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Originally published as JCO Early Release 10.1200/JCO.2008.18.5686 on October 14 2008 © 2008 American Society of Clinical Oncology.
Epstein-Barr Virus Associated Large B-Cell Cardiac Lymphoma With Simultaneous Manifestation in the Forearm
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany
Skin Cancer Center Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany A 60-year-old man was referred to hospital due to rapidly increasing swelling and pain in his right forearm over 4 weeks. History included a larynx carcinoma, treated by surgery and focal radiotherapy 2 years before, achieving complete remission. Physical examination showed a large subcutaneous mass of the right forearm (15 x 5 cm). The patient reported no B symptoms, dyspnea, or arrhythmia. Laboratory investigations showed healthy blood-cell counts but an elevated lactate dehydrogenase value of 343 IU/L (normal: < 248 IU/L). HIV test was negative. The patient had no history of rheumatoid arthritis, methotrexate therapy, or organ transplantation. Both T1- and T2-weighted magnetic resonance imaging of the forearm showed a bulky subcutaneous tumor (14 x 4 x 4 cm) with no sharp demarcation of the skeletal muscle as cause of the swelling (Figs 1A, transversal axis; 1B, sagittal axis). A rhabdomyosarcoma was suspected; surprisingly, histological investigation of biopsies resulted in diagnosis of Epstein-Barr virus (EBV)–induced large B-cell non-Hodgkin's lymphoma. Further screening investigations, including bone marrow biopsy and computed tomography scan of the thorax and abdomen, were negative. However, prechemotherapy echocardiography showed a mass (6 x 5 cm) attached to the interatrial septum by a pedicle and filling the right atrium (RA; Figs 2A, transesophageal; 2B, transthoracic echocardiography). Because of the rapid growth of the subcutaneous tumor of the forearm, radiation therapy (3 Gy single dose, total 12 Gy) was first performed. To avoid emboli of necrotic tumor cells during chemotherapy, the cardiac mass was completely resected 3 weeks later via right lateral thoracotomy using extracorporeal circulation. Intraoperative findings confirmed the echocardiographic diagnosis. The mass was located at the upper edge of the oval fossa, filling the RA without infiltrating other cardiac structures (Figs 2C, intraoperative; 2D, macroscopic finding 5.7 x 3.8 cm). The postoperative course was uneventful. In addition, the patient received six cycles of a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy. Currently, the 30-month follow-up is event-free. Histological examination of RA and forearm tumor biopsy revealed extensive necrosis with a rim of vital, highly proliferating lymphoid B-cell blasts (Fig 3A). The subcutaneous forearm biopsy showed similar B-cell blasts infiltrating fat and skeletal muscle. The tumor cells were morphologically immunoblasts, with some centroblasts. Immunohistologically (alkaline phosphatase/antialkaline phosphatase staining), the tumor cells of both biopsies were CD20+ (Fig 3B), BCL-6+, BCL-2+, CD10–, CD21–, IRF4–, TdT– and cyclin D1–. The proliferation rate was up to 100% (Ki-67). EBV infection of the tumor cells was diagnosed by LMP1 (CS1-4) expression test. The occurrence of EBV-encoded EBNA 2 (PE 2) and ZEBRA (BZ1) in the tumor cells suggested a lytic EBV infection (Fig 3C). The final diagnosis was EBV-associated lymphoproliferation in the setting of diffuse large B-cell lymphoma (DLBCL) with signs of lytic EBV infection.
Primary tumors of the heart are rare, and in up to 75% of cases, benign; 50% of these are solitary myxomas located in the left atrium.1 Malignant lymphoma of the heart is a rare disorder making up less than 1% of all lymphomas.1,2 Presenting symptoms are usually chest pain, congestive heart failure, pericardial effusions or arrhythmias, therefore mimicking typical unspecific heart symptoms and leading to a delay of the definitive diagnosis. The clinical course is characteristically acute in onset and short in duration, with a high early death rate. Prolonged survival has been reported after chemotherapy, but prognosis remains poor.3 DLBCL resembles the largest category of aggressive lymphomas and is regarded as a heterogeneous group of lymphomas in terms of clinicopathologic profiles and biologic properties.4 EBV-associated DLBCLs are usually associated with underlying iatrogenic and/or endogenous immune suppression and are among lesions occurring within the spectrum of post-transplant–, human immunodeficiency–, and methotrexate-associated lymphoproliferative disease.5 Of these, post-transplant lymphoproliferative disease is the most common subtype with an incidence of 1% to 20%, depending on the organ transplanted and the intensity of immunosuppression.5 In our patient, the development of the larynx carcinoma may indicate underlying chronic immune dysregulation, explaining the occurrence of the EBV-associated lymphoma. In addition, patients’ age has been discussed as a predisposing factor, with the term "senile EBV-associated B-cell lymphoproliferative disorders" referring to the development by elderly (age > 60 years) immunocompetent patients of EBV-associated B-cell lymphomas with the involvement of several extranodal sites simultaneously.6 Although there is a lack of larger studies of this entity, the prognosis of age-related EBV-positive B-cell lymphomas seems to be significantly poorer than that of EBV-negative lymphomas.6 Organ involvement includes the skin, stomach, respiratory tract, and pancreas. However, to our knowledge, involvement of the heart has not been described before. The absence of tumor infiltration into cardiac muscle or obstruction of the tricuspid valve in our patient explains the lack of cardiac failure symptoms. In conclusion, EBV-associated B-cell lymphoma may manifest in any organ, including the heart. In this condition, a multidisciplinary approach, including that of cardiac surgery, should be considered to achieve best results. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
ACKNOWLEDGMENTS We thank A. Benhennour for literature research, and A. Gale for editorial assistance. NOTES published online ahead of print at www.jco.org on October 13, 2008 REFERENCES 1. Burke A, Virmani R: Tumors of the heart and great vessels, in Rosai J (ed) Atlas of Tumor Pathology (fascicle 16, third series). Washington, DC, Armed Forces Institute of Pathology, 1995 2. Roberts WC, Glancy DL, DeVita VT: Heart in malignant lymphoma: A study of 196 autopsy cases. Am J Cardiol 22:85-107, 1968[CrossRef][Medline] 3. Nascimento AF, Winters GL, Pinkus GS: Primary cardiac lymphoma: Clinical, histologic, immunophenotypic, and genotypic features of 5 cases of a rare disorder. Am J Surg Pathol 31:1344-1350, 2007[CrossRef][Medline] 4. Fisher R, Miller T, O'Connor O: Diffuse aggressive lymphoma, in Broudy V, Berliner N, Larson R, Leung L (eds), Hematology 2004 (Am Soc Hematol Educ Program Book). American Society of Hematology, 2004, pp 221-236 5. Timms JM, Bell A, Flavell JR, et al: Target cells of Epstein-Barr-virus (EBV)–positive post-transplant lymphoproliferative disease: Similarities to EBV-positive Hodgkin's lymphoma. Lancet 361:217-223, 2003[CrossRef][Medline] 6. Oyama T, Ichimura K, Suzuki R, et al: Senile EBV+ B-cell lymphoproliferative disorders: A clinicopathologic study of 22 patients. Am J Surg Pathol 27:16-26, 2003[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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