Right atrial thrombus in treatment-naive patient with an early-stage classical Hodgkin lymphoma: a case report and review of the literature

Introduction

Patients with hematologic malignancies are well recognized to be at increased risk of thrombotic complications, reflecting the complex interplay between malignancy-related hypercoagulability, endothelial dysfunction, and treatment-related factors. The incidence and severity of thrombotic events vary according to tumor type, disease stage, therapeutic regimen, and the use of central venous access devices (1). Given the heterogeneity of thrombotic risk, it is important to identify patients at higher risk of venous thromboembolism (VTE) who may benefit from some form of prophylaxis (2). In most cases, thrombotic events occur during active chemotherapy or as complications of central venous catheter placement. Only a minority of events have been reported in the interval between diagnosis and initiation of systemic therapy. Deep vein thrombosis and pulmonary embolism represent the most frequently observed manifestations; however, thrombosis may also involve atypical sites, including the cardiac chambers (3, 4). Right atrial thrombosis is an uncommon but potentially life-threatening condition, associated with significant mortality if left untreated (5). Previous studies have evaluated the incidence of thrombosis in patients with lymphomas, with reported rates ranging from 1.5% to 13%; however, data specifically addressing Hodgkin lymphoma remain scarce (3). We report the case of a 21-year-old woman with newly diagnosed classical Hodgkin lymphoma (cHL) in whom a right atrial thrombus was identified during routine diagnostic work-up, prior to the initiation of chemotherapy and after recent PICC placement.

Case presentation

A 21-year-old woman was referred to our Hematology Unit for evaluation of self-detected painful laterocervical lymphadenopathy, profuse night sweats, generalized pruritus, and unintentional weight loss of 8 kg over 1 month. Laboratory investigations revealed neutrophilic leukocytosis, mild anemia, and mild thrombocytosis (WBC: 15.95 × 10⁹/L; N: 11.50 × 10⁹/L; Hb: 104 g/L; PLTs: 548 × 10⁹/L; ESR: 92 mm/h; LDH: 185 U/L). A head and neck ultrasounds was performed, demonstrating multiple enlarged, hypoechoic lymph nodes (largest diameter 2–3 cm), some of which exhibited irregular vascularization. Given the suspicion of a lymphoproliferative disorder, diagnostic work-up was pursued with an excisional lymph node biopsy, which confirmed the diagnosis of cHL, nodular sclerosis subtype (G1 according to the BNLI criteria). A staging PET-CT scan was therefore performed, showing hypermetabolism in multiple supradiaphragmatic lymphadenopathies and leading to classification of the disease as stage IIB. Additionally, it demonstrated increased FDG uptake in the right pericardiac region (Figure 1a), consistent with disease involvement. Before chemotherapy initiation, a peripherally inserted central catheter (PICC) was placed. The patient also underwent a staging total-body CT scan which confirmed the disease stage.

Prior to treatment initiation, 13 days after PICC line placement, a transthoracic echocardiography (TTE) was performed and revealed a multilobulated isoechoic mass (3.5 × 2.4 cm) adherent to the lateral wall of the right atrium and extending toward the tricuspid valve plane, without evidence of vena cava inflow obstruction or hemodynamic compromise (Figure 1c). Considering this finding, anticoagulation with low-molecular-weight heparin (6,000 IU daily) was initiated. Given the need for further characterization of the suspected lesion, cardiac magnetic resonance imaging (CMR) was performed demonstrating findings consistent with a right atrial thrombus. (Figure 1b) Heparin was therefore escalated to full therapeutic dosing (8,000 IU b.i.d) and upon specialist consultation, anticoagulation was subsequently transitioned to apixaban (5 mg b.i.d) which is currently ongoing. The pre-treatment assessment revealed no contraindications to systemic therapy, and the patient was deemed eligible for treatment. She received therapy according to the HD17 regimen (2 cycles of BEACOPP escalated followed by 2 cycles of ABVD) and completed the planned course without significant treatment-related or thrombotic complications. End-of-treatment PET-CT demonstrated a complete metabolic response (Deauville score 2). A follow-up TTE, performed 1 month after treatment completion, showed a significant reduction in the size of the previously described right atrial mass (1.7 cm × 1.2 cm), still with no evidence of obstruction to vena cava inflow. (Figure 1d) The patient is currently undergoing follow-up, and with no relapse or other significant clinical events being recorded (Figure 2).

Discussion

Thrombotic events represent relatively common complications in hematologic malignancies and are most frequently associated with the presence of a central venous access device (6). The overall incidence of VTE in lymphoma patients has been reported to range from 4% to 10%, with higher rates observed in advanced-stage disease and in patients receiving intensive chemotherapy regimens (4). However, most thrombotic events occur during active treatment or following central venous catheter placement. Thrombotic manifestations occurring prior to treatment initiation remain relatively uncommon (7). Deep vein thrombosis and pulmonary embolism represent the most frequently reported clinical manifestations of cancer-associated thrombosis. Nevertheless, thrombotic events may occasionally occur in unusual locations, including the splanchnic veins, cerebral venous sinuses, and cardiac chambers. Intracardiac thrombosis, particularly involving the right atrium, represents a rare entity and may pose significant diagnostic challenges, as it can mimic other intracardiac masses such as vegetations and primary cardiac tumors (8). Several case reports and small series have described catheter-related right atrial thrombi in oncologic patients, often detected incidentally during imaging performed for staging or treatment monitoring. Only a limited number of cases of intracardiac thrombosis associated with cHL have been reported in literature and all occurred during or after treatment (Table 1). Conversely, in our patient, although the thrombus was identified during the initial staging work-up, considering the temporal relationship between PICC line placement and the detection of the mass, a catheter-related mechanism cannot be excluded and may have contributed to thrombus formation. The presence of a central venous catheter may promote thrombus formation through several mechanisms, including local endothelial injury during insertion, catheter-related flow disturbance, and activation of coagulation on the foreign-body surface. These mechanisms may be particularly relevant in patients with active malignancy, in whom baseline hypercoagulability may lower the threshold for catheter-associated thrombosis. In our case, the interval of 13 days between PICC placement and TTE detection of the right atrial mass supports the possibility of a catheter-related or catheter-contributed thrombotic event. However, in the absence of cardiac imaging before PICC placement, it is not possible to determine whether the thrombus was already present, partially formed, or entirely catheter-induced. Right atrial masses detected during oncologic work-up therefore require careful evaluation and a comprehensive differential diagnosis. Multimodality imaging plays a crucial role in the accurate characterization of intracardiac lesions and in guiding subsequent management. TTE is typically the first-line imaging modality and allows rapid identification of intracardiac masses as well as assessment of their hemodynamic consequence. However, further characterization is often required to distinguish between thrombotic and neoplastic lesions. In this context, CMR imaging has emerged as a valuable diagnostic tool, providing detailed tissue characterization (13).

Table 1. Summary of reported case reports of intracardiac thrombosis in HL.

VTE, venous-thrombus embolism; LMWH, low-molecular weight heparin; NA, not available; nos, not otherly specified.

In the present case, the focal increase in FDG uptake in the pericardiac region observed on staging PET-CT, followed by the TTE detection of a multilobulated right atrial mass during pre-treatment assessment, raised concern for possible cardiac disease involvement. This was a clinically relevant diagnostic issue for two reasons: first, the intracardiac mass itself required differentiation between thrombus and neoplastic involvement; second, local cardiac or pericardiac disease involvement could have represented a potential contributing mechanism to thrombus formation. Following specialist review and detailed reassessment of the multimodality imaging findings, the FDG uptake was not anatomically concordant with the interatrial mass identified on TTE. Moreover, CMR demonstrated features consistent with thrombus, without evidence supporting direct neoplastic infiltration. Specifically, it showed a right atrial mass with isointense signal on cine, T1-weighted, and T2-weighted sequences, internal signal heterogeneity, and absence of both first-pass perfusion and late gadolinium enhancement. These findings were consistent with an avascular intracardiac lesion and therefore favored thrombus rather than lymphomatous infiltration, thereby allowing appropriate management with anticoagulation therapy.

The optimal management of right atrial thrombosis remains a matter of debate, as evidence is largely derived from case reports and small case series. Treatment strategies typically include systemic anticoagulation, thrombolysis, or surgical thrombectomy in selected cases, depending on thrombus size, mobility, associated hemodynamic compromise, and risk of embolization. In patients with cancer-associated thrombosis who are clinically stable, anticoagulation therapy remains the cornerstone of treatment. Current guidelines recommend low-molecular-weight heparin or direct oral anticoagulants as first-line options for the management of cancer-associated VTE (14).

The choice of anticoagulant therapy should also consider the presence of active chemotherapy, given the potential for drug–drug interactions. In our case, Doxorubicin may reduce the area under the curve (AUC) of Apixaban, potentially decreasing its systemic exposure (15). For this reason, anticoagulation therapy was initially started with low-molecular-weight heparin and subsequently transitioned to Apixaban. This approach allowed safe continuation of the oncologic treatment and was associated with progressive reduction in thrombus size without thromboembolic or hemorrhagic complications. Overall, this case underscores the importance of maintaining a high index of suspicion for atypical thrombotic manifestations in patients with newly diagnosed lymphoma. Multimodal imaging plays a key role in establishing the correct diagnosis, while early anticoagulation may allow safe continuation of oncologic treatment. The main limitation of this case is the absence of cardiac imaging before PICC placement. Therefore, although the thrombus was detected before chemotherapy initiation, it cannot be established with certainty whether it was already present before central venous catheter insertion or whether it developed, at least in part, as a catheter-associated complication. Nevertheless, this observation highlights an uncommon presentation of cancer-associated thrombosis and emphasizes the importance of considering intracardiac thrombi in the differential diagnosis of right atrial masses detected during the diagnostic work-up of lymphoma.

Conclusion

Intracardiac thrombosis is a rare but potentially serious manifestation of cancer-associated hypercoagulability. This case highlights that right atrial thrombi may be detected at the time of lymphoma diagnosis, during the diagnostic work-up, even before initiation of systemic therapy and in the absence of overt symptoms. Early recognition, supported by multimodality imaging, allows prompt anticoagulation and may enable the safe continuation of curative oncologic treatment.

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Footnotes

Edited by: Guido Gini, Azienda Ospedaliero Universitaria Ospedali Riuniti, Italy

Reviewed by: Miguel Q. Clemente Afonso, Hermanos Ameijeiras Hospital, Cuba

Mohamed Zuhail Kizhakka Peediyakkal, Hamad Medical Corporation, Qatar