and 10-19 had similarly favorable progression free survival (PFS), while those with ≥20 mitotic figures per 2 mm² had remarkably worse outcomes. Therefore, A/AB patients were classified as typical if mitotic count was 0-19/2 mm² and atypical if ≥20 mitotic figures per 2 mm². Multivariate Cox proportional hazard models were performed in the entire population. The strongest prognostic factors were the new subtype classification, the presence of necrosis, the status of surgical margins and neoadjuvant treatment.

Conclusions: Our results suggest atypical type A and AB could be defined as tumors with ≥20 mitotic figures per 2 mm².

[This retracts the article DOI: 10.21037/med-22-30.].

Atypical thymomas are a rare form of primary thymic epithelial neoplasm that are characterized by conservation of most of the organotypical features of thymic differentiation, but show atypical cytological features. The spectrum of histologic features and growth patterns these tumors can exhibit have not been extensively documented or illustrated in the literature. The basic histologic growth patterns seen in atypical thymomas include the epithelioid or "Squamoid" subtype and the spindle cell subtype. The histologic picture may often be confused with thymic carcinomas or metastatic disease, in particular squamous cell carcinoma due to the overlap in histologic features. In addition, these subtypes may be seen in combination with each other or in combination with conventional types of thymoma including type A, type AB, type B1 and type B2. Cases of thymic carcinoma arising from atypical thymoma have also been documented in the literature. The biologic behavior of atypical thymomas is intermediate between conventional thymoma and thymic carcinoma. The tumors tend to present with aggressive behavior and an increased rate of metastasis and thus achieving the correct diagnosis is of utmost importance. We present a review of the various morphologic appearances of these tumors to emphasize the wide spectrum of histologic features that they can display, with a discussion of the current nomenclature and approach to these neoplasms.

Background and objective: Surveillance after thymic epithelial tumors (TETs) is widely recommended yet poorly studied. While this is not a situation unique to TETs, we seek to evaluate the rational of surveillance after treatment of TETs and summarize current available guidelines.

Methods: A literature review was conducted in PubMed/MEDLINE and Google Scholar databases. Articles were included if they discussed the following: (I) the epidemiology and natural history of TETs; (II) the diagnosis of recurrent TETs; (III) the treatment and outcomes of recurrent TETs; (IV) current available guidelines for surveillance or follow-up after treatment of TETs.

Key content and findings: TETs are rare group of neoplasms that include thymoma, thymic carcinoma and neuroendocrine neoplasms. Thymomas have excellent overall survival but can recur over longer periods of time compared to other malignancies. Thymic carcinoma and neuroendocrine neoplasms have less favorable outcomes but still have prolonged survival even at advanced stages. Moreover, recurrence tends to be asymptomatic and localized to the chest and pleura, making it amenable to local treatments such as surgery and/or radiation. As such, TETs may be positioned to benefit from surveillance but also present unique challenges regarding surveillance. There are no prospective studies addressing surveillance in TETs, but at least 5 guidelines have made recommendations that mostly recommend computed tomography (CT) of the chest in variable frequencies and durations. Most agree that the duration for thymoma surveillance should be 10 years or longer. Thymic malignancies are frequently associated with paraneoplastic syndromes which can be a symptom of recurrence, and knowledge of these disorders should be a component of surveillance.

Conclusions: Surveillance after treatment for TETs is felt to be beneficial, but there is a paucity of evidence directly studying this. Currently available guidelines do offer some direction based on expert opinion. Given the rare occurrence of TETs and recurrences after treatment, pooling of data such as the International Thymic Malignancy Interest Group (ITMIG) database to study follow up will be necessary to develop more effective surveillance strategies.

Background: Accurate mediastinal restaging in patients with non-small cell lung cancer (NSCLC) following neoadjuvant therapy is crucial for treatment planning. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), the standard technique, has limitations such as low diagnostic yield and false negatives, often requiring invasive mediastinoscopy. This study evaluates the performance of endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) as a potential alternative to EBUS-TBNA in mediastinal restaging following neoadjuvant therapy. This study compares the diagnostic accuracy of EBUS-TBNA and EBUS-TMC, specifically focusing on diagnostic yield, false-negative rates, sample adequacy for molecular and immunohistochemical analyses, as well as the potential need for mediastinoscopy.

Methods: This prospective study was conducted on 22 NSCLC patients undergoing mediastinal restaging after neoadjuvant therapy from September 2023 to October 2024. Each patient underwent both EBUS-TBNA and EBUS-TMC in the same procedure. Mediastinoscopy was performed only in cases where both EBUS-TBNA and EBUS-TMC results were negative or non-diagnostic, serving as the reference standard.

Results: EBUS-TMC demonstrated superior diagnostic sensitivity (95.45% vs. 63.63%) and achieved sample adequacy for molecular and immunohistochemical analysis in 94.11% of cases compared to 29.41% for EBUS-TBNA. EBUS-TMC identified six additional malignancy cases and had fewer non-diagnostic results (4.5% vs. 22.7%). No complications were reported for any procedure, and mediastinoscopy confirmed all negative EBUS-TMC cases as true negatives.

Conclusions: EBUS-TMC significantly improves diagnostic accuracy and sample adequacy for restaging NSCLC following neoadjuvant therapy, reducing the need for mediastinoscopy. Its integration into clinical practice could enhance patient outcomes, lower healthcare costs, and support personalized treatment strategies. This is the first study to demonstrate EBUS-TMC's transformative potential in thoracic oncology.

Background and objective: Thymic epithelial tumors (TETs) are the most common mediastinal neoplasms and include thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms (TNENs). The staging system of TETs has been based on the Masaoka-Koga system or the 8th edition of the TNM classification, which does not consider tumor size as a T descriptor. The 9th edition of the TNM classification was released in January 2025, and tumor size was incorporated, with the T1 category subdivided into T1a (≤5 cm) and T1b (>5 cm). Thus, the clinical importance of tumor size in TETs has attracted increasing attention. This review summarizes previous reports focusing on tumor size as a prognostic factor for TETs and highlights the association between tumor size, prognosis, and clinicopathological features of TETs.

Methods: The literature search was performed using PubMed for the narrative review. Eligible articles were published in English between January 1, 2004 and December 1, 2024.

Key content and findings: We identified 35 articles investigating the effect of TET tumor size. Tumor size assessed using surgical specimens was a useful predictor for prognosis in all stages of thymomas. A large tumor size was associated with tumor invasion into adjacent tissues, which contributes to advanced-stage disease and incomplete resection. Thus, large tumor size was shown to be related to a high recurrence rate and poor prognosis. In addition, tumor size had a strong prognostic impact in patients with early-stage thymoma. Consistent with the evaluation of surgical specimens, preoperative assessment of tumor size using computed tomography also contributed to the postoperative prognosis. Furthermore, evaluation of tumor size may help determine treatment strategies, such as surgical approaches and adjuvant radiotherapy. However, the prognostic role of tumor size in thymic carcinoma and TNENs was unclear because of their rarity.

Conclusions: Primary tumor size was identified as an important prognostic factor in patients with thymoma. However, the significance of thymic carcinoma or TNEN remains unclear. Further prospective large-scale studies are warranted to investigate the clinical significance of tumor size in TETs.

Background and objective: Thymic pathology is observed in approximately 80% of patients with acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG). Among these thymic abnormalities, thymic follicular hyperplasia (TFH) is commonly associated with early-onset MG (EOMG). TFH is characterized by the presence of lymphoid follicles and germinal center (GC) formation, which are closely linked with the breakdown of tolerance to the AChR. GCs promote the development of autoreactive plasma cells that secrete autoantibodies against the AChR, contributing to the disease pathology. In this review, we examine current knowledge on thymic pathology in EOMG, immunological and environmental factors contributing to the development of thymic hyperplasia and highlight avenues for future research.

Methods: A comprehensive literature search was conducted using PubMed without restriction on publication date. Articles were included if they discussed the function of the thymus, thymic pathology in MG, thymic hyperplasia in EOMG, or focused on cellular or molecular mechanisms associated with TFH in EOMG.

Key content and findings: TFH is a hallmark of EOMG, characterized by GC formation and intrathymic production of AChR autoantibodies. The hyperplastic thymus exhibits heightened interferon (IFN) signaling, toll-like receptor (TLR) activation, altered chemokine expression, accumulation of B and T cells, and expression of AChR by thymic epithelial cells, creating a pro-autoimmune environment. Sex-related differences, particularly estrogen's effects on autoimmune regulator gene (AIRE) expression and immune tolerance, may contribute to the female predominance in EOMG. Emerging technologies such as single-cell and spatial transcriptomics, along with thymic organoid models, offer new avenues to study the mechanisms driving TFH.

Conclusions: TFH reflects the convergence of immune dysregulation and structural abnormalities that together promote the loss of tolerance in EOMG. The interindividual variability in thymic pathology and treatment response underscores the need for more personalized therapeutic strategies. Advances in high-resolution profiling and experimental modeling will be essential to uncover the underlying drivers of thymic hyperplasia and to guide the development of targeted therapies for MG.