Ann Thorac Surg 2006;81:1897-1899
© 2006 The Society of Thoracic Surgeons
Case report
Pulmonary Artery Leiomyosarcoma Expressing Epstein-Barr Virus in an Immunocompetent Individual
Sana Yokoi, MD, PhD
a
,
Toshihiko Iizasa, MD, PhD
a
,
Kenzo Hiroshima, MD, PhD
b
,
Yukio Saitoh, MD, PhD
a
,
Takehiko Fujisawa, MD, PhD
a
,
*
a Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
b Department of Basic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan
Accepted for publication May 20, 2005.
* Address correspondence to Dr Fujisawa, Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670 Japan (Email: fujisawa{at}med.m.chiba-u.ac.jp).
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Abstract
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Primary leiomyosarcoma of the pulmonary artery is extremely uncommon and its cause remains unclear. We document a case of pulmonary artery leiomyosarcoma expressing Epstein-Barr virus DNA sequences in an immunocompetent patient 4 years after symptomatic Epstein-Barr virus infection.
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Introduction
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Primary leiomyosarcoma of the pulmonary artery is rare and usually fatal [1]. A cause of the neoplasm of the pulmonary artery remains unclear. Some reports have suggested that smooth muscle tumors with an immunosuppressive status are correlated with Epstein-Barr virus (EBV) infection [2]. We present a surgical resected case of pulmonary artery leiomyosarcoma with confirmed presence of EBV that had developed 4 years after the manifestation of the EBV infection without immunosuppressive status.
A 28-year-old nurse was referred to our hospital in August 1998, suffering from right back pain and a 4 kg weight loss over 5 months. Her breath sounds were decreased over the right lower lung field. Laboratory results were within normal limits, except for cancer antigen 125 of 83.7 U/mL (normal range, < 35 U/mL) and erythrocyte sedimentation rate of 35 mm/hr (normal range, < 15 mm/hr). Serological examination revealed that the level of anti-EBV immunogloblin (Ig) G antibodies to viral capsid antigen (EBV-VCA-IgG) was elevated 80-fold compared with normal serum, the level of IgM antibody to EBV viral capsid antigen (EBV-VCA-IgM) was negative, and the anti-EBV IgG antibodies to EBV nuclear antigen (EBV-EBNA) was elevated 40-fold. These serological findings demonstrated her previous infection with EBV. Her HIV antibody was negative in serum. A computed tomographic scan of the chest disclosed a right pulmonary artery embolism with extension to the pulmonary artery, and multiple wedge-shaped nodules in the middle and lower lobe of the right lung without lymphadenopathy (Fig 1). Cardiac catheterization and pulmonary artery angiography showed the right pulmonary artery to be completely obstructed, while pressures in the right ventricle, and the main and left pulmonary arteries were within normal ranges. An aspiration biopsy during catheterization showed the leiomyosarcoma.
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Fig 1. (A) Computed tomographic scan showed a right central pulmonary artery obstruction with extension to the pulmonary trunk by an inhomogeneous tumor, and (B) multiple sphenoid nodules in subpleural regions of the middle and lower lobe of the right lung.
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She had no history of transplantation, leucopenia, or diabetes. Four years before recognizing the symptoms, the patient had been diagnosed with infectious mononucleosis in another hospital. She was febrile, around 40°C, with hepatosplenomegaly and lymphadenopathy. A blood chemical examination showed 231 mg/dL (normal range, 5 to 40 mg/dL) glutamic-oxaloacetic transaminase and 293 mg/dL (normal range, 0 to 35 mg/dL) glutamic-pyruvic transaminase. Serological examination showed that the EBV-VCA-IgG was elevated 640-fold compared with normal serum, and that the EBV-VCA-IgM was elevated 40-fold. White blood cell counts were 14,500 cells/mm3 (normal range, 4,000 to 9,000 cells/mm3), and the rate of atypical lymphocytes in white blood cells was 3.5%.
In November 1998, a right pneumonectomy, resection of the right and main pulmonary artery and anterior cusp of the pulmonary valve, and insertion of a synthetic graft between the pulmonary valve and the left pulmonary artery were successfully performed utilizing extracorporeal circulation, because the tumor was found to be extended to the pulmonary valve. No invasive findings of the tumor to the mediastinal organs outside the pulmonary artery were observed. The resected tumor in the pulmonary artery was confirmed as a leiomyosarcoma by conventional pathologic study and immunohistochemical staining. The multiple pulmonary nodules on the right side of the lung were identified as pulmonary infarctions without tumor cells. The patient was hospitalized for a month after surgery. Twelve months later she suddenly died at her home with local recurrence and multiple pulmonary metastases.
We investigated for the expression of EBV DNA sequence in the patient's tumor to clarify the association between the tumorigenesis of the lesion and the EBV infection. Polymerase chain reaction using EBV-specific sequences was performed on three cases with leiomyosarcoma [2, 3]. Polymerase chain reaction products were detected only in the tumor DNA from two of the three cases including the present case (lane 1) (Fig 2).
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Fig 2. Results of polymerase chain reaction amplification of a 140 base pair product derived from the BamH I W fragment of Epstein-Barr virus performed on 5 DNA samples by agarose gel electrophoresis. Samples were derived from resected tumor (lane 1) and normal lung tissue (lane 2) from the patient presented in this report, pulmonary artery leiomyosarcoma (lane 3) and normal lung tissue (lane 4) from an autopsy sample from a different patient, another pulmonary artery leiomyosarcoma autopsy from a different patient (lane 5), and the Raji cell line as a positive control (lane 6). The primers W-1 (5'-GTTCGCGTTGCTAGGCCACC-3') and W-2b (5'-TGGCGCTCTGATGCGACCAG-3') were used from previously reported conditions (40 cycles, annealing at 57°C for 2 minutes) [2].
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Comment
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Cases of primary leiomyosarcoma of the pulmonary artery are extremely rare. Most cases are initially misdiagnosed as pulmonary thromboembolism with symptoms of dyspnea, chest pain, cough, and hemoptysis [1, 4]. However, the absence of predisposing factors for pulmonary embolism, persistence of symptoms despite sufficient anticoagulation, and unilateral massive perfusion defect should lead the clinician to consider the possibility of pulmonary artery tumor [5]. The median survival time of pulmonary artery leiomyosarcoma patients has been reported to be 1.5 months, although this can be prolonged to 10 months with surgery [4]. The EBV infection has been associated with the tumorigenesis of some malignancies in humans. Some reports have suggested that smooth muscle tumors with an immunosuppressive status are associated with the EBV infection [2, 6]. However, for the present case, pulmonary artery leiomyosarcoma with confirmed presence of the EBV had developed 4 years after apparent EBV infection in an immunocompetent status. This suggests that the integration of EBV into the smooth muscle cells may play a critical role in the development of leiomyosarcoma in the absence of an immunosuppressive status. Consideration of leiomyosarcoma tumorigenesis after manifested EBV infection may be beneficial for the early recognition, treatment by complete resection, and prolonged survival of this malignant disease.
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References
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- Mayer E, Kriegsmann J, Gaumann A, et al. Surgical treatment of pulmonary artery sarcoma J Thorac Cardiovasc Surg 2001;121:77-82.
- McClain KL, Leach CT, Jenson HB, et al. Association of Epstein-Barr virus with leiomyosarcomas in young people with AIDS N Engl J Med 1995;332:12-18.[Abstract/Free Full Text]
- Cheung A, Kieff E. Long internal direct repeat in Epstein-Barr virus DNA J Virol 1982;44:286-294.[Abstract/Free Full Text]
- Krüger I, Borowski A, Horst M, de Vivie ER, Theissen P, Gross-Fengels W. Symptoms, diagnosis, and therapy of primary sarcomas of the pulmonary artery Thorac Cardiovasc Surg 1990;38:91-95.[Medline]
- Olsson HE, Spitzer RM, Erston WF. Primary and secondary artery neoplasia mimicking acute pulmonary embolism Radiology 1976;118:49-53.[Abstract]
- Ferri L, Fraser R, Gaboury L, Mulder D. Epstein-Barr virus-associated pulmonary leiomyosarcoma arising twenty-nine years after renal transplantation J Thorac Cardiovasc Surg 2003;126:877-879.[Free Full Text]
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Abstract
Introduction
