Efficacy of robot-assisted thoracoscopic surgery for managing thymoma recurrence following sternotomy: a case report.

This report addresses the management strategy and effectiveness of robot-assisted thoracoscopic surgery (RATS) for treating local recurrence of thymoma, a condition often complicated by severe adhesions and limited data on re-operation following median sternotomy. We report about a 43-year-old man with thymoma recurrence 4 years after thymothymectomy via a median sternotomy. Follow-up computed tomography revealed a nodule adjacent to the left brachiocephalic vein, indicating possible thymoma recurrence. Thus, re-operation was performed using a left-sided approach via RATS with an artificial pneumothorax. The manipulation space was secured with an artificial pneumothorax, and multidirectional manipulation using RATS demonstrated good efficacy. Collectively, this case highlights the efficacy of RATS as a viable approach for managing thymoma recurrence in mediastinal locations, particularly when sternotomy is complicated by severe adhesions.

[Intraspinal Metastasis of Thymic Carcinoma:Report of One Case].

Intraspinal metastasis from malignant carcinomas in other body parts is rarely reported.Intraspinal metastases are often epidural,with primary tumors mostly from the lung and prostate.The extramedullary subdural metastasis of thymic carcinoma is particularly rare and prone to misdiagnosis due to overlapping imaging features with primary intraspinal tumors.This article reports one case of intraspinal metastasis of thymic carcinoma,with the main diagnostic clues including a history of thymic carcinoma,fast growth rate,and irregular shape.

Ectopic cervical thymoma: a rare entity in the anterior neck.

Thymoma is a rare malignancy with usual location in the antero-superior mediastinum. Ectopic cervical thymoma (ECT) is an extremely rare tumor that originates from ectopic tissue, and is caused by the aberrant migration of the embryonic thymus. Our patient was a 56-year-old man who had a nodular lesion in the neck for several years. Computed tomography and Enhanced magnetic resonance imaging were performed. He underwent surgery, and a histological examination resulted in a diagnosis of type AB thymoma.

Ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis: a case report.

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Intrathyroidal thymic carcinoma.

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.

Type B thymomas in patients with myasthenia gravis display a distinctive pattern of αß TCR and IL-7 receptor α expression on CD4+CD8+ thymocytes.

Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some patients with thymoma develop MG and others do not. In this study, we conducted a comparative phenotype analysis of thymocytes in type B thymomas in patients with MG (MG (+) thymomas) and without MG (MG (-) thymomas) via fluorescence-activated cell sorting (FACS). Our results show that the developmental stages defined by the expression of CD3, CD4, and CD8 were largely maintained in both MG (+) and MG (-) thymomas, with CD4+CD8+ cells constituting the majority of thymocytes in type B thymoma, and no significant difference between this cell population was observed in MG (+) and MG (-) thymomas.We discovered that CD4+CD8+ thymocytes in MG (+) thymomas expressed low levels of αß TCR and high levels of IL-7 receptor α (IL-7Rα), whereas in MG (-) thymomas, CD4+CD8+ thymocytes exhibited the opposite pattern of αß TCR and IL-7Rα expression. These results suggest that the positive and negative selection processes of CD4+CD8+ thymocytes might differ between MG (+) thymomas and MG (-) thymomas. The expression of the Helios transcription factor is induced during negative selection and marks a group of T cells that have undergone negative selection and are likely to be deleted due to strong TCR binding with self-peptides/MHC ligands. We observed that the percentage of Helios-positive CD4SP T cells was greater in MG (-) than in MG (+) thymomas. Thus, the differentially regulated selection process of CD4+CD8+ thymocytes, which involves TCR and IL-7/IL-7Rα signaling, is associated with the presence of MG in type B thymomas.

ERK5 Activity Prevention Improves the Antitumor Efficacy of Fluvastatin on Thymic Carcinoma.

BACKGROUND/AIM: Thymic carcinoma is a rare cancer type with limited treatment options. Our previous study demonstrated that statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, can prevent thymic carcinoma. However, the mechanisms through which statins affect intracellular events in cancer cells are not well understood. The aim of the study was to determine how thymic carcinoma modulates the intracellular signals in response to statin administration. MATERIALS AND METHODS: We analyzed statin-induced protein phosphorylation in Ty82 human thymic carcinoma cells, which were cultured with fluvastatin, and protein phosphorylation was examined using western blotting. RESULTS: Treating Ty82 with fluvastatin led to ERK5 phosphorylation via protein prenylation attenuation. The antitumor effects of fluvastatin on thymic carcinoma were enhanced when combined with an ERK5 inhibitor. CONCLUSION: Statin therapy in combination with ERK5 inhibition may be a promising therapeutic approach for treating thymic carcinoma.

Deep learning for risk stratification of thymoma pathological subtypes based on preoperative CT images.

OBJECTIVES: This study aims to develop an innovative, deep model for thymoma risk stratification using preoperative CT images. Current algorithms predominantly focus on radiomic features or 2D deep features and require manual tumor segmentation by radiologists, limiting their practical applicability. METHODS: The deep model was trained and tested on a dataset comprising CT images from 147 patients (82 female; mean age, 54 years ± 10) who underwent surgical resection and received subsequent pathological confirmation. The eligible participants were divided into a training cohort (117 patients) and a testing cohort (30 patients) based on the CT scan time. The model consists of two stages: 3D tumor segmentation and risk stratification. The radiomic model and deep model (2D) were constructed for comparative analysis. Model performance was evaluated through dice coefficient, area under the curve (AUC), and accuracy. RESULTS: In both the training and testing cohorts, the deep model demonstrated better performance in differentiating thymoma risk, boasting AUCs of 0.998 and 0.893 respectively. This was compared to the radiomic model (AUCs of 0.773 and 0.769) and deep model (2D) (AUCs of 0.981 and 0.760). Notably, the deep model was capable of simultaneously identifying lesions, segmenting the region of interest (ROI), and differentiating the risk of thymoma on arterial phase CT images. Its diagnostic prowess outperformed that of the baseline model. CONCLUSIONS: The deep model has the potential to serve as an innovative decision-making tool, assisting on clinical prognosis evaluation and the discernment of suitable treatments for different thymoma pathological subtypes. KEY POINTS: • This study incorporated both tumor segmentation and risk stratification. • The deep model, using clinical and 3D deep features, effectively predicted thymoma risk. • The deep model improved AUCs by 16.1pt and 17.5pt compared to radiomic model and deep model (2D) respectively.

Postoperative radiotherapy does not improve survival in patients with Masaoka-Koga stage IIB thymomas: A propensity score matching study based on the SEER database.

This study, based on a population, explored the prognostic value of postoperative radiotherapy (PORT) for Masaoka-Koga IIB stage thymomas. Patients diagnosed with thymoma from 2004 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) database were included in the retrospective study. Through propensity score matching, the baseline characteristics of the patients were successfully matched to mitigate the selection bias of PORT. Survival rates and survival curves were compared between the PORT and non-PORT groups, with potential confounding factors addressed using a multivariate Cox regression model. In this study, 785 cases of IIB stage thymoma were included from the SEER database, and 303 patients were successfully matched between PORT and non-PORT groups through propensity score matching, with no significant differences in baseline characteristics. In the PORT and non-PORT groups, 10-year overall survival rates were 65.2% versus 59.6%, and cancer-specific survival rates were 87.0% vs. 84.4%, PORT did not yield statistically significant improvements in overall survival (P = .275) or cancer-specific survival (P = .336) for stage IIB thymomas. Based on the SEER database, the results of our study indicated that PORT does not confer a significant survival benefit for IIB stage thymomas.

A case of thymoma presenting as pyrexia of unknown origin.

ABSTRACT: Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of investigations for the confirmation of diagnosis. Thymomas are rare mediastinal tumors that present as anterior mediastinal mass; however, thymomas presenting as pyrexia of unknown origin has rarely been reported in the literature. We report an interesting case of a middle-aged male who presented as pyrexia of unknown origin due to thymoma.

Long-term follow-up and exploratory analysis of lenvatinib in patients with metastatic or recurrent thymic carcinoma: Results from the multicenter, phase 2 REMORA trial.

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.

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.

Postoperative radiotherapy results in 192 epithelial thymic tumours patients with 10 years of follow-up.

PURPOSE: To assess the prognostic factors and patterns of failure of patients consecutively treated with surgery and postoperative radiation therapy (PORT) for thymic epithelial tumours (TET). PATIENTS AND METHODS: Data from 192 TET patients who were operated and received PORT at a single centre from 1990 to 2019 was retrospectively analysed. RESULTS: Most patients had thymoma (77 %, B247%), were classified Masaoka-Koga stage III (35 %) or IV (32 %) and had a R0 (75 %) resection. Radiotherapy was delivered at a median dose of 50.4 Gy (range, 42-66 Gy; ≥ 60 Gy in 17 %), 63 (33 %) patients were treated by intensity-modulated radiation therapy and elective nodal radiotherapy was used for 37 %. At a median follow-up of 10.9 years, the 10-year overall survival (OS) and progression-free survival (PFS) rates were 62 % (95 % CI: 54-70 %) and 47 % (95 % CI: 39-55 %), respectively. Locoregional recurrence (LRR) occurred in 72/192 (38 %) patients, distributed as 6 local, 45 regional and 21 both local and regional. LRR were mainly located to the pleura: 66/72 (92 %) and 16/72 (22 %; 16/192 in total, 8 %) were in-field. Distant relapse (DR) were observed in 30 patients (16 %), resulting in 10-year locoregional (LRC) and distant control rates of 58 % (95 % CI: 50-66 %) and 82 % (95 % CI: 77-88 %), respectively. In the multivariate analysis, Masaoka-Koga stage (HR [hazard ratio]: 1.9; p = 0.001), thymic carcinomas/neuroendocrine tumours (TC) (HR: 1.6; p = 0.045) and ECOG PS > 1 (HR: 1.9; p = 0.02) correlated with poorer OS. Higher Masaoka-Koga stage (HR: 2.6; p < 0.001) associated with a decreased LRC but not R1 status (HR: 1.2; p = 0.5) or WHO histology classification. TC (HR: 3.4; p < 0.001) and a younger age (HR: 2.5; p = 0.02) correlated with DR. CONCLUSION: Approximately one-third of the TET in our study experienced a LRR, mainly to the pleura, and 8% in total were in-field. The place of radiotherapy should be better defined in higher risk thymoma patients within prospective randomized studies.

Analysis of 25 surgical cases of thymic neuroendocrine tumors and thymic carcinoma.

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).

Long-term follow-up of non-myasthenic patients with early-stage thymoma who underwent extended thymectomy or limited resection.

BACKGROUD: The standard resection for early-stage thymoma is total thymectomy and complete tumour excision with or without myasthenia gravis but the optimal surgery mode for patients with early-stage non-myasthenic thymoma is debatable. This study analysed the oncological outcomes for non-myasthenic patients with early-stage thymoma treated by thymectomy or limited resection in the long term. METHODS: Patients who had resections of thymic neoplasms at Taipei Veteran General Hospital, Taiwan between December 1997 and March 2013 were recruited, exclusive of those combined clinical evidence of myasthenia gravis were reviewed. A total of 113 patients were retrospectively reviewed with pathologic early stage (Masaoka stage I and II) thymoma who underwent limited resection or extended thymectomy to compare their long-term oncologic and surgical outcomes. RESULTS: The median observation time was 134.1 months [interquartile range (IQR) 90.7-176.1 months]. In our cohort, 52 patients underwent extended thymectomy and 61 patients underwent limited resection. Shorter duration of surgery (p < 0.001) and length of stay (p = 0.006) were demonstrated in limited resection group. Six patients experienced thymoma recurrence, two of which had combined myasthenia gravis development after recurrence. There was no significant difference (p = 0.851) in freedom-from-recurrence, with similar 10-year freedom-from-recurrence rates between the limited resection group (96.2 %) and the thymectomy group (93.2 %). Tumour-related survival was also not significantly different between groups (p = 0.726).result CONCLUSION: Patients with early-stage non-myasthenic thymoma who underwent limited resection without complete excision of the thymus achieved similar oncologic outcomes during the long-term follow-up and better peri-operative results compared to those who underwent thymectomy.

Survival Outcome After Surgery in Patients With Thymoma Distant Recurrence.

OBJECTIVE: The aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the definition of the International Thymic Malignancy Interest Group. METHODS: Data of patients affected by thymoma recurrence from four different institutions were collected and retrospectively reviewed. Patients with locoregional metastases who underwent nonsurgical therapies and with incomplete data on follow-up were excluded. According to the International Thymic Malignancy Interest Group distant recurrence definition, patients with recurrence due to hematogenic localization were included. Clinical and pathologic characteristics were described using descriptive statistics, whereas survival outcome was calculated using Kaplan-Meier curves and Cox regression analysis. RESULTS: The analysis was conducted on 40 patients. A single localization was present in 13 patients, the relapse was intrathoracic in 28 cases (70%), and lung involvement was found in 26 cases. The liver was operated in seven cases, whereas other kinds of abdominal involvement were detected in eight cases. Adjuvant treatment was administered in 22 cases (55%).Five- and 10-year overall survival (OS) were 67% and 30%, respectively. Univariable analysis identified as significant favorable factor a low-grade histology (A, B1, B2): five-year OS at 92.3% versus 53.3% in high-grade (B3-C) (p = 0.035). Site of recurrence and number of localization did not influence the prognosis, but in patients with adjuvant therapy administration, there was a survival advantage also if not statistically significant: five-year OS 84.8% versus 54.5% in patients without adjuvant therapy (p = 0.101).Multivariable analysis confirmed as independent prognostic factor low-grade histology: hazard ratio = 0.176, 95% confidence interval 0.042-0.744, p = 0.018. CONCLUSIONS: Our study revealed a good survival outcome in patients who underwent surgery for distant thymoma recurrence, independently from the number and site of the relapse localization. Patients with A, B1, or B2 histology presented a significantly better survival than patients with B3-C.

Recommendations for Post-Operative RadioTherapy After Complete Resection of Thymoma-a French DELPHI Consensus Initiative.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement. RESULTS: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years. CONCLUSION: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

[Severe complications of systemic treatment in thoracic oncology]. / Complications sévères des traitements systémiques du patient cancéreux thoracique (complications hors infections et urgences respiratoires).

Primary thoracic cancers affect a large number of patients, mainly those with lung cancer and to a lesser extent those with pleural mesothelioma and thymic tumours. Given their frequency and associated comorbidities, in patients whose mean age is high, these diseases are associated with multiple complications. This article, the last of a series dedicated to emergencies in onco-haematological patients, aims to present a clinical picture of the severe complications (side effects, immune-related adverse events) associated with systemic treatments, excluding infections and respiratory emergencies, with which general practitioners and specialists can be confronted. New toxicities are to be expected with the implementation of innovative therapeutic approaches, such as CAR-T cells, along with immunomodulators and antibody-drug conjugates.