B3 Thymoma Research Articles

The Role of [18F]F-FDG PET/CT for Predicting Histology and Prognosis in Patients with Thymic Lesions.

To investigate whether 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]F-FDG PET/CT) metabolic parameters were associated with histology and to assess their prognostic role in patients with thymic lesions. In total, 116 patients (49/67 M/F; mean age 59.5 years) who underwent preoperative [18F]F-FDG PET/CT and thymectomy from 2012 to 2022 were retrospectively analyzed. Associations between histology and metabolic parameters (maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), ratio between target lesion and liver SUVmax (rPET), quotient of SUVpeak in the tumor residual and SUVmean in a 20-cm3 volume of interest (qPET), and tumor-to-mediastinum (T/M) were analyzed. Freedom from recurrence (FFR) was determined and compared using the Kaplan-Meier and the log-rank test. The median follow-up was 38 months (range 14-72 months). In total, 27 thymic hyperplasia, 41 low-risk thymomas (LRT) (types A, AB, and B1), and 48 high-risk thymomas (HRT) (B2, B3 thymoma, and carcinoma) were included. SUVmax, SUVmean, SUVpeak, rPET, qPET, and T/M were significantly higher in HRT than LRT and hyperplasia (p < 0.001). TLG and MTV were significantly higher in patients with LRT (p < 0.001). Only rPET, qPET, and T/M remained significantly higher in HRT than in LRT subgroups (p = 0.042, p = 0.049, and p = 0.028, respectively). SUVmax, SUVmean, and SUVpeak cutoffs of < 4.3, < 2.87, and 4.03, respectively, significantly distinguished patients with longer FFR (p = 0.009, p = 0.05, and p = 0.05). Positron emission tomography (PET) metabolic parameters could help to differentiate thymic histotypes. Standardized uptake value (SUV)-based parameters appear promising to predict recurrent disease.

A Case of Rapid Emergence of Small-cell Carcinoma due to Malignant Transformation or de novo Formation in the Anterior Mediastinum Following Thymoma Resection: The Importance of a Re-biopsy.

A 59-year-old woman presented with multiple mediastinal masses 6 months after post-thymectomy for type B2 thymoma. A diagnosis of small-cell carcinoma (SmCC) via a computed tomography-guided biopsy and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography revealed no primary lesions outside the anterior mediastinum. The pathologically reevaluated post-thymectomy specimen showed no neuroendocrine differentiation. SmCC is presumed to arise either from malignant transformation of the thymoma or de novo formation. She was treated with carboplatin and paclitaxel to achieve complete response. This case highlights the importance of a re-biopsy to guide appropriate treatment in cases of rapid progression during the course of thymoma.

Choosing the proper path: outcomes of subxiphoid vs. lateral intercostal approaches in the resection of anterior mediastinal masses.

While the subxiphoid approach (SA) in thoracoscopic thymectomy offers benefits in terms of fat removal and pain reduction, it remains unclear which patients with anterior mediastinal masses benefit most from the subxiphoid vs. the lateral intercostal approach (LA). This retrospective study analyzed patients treated for anterior mediastinal masses at our center from January 2019 to December 2023. Patients were categorized into two groups based on the surgical approach: SA (35 cases) and LA (56 cases). Demographic data, clinical characteristics, perioperative metrics, and short-term outcomes were compared. Ninety-one patients were included, with diagnoses including thymic cysts (43), thymomas types A, AB, and B1 (24), B2 thymomas (18), thymic carcinoma (6).No significant differences were found between the groups in terms of gender, age, tumor size, body mass index, conversion to sternotomy, or blood loss. The LA group, however, experienced shorter surgical durations (P < 0.001), less drainage (P = 0.021), shorter hospital stays (P < 0.001), and lower hospitalization costs (P = 0.024). Pain scores on the visual analogue scale were similar between groups on the day of surgery and the first postoperative day. The findings suggest that the lateral intercostal approach is preferable for patients with thymic cysts and Masaoka stage I-II thymomas without myasthenia gravis due to its efficiency and cost-effectiveness.

Rare Thymoma With Solitary Liver Metastasis

ABSTRACT Thymomas are rare, malignant, epithelial tumors of the thymus gland. Extrathoracic metastasis of thymoma is exceedingly rare, particularly when isolated to the liver. We report an 89-year-old man who presented with urinary retention. Exploratory computed tomography imaging revealed a heterogeneous mass in the aortopulmonary window and a 1.9 cm lesion in the left hepatic lobe. Results from magnetic resonance imaging, positron emission tomography-computed tomography, and histopathological analysis of biopsy samples collectively supported a diagnosis of metastatic type B2 thymoma. To the best of our knowledge, this is the oldest patient to be diagnosed with metastatic type B2 thymoma. Metastatic thymoma is difficult to identify, and patients with mediastinal mass identified after any presentation should be evaluated for malignant spread.

AB056. Spatial analysis of T-cell development in type B2 thymoma tumour microenvironment at single-cell resolution

AB056. Spatial analysis of T-cell development in type B2 thymoma tumour microenvironment at single-cell resolution

PAX5 and CD70 are expressed in thymic carcinoma but not in atypical thymoma (WHO type B3 thymoma): an immunohistochemical analysis of 60 cases

AimsThymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that...

Postoperative irradiation in stage II thymomas: is it worth it?-shedding some light in the guidelines' gray zone.

Thymomas are rare, indolent tumors. Early stages (I-II) benefit from surgical treatment, while locally advanced diseases (stages III-IV) usually require a multidisciplinary approach. The role of postoperative radiotherapy (PORT) on anterior mediastinum for radically resected Masaoka-Koga stage II thymomas remains controversial. This study aims to determine the impact of PORT on the disease-free survival (DFS) of stage II thymomas. We retrospectively collected the clinical and oncologic data [age, sex, myasthenia gravis (MG) prevalence, Masaoka-Koga stage, World Health Organization (WHO) histologic subtype] of those patients who underwent radical exeresis in our Unit between January 2000 and December 2020. Kaplan-Meier estimates of DFS were then performed. Our study included 195 patients (M/F = 98/97). Almost all patients were affected by MG (90.7%) and most of them were operated by median sternotomy (93.3%). Thymoma stage was IIa in 87 cases (44.6%) and IIb in 108 cases (55.4%). The most represented histologic subtype was AB (27.7%), followed by B2 (24.6%), A (19%), B1 (14.9%) and B3 (13.8%). PORT was performed in 113 patients (58%, 39 stage IIa and 74 stage IIb). During the surveillance, 8 patients (4.1%) presented pleural recurrences and no local relapses. DFS was comparable in stage IIa and IIb patients, independently from PORT administration (p = .395 and p = .858, respectively). Moreover, PORT did not affect DFS considering the histologic subtypes (p = .304 for A and AB thymomas, p = .608 for B1, B2 and B3 thymomas). In our wide series, PORT administration didn't show any additional benefit on DFS. Therefore, based on our experience, patients with stage II thymoma who underwent radical surgery should not undergo any local adjuvant treatment.

An extremely rare case of thymic squamous cell carcinoma complicated with B3 thymoma and myasthenia gravis: a case report

BackgroundThymomas complicated with myasthenia gravis are conventionally treated during thoracic surgery. Particularly, invasive thymomas are resected alongside the surrounding organs. Here, we present a case where surgical and perioperative management was performed under the presumption of thymoma with myasthenia gravis. However, definitive pathology revealed the co-occurrence of B3 thymoma and thymic squamous cell carcinoma. This case highlights the unique presentation and exceptional rarity of thymomas that are complicated by myasthenia gravis and thymic carcinoma. Case presentationA 65-year-old female presented with eyelid ptosis at our hospital. Following a comprehensive examination, the patient was diagnosed with myasthenia gravis. Her computed tomography (CT) scan revealed an anterior mediastinal tumor suggestive of a thymoma, prompting a referral to the Department of Thoracic Surgery. Moreover, preoperative assessment could not definitively exclude pericardial invasion. She subsequently underwent an extended thymectomy via a longitudinal sternal incision. The tumor exhibited partial invasion of the pericardium, necessitating resection and reconstruction. Definitive pathological examination confirmed the co-occurrence of B3 thymoma and thymic squamous cell carcinoma. Positive lymph node metastasis classified the patient as stage IVa according to the Union for International Cancer Control (UICC) TNM Classification of Malignant Tumors, 8th Edition, and she was started on adjuvant radiotherapy postoperatively. Currently, the patient remains under observation, with follow-up CT scans showing no signs of recurrence.ConclusionsThis report describes an extremely rare case of thymoma complicated with myasthenia gravis and thymic squamous cell carcinoma.

A case report of elevated bromide levels from pyridostigmine bromide for treatment of myasthenia gravis.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Elevated serum bromide levels can cause dermatological, gastrointestinal, and neurological abnormalities. As bromide and chloride are both halogens, bromide may interfere with chloride assays, causing a falsely high serum chloride concentration and a low or negative anion gap. There is a paucity of data describing bromide toxicity from high doses of pyridostigmine bromide (PB). This case report describes a patient with an elevated bromide level with neurological symptoms from a therapeutic dose of PB. A 37-year-old male with myasthenia gravis secondary to type B2 thymoma status following thymectomy presented in myasthenic crisis. He required mechanical ventilation and was managed with steroids, intravenous immune globulin, plasmapheresis, and PB. On day 9, the patient experienced acute agitation. He had an anion gap of 2 mEq/L and a chloride concentration of 109 mEq/L. The plasma creatinine concentration was 0.63 to 1.15mg/dL and urine output was 0.76 to 1.79mL/kg/h throughout his admission. All other laboratory values were normal. The daily dose of PB was 660mg on day 9, but the patient received 76mg of intravenous PB over the first few days of his admission with the largest dose in 24 hours equal to 48mg. On day 10, the patient's bromide level was 37 μg/mL. His agitation was initially managed with quetiapine, followed by PB dose reduction. To our knowledge, there are 2 cases in the literature of bromide toxicity secondary to PB. These patients experienced neurological symptoms with bromide levels of 88 to 90 μg/mL. Bromide concentrations of more than 12 μg/mL are associated with a higher risk of neuronal dysfunction demonstrated as disturbances on an electroencephalogram, and levels greater than 50 μg/mL are considered toxic. While our patient's bromide level was not as high as those previously reported, no other causes for his agitation were identified. Elevated bromide levels from therapeutic PB can occur, and monitoring of these levels should be considered.

Immunohistochemistry for YAP1 N-terminus and C-terminus highlights metaplastic thymoma and high-grade thymic epithelial tumors by different staining patterns.

Metaplastic thymoma (MT), a rare subtype of thymic epithelial tumors (TETs), harbors YAP1::MAML2 fusions. Poroma, a skin tumor, also carries these fusions and exhibits a unique staining pattern for YAP1 immunohistochemistry (IHC), namely, a YAP1 N-terminus (YAP1[N])-positive but YAP1 C-terminus (YAP1[C])-negative pattern. In this context, MT was recently reported to lack YAP1(C) expression exclusively among TET subtypes. However, a lack of information about YAP1(N) expression in that study and another report that wild-type YAP1 expression was diminished in type B3 thymoma and thymic carcinoma warrants further studies for YAP1 expression in TETs. Thus, we immunohistochemically examined YAP1(N) and YAP1(C) staining patterns in our TET samples, including 14 cases of MT. In addition, 11 of the 14 MT cases were genetically analyzed with the formalin-fixed paraffin-embedded tissues if they harbored YAP1::MAML2 fusions. MT consistently exhibited YAP1(N)-positive and YAP(C)-negative staining, whereas type B3 thymoma and thymic carcinoma showed relatively heterogeneous staining patterns for YAP1(N) and YAP1(C) and were sometimes negative for both antibodies. Furthermore, a lower expression of YAP1 was found in type B3 compared to B2 thymomas. Among genetically analyzed 11 MT cases, 6 cases showed YAP1::MAML2 fusions, whereas the analysis failed in 5 very old cases due to poor RNA quality. These results indicate that IHC of both YAP1(N) and YAP1(C) is recommended to obtain staining patterns almost unique to MT. The biological significance of YAP1 in high-grade TETs warrants further investigation.

Clinical features of thymoma with and without myasthenia gravis.

To explore the clinical features of thymoma with and without myasthenia gravis (MG). This was a retrospective study. Two hundred and thirty-three patients with mediastinal masses who were initially diagnosed in People's Hospital of Shijiazhuang, China, between January 2014 and June 2022 and had complete clinical data and underwent surgical treatment at People's Hospital of Shijiazhuang were retrospectively analyzed. The age of patients with thymoma alone was significantly older than that of thymoma patients complicated with MG. The number of female patients was slightly more than males for both groups. Proportions of type A, AB, B1, B2, and B3 thymomas in Group-A were 0.77, 11.54, 11.51, 33.85, and 31.54%, respectively, and the proportions in Group-B were 9.68, 22.58, 12.90, 32.26, and 22.58%. The size of tumors in patients with thymoma alone was larger than that of patients with thymoma complicated with MG. The proportion of patients with tumor size of more than 10 cm in the thymoma alone group was significantly higher than that in the MG group. There were no relapses in patients with type A disease and relapses were noted in a few patients with type B1, B2 and B3 diseases. The same survival rates were reported for the two groups. MG rarely occurs in type A and type C diseases. The prognosis of thymoma with MG is similar to that of thymoma alone. The main causes of death may be myasthenia crisis in thymoma patients with MG and advanced tumor stage in patients with thymoma alone.

Multidisciplinary treatment of giant thymoma, paving the way to complete surgical resection: a case report

BackgroundA multidisciplinary treatment approach is recommended for patients with extensive, advanced, or recurrent thymomas. However, detailed treatment strategies, such as chemotherapy regimens and optimal surgical procedures, are still under debate.Case presentationWe report a case of gigantic locally advanced thymoma. A 70-year-old male was referred to our hospital following the detection of abnormal chest shadows. Chest X-ray and computed tomography (CT) scans revealed a 21-cm mass in the anterior mediastinum, encircling the pulmonary hilum and extending into the left thoracic cavity. PET/CT showed increased 18F-fluorodeoxyglucose uptake at the tumor site. Based on a trans-percutaneous CT-guided needle biopsy, the tumor was diagnosed as a Type B2 thymoma at the clinical IIIA stage. The patient underwent four cycles of preoperative induction chemotherapy, including cisplatin, doxorubicin, and methylprednisolone (CAMP), resulting in a partial response; the tumor shrank to 12 cm and FDG uptake decreased. Considering the patient’s age and comorbidities, we performed total thymectomy, along with partial resections of the parietal, mediastinal and visceral pleura, pericardium, and left upper lobectomy. This approach achieved complete histological resection, mitigating the risk of recurrence. Pathological analysis confirmed a thymoma, ypT3 (lung) N0M0 stage IIIA, with no malignancy in the pericardial or pleural effusions. No recurrence was detected 9 months post-surgery.ConclusionsWe report a case of giant thymoma successfully treated with multidisciplinary strategy. Surgical treatment alone may not have achieved complete resection, but after inducing significant tumor shrinkage with preoperative CAMP therapy, we were able to achieve complete resection. This treatment strategy may be effective in large thymoma cases.

Extended-sleeve resection for endoluminal recurrence of B3 thymoma: does aerogenous spread really exist?

Thymomas are a variant of thymic epithelial tumours. They are considered malignant due to their tendency to local invasion and they showed lower metastatic behaviour. Distal metastasis is rare and an endobronchial mass is a rare presentation. First-line treatment for early-stage thymomas is surgery; for Masaoka-Koga stage III, neoadjuvant or adjuvant chemoradiation therapy should be considered in association with surgery after Multidisciplinary Tumour Board evaluation. We report a rare case of radical resection with type A extended-sleeve lobectomy in a 63-year-old woman who was affected by endobronchial recurrence of B3 thymoma, 31 months after complete and radical thymectomy.

A phase 1 study of REGN6569, a GITR mAb, in combination with cemiplimab in patients (pts) with advanced solid tumor malignancies: Initial dose-escalation results.

2650 Background: REGN6569 is a fully human immunoglobulin G1 monoclonal antibody (mAb) that is highly specific for glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR). GITR is expressed on several immune cell subtypes, notably regulatory T cells (Tregs), and activated natural killer (NK) cells. REGN6569 demonstrated greater in vitro antibody-dependent cell-mediated cytotoxicity against GITR-expressing Tregs, as compared to GITR-expressing CD8+ T cells. Mouse studies showed that REGN6569 + cemiplimab (anti-PD-1) combination treatment achieved longer-term tumor responses compared with either drug alone. Methods: This is a first-in-human study (NCT04465487) evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of REGN6569 administered intravenously (IV) every 3 weeks (Q3W) + cemiplimab 350 mg IV Q3W, in pts with advanced solid tumors for which immune checkpoint inhibitor therapies have not been approved or are not available. The study includes a dose-escalation part with 5 dose levels (DL1-DL5) for REGN6569 (“4+3” design), with an initial dose of REGN6569 monotherapy given as a safety lead-in followed by REGN6569 + cemiplimab in subsequent doses. Results: As of the data cutoff date Oct 20, 2023, the dose-escalation part has been completed. 29 pts (median age 58.0 years, 62.1% male) were treated with REGN6569 + cemiplimab, up to the 1200 mg dose level (DL5), across many solid tumor types. The most common tumor type was colorectal cancer (34.5%). One pt (40 mg DL2) experienced a dose-limiting toxicity (Grade 3 hepatic failure); maximum tolerated dose was not reached. Twelve pts (41.4%) had a Grade ≥3 treatment-emergent adverse event (TEAE) and 16 pts (55.2%) had a treatment-related TEAE (any grade). The most frequent TEAEs (any grade) were arthralgia (24.1%), infusion-related reactions, and abdominal pain (20.7% each). There were no treatment-related deaths; 19 (65.5%) pts had disease progression leading to death. Two pts achieved ongoing partial responses by investigator assessment with REGN6569 + cemiplimab treatment: 1 pt with mucoepidermoid tumor of the parotid gland treated with 120 mg (DL3) REGN6569 and 1 pt with B3 thymoma treated with 400 mg (DL4) REGN6569, with duration of responses, 5.6 and 10.4 months, respectively. Full receptor occupancy on circulating Tregs was observed in all dose cohorts following REGN6569 treatment. Increased frequency (~10–50%) of proliferating NK cells in peripheral blood was observed post REGN6569 treatment across all dose cohorts. Conclusions: In this dose-escalation study, REGN6569 was administered up to 1200 mg (DL5) in combination with cemiplimab with one dose-limiting toxicity. The study has progressed to dose-expansion cohorts in anti–PD-1-resistant head and neck cancer, with pts treated with REGN6569 (DL5) + cemiplimab. Clinical trial information: NCT04465487 .

Acute mediastinal mass syndrome after surgical biopsy of a massive anterior mediastinal tumor: a case report.

Mediastinal lymphatic tumors are relatively rare. The prognosis is poor but has improved due to recent advances in treatment strategies. Herein, we report a case of mediastinal lymphoma diagnosed using surgical biopsy, which was complicated by mediastinal mass syndrome due to general anesthesia. A 25-year-old man with cough, fever, dyspnea, and night sweats was transferred to our hospital for resection of a large anterior mediastinal tumor. Although his preoperative diagnosis was WHO type B1 thymoma, the clinical findings suggested a lymphoma. A repeat surgical biopsy was performed under general anesthesia. Immediately after extubation, the patient developed acute respiratory failure with hypolucency of the right lung field on chest radiography. He was reintubated immediately and was diagnosed with negative pressure pulmonary edema in the right lung. He was managed with positive-pressure ventilation and his respiratory distress resolved within 5 days. Pathological examination of surgical specimens confirmed the diagnosis of lymphoma. Surgical biopsy is useful for the diagnosis of mediastinal tumors. However, the risk of perioperative mediastinal mass syndrome should be carefully assessed before administering general anesthesia.

Diagnosis, combined treatment, and long-term follow-up of a thymoma patient

Thymic neoplasms account for 20 – 25% of primary mediastinal tumors. Nonspecific clinical symptoms are often associated with delayed diagnosis of thymoma, leading to a distinctive problem of late diagnosis. Nowadays, surgical removal of the tumor is the method of choice for thymoma treatment. Combination treatment is indicated in the case of an unresectable tumor. Modern therapy (various combinations of anticancer drugs) helps reduce neoplasm size, stop metastasis, and maintain good quality of life in patients with thymoma.Aim. The presented clinical case of type B3 thymoma (with invasion into surrounding organs and metastatic pleura) is characterized by a long asymptomatic period of the disease, the onset of symptoms after suffering COVID-19 (COronaVIrus Disease 2019) and successful long-term polychemotherapy. The causes of late diagnosis, as well as insufficient oncologic vigilance in evaluating the results of laboratory and instrumental tests, are discussed based on this clinical case.Conclusion. A correct diagnosis, as well as successful treatment, requires a multidisciplinary approach involving physicians from different specialties – general practitioners, oncologists, surgeons, radiologists, and morphologists.

Quantitative CT parameters combined with preoperative systemic inflammatory markers for differentiating risk subgroups of thymic epithelial tumors

BackgroundThymic epithelial tumors (TETs) are the most common primary neoplasms of the anterior mediastinum. Different risk subgroups of TETs have different prognosis and therapeutic strategies, therefore, preoperative identification of different risk subgroups is of high clinical significance. This study aims to explore the diagnostic efficiency of quantitative computed tomography (CT) parameters combined with preoperative systemic inflammatory markers in differentiating low-risk thymic epithelial tumors (LTETs) from high-risk thymic epithelial tumors (HTETs).Methods74 Asian patients with TETs confirmed by biopsy or postoperative pathology between January 2013 and October 2022 were collected retrospectively and divided into two risk subgroups: LTET group (type A, AB and B1 thymomas) and HTET group (type B2, B3 thymomas and thymic carcinoma). Statistical analysis were performed between the two groups in terms of quantitative CT parameters and preoperative systemic inflammatory markers. Multivariate logistic regression analysis was used to determine the independent predictors of risk subgroups of TETs. The area under curve (AUC) and optimal cut-off values were calculated by receiver operating characteristic (ROC) curves.Results47 TETs were in LTET group, while 27 TETs were in HTET group. In addition to tumor size and CT value of the tumor on plain scan, there were statistical significance comparing in CT value of the tumor on arterial phase (CTv-AP) and venous phase (CTv-VP), and maximum enhanced CT value (CEmax) of the tumor between the two groups (for all, P < 0.05). For systemic inflammatory markers, HTET group was significantly higher than LTET group (for all, P < 0.05), including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). Multivariate logistic regression analysis showed that NLR (odds ratio [OR] = 2.511, 95% confidence interval [CI]: 1.322–4.772, P = 0.005), CTv-AP (OR = 0.939, 95%CI: 0.888–0.994, P = 0.031) and CTv-VP (OR = 0.923, 95%CI: 0.871–0.979, P = 0.008) were the independent predictors of risk subgroups of TETs. The AUC value of 0.887 for the combined model was significantly higher than NLR (0.698), CTv-AP (0.800) or CTv-VP (0.811) alone. The optimal cut-off values for NLR, CTv-AP and CTv-VP were 2.523, 63.44 Hounsfeld Unit (HU) and 88.29HU, respectively.ConclusionsQuantitative CT parameters and preoperative systemic inflammatory markers can differentiate LTETs from HTETs, and the combined model has the potential to improve diagnostic efficiency and to help the patient management.

The Role of Gene Fusions in Thymic Epithelial Tumors

Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials. Gene fusions that have been identified in TET include MAML2 rearrangements in 50% to 56% of mucoepidermoid carcinomas (MAML2::CRTC1), 77% to 100% of metaplastic thymomas (YAP1::MAML2), and 6% of B2 and B3 thymomas (MAML2::KMT2A); NUTM1 rearrangements in NUT carcinomas (most commonly BRD4::NUTM1); EWSR1 rearrangement in hyalinizing clear cell carcinoma (EWSR1::ATF1); and NTRK rearrangement in a thymoma (EIF4B::NTRK3). This review focuses on TET in which these fusion genes have been identified, their morphologic, immunophenotypic, and clinical characteristics and potential clinical implications of the fusion genes. Larger, multi-institutional, global studies are needed to further elucidate the molecular characteristics of these rare but sometimes very aggressive tumors in order to optimize patient management, provide patients with the opportunity to undergo targeted therapy and participate in clinical trials, and to elucidate the pathogenesis of these tumors.

Abstract 14677: Surgical Thymectomy for Autoimmune Encephalitis With CRMP-5 and AMPAR Antibodies Induced by SARS-CoV-2 Infection

Introduction: SARS-CoV-2 has been linked to development of autoimmune diseases. We describe a case of a patient with untreated thymoma who developed 2 cross-reactive autoantibodies between thymus and brain: collapsing response mediator protein-5 (CRMP-5) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid receptor (AMPAR), triggered by SARS-CoV-2, inducing encephalitis and coma. Emergency thymectomy reduced anti-CRMP-5 and anti-AMPAR antibodies and restored patient neurologic function within 3 months. Description of Case: A 31-year-old male with a known history of thymoma with myasthenia gravis presented with a 1-day history of memory loss, hallucinations, ataxia, involuntary movements, and tachypnea. Rapid nasal swab COVID-19 test was positive. Over several hours, the patient became unresponsive, requiring urgent intubation for airway protection. Brain computed tomography and magnetic resonance imaging with gadolinium showed no abnormalities. Cerebrospinal fluid (CSF) analysis revealed leukocytosis with lymphocytic predominance. Four days later, CSF and serum were tested for and demonstrated high levels of CRMP-5 and AMPAR antibodies, consistent with autoimmune encephalitis. Complete robotic thymectomy was performed. Pathologic analysis revealed type B2 thymoma with negative resection margins. Three months after surgical intervention, antibody titers normalized, the patient regained consciousness, and had no neurologic deficits. Discussion: Surgical thymectomy effectively treats autoimmune encephalitis in patients with thymoma and positive CRMP-5 and AMPAR antibodies in the setting of SARS-CoV-2 infection. This rare condition is typically seen in patients with thymoma or small cell lung cancer who experience acute viral infection. Although autoantibodies to CRMP-5 and AMPAR are known to be induced by viral infection, this is the first time it has been reported for SARS-CoV-2. Timely surgical intervention is necessary to reverse obtundation and acute encephalitis by removing the cross reactive epitopes in the thymus gland. Future studies are needed to explore the molecular mechanism of SARS-CoV-2 induced immune dysfunction and autoimmunity involving cross-reactive epitopes in this deadly syndrome.

P2.20-04 Differential Expression of Genes in Type A and B3 Thymomas and Thymic Carcinomas

P2.20-04 Differential Expression of Genes in Type A and B3 Thymomas and Thymic Carcinomas