As tumor mutational burden (TMB) has been approved as a predictive biomarker for immune checkpoint inhibitors (ICIs), next-generation sequencing (NGS) TMB panels are being increasingly used clinically. However, only a few of them have been validated in clinical trials or authorized by administration. The harmonization and standardization of TMB panels are thus essential for clinical implementation. In this review, preanalytic, sequencing, bioinformatics and interpretative factors are summarized to provide a comprehensive picture of how the different factors affect the estimation of panel-based TMB. Among the factors, poor DNA quality, improper formalin fixation and residual germline variants after filtration may overestimate TMB, while low tumor purity may decrease the sensitivity of the TMB panel. In addition, a small panel size leads to more variability when comparing with true TMB values detected by whole-exome sequencing (WES). A panel covering a genomic region of more than 1Mb is more stable for harmonization and standardization. Because the TMB estimate reflects the sum of effects from multiple factors, deliberation based on laboratory and specimen quality, as well as clinical information, is essential for decision making.
Immune thrombocytopenia purpura (ITP) is initially treated with steroids, but TPO‐RAs such as eltrombopag are used for chronic cases. Though effective, eltrombopag has been linked to thromboembolic events, with cerebral venous thrombosis (CVT) being a rare complication. A 20‐year‐old woman with ITP developed severe headaches, nausea, and vomiting five days after starting eltrombopag. CT scans revealed a dense clot in the right transverse sinus, indicating CVT. Lab data showed elevated platelet counts and D‐dimer levels. MRV confirmed CVT, leading to the discontinuation of eltrombopag and initiation of anticoagulant therapy. Recurring thrombocytopenia necessitated further treatment adjustments, including rituximab and cyclosporine, resulting in improved platelet counts and CVT resolution. This case highlighted that CVT is a serious but rare side effect of eltrombopag in ITP patients. Early detection, prompt anticoagulation, and cautious TPO‐RA management are crucial for preventing thromboembolic events.
Adult haemophagocytic lymphohistiocytosis (HLH) is an infrequent and life-threatening condition. The most common triggers of HLH are malignancy and virus, and bacterial infections are rarely implicated. We present a case of HLH secondary to Staphylococcus aureus infection and systemically searched the PubMed database for publications on HLH associated with Staphylococcus aureus infection and reviewed nine cases from seven studies. A marked third of patients had infective endocarditis, while the mortality rate was 44 %. HLH developed in our case despite elimination of MRSA from the bloodstream, leading to eventual demise of our patient, suggesting that prolonged hyperimmune response may persist even after the elimination of initial triggering factor. Our case highlights the necessity of high clinical suspicion and prompt diagnosis of HLH.
3 June 2025 in European Journal of Case Reports in Internal Medicine
Introduction: Hairy cell leukaemia (HCL) is a rare B-cell neoplasm and pulmonary involvement in HCL is exceedingly rare, often leading to diagnostic challenges. Non-resolving pulmonary infiltrates have a broad differential, including infections, malignancies, and autoimmune diseases, requiring a multidisciplinary approach for diagnosis. Case report: We report the case of a 61-year-old man who presented with fever, dyspnoea, weight loss, and bicytopenia. Initial chest imaging showed bilateral lower lung opacities, and empirical antibiotic therapy was administered. Despite treatment, symptoms persisted, prompting further investigations. High-resolution computed tomography scan revealed consolidations and ground-glass opacities. Extensive infectious workup was negative. Bronchoscopy with endobronchial ultrasound biopsy showed organizing pneumonia, and a bone marrow biopsy confirmed HCL with pulmonary involvement. The patient declined a surgical lung biopsy, but his pulmonary infiltrates and bicytopenia improved with corticosteroid and cladribine chemotherapy. Conclusion: This case highlights the importance of considering haematologic malignancies in non-resolving pulmonary infiltrates and persistent bicytopenia. A stepwise diagnostic approach, including bone marrow biopsy and bronchoscopy, was crucial in establishing the diagnosis. Successful treatment with cladribine reinforces its efficacy in HCL and suggests similar cases may benefit from this approach. Further research is needed to optimize diagnostic and treatment strategies for HCL with pulmonary involvement.
Cardiac involvement in diffuse large B-cell lymphoma (DLBCL) is rare but often complicated by life-threatening arrhythmias, conduction disturbances, and heart failure. Electrocardiography (ECG) is essential for early recognition and guiding intervention. To characterize ECG manifestations of cardiac-involved DLBCL and evaluate strategies for managing associated cardiac complications. This study is a retrospective institutional case series conducted at MacKay Memorial Hospital from 2010 to 2025. We reviewed five patients with histologically confirmed primary or secondary cardiac DLBCL. Data on tumor location, ECG and echocardiographic findings, cardioprotective and anti-arrhythmic therapy, chemotherapy regimens, and outcomes were analyzed to correlate electrical abnormalities with anatomical involvement and therapeutic response. ECG patterns varied according to tumor distribution. Right atrial involvement was often associated with atrial tachycardia or atrial fibrillation. Pericardial infiltration produced low-voltage QRS complexes and electrical alternans in cases of massive effusion, whereas minimal effusion preserved normal sinus rhythm. Myocardial infiltration appeared to increase the risk of ventricular tachycardia and high-grade atrioventricular block, which is supported by the previous research about the reentry circuits at tumor–myocardium interfaces. Chemotherapy remains the principal therapeutic approach for cardiac DLBCL; however, our limited observations suggest that integrating anti-arrhythmic and cardioprotective therapy may improve chemotherapy tolerance. Successful arrhythmia control frequently correlated with improved clinical outcomes. However, the optimal use of anthracycline-based regimens in cardiac DLBCL remains uncertain and warrants further investigation. Our findings highlight the importance of early recognition and multidisciplinary management for cardiac complications in the patients with cardiac-involved DLBCL. Cardioprotective strategies, anti-arrhythmic management, and careful chemotherapy selection are crucial to balance oncologic efficacy with cardiovascular safety.