Rare Occurrence of Myxoma in Heart Transplant Recipient: A Case Report

Introduction

Primary cardiac tumors are rare, with an incidence ranging from 0.001% to 0.03% in autopsy studies [1]. Myxomas represent the majority of benign cardiac tumors, accounting for approximately 50% to 70%, and most often arise in the left atrium. Their occurrence in transplanted hearts is exceptionally uncommon, with fewer than 5 cases documented to date [2–4].

The pathogenesis in transplant recipients remains uncertain. Hypotheses include donor-derived dormant cells, recipient stem cell engraftment, the oncogenic influence of chronic immunosuppression, and post-surgical reparative processes [5–8]. Given the rarity and clinical implications, we report a patient who developed a left atrial myxoma 5 years after an orthotopic heart transplant and review potential mechanisms of tumorigenesis, emphasizing the importance of lifelong surveillance.

Case Report

A 57-year-old woman with end-stage heart failure due to coronary artery disease underwent an orthotopic heart transplant in August 2017 with the use of the bicaval technique. She was maintained on immunosuppressive therapy with tacrolimus, mycophenolate mofetil, and prednisone. Two episodes of moderate acute rejection occurred during the early post-transplant period. She denied smoking, alcohol, or substance abuse. Comorbidities included hypertension and hyperlipidemia.

Early post-transplant echocardiography demonstrated no abnormalities (Figure 1). In May 2022, during a routine follow-up, transthoracic echocardiography detected a mobile left atrial mass. The patient was asymptomatic, reporting no dyspnea, palpitations, or embolic phenomena.

Transesophageal echocardiography revealed a nodular lesion measuring 1.6×2.4 cm attached to the septal side of the oval fossa in the left atrium (Figure 2). Contrast-enhanced cardiac computed tomography (CT) demonstrated a 2.5×1.6×1.5 cm contrast-enhancing mass arising from the interatrial septum (Figure 3).

Surgical excision was performed under extracorporeal circulation, with resection of the mass and a portion of the interatrial septum (Figure 4). Gross pathology demonstrated a gelatinous tumor measuring 2×2 cm. Histopathology confirmed the diagnosis of myxoma. DNA profiling yielded inconclusive results, most likely due to contamination or microsatellite instability, preventing a definitive distinction between donor and recipient origin.

The postoperative course was uneventful. At 1-year follow-up, the patient remained asymptomatic, with preserved graft function and no recurrence.

Discussion

This case represents the fourth reported occurrence of myxoma in a transplanted heart. Previous cases have identified donor-derived and recipient-derived tumors [2–4]. Myxomas have also been observed in patients after other types of transplantation, including bone marrow [9] and combined kidney–pancreas [10]. All cases involved immunosuppressive therapy with calcineurin inhibitors (tacrolimus or cyclosporine) in combination with mycophenolate mofetil or azathioprine.

Several mechanisms may explain the development of myxomas in this setting. First, in donor-derived neoplasia, dormant cells from the donor heart proliferate under immunosuppression. Second, in recipient-derived origin, circulating host stem cells engraft within the donor organ. Third, in post-transplant reparative processes, localized endothelial proliferation and fibrosis may trigger myxomatous growth. Finally, in immunosuppression-related tumorigenesis, calcineurin inhibitors and antimetabolites increase malignancy risk [5–8]; whether they predispose to benign tumors is unknown. Calcineurin inhibitors, such as tacrolimus and cyclosporine, which form the backbone of most post-transplant immunosuppressive regimens, act by inhibiting T-cell activation through blockade of the calcineurin–NFAT signaling pathway. Although highly effective in preventing rejection, calcineurin inhibitors are associated with an increased incidence of post-transplant malignancies, particularly skin cancers, lymphomas, and Kaposi sarcoma. This oncogenic potential is attributed to impaired immune surveillance, reduced DNA repair capacity, and pro-oncogenic signaling effects, including upregulation of vascular endothelial growth factor and transforming growth factor β. Whether these mechanisms could contribute to benign tumorigenesis, such as the formation of myxomas, remains unclear. Nevertheless, all previously published cases of post-transplant myxomas – and the present case – occurred under calcineurin inhibitor-based immunosuppression, suggesting a potential but unproven association.

Antimetabolites, such as mycophenolate mofetil, also play a central role in transplant immunosuppression by inhibiting inosine monophosphate dehydrogenase, thereby reducing lymphocyte proliferation. While mycophenolate mofetil is generally considered less oncogenic than azathioprine, its contribution to benign cardiac tumor formation has not been systematically evaluated. The coexistence of calcineurin inhibitor and antimetabolite therapy, present in all reported cases, may produce cumulative or synergistic effects on cellular proliferation and tissue repair processes.

In an effort to clarify tumor origin, DNA profiling is often used to distinguish donor-derived from recipient-derived tissue. Techniques typically rely on short tandem repeat (STR) analysis, enabling identification of genetic markers specific to either individual. However, STR profiling is vulnerable to limitations, including poor DNA quality, microsatellite instability, and contamination with recipient blood cells. In the present case, profiling was inconclusive – an outcome consistent with earlier reports – highlighting both the technical challenges and the need for more advanced genomic methods, such as next-generation sequencing or single-cell DNA analysis.

Clinically, the asymptomatic presentation in this and previous cases underscores the risk of silent progression and the potential for serious complications such as embolization or obstruction. As transplanted hearts are routinely monitored with echocardiography, the detection of rare tumors such as myxomas becomes feasible, illustrating the crucial role of lifelong imaging surveillance.

Conclusions

In summary, although myxomas are exceedingly rare in transplanted hearts, their occurrence raises important questions about the interplay between donor tissue biology, host factors, and chronic immunosuppression. Further studies are needed to clarify the mechanisms underlying benign cardiac tumorigenesis in the transplant population. Also, this case highlights the importance of lifelong echocardiographic surveillance in transplant recipients.