NUCLEAR CARDIOLOGY BULLET Primary cardiac lymphoma detected by 18F-FDG PET scan: A case report Jussara Bianchi Castelli, MD, PhD,a Leonardo Alexandre, MD,b Guilherme Futuro, MD,c Maurı´cio Scanavacca, MD, PhD,c and ´ Soares Ju ´nior, MD, PhDb Jose Introduction. Cardiac lymphoma is a rare type of non-Hodgkin lymphoma of extranodal location, exclusively located in the heart and/or pericardium.1,2 Cardiac involvement secondary to disseminated disease is more common, occurring in 10%-20% of cases, while their presentation as primary tumor corresponds to only 0.5% of all lymphomas.2 The incidence of cardiac lymphoma is higher in the seventh decade of life and affects more male than female patients, especially those immunocompromised.1,2 Its variable clinical presentation makes diagnosis difficult, and the delay in diagnosis is the main determinant of prognosis.2 Nuclear medicine, through the use of positron emission tomography, using fluoro-2-deoxy-D-glucose labeled with fluorine-18 (18F-FDG PET), has become an established method for staging of lymphomas. It has high sensitivity for the detection of the disease, since lymphomatous cells have high glucose consumption that translate into increased uptake areas in the images.3 18 F-FDG PET provides information on the metabolism and degree of cell proliferation in the lesions through the intensity of uptake of 18F-FDG, which is directly related to the degree of malignancy of the lesion. The method provides an assessment of the extent of tumor with more accurate staging, aiming for the most appropriate treatment for the patient. It provides opportunity for monitoring the evolution of disease after institution of chemotherapy, which is of great value in assessing therapeutic efficacy and prediction of recurrence. It may also identify residual masses after the end
From the Laboratory of Pathology,a Nuclear Medicine and Molecular Imaging Unit,b Clinical Arrhythmia and Pacemaker Unit,c Heart Institute of the University of Sa˜oPaulo Medical School (InCorHCFMUSP), Sa˜o Paulo, SP, Brazil. Reprint requests: Jussara Bianchi Castelli, MD, PhD, Laboratory of Pathology, Heart Institute of the University of Sa˜o Paulo Medical School (InCor-HCFMUSP), Sa˜o Paulo, SP, Brazil; jussara.
[email protected]. J Nucl Cardiol 2011;18:974–7. 1071-3581/$34.00 Copyright Ó 2011 by the American Society of Nuclear Cardiology. doi:10.1007/s12350-011-9418-4 974
of treatment, if they represent viable tumor tissue or fibrosis, with a specificity of 92%.3,4 Case Presentation. A male patient 51 years of age was diagnosed with typical atrial flutter in 1999. This arrhythmia was successfully eliminated with radiofrequency ablation. In the same year he developed sustained ventricular tachycardia. The patient subsequently underwent three more radiofrequency ablation procedures. During the last one, a right ventricular tachycardia originating in the high ventricular septum was successfully eliminated. He developed total atrioventricular block, with need of a permanent dual chamber pacemaker as a complication. Six years later, he presented with symptoms of dyspnea and cervical tightness. The presence of atrial fibrillation was confirmed during the diagnostic investigation. A transesophageal echocardiography was then performed and demonstrated the presence of a mass infiltrating the anterior wall of the right ventricle, right atrium, interatrial septum, left atrial appendage, and the pulmonary trunk and aorta root. It also showed a pericardial effusion (Figure 1A, B). Because of this finding the patient was investigated with computed tomography that showed the presence of a solid lesion infiltrating the wall of the right atrium and ventricle extending to its outflow tract and compromising the origin of the pulmonary artery (Figure 1C). 18F-FDG PET was requested and performed after a 24-hour low-carbohydrate diet following by a fasting period of 6 hours before 18F-FDG injection in order to reduce the uptake of the radiopharmaceutical in the heart. Approximately 370 MBq of 18 F-FDG was injected intravenously and images were acquired 60 minutes later. It showed marked heterogeneous uptake of radiopharmaceutical in the same location, with a standard uptake value maximum (SUVmax) of 10.7 (Figure 2). The histology of the endomyocardial biopsy in the affected area displayed myocardial and endocardial infiltration by large and atypical lymphoid cells (Figure 3A), with B cell phenotype demonstrated by immunohistochemical positivity with the antibodies CD 20 (clone L26) (Figure 3B) and bcl2-oncoprotein (clone SC509). This was consistent with cardiac involvement by a diffuse large B cell lymphoma (according to the
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Figure 2. Positron emission tomography with FDG-F18 (coronal A, sagital B, axial C, MIP D) showing extensive area with heterogeneous and marked FDG-F18 uptake (SUVmax = 10.7) located in the mediastinum (arrows).
Figure 1. A, B Transesophageal echocardiograms showing a cardiac infiltrative process, involving the initial portion of the great vessels and coronary arteries (large and small arrows, respectively), the atrial septum, the left atrial wall and the right ventricular free wall (LA, left atrium; RA, right atrium; Ao, aorta; LV, left ventricle; RV, right ventricle). C Chest computed tomography showing thickening of the anterior heart wall and right atrium and ventricle (large arrow), difficult to distinguish from the pericardial space. The pacemaker lead is pointed by the small arrow.
current 2008 World Health Organization classification system). The clinical staging showed the lymphoma involving only the heart. In 2006, the patient underwent eight courses of chemotherapy with cyclophosphamide, vincristine and rituximabe; adriamycin was added after the fourth cycle of chemotherapy (R-CHOP scheme). In January 2007, after completion of chemotherapy, another PET scan was performed which did not show the abnormal accumulation of 18F-FDG in the area previously affected, suggesting good response to chemotherapy (Figure 4). After a follow-up of 22 months, the patient presented with clinical symptoms of sweating and weight loss. A repeat transesophageal echocardiogram showed the infiltrating process in the same cardiac location as previously described (Figure 5A). The chest computed tomography showed the same thickening of the right atrium and ventricle previously observed, with an area of necrosis/fibrosis (Figure 5B). A new 18F-FDG PET was performed but there was no 18F-FDG abnormal uptake in that region (Figure 5C). The tissue was considered fibrotic corroborating the efficacy of the chemotherapy. The patient was diagnosed as having renal cell carcinoma that was surgically treated with left nephrectomy and the symptoms disappeared. Currently, the patient remains asymptomatic, with no clinical or laboratory abnormalities. There is no schedule defined for repeating the PET scan.
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Figure 4. Positron emission tomography with FDG-F18 (coronal A, sagital B, axial C, MIP D) showing the absence of areas with anomalous accumulation of the radiotracer in the projection of the heart area after chemotherapy.
Figure 3. A Histological findings of the endomyocardial biopsy with infiltration by large and atypical lymphoid cells (inset) permeating the myocardial fibers (M) and thickening the endocardium (E). B Immunohistochemical reaction with antibody against CD20 (a molecule that characterizes the B lymphocytes and is present in B cell lymphomas), evidencing the nature of most cellular infiltrate as large B cells (inset). The meaning of the brown color is positive.
Discussion. Primary cardiac lymphoma is a subtype of non-Hodgkin lymphoma that affects the heart or pericardium, without systemic dissemination. Its occurrence is rare with an incidence estimated at 2% of all cardiac tumors.1 Its presentation as a primary tumor comprises only 0.5% of all lymphomas and approximately 80% of cases can be classified as diffuse large B cell.2 It affects adults with a mean age of 62 years, with male gender predominating.1,2 Its location is in the right atrium in 69% of cases and sometimes extend to the right ventricle.1 The onset of symptoms is related to tumor growth, leading to compression of vessels, reduced cardiac output, embolic events, and localized and/or systemic symptoms such as chest pain, dyspnea,
fever, malaise, and weight loss, the most frequent manifestations of the disease.1 Others nonspecific symptoms such as atrioventricular total blockade, right bundle branch blockade or arrhythmias can also be present. Sudden death occurs in approximately 3% of cases.1 However, this disease occurs more frequently in the absence of symptoms which makes diagnosis difficult.1 Chest radiography may show nonspecific findings such as cardiomegaly and pleural effusion.1 Transthoracic echocardiography is the imaging method most used for diagnosis, but transesophageal echocardiography is superior when images of the heart base were needed and external interference such as body weight has to be suppressed.1 Computed tomography demonstrates greater diagnostic accuracy than transthoracic echocardiography in detecting tumor mass involving the pericardium.1 The application of diagnostic methods based on metabolism as with PET using 18F-FDG is of great importance in the staging of non-Hodgkin lymphomas.3 It can also contribute to establishing the degree of malignancy of the disease by the intensity of uptake of 18F-FDG, since the uptake of this radiopharmaceutical is directly proportional to it.3,4 The uptake level of 18 F-FDG can be analyzed visually, but should also be measured through the SUVmax, an index that is calculated as a rate of tissue radioactivity concentration at time t and the injected dose normalized to body weight, lean body weight or body surface area [SUVbw = CPET(t)/(Injected dose/patient’s weight)].5 It also allows
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b Figure 5. Images 22 months after chemotherapy. A Trans-
esophageal echocardiogram (October 2008) showing the cardiac infiltrating process with distribution similar to that observed in Figure 1 (LA, left atrium; RA, right atrium; LV, left ventricle; RV right ventricle). B Computed tomography (March 2009) showing thickening of the anterior heart wall (large arrow), difficult to distinguish with the pericardial space, similar to the aspect observed before the chemotherapy treatment showed in Figure 1. The small arrow corresponds to the pacemaker lead. C Positron emission tomography with FDG-F18 (coronal A, sagital B, axial C, MIP D) showing absence of areas with anomalous accumulation of the radiotracer.
lower rate of recurrence in comparison to those that show persistent uptake of 18F-FDG in the lesions.3 18 F-FDG PET is also performed after completion of chemotherapy to evaluate the final treatment response and/or to differentiate between viable tumor and fibrotic tissue.3,4 The disappearance of 18F-FDG activity in tumor tissue is an indicator of absence of disease, and additional examinations are not required.3 Thus, this is the main difference between this method compared to others and is well demonstrated in the case described in this report. The rate of treatment response in cardiac lymphoma is considered fairly good, depending on staging.6 In this rare case of cardiac lymphoma, the diagnostic strategies corroborate the importance of 18F-FDG PET in the initial evaluation—detecting abnormal metabolic activity restricted to the mediastinum—and after chemotherapy. The finding of lack of abnormal FDG uptake in residual masses present on echocardiography and computed tomography after chemotherapy was crucial to demonstrating that there was no tumor activity, allowing conservative and appropriate clinical management. Conflict of interest The author has indicated no financial conflicts of interest. References
the assessment of treatment response by analyzing the reduction of 18F-FDG tumor uptake.3,4 The lower degree of 18F-FDG uptake after two cycles of chemotherapy suggests good response to treatment. In this situation, the patient is considered as having a better prognosis and
1. Chalabreysse L, Berger F, Loire R, Devouassoux G, Cordier JF, Thivolet-Bejui F. Primary cardiac lymphoma in immunocompetent patients: A report of three cases and review of the literature. Virchows Arch 2002;441:456-61. 2. Antoniades L, Eftychiou C, Petrou PM, Bagatzounis A, Minas M. Primary cardiac lymphoma: case report and brief review of the literature. Echocardiography 2009;26:214-9. 3. Jhanwar YS, Straus DJ. The role of PET in lymphoma. J Nucl Med 2006;47:1326-34. 4. Cho JM, Sohn IS, Yang YJ. Heart in the heart: dual faced primary cardiac lymphoma on PET-CT. Int J Cardiol 2009;142:e40-1. 5. Thie JA. Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med 2004;45:1431-4. 6. Petrich A, Cho SI, Billett H. Primary cardiac lymphoma: an analysis of presentation, treatment, and outcome patterns. Cancer 2011;117:581-9.
