Cardiac Sarcoma as an Unusual Presentation of Relapse of Acute Myeloid Leukemia

Doris Licely Canché Aguilar, MD, Diego Leonardo Meza Neri, MD, Sandra Graciela Rosales Uvera, MD

Department of Radiology; National Institute of Medical Sciences and Nutrition “Salvador Zubirán” (INCMNSZ), Mexico City, Mexico 

Clinical History

We present the case of a 21-year-old female with a history of acute myeloid leukemia (AML) initially diagnosed at age 17. She received chemotherapy until achieving complete hematologic remission at age 19, at which point treatment was electively discontinued. She was treated with doxorubicin, and given the risk of cardiotoxicity, a follow-up echocardiogram was performed. A 49×26 mm infiltrative mass was found, involving the inferior two-thirds of the interatrial septum, the retroaortic portion, and the base of the anterior leaflet of the mitral valve (Movies 1 and 2). The mass was immobile with some calcified areas.  The left ventricle demonstrated generalized hypokinesia, a left ventricular ejection fraction (LVEF) of 45%, and global longitudinal strain (GLS) of –17%.  Cardiac magnetic resonance was performed to complete the diagnostic protocol.

Movie 1: Transesophageal echocardiogram 4-chamber view demonstrating mass involving the atrial septum extending to the crux of the heart.

Movie 2: Transesophageal echocardiogram 45 degree view demonstrating mass involving the retroaortic space.

CMR Findings

A CMR study was performed on a GE 1.5T Signa HDxt scanner. Cine balanced steady-state free precession (bSSFP) sequences were acquired for the assessment of biventricular anatomy, function, and mobility (Movies 3 and 4). LVEF was estimated at 50%, and right ventricular ejection fraction (RVEF) at 49%.

Movie 3:  Cine bSSFP in long-axis views, two, three, four chamber, and right ventricle.  There is an interatrial septal mass identified.

Movie 4: Cine bSSFP short-axis stack for biventricular function assessment. Left ventricular mobility is reduced, with segmental motion abnormalities characterized by basal and mid anteroseptal dyskinesia, basal and mid inferoseptal hypokinesia, and apical septal hypokinesia. The right ventricle shows apical hypokinesia.

Tissue characterization sequences were performed: T2-weighted for edema assessment, T1-weighted pre- and post-contrast for evaluation of hyperemia, as well as T1 gradient recalled echo (GRE) after contrast administration (Figures 1 and 2).

Figure 1: Tissue characterization in short axis (upper panels) and axial (lower panels) projection of T2 short tau inversion recovery (STIR, upper left) and T1 double inversion recovery (DIR) pre-contrast (upper right, lower left) and post-contrast (lower right).  The T2-weighted sequence showed evidence of edema with a value of 3.3 (signal intensity ratio between myocardium and skeletal muscle; upper left).  The T1-weighted sequence was negative for hyperemia with a value of 1.12 (upper right, lower left).

Figure 2: Short axis stack post-contrast GRE inversion recovery (IR).  There is mid-inferoseptal mid-myocardial late gadolinium enhancement. Segmental late enhancement of the pericardium.

A dedicated mass protocol was performed: cine sequences at the level of the mass (Movie 5), T1-weighted, T2-weighted, T1-weighted with fat saturation, first-pass perfusion, and late gadolinium enhancement (Figure 3, Movie 6). T1 and T2 mapping sequences were not performed as they were not available on the system.

Movie 5:  Cine bSSFP basal short axis (upper panels), 4 chamber (lower left panel), and 3 chamber (lower right panel) at the level of the mass.  There is an infiltrative mass involving the interatrial septum and both anterior atrial walls, with a maximum thickness of 10.7 mm on the right and 12.4 mm on the left. In short-axis view, retroaortic extension is observed, surrounding the left coronary and non-coronary cusps without infiltrating them, with additional extension into the interventricular septum. In its upper third, the mass contacts the anterior leaflet of the mitral valve.

Figure 3: Short axis base images of the cardiac mass.  Cine bSSFP (upper left): mass isointense relative to myocardium. T2 STIR (upper middle): mass hyperintense on T2-weighted sequence. T1 DIR (upper right): mass isointense on T1-weighted sequence. T1 DIR with fat saturation (lower left): mass with no fat component on T1-weighted imaging with fat saturation. First-pass perfusion (lower middle): mass shows heterogeneous enhancement.  T1 GRE IR (lower right): mass demonstrates heterogeneous late gadolinium enhancement.

Movie 6. First-pass perfusion short axis base.  The mass shows heterogeneous enhancement.

Conclusion

The study was concluded as an infiltrative mass with malignant characteristics, given its size, the presence of heterogeneous perfusion within the mass (unlike benign masses, which generally do not perfuse, except for hemangioma), as well as the presence of late gadolinium enhancement in the mass. These findings suggest malignancy. In addition, myocardial injury related to chemotherapy was observed, indicated by biventricular dysfunction, positive T2-weighted sequence for edema, mid-inferoseptal epicardial late gadolinium enhancement, and segmental pericardial late gadolinium enhancement. Based on these findings, a PET-CT was performed, revealing increased metabolic activity (Maximum Standardized Uptake Value (SUVmax) 8.8, Figure 4). This significantly elevated SUVmax is specific for malignancy. A cardiac mass biopsy performed via thoracotomy reported the presence of CD45+ lymphocytes, MPO–, calretinin–, S100–, confirming myeloid sarcoma. Second-line treatment was initiated; however, the patient refused HSCT (Hematopoietic Stem Cell Transplantation). The patient is currently under follow-up in the hematology clinic.

Figure 4. FDG-PET (18F-FDG). Hypermetabolic solid interatrial tissue extending to the aortic root, consistent with neoplastic activity of undetermined lineage.

Perspective

In the presented case, a mass larger than 50 mm with retroaortic extension was identified, which increases the likelihood of malignancy. Cardiac magnetic resonance imaging has the ability to differentiate malignant from benign masses using first-pass perfusion sequences, with a sensitivity of 84%, specificity of 53%, positive predictive value of 75%, negative predictive value of 67%, and diagnostic accuracy of 73%.[1,2] Likewise, late gadolinium enhancement demonstrates a sensitivity of 92%, specificity of 59%, positive predictive value of 78%, negative predictive value of 83%, and diagnostic accuracy of 79%.[3] On T1-weighted sequences the mass appears isointense, on T2-weighted sequences it appears hyperintense, and following gadolinium administration it demonstrates heterogeneous enhancement, findings that support the diagnosis of sarcoma.[4,5]

Primary malignant cardiac tumors are extremely rare, accounting for only 5% of primary cardiac tumors. Among these, cardiac sarcomas are the most frequent, followed by primary cardiac lymphomas. Sarcomas are characterized by rapid growth and a tendency to infiltrate adjacent cardiac and pericardial structures, resulting in poor prognosis.[6] Within the group of sarcomas, angiosarcoma is the most common subtype, while leiomyosarcoma is rare but aggressive. Finally, primary cardiac lymphoma is another entity, typically observed in immunocompromised patients.[7]

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References

1. Zhu D, Zhang J, Gong L, Zhou S, Xu H, Zhou H, et al. Cardiac MRI-based multimodality imaging in clinical decision-making: Preliminary assessment of a management algorithm for patients with suspected cardiac mass. Int J Cardiol. 2015 Sep 1;197:150–6.
2. Fussen S, De Boeck BW, Zellweger MJ, Bremerich J, Goetschalckx K, Zuber M, et al. Cardiovascular magnetic resonance imaging for diagnosis
   and clinical management of suspected cardiac masses and tumours. Eur Heart J. 2011 May;32(12):1551–60.
3. Neilan, T, Shah, R, Abbasi, S. et al. The Incidence, Pattern, and Prognostic Value of Left Ventricular Myocardial Scar by Late Gadolinium Enhancement in Patients With Atrial Fibrillation. JACC. 2013 Dec, 62 (23) 2205–2214. 
4.  Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler- Klein J, et al. 2020 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). JACC CardioOncol. 2020;2(3):293–311.
5. Motwani M, Kidambi A, Herzog BA, Uddin A, Greenwood JP, Plein S. MR imaging of cardiac tumors and masses: A review of methods and clinical applications. Radiology. 2013 Jul;268(1):26–43.
6. Jacquier A, Giorgi R, Esterni B. CMR and MDCT in cardiac masses. In: Castaigne C, editor. Cardiac Imaging: A Multimodality Approach. Berlin,
   Heidelberg: Springer-Verlag; 2011. p. 111–30.
   7. Oliveira GH, Al-Kindi SG, Hoimes C, Park SJ. Characteristics and survival of malignant cardiac tumors: A 40-year analysis of >500 patients. Circulation. 2015 Dec 22;132(25):2395–402.

Case Prepared By:
Robert D. Tunks, MD, MHS
Editorial Board, Cases of SCMR
Penn State Health Children’s Hospital
Hershey, PA