The role of¹⁸F-FDG PET/CT (PET/CT)in the assessment of patients with lymphoma is well established and this technique is used as a routine study for staging (baseline study),evaluation of response to treatment and residual disease and identification of possible disease relapse. Although being rare it is important to diagnose cardiac lymphoma localizations and PET/CTcan play an important role in that respect.

 Conventional imaging, like CT or MRI, allowsthe depiction of extension and anatomical details of apotentially tumoral cardiac mass, but cannot show the grade of metabolic activity of the lesion as PET/CTis able to do.

 However physiological FDG uptake in myocardial tissue can interfere with the study of this region, beingusually highlyvariableand unpredictable. In order to minimize this phenomenonthe patient has to undergo a preparation consisting of a carbohydrate-freedietthe daybeforeexamination and of fasting for at least six hours before the scan.

 Case Report

In January 2009, a 71-year-old man was diagnosed with a testicle large B-cell lymphoma (NHL) and he wassubsequently operated (right orchiectomy) andtreated with eight cycles of R-CHOP first-line chemotherapy (February-July 2009).Treatment evaluation was performed by the mean of CT and PET/CT imaging after six cycles of therapy (mid-treatment scan) and a complete early response was proved.

Patient’s follow up was then in charge of the Haematology Unit. In December 2010, 22 months after diagnosis,the patient suddenly started suffering fromdyspnoea with minimal exertion, superior vena cava syndromeand collar of Stokes: he was admitted to the Emergency Room and afterwards,to the Haematology Unit for an adequate treatment. A CT scan showed a 60 x 44 mm mass in the right atrium, with alongitudinal diameter of80mm andirregular shape, partiallyinvolvingsuperior vena cava, right jugular vein and left brachiocephalic vein up to the left jugular vein; a concurrent thickening of the left atrial wall was also demostrated. The mass did not show a significant density enhancement after contrast agent administration

Radiologist suggested afurther study with MRI in order to clarify the nature of that mass: BB T1, T2 and FAT-SAT sequences were performed. The right atrial mass, partiallyinvolvingsuperior vena cava and upper veins, was confirmed. The mass showed only mild contrast agent uptake. Therefore, the study was not considered fully conclusiveconcerning the differential diagnosis between clot and lymphoma lesion. (Figure 2,3).

Subsequent echocardiography similarly just confirmed the already known mass.It was then decided to perform aPET/CTscan (January 2011), as suggested by radiologist; the study revealed an intenseFDG uptake involving the whole right atrium with an SUV max equal to 9.4, indicating a tumour lesion rather than a clot, but no metabolic activity was observed in the upper veins, and no evidence of pathologic distant hypermetabolic localizations was found(Figure 4).

CT showed lesional involvement. The highly metabolic right atrial masswas later histologically defined as lymphoma relapse. Therefore the patient was addressed to chemotherapy.

An endocardiac biopsy confirmed the clinical suspicion of large B-cell non-Hodgkin lymphoma. The Patient was therefore treated with 8 cycles ofchemotherapy (R-COMP), thrombotic prophylaxis, steroids, diuretic, antibiotic therapy and neutrophil growth factors for neutropenia prophylaxis. The patient had a fast resolution of previously reported symptoms (such as dyspnoea, collar of Stokes, pleural effusion). During therapy an episode of urinary infection by KlebsiellaPneumoniae, treated with antibiotic, and an episode of atrial fibrillation with spontaneous resolution occurred. The chemotherapy was welltolerated, and a PET/CT scan after the seventh cycle of R-COMP (June 2011) showed a complete metabolic disease remission (SUVmax of 1.9 versus previous valueof 9.4)(Figure 5). USexamination after treatment completionshowed a thickening of the right atrial wallin absence of the previously detectedmass.

Discussion

Cardiac masses that arise in the heart are potentially lethal, either benign or malignant. Almost 75% of primary cardiac masses are benign, but, when malignant, they are mainly sarcomas or lymphomas [1].Secondary cardiac involvement is far more common than primary cardiac tumoursand it has been documented in 8.7-27.2% of clinical cases of lymphoma[2].

 The majority of intracavitarytumoursdevelop on the right side of the heart, a finding thatremains unclear [3]in fact, no tendency in the site of cardiac tumours formation has also been reported, especially for primary cardiac involvement [4].

 The onset of a secondary cardiac mass typicallyoccurs a few years after primary NHL diagnosis,with a median of 20 months after diagnosis [5,6]:our case meets literature findings having been detected 22months after diagnosis. Cardiac involvement by lymphoma in autopsy has been described in 16% of patients with Hodgkin disease and 18% of patients with NHL[5].Even ifsometimes the myocardial involvement is important, clinical signs and symptoms of cardiac dysfunction (such as chest pain, dyspnoea, arrhythmia and oedema) may remain undetectable, with cardiac involvement being found only after patient’s death.Patientsaffected by malignant lymphoma associated with cardiac lesions are at high risk of sudden death, even if they are at an early stage based on clinical findings. Their prognosis is poor and most of these patients die before the starting of therapy [5-8]. This poor outcome may be, in most cases, due to a delayed diagnosis and treatment. Available literature suggests systemic chemotherapy is the only effective therapy, with,however,a theoretical risk of cardiac wall perforationasdrawback [9,10].

 In a recentretrospective analysis of 94 cases of NHL with biopsy-proven cardiac involvement publishedin PubMed between 1990 and 2015,Gordon MJ et al. [11] found that chemotherapy treatment was associated with a significant prolongation in median survival (18 vs. 1 month, HR 0.16, 95% CI, 0.47–0.54, P = 0.0003), and patients diagnosed in the chemo-immunotherapy era demonstrated a trend toward better outcomes as well as those who survived more than 1 month after diagnosis. Those findings have strong implications indicating that patients with cardiac involvement by NHL may be salvaged with modern regimens. In our case, eight cycles of R-COMP led to a complete remission without significant complications.Moreover they highlight the importance of early diagnosis and prompt treatment for those patients. Clinicians should be aware of the potential for cardiac involvement in patients with NHL, including indolent subtypes[11].Furthermore, primary testicular lymphoma (that in the vast majority of cases is histologically diffuse large B-cell Lymphoma)hasmarkedextranodaltropism, andshows a tendency to disseminate systematically to severalextranodalsites;in fact, relapsesoftenoccurat multiple extranodalsitesincluding the centralnervousystem, skin, contralateraltestis, lung, pleura, soft tissues,adrenalglands, liverand bone marrow[12-14].

 Conventional diagnostic techniques show limitations in the early diagnosis and characterization of cardiac involvement from malignant lymphoma. In our case, MRI, cardiac US and PET/CTprovided more specific findings than CT.

 Echocardiography is the first non-invasive way to examine the four chambers of the heart and pericardium and assessphysio-pthologic and hemodynamic effects of a cardiac mass, but the transthoracic approach is burdened with a restricted acoustic window.Trans-EsophagealEchocardiography (TEE) provides a larger imaging field with higher sensitivity compared to the transthoracic approach [15,16].

 CTshows morphology, location and extension of cardiac masses with a larger field of view, while MRI signal intensity with contrast enhancement results in better-quality images as far as tumoral anatomy andmyocardial and pericardial infiltration,blood flow and cardiac function are concerned[17,18].

 PET/CT imaging has been reported to reveal previously unsuspected cardiac involvement, to characterizethe extension and the metabolic activity of the cardiac mass in order to help determine whether it is benign or malignant, and subsequentlyto assess the response to therapy [19-21].In our case it was possible to suspect lymphoma, better characterize tumour activity and assess its complete response to chemotherapy before echocardiography.Moreover, due to lymphoma history, on the basis of CT findings, PET/CT could clinically have been considered before MRI for mass characterization and restaging.

 Varioustumours presentingin the heart, including angiosarcoma, may show similar features on different imaging modalities, including FDG uptake, even though alower radiotracer avidity may suggest such histotype; in that respect,biopsy remainscrucial in order to reach a correct histologic diagnosis and chose the appropriate treatment [22]: e.g. chemotherapy for lymphoma and surgery for angiosarcoma. Being a whole body imaging modality, PET/CT is also useful for the detection of distant disease localizations, which may be missed on conventional imaging modalities[22].

 It is recommended to adopt a proper preparation in order to reduce myocardial FDG uptake and obtain a favourable tumour to background contrast: patient has to fast for at least six hours before the scan and have a carbohydrate-freediet (fattymeals) the daybeforeexamination (startingatleast 18 hours prior to examination)[2324].

The case we are reporting highlights how lymphoma can present in atrium, and, besides,how PET/CT can early detect and better characterize lesionsin the heart compared to conventional imaging. In fact it was initially thought that the atrial mass was a clot: US, CT and MRI were not able tofully clarifyits nature, whereas PET/CT enabled to suspect a lymphoma relapse later confirmed by biopsy. It is important to early diagnose cardiac involvement, which is a clinically underestimatedoccurrence that determines a poor prognosis:PET/CT turned out to be especially valuable in this case.

 These findings strengthen the important role of PET/CT in cardiac lymphoma reported in literature in other case reports. It could be useful to use it widely in future in this kind of patients to improve conventional imaging performance, adding the metabolic evaluation of lesions, in order to reach a timely diagnosis and set a tailored therapy and a proper patient management.

Figure 1:December 2010 - CT scan demostratinganirregular shaped mass in the right atrium (60 x 44 mm, with a longitudinal diameter of 80 mm), partially involving superior vena cava, right jugular vein and left brachiocephalic vein up to the left jugular vein: the finding did not show significant hyperintensity after contast enhanced agent. A concurrent thickening of the left atrial wall was also displayed.

Figure 2:January 2011 -An MRI scan was suggested in order to clarify the nature of the finding demonstrated by CT.The BB T1 sequencesabove confirmedthe right atrial mass, partially involving superior vena cava.

Figure 3:January 2011 - Contrast enhanced MRI images after gadolinium administration:BBT1 sequences showed mild delayed enhancement in the right atrial mass.

Figure 4: January 21st 2011 -¹⁸F-FDG-PET/CT scan showing an intense uptake in the right atrium (SUV max 9.4) indicating a tumour lesion rather than a clot. No metabolic activity was observed in the upper veins where CT showed lesional involvement. The highly metabolic right atrial masswas later histologically defined as lymphoma relapse. Therefore the patient was addressed to chemotherapy.

Figure 5:June 2011–¹⁸F-FDG PET/CT scan after 7 of 8 courses of chemotherapy (R-COMP) demonstrated radiotracer uptake normalization in the right atrium (SUV max of 1.9 versus pre-treatment value of 9.4): the right atrial lymphoma relapse showed a complete metabolic response to treatment.

1. Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR (2000) Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation. Radiographics 20: 1073-1103.
2. Ban-Hoefen M1, Bernstein SH, Bisognano JD, Pryor JG, Friedberg JW (2009) Symptomatic intracardiac diffuse large B-cell lymphoma. Am J of Hematol 84: 683-685.
3. Tanaka T, Sato T, Akifuji Y,Sakamoto M, Shio H, et al. (1996) Aggressive non-Hodgkin’s lymphoma with massive involvement of the right ventricle. Intern Med 35: 826-830.
4. Delmas-Marsalet B, Molinie V, Jary L, Teillet-Thiebaud F, Estagnasie P, et al. (1995) Cardiac localization of non Hodgkin’s lymphoma: two case reports and review of literature. Nouv Rev FrHematol 37: 223-230.
5. Petersen CD, Robinson WA, Kurnick JE (1976). Involvement of the heart and pericardium in the malignant lymphomas. Am J Med Sci 272: 161-165.
6. Zaharia L, Gill PS (1991) Primary cardiac lymphoma. Am J ClinOncol 14: 142.
7. Rosenberg, Saul A, Diamond, Henry D, Jaslowitz B, et al. (1961) Lymphosarcoma: A review of 1269 cases. Medicine 41: 31.
8. Hanfling, Stanley M (1960) Metastatic cancer to the heart. Review of the literature and report of 127 cases. Circulation 22: 474.
9. Ceresoli GL, Ferreri AJ, Bucci E, Ripa C, Ponzoni M, et al. (1997) Primary cardiac lymphoma in immunocompetent patients: diagnostic and therapeutic management. Cancer 80: 1497-1506.
10. O’Mahony D, Piekarz RL, Bandettini WP, A E Arai, WH Wilson, et al. (2008) Cardiac involvement with lymphoma: A Review of the Literature. Clin Lymphoma Myeloma 8: 249-252.
11. Gordon MJ, Danilova O, Spurgeon S, Danilov A (2016) Cardiac non-Hodgkin lymphoma: clinical characteristics and trends in survival. Eur J Haematol.
12. Cheah CY, Wirth A, Seymour JF (2014) Primary testicular lymphoma. Blood 123: 486-493.
13. Zucca E, Conconi A, Mughal TI, Sarris AH, Seymour JF, et al. (2003) International Extranodal Lymphoma Study Group. Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group. J ClinOncol 21: 20-27.
14. Fonseca R, Habermann TM, Colgan JP, O'Neill BP, White WL et al. (2000) Testicular lymphoma is associated with a high incidence of extranodal recurrence. Cancer 88: 154-161.
15. Majano-Lainez RA (1997) Cardiac tumors: a current clinical and pathological perspective. Crit Rev Onco 8: 293-303.
16. Meng Q, Lai H, Lima J, Tong W, Qian Y, et al. (2002) Echocardiographic and pathologic characteristics of primary cardiac tumors: a study of 149 cases. Int J Cardiol 84: 69-75.
17. Hoffmann U, Globits S, Shima W, Loewe C, Puig S,et al. (2003) Usefulness of magnetic resonance imaging of cardiac and paracardiac masses. Am J Cardiol 92: 890-895.
18. Wang ZJ, Reddy GP, Gotway MB, Yeh BM, Hetts SW, et al. (2003) CT and MR imaging of pericardial disease. Radiographics 23 Spec No: S167-180.
19. Nguyen JD, Carrasquillo JA, Little RF, Ryan QC, Wilson W, et al. (2003) Fluorodeoxyglucose positron emission tomography in the presence of cardiac metastases. ClinNucl Med 28: 979-980.
20. Romer W, Garbrecht M, Fuchs C, Schwaiger M (1998) Images in cardiovascular medicine. Metabolic imaging identifies non-Hodgkin’s lymphoma infiltrating heart. Circulation 97: 2577-2578.
21. Nijjar PS, Masri SC, Tamene A, Kassahun H, Liao K, et al. (2014) Benefits and Limitations of Multimodality Imaging in the Diagnosis of a Primitive Cardiac Lymphoma. Texas Heart Institute Journal 41: 657-659.
22. KalvakuriK, Banga S, Upalakalin N, Shaw C Davila WF, et al. (2016) Metastatic right ventricular mass with intracavitary obliteration. J Community Hosp Intern Med Perspect 6: 31679.
23. Demeure F, Hanin FX, Bol A, Vincent MF, Pouleur AC, et al. (2014) A randomized trial on the optimization of 18F-FDG myocardial uptake suppression: implications for vulnerable coronary plaque imaging. J Nucl Med 55: 1629-1635.
24. Kobayashi Y, Kumita S, Fukushima Y, Ishihara K, Suda M, et al. (2013) Significant suppression of myocardial (18)F-fluorodeoxyglucose uptake using 24-h carbohydrate restriction and a low-carbohydrate, high-fat diet. J Cardiol. 62: 314-319.