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J Thorac Cardiovasc Surg 2003;126:877-879
© 2003 The American Association for Thoracic Surgery

Brief communications

Epstein-Barr virus-associated pulmonary leiomyosarcoma arising twenty-nine years after renal transplantation

^a Department of Surgery, McGill University, Montréal, Québec, Canada
^b Department of Pathology, McGill University, Montréal, Québec, Canada
^c Department of Pathology, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada

Received for publication January 15, 2003; accepted for publication March 17, 2003.

^* Address for reprints: Lorenzo Ferri, MD, McGill University Health Centre, Montreal General Hospital, Room D10.168, 1650 Cedar Ave, Montréal, Quebec H3G 1A4, Canada
lferri{at}po-box.mcgill.ca

An increased incidence of several malignancies, the most common being lymphoma and carcinoma of the skin, is a well-recognized complication of chronic immunosuppression therapy. Smooth muscle tumors arising in recipients of solid organ transplants are rare, with only 14 cases reported in the English language literature. Epstein-Barr virus (EBV) infection has been implicated in the pathogenesis of these tumors because of diminished immune function due to immunosuppressive therapy. We report the case of a 61-year-old woman who had a leiomyosarcoma arising in a bronchus 29 years after renal transplantation. The presence of EBV was demonstrated in tumor tissue by in situ hybridization.

Clinical summary

A 61-year-old woman had productive cough for several weeks, fatigue, and a 15-pound weight loss. She had end-stage renal disease caused by post-streptococcal glomerulonephritis and had received a living related kidney transplant from her mother 29 years earlier. Low-dose prednisone (5 mg/d) was the sole agent used for long-term posttransplant immunosuppression. A chest radiograph at the time of admission demonstrated left upper lobe collapse. A computed tomographic scan of the thorax confirmed the presence of a tumor in the left upper lobe bronchus associated with post-obstructive atelectasis (Figure 1). Bronchoscopy revealed an obstructing endobronchial tumor at the orifice of the left upper lobe bronchus. Biopsies of the tumor demonstrated a spindle cell lesion suggestive of a smooth muscle neoplasm. There was no radiographic evidence of lymph node enlargement. At thoracotomy, the tumor was found to be very proximal, and although a left upper lobe sleeve resection was contemplated, a pneumonectomy was required to ensure adequate margins. The patient recovered rapidly from the procedure and her renal graft function was not significantly altered. Two years later the patient is well with no recurrence.

View larger version (112K): [in this window] [in a new window]   Figure 1. Computed tomography scan of the thorax demonstrating a tumor in the proximal left upper lobe bronchus with post-obstructive atelectasis.

The resected left lung weighed 230 g and the upper lobe appeared atelectatic with mucus plugging consistent with post-obstructive pneumonitis. A well-circumscribed tumor measuring 2.8 by 1.5 cm was identified within the lumen of the left upper lobe bronchus. Two small nodules (0.2 and 0.5 cm) were identified in the lower lobe. Microscopic examination of the upper lobe tumor showed a proliferation of spindle cells organized in broad fascicles (Figure 2). There was a moderate degree of nuclear pleomorphism. Focal necrosis was evident. Mitotic figure count was 10 per 10 high power fields. Examination of the lower lobe nodules showed identical smooth muscle proliferations in the parenchyma. It was not clear whether these represented metastases or independent tumors. Immunohistochemical study showed strong positive reactions for vimentin and smooth muscle actin. The reactions to cytokeratin (CAM 5.2) and other epithelial markers were negative. Analysis of a fragment of formalin-fixed tissue by in situ hybridization using an EBV-encoded RNA probe (EBER) demonstrated EBV genomic material in the vast majority of smooth muscle cell nuclei.

View larger version (153K): [in this window] [in a new window]   Figure 2. Representative photomicrograph of the left upper lobe tumor demonstrating proliferating spindle cells organized in broad fascicles (arrowhead).

An increased incidence of smooth muscle neoplasms has been described in a number of patients with AIDS and recipients of solid organ transplants.^1,2 Fourteen cases have been reported after transplantation to date.² Most have been found in children and young adults (median, 7 years), typically within 5 years of transplantation (median, 48 months). They can originate in either host or graft tissues.¹ The case described here is exceptional both for the advanced age of the patient (61 years) and the prolonged interval period between transplantation and tumor presentation (29 years). This interval represents the longest interval from transplant to tumor in the literature.

Several methods of investigation have demonstrated EBV genomic material and products in the cells of these posttransplant neoplasms, including in situ hybridization (as in the present case), immunohistochemistry, polymerase chain reaction, and reverse-transcriptase polymerase chain reaction. Smooth muscle cells have been shown to express CD21, the cell surface receptor for EBV,³ and the EBV-encoded latent membrane protein-1 oncogene has been implicated in neoplastic transformation of lymphoid tissue.⁴ However, the exact pathophysiologic mechanism by which EBV induces native smooth muscle to undergo neoplastic transformation is not entirely clear. The virus appears to be sufficient but not necessary for the development of smooth muscle cell tumors, as at least 1 reported case failed to demonstrate EBV genomic material in the tumor cells by in situ hybridization.⁵

This present case supports the concept of a pathogenetic relationship between EBV and posttransplant smooth muscle tumors and shows that these tumors can arise at an advanced age and after a prolonged interval after transplantation.

References

1. Somers GR, Tesoriero A, Hartland E, et al. Multiple leiomyosarcomas of both donor and recipient origin arising in a heart-lung transplant patient. Am J Surg Pathol. 1998;22:1423–1428[Medline]
   
2. Rogatsch H, Bonatti H, Menet A, Larcher C, Feichtunger H, Dirnhofer S. Epstein-Barr virus associated multicentric leiomyosarcoma in an adult patient after heart transplantation. Am J Surg Pathol. 2000;24:614–621[Medline]
   
3. McClain H, Leach C, Jenson H, et al. Association of Epstein-Barr virus with leiomyoscarcomas in young people with AIDS. N Engl J Med. 1995;332:12–18[Abstract/Free Full Text]
   
4. Knecht H, Berger C, Rothenberger S, Odermatt B, Brousset P. The role of Epstein-Barr virus in neoplastic transformation. Oncology. 2001;60:289–302[Medline]
   
5. van Gelder T, Jonkman FA, Neisters HG, Vuzevzki VD, Spillenaar Bilgen EJ, Weimar W. Absence of Epstein-Barr virus involvement in an adult heart transplant recipient with epithelioid leiomyosarcoma. J Heart Lung Transplant. 1996;15:650–651[Medline]
   

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