Bystander effect and abscopal effect in recurrent thymic carcinoma treated with carbon-ion radiation therapy:A case report

BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma.CASE SUMMARY A 44-year-old female presented with shortness of breath.Eleven years prior,she was diagnosed with athymic tumor located in the anterosuperior mediastinum.She underwent extensive tumor resection,and the postoperative pathologic diagnosis was thymic carcinoma.She was administered 50 Gy/25 Fx of postoperative radiation.In 2019,she was diagnosed with a recurrence of thymic carcinoma,with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity,the largest of which was in the diaphragm pleura proximal to the pericardium,with a size of 6.7 cm×5.3 cm×4.8 cm.She received carbonion radiotherapy.After carbon-ion radiotherapy treatment,the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging.We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case.CONCLUSION This report is the first of obvious abscopal and bystander effects following carbonion irradiation in a human patient,and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.

EFFECTS OF p53 OVEREXPRESSION ON NEOPLASTIC CELL PROLIFERATION AND APOPTOSIS IN THYMIC CARCINOMA

Objective: To investigate p53 overexpression and its correlation with neoplastic cell proliferation and apoptosis in 20 thymic carcinomas. Methods: 20 surgical samples of thymic carcinoma were collected randomly during the past 15 years in the Guangzhou area. Immunohistochemical staining was performed using LSAB method with anti-p53 monoclonal antibody (DO-7) and proliferating cell nuclear antigen (clone PC 10) as primary antibodies. The p53 index was indicated by the number of p53 positive cells among 100 carcinoma cells. More than 25 percentage of p53 positive cells found in tissue sections was recognized as p53 overexpression. Carcinoma cell proliferation activity was assayed by PCNA index (PI), and apoptosis degree was evaluated by TUNEL (TdT-mediated dUTP-X nick end labeling) index (TI) using Boehringer MannheimIn Situ Death Detection Kit. Results: P53 positive cells could be found in vast majority of thymic carcinomas (19/20) and the overexpression rate reached 35% (7/20). The median PI (40%) of 7 cases with p53 overexpression was higher than that (31%) of 13 cases without p53 overexpression, but there was no statistical significance that existed between these two data (P>0.05). The median TI (0.5/HPF) of 7 p53 overexpression cases was much lower than that (4.5/HPF) of 13 non-overexpression cases, and there was a significant difference statistically (P<0.05). Conclusion: p53 expression was a frequent finding in thymic carcinoma cells, and the p53 overexpression which might represent p53 inactivation or gene mutation was often involved in thymic carcinogenesis. The median PCNA index of p53 overexpression group was higher than that of non-overexpression group though there existed no statistical difference. This indicates that the inhibiting function of p53 on cell proliferation seemed lost in p53 overexpressed thymic carcinomas. It is worthy to be specially mentioned that the inducing function of p53 on cell apoptosis was markedly lost in p53 overexpressed thymic carcinomas. Taken together, the overexpressed p53 that could represent aberrant p53 protein had not only lost its proliferation-inhibiting but also its apoptosis-inducing function in thymic carcinomas which might play an important role in thymic carcinogenesis.

Rare solitary splenic metastasis from a thymic carcinoma detected on fluorodeoxyglucose-positron emission tomography:A case report

BACKGROUND Thymic carcinoma is a rare,aggressive tumor arising from the thymus.In less than 7%of patients with thymic carcinoma,extrathoracic metastases occur in the extrathoracic lymph nodes,liver,and bone.Isolated splenic metastasis can occur but is very uncommon.To date,only 2 cases of splenic metastases from thymic carcinoma have been reported.CASE SUMMARY A 45-year-old man presented with chronic cough,dyspnea,persistent hoarseness and unintentional weight loss 17 kgs in 6 mo.Neck magnetic resonance imaging revealed a large,lobulated,soft-tissue mass measuring 5.4 cm×6.6 cm×3.8 cm which involved the left superior mediastinum and supraclavicular fossa.Chest computed tomography(CT)revealed a confluent and lobulated soft tissue mass encased the right brachiocephalic artery,right and left carotid arteries,and left subclavian artery in the mediastinum.A fluorodeoxyglucose-positron emission tomography was arranged for malignancy survey.The image revealed intense fluorodeoxyglucose avidity in a soft tissue lobulated mass occupying the superior mediastinum,over the cystic lesion in the spleen and in few enlarged nodules over the left supraclavicular fossa.CT-guided biopsy of the thymic mass and the ultrasound-guided biopsy of the splenic lesion were consistent with a thymic carcinoma with splenic metastasis.The patient was diagnosed of thymic carcinoma,cT2N2M1b,stage IVb.CONCLUSION A fluorodeoxyglucose(FDG)-positron emission tomography(PET)scan can provide a useful diagnostic value in conjunction with pathological result in evaluating tumor staging.Our case emphasizes the utility of FDG-PET for metastasis detection in thymic carcinoma.

Clinical Analysis of 45 Patients with Thymic Carcinoma

OBJECTIVE To retrospectively evaluate the prognostic factorsfor advanced thymic carcinoma.METHODS The data from 45 patients with advanced thymiccarcinoma were retrospectively analyzed according to Masaokastage criteria. There were 29 Stage Ⅲ patients and 16 StageⅣ patients (13 Stage ⅣA patients and 3 Stage ⅣB patients).According to the World Heath Organization Histological Criteria(2004), 25 cases were identified as low-grade and 20 caseswere identified as high-grade. All diagnoses were confirmedby biopsy. Five patients underwent gross total resection, 21patients underwent subtotal resection and 19 patients underwentbiopsy alone. Forty-two patients received radiotherapy with amedian dose of 60 Gy, and 37 patients underwent conventionalradiotherapy, including local irradiation and expanded irradiation.Local irradiation volume covered the primary tumor bed andapproximately 1-2 cm^2 surrounding the tumor (according topreoperative imaging). Expanded irradiation volume coveredthe full mediastinal and pericardium areas (with or withoutprophylactic irradiation in the supraclavicular area). Five casesreceived stereotactic radiotherapy. Thirty-one patients were alsotreated with chemotherapeutics, including Cisplatin, VP-16,Endoxan, 5-FU and taxol.RESULTS The median follow-up period was 59 months. Theoverall 3-year survival rate was 57.8%, and the median survivalwas 45 months. Univariate statistical analysis showed that thehistological subtype and Masaoka stage were prognostic factors.The 3-year survival rate was 61.9% in patients treated withgross total resection and 55.0% in those who underwent biopsyonly. The 3-year survival rate was 59.5% in patients treatedwith conventional radiotherapy and 80% in those treated withstereotactic radiotherapy. The 3-year survival rate was 64.5% inpatients treated with simultaneous chemotherapy and 42.9%in patients treated without simultaneous chemotherapy (P >0.05). Chemotherapy in combination with radiation treatmentand surgery achieved better outcomes for Stage Ⅳ patients thanradiation treatment and surgery without chemotherapy (P < 0.05).CONCLUSION For patients with Stage Ⅲ and Ⅳ thymiccarcinoma, complete resection and postoperative radiotherapy orfractionated stereotactic radiotherapy constitute the best treatmentsolution. Chemotherapy can also be used in combination toimprove prognosis. For patients with Stage Ⅳ thymic carcinoma,chemotherapy is necessary.

THYMIC CARCINOMA(REPORT OF 14 CASES)

This paper reports of 14 cases of thymic carcinoma. Most of them with symptoms of chest pain, cheststuffy and discomfort, but without combined with extrathoracic syndromes, The tumors always were largein size and frequently invaded adjacent organs, hence with low resection rate. ln this series, complete re-section of tumor only 2 cases, partial resection in 7 cases, exploratory thoracotomy in 5 cases. Thymic car-cinoma was an extremely malignant tumor with extensive invasion intrathoracally and early metastasis ex-trathoracally. The common sites of metastasis were bone, liver,lung and extrathoracic lymph nodes. Adju-vant therapy postoperatively was given to all patients. Follow-up of lbo 8 years showed 1O cases death,ofwhich 5 cases died within the first year after surgery,3 cases within the second year. Four patients werestill alive so far, in which 3 patients were within 1. 5 years postoperatively. Pathological studies revealed 9cases of squamous epithe1ial cell thymic carcinoma, 3 of lymphoepithelioma - like thymic carcinoma and 2 ofsmall cell undifferentiate thymic carcinoma.

Multimodality Treatment for Thymic Carcinoma: Review of 11 Cases at a Single Institute

Background: We reported our experience with thymic carcinomas and review their clinical features, treatment strategies, and prognoses. Methods: From April 1998 to November 2012, 11 patients pathologically diagnosed with thymic carcinoma and treated in our hospital were investigated. Results: There were 7 men and 4 women, with a median age of 62 years (range, 35 - 72). According to the Masaoka staging system, 3 patients had stage II, 1 stage III disease, 3 stage IVa disease and 4 stage IVb disease. Ten patients had squamous cell carcinoma, whereas 1 had large cell neuroendocrine carcinoma (LCNEC). We performed surgery or multimodality therapy including surgery as the initial therapy for 8 patients. Of the non-surgical cases, 1 patient received chemoradiotherapy and survived for over 6 years without recurrence, whereas 2 received palliative care. Three of 4 patients who underwent complete resection survived without disease recurrence, whereas only 1 patient with LCNEC survived in the incomplete resection group. Multimodality therapy with cisplatin and docetaxel was provided to 3 patients, and recurrence has not been observed in any of the cases. Conclusions: Favorable outcomes could be achieved in patients with thymic carcinoma who underwent intensive treatment. In particular, surgery combined with cisplatin and docetaxel plus thoracic irradiation may be an attractive approach for thymic carcinoma.

Myasthenia gravis as a form of clinical presentation of thymic carcinoma

Thymic carcinomas are rare tumors of the thymus arising in the thymic epithelium. They represent less than 1% of thymic malignancies. They often present with an advanced disease and metastasize to regional lymph nodes and distant sites. They have a worse prognosis with a 5-year survival rate of 30%-50%, while thymomas are much less invasive and have a 5-year survival of approximately 78%. We report a rare form of clinical presentation of a thymic carcinoma in which the diagnosis of myasthenia gravis was the cornerstone of the diagnosis of cancer. Surgery is considered the salvage treatment when possible. Radiotherapy is a second choice of salvage treatment, when possible depending on its localization and relation to nearby structures such as vascular structures. Molecular target therapy is a more directed, more expensive but less toxic treatment. Further studies need to be carried out for its approval worldwide, outside clinical trials.

A Rare Case of Thymic Carcinoma

Thymic carcinomas are unusual tumors of the thymus gland. Basaloid carcinoma, an unusal epithelioid varient of a thymic carcinoma, is a rare histopathological subtype, and is not well charecterized in the literature. We present the anatomical and histogical features of a basoloid thymic carcinoma, and discuss current diagnosis and imaging strategies, as well as the operative and oncologic care of this type of thymmic carcinoma. Basaloid carcinomas of the thymus after complete surgical resection and adjuvant therapy genarally have a favorable long-term prognosis.

Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways

Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic malignancy.Traditional therapy for advanced TCs and TNENs has limited outcome.New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.Methods:We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017.Patient samples were sequenced using a 324-gene platform with licensed technologies.In this study,we focused on clinically relevant genomic alterations(CRGAs),which are previously proven to be pathogenic alterations,to identify the pathology-specific mutational patterns,prognostic signatures of TCs and TNENs.Results:The mutational profiles between TCs and TNENs were diverse.The genetic alterations that ranked highest in TCs were in CDKN2A,TP53,ASXL1,CDKN2B,PIK3C2G,PTCH1,and ROS1,while those in TNENs were in MEN1,MLL2,APC,RB1,and TSC2.Prognostic analysis showed that mutations of ROS1,CDKN2A,CDKN2B,BRAF,and BAP1 were significantly associated with worse outcomes in TC patients,and that mutation of ERBB2 indicated shortened disease-free survival(DFS)and overall survival(OS)in TNEN patients.Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control,chromatin remodeling/DNA methylation,phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and receptor tyrosine kinase(RTK)/RAS/mitogen-activated protein kinase(MAPK)signaling.Conclusion:We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors,and identified the pathology-specific mutational patterns,prognostic signatures,and potential therapeutic targets for TCs and TNENs.

Thymic carcinoma involving sternum： a case report

Thymic carcinoma is a malignancy of the anterior mediastinum with a poor prognosis that is thought to be derived from thymic epithelium and they represent approximately 6% of primary mediastinal tumors. Because of the lack of literature discussing the clinical and pathologic features and treatment of this tumor, thymic carcinoma has been a somewhat controversial disease up to now. Here, we report a female patient suffering from thymic carcinoma involving the sternum. The tumor was resected and the sternum was replaced with a refrigerated homograft.

Encased heart and aorta by the thymic carcinoma

Thymic carcinoma is a very rare and aggressive malignant tumor. It is indolent and invasive cancer that easily metastasis. Invasive thymoma occurs most commonly into the pleura, pericardium, lungs, and recurrent laryngeal nerve, but invasion into the intracardiac and great vessel is rare.1 We reported a rare case ofinvasive thymic carcinoma which extended into aorta, pericardium, and right ventricular outflow tract （RVOT）, causing right ventricular outflow tract flow acceleration.

Molecular pathology of thymoma and thymic carcinoma

Thymic epithelial tumors(TETs)comprise a heterogeneous group of epithelial-derived thymic neoplasms with diverse clinical behavior and underlying molecular genetic features.Owing to their rare nature,the molecular classification of TETs has only recently begun to be fully explored.The advent of advanced molecular studies,particularly the ability to sequence the DNA and RNA of tumors in a massively parallel fashion,has led to an increased understanding of the molecular underpinnings of thymic neoplasia.Thymomas,characterized by a heterogeneous group of molecular alterations,tend to have low mutational burdens and various copy number abnormalities including a characteristic loss of chromosomal material in the region of 6q25.2-p25.3,a recurrent,specific point mutation GTF2I p.L424H,and specific expression of certain microRNAs.Thymic carcinomas,in contrast,are generally characterized by increased tumor mutational burdens,multiple copy number alterations,and varied,non-recurrent,somatic mutations.Advances in molecular knowledge of TETs allow for more precise molecular classification of these tumors,and the presence of specific alterations aids in the diagnosis of borderline lesions.In the future,additional molecular studies will better delineate the molecular landscape of these tumors and may one day allow for more targeted treatment algorithms.This review aims to cover the current understanding of the molecular alterations thus far identified in thymomas and thymic carcinomas.

Thymic carcinoma:review and update

Thymic carcinoma(TC)is a rare thymic epithelial neoplasm with an aggressive clinical course.There are many recognized histologic subtypes as described by the fifth edition of the World Health Organization(WHO)Classification of Thoracic Tumors;however,given the rarity of this tumor group,diagnosis remains a challenge,especially on limited tissue samples.Additionally,rare variants of TC are continuing to be established,particularly in the era of molecular diagnostics.Herein,histologic subtypes are described as the rare subtypes of TC in the context of their immunoprofile,cytogenetic or molecular features,clinical presentation,and ensuing challenges.

A Case Report:Severe Bullous Skin Reaction Induced by Anti-PD-1 Antibody(Toripalimab)Therapy in a Patient with Thymic Carcinoma

The development of immune checkpoint inhibitors,such as those targeting programmed cell death protein 1(PD-1),represents a major breakthrough in cancer therapy.Although immune checkpoint blockade therapy has a favorable risk/benefit ratio,it causes significant immune-related adverse events(irAEs),such as cutaneous reactions,in particular,severe bullous skin reactions and toxic epidermal necrolysis.Here,we report a case of a 51-year-old woman with malignant thymoma who developed a severe bullous skin reaction(characterized by a systemic rash,bullae,epidermal desquamation,and Stevens-Johnson syndrome)as a result of treatment with the PD-1 inhibitor toripalimab.The patient was treated with high doses of glucocorticoid,intravenous immunoglobulin,and intensive care,and eventually recovered from the severe irAEs.The intravenous injection of anti-PD-1 antibodies induces cutaneous reactions,which are associated with higher mortality rates.High doses of glucocorticoid combined with intravenous immunoglobulin are effective in alleviating such irAEs.Thus,improving the level of care and preventing skin infections can effectively reduce the risk of death.

胸腺癌椎管内转移一例

椎管内转移瘤是一种少见的从全身各部位恶性肿瘤转移至椎管内的恶性肿瘤。常见的椎管内转移瘤多位于硬膜外,原发灶多为肺脏、前列腺等,原发灶为胸腺癌的髓外硬膜下转移瘤十分罕见,既往报道的病例影像学表现与原发性椎管内肿瘤也存在一定重叠性,非常容易误诊。现报道胸腺癌椎管内转移瘤1例,主要诊断线索包括:(1)胸腺癌病史;(2)生长速度快;(3)形态不规则。

甲状腺内胸腺癌临床诊断和治疗的研究进展

甲状腺内胸腺癌是发生在甲状腺内的胸腺上皮来源的恶性肿瘤,临床以进行性增大的颈部肿块为特点,常与甲状腺肿瘤相混淆。影像学检查是最常用的检查方法,免疫组化检测CD5和CD117呈高表达,基因检测不存在BRAF基因突变,少数存在TERT启动子突变。确诊需要依靠术后病理学,辅以免疫组化检测,治疗采取以手术切除为主,术后辅以放疗和化疗,可以有效延长生存期和降低复发率。本文通过对甲状腺内胸腺癌的临床表现、影像学检查、病理组织形态学、免疫表型特点以及目前的治疗方式等作一综述,旨在帮助提高临床医生对甲状腺内胸腺癌的诊断与治疗水平。

双重癌:左肺腺癌合并甲状腺内胸腺癌1例

多原发癌(MPC)又名重复癌,是指同一机体内同时或先后发生的两种或两种以上不相关的原发性恶性肿瘤。随着现代医学进步,多原发癌并不罕见,所有肿瘤患者的多原发恶性肿瘤(MPM)发病率约为0.73%~5.20%,这种广泛的差异与不同医院的医生和诊断工具不同有关。肺癌死亡率最高,由于低剂量肺癌筛查及人们健康意识的提高,大量早期肺癌被筛查出来,随着治疗方式的改进,如分子靶向治疗,使肺癌预后取得了大量进步,因此患者存活的时间足够长,可以发展为随后的原发肿瘤,但肺癌合并甲状腺内胸腺癌(ITTC)实属罕见。

Primary Mucinous Adenocarcinoma of the Thymus: A Case Report and Literature Review

THYMIC carcinoma is a rare malignant tumor, but the most common malignant tumor of the ante-rior mediastinum. According to the latest World Health Organization （WHO） classification, primary thymic carcinoma has a variety of histological types, mainly including squamous cell, basaloid, mucoepidermoid,lymphoepithelioma-like, sarcomatoid, clear cell and neuro-endocrine carcinomas, and papillary adenocarcinoma.1-4 Thymic mucinous adenocarcinoma was discovered in re-cent years, and only 10 cases were reported. In this paper, we described a case of thymic mucinous adenocarcinoma, the histopathological findings and immunohistochemical results.

多层螺旋CT在低危和高危胸腺瘤及胸腺癌鉴别诊断中的价值

目的 探究多层螺旋CT在低危和高危胸腺瘤及胸腺癌鉴别诊断中的价值。方法 回顾性分析2019年5月至2021年5月在本院经手术及病理证实为低危、高危胸腺瘤与胸腺癌的70例患者,比较低危胸腺瘤、高危胸腺瘤及胸腺癌患者的临床症状,记录其CT特征。结果 低危组患者出现胸痛或胸部其他不适的概率低于胸腺癌组,无症状概率高于高危组及胸腺癌组(P<0.05),3组出现重症肌无力、咳嗽和呃逆等症状的概率差异无统计学意义(P>0.05)。低危组的肿瘤最小直径、肿瘤边缘光滑概率大(高)于高危组和胸腺癌组,胸腔积液和胸膜转移概率低于高危组,坏死概率低于胸腺癌组(P<0.05);高危组肿瘤边缘光滑概率高于胸腺癌组(P<0.05);低危、高危组大血管受侵、肺受侵、淋巴结及远处转移、心包受侵、灌铸式生长发生率低于胸腺癌组,而强化均匀概率高于胸腺癌组(P<0.05);3组患者关于其他CT表现的检出率差异无统计学意义(P>0.05)。结论 多层螺旋CT对于低危、高危胸腺瘤和胸腺癌的鉴别诊断具有一定鉴别价值。

Micronodular thymic tumor with lymphoid stroma: A case report and review of the literature

BACKGROUND Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma(MNT)and micronodular thymic carcinoma with lymphoid hyperplasia(MNC),whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells.This type of tumor is rare;therefore,the corresponding clinical guidelines,histopathological diagnostic criteria,prognostic factors,and therapeutic regimens have not been established.CASE SUMMARY This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods.Morphologically,this tumor type is a series of benign to malignant pedigrees.We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma:(1)Tumor cells with moderate-to-severe dysplasia;(2)Tumor cell mitotic figures>2/10 high-power fields;(3)Appearance of neoplastic necrosis;(4)No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor;(5)Tumor cells with a Ki-67 index≥10%;and(6)Tumor cells express CD5.Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT.It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above.CONCLUSION Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis,which offers a practical reference for oncologists and pathologists.