An unusual marrow transplant complication: cardiac myxoma

Bone Marrow Transplantation, (1998) 21, 825–827  1998 Stockton Press All rights reserved 0268–3369/98 $12.00

Case report An unusual marrow transplant complication: cardiac myxoma D Baronciani1, E Angelucci1, P Polchi1, F Martinelli2, E Mariotti3, A Marzocchi4, M Longo5, S Poggi6, S Pileri6 and G Lucarelli1 1

Divisione Ematologica e Centro Trapianto di Midollo Osseo di Muraglia, 2Servizio di Anestesia e Rianimazione, 3Divisione Cardiologia, Azienda Ospedale di Pesaro, Pesaro; 4Istituto Cardiologia, 5Istituto Chirurgia Cardiovascolare, 6Sezione di Emolinfopatologia, Istituto di Ematologia, Universita′ di Bologna, Bologna, Italy

Summary: We report a right atrial myxoma which suddenly developed in a thalassemic patient after allogeneic bone marrow transplantation. The tumor was first detected by echocardiography on day +47 after transplant and the patient underwent surgical removal of the myxoma on day +103. The post-operative course was uneventful, and at more than 3 years from the event, he is alive and well, cured from his congenital disease, with no detectable intra-cardiac tumor. The onset of the myxoma in the early post-transplant period and the extremely high velocity of growth suggest a possible relationship of this condition with the immunosuppressive status. Keywords: myxoma; BMT; thalassemia

Bone marrow transplantation (BMT) is a situation which may allow the development of rare and sometimes unrecognised complications1,2 due to the conditioning regimen, immunosuppression, graft-versus-host disease (GVHD) etc. Cardiac myxoma is a rare form of heart tumor whose origin is still under discussion.3,4 Here, we report the occurrence of a right atrial myxoma in a young thalassemic patient in the early period after BMT.

function. No morphological abnormalities were observed in the right heart. The patient underwent BMT on 1 September 1994 from his HLA-identical brother. Preparation for BMT was performed following the scheme at that time in use for class 3 patients6 (busulfan 14 mg/kg over 4 consecutive days followed by cyclophosphamide 120 mg/kg over 4 days and anti-lymphocytic globulin 2 ml/kg from day −8 to day −2). The early post-BMT course was uneventful and the patient was discharged on day +16 with documented allogeneic engraftment. Because of severe metabolic problems (fasting serum glucose: 44 mmol/l, serum triglycerides: 33 mmol/l) he was readmitted to the ward on day +34. During hospitalization he experienced two episodes of symptomatic hypotension (blood pressure 80/40 mm Hg). Echocardiographic examination performed on 18 October (day +47) revealed ‘a large intra-cardiac tumor (oval in shape with maximum diameter = 3.1 cm) with ultrasound density similar to the myocardium, immotile, attached to the lateral wall of the right atrium, below the tricuspid anulus, near to the apex of the central venous catheter, without doppler findings of valve orifice stenosis’ (Figure 1). After initial anticoagulant treatment, a MRI scan (Figure 2) was performed (27 October, day +56) which confirmed the presence of tumor, excluded a thrombotic origin, but did not permit a definitive diagnosis. He was also investigated for various infections: Epstein–Barr virus (EBV), cytomegalovirus

Case report The patient was a 17-year-old male suffering from homozygous B thalassemia, referred to our Unit in August 1994 to be evaluated for allogeneic BMT. Following the Pesaro classification system5 he was evaluated as a class 3 patient. A complete clinical and echocardiographic evaluation was performed before the transplant; twice in his home town and once in Pesaro. Diagnostic conclusions were consistent between the three different cardiologists and showed mild left ventricle dilatation (5.3 cm) with normal myocardial wall thickness and normal regional and global systolic Correspondence: Dr D Baronciani, Divisione Ematologica di Muraglia e Centro Trapianto di Midollo Osseo, Azienda Ospedale di Pesaro, 61100 Pesaro, Italy Received 12 May 1997; accepted 11 November 1997

Figure 1 Two-dimensional echocardiogram (apical four chamber view) showing a large right atrial tumor arising from the lateral wall, below the tricuspidal anulus.

Cardiac myxoma after BMT D Baronciani et al

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Figure 3 Abundant myxoid matrix, containing a variable number of fibroblast-like cells (lepidic cells) (hematoxylin and eosin × 250).

Figure 2 Magnetic resonance imaging showing a 15 mm mass at the inferior wall of right atrium. The mass is isointense in comparison to the ventricular myocardium signal intensity.

(CMV), bacterial and fungal infections. All tests were negative except for a CMV viremia. He underwent surgical resection of the right atrial mass via a right atriotomy7–9 on day 103 post BMT. A solid intra-cardiac tumor (diameter 2.7 cm) was removed; histological examination and immunohistochemistry confirmed a diagnosis of myxoma with thrombosis (Table 1 describes materials and methods used for the histology and immunophenotyping. Figures 3 and 4 (a and b) show microphotographs of the tumor sections). The post-surgery course was complicated by an episode of pneumonia. The patient returned from the surgical ward on day +118 and was discharged on day +125. On day +149 he returned to his home town on anticoagulant therapy. He was subsequently examined 6, 12, 24 and 36 months after Table 1

Panel of antibodies applied to paraffin section

Antibody Vimentin/V9 Actin/1A4 Desmin/D33 CD68/PGM1 Cytokeratin/MNF116 Neutrophil elastase/NP57 LMP/CS1-4 EBV (EBER)

Staining positive positive/negative rare positive negative negative negative negative negative

All reagents were from Dako Produktionsvej 42, DK 2600 Glostrup, Denmark.

Figure 4 The majority of myxoma cells are positive for vimentin (a) and for actin (b) (Immunohistochemistry, APAAP method × 250).

the transplant. Echocardiographic and MRI examinations were negative for intra-cardiac lesions. Other cardiac parameters were similar to those found pre-transplant. The patient is currently alive and well, cured from his congenital disease and off immunosuppressive therapy.

Cardiac myxoma after BMT D Baronciani et al

Discussion Cardiac myxomas represent approximately 50% of primary tumors of the heart and can occur in two forms: sporadic and familiar. Sporadic tumors are more common in middleaged women while the familiar forms are associated with different conditions: cutaneous lentiginosis, cutaneous myxomas, adrenocortical nodular dysplasia, Cushing’s syndrome, testicular tumors. Even if they are histologically benign these tumors may be lethal because of their strategic position; in addition, some cases of malignant atrial myxomas have been reported.10–12 Myxomas usually develop in the atria, more frequently in the left atrium (75%), but they can arise both in the right atrium and in other parts of the heart. They seem to take origin from the endocardium, but because of particular immunohistochemical and histological features a neural origin has also been postulated.3 Clinically, myxomas can present with different symptoms depending on their position, size and mobility. Systemic embolism, dyspnea, heart failure, hypotension, pulmonary edema and other non-specific non-cardiac signs (fever, malaise, arthralgia, etc) can be variously present. Echocardiography, computed tomography (CT) and MRI currently remain the most important non-invasive diagnostic imaging methods, while prompt surgical resection is the treatment of choice. Because myxomas are rare tumors and their pathogenesis is not clearly understood in relation to an immunosuppressed status as in this setting, we attempted to identify a possible relationship with the BMT procedure. Many complications can occur after transplant including toxicity, infections and secondary tumors. In this case the observation of a solid intra-cardiac mass required a differential diagnosis from other proliferative disorders or infectious complications. In addition, the location also suggested the possibility of a thrombotic event in a patient with a long-term central venous catheter. The post-surgical diagnosis of cardiac myxoma was an unusual finding, because this kind of tumor is not reported in transplant recipients or in general in immuno-compromised hosts. The immunosuppression may have been implicated in view of the extremely high velocity of growth of the tumor. Different authors13,14 have suggested that primary intra-cardiac myxomas grow rapidly, but the growth rate of these tumors has always been difficult to determine and has generally been determined for recurrent lesions. In a paper from Malekzadeh and Roberts15 the interval from first surgical excision to surgery for recurrent myxoma ranged from 11 to 76 months (mean 33 months); in the same study the recurrent myxomas increased in size with an average of 0.15 cm/month.

The case described here had the fastest growth reported in the literature (about 1.35 cm/month). The patient was profoundly immunosuppressed with cyclosporin A; he did not discontinue any treatment and had a good immunologic recovery post-transplant. Since late recurrences are possible, long-term clinical and echocardiographic follow-up will be undertaken. References 1 Press OW, Schaller RT, Thomas ED. Bone marrow transplant complications. In: Toledo-Pereyra LH (ed). Complications of Organ Transplantation, Chap. 22. Marcel Dekker: New York, 1986, pp 399–424. 2 Angelucci E, Mariotti E, Lucarelli G et al. Sudden cardiac tamponade after chemotherapy for marrow transplantation in thalassemia. Lancet 1992; 339: 287–289. 3 Krikler DM, Rode J, Davies MJ et al. Atrial myxoma: a tumor in search of its origin. Br Heart J 1992; 67: 89–91. 4 Govoni E, Severi B, Cenacchi G et al. Ultrastructural and immunohistochemical contribution to the histogenesis of human cardiac myxoma. Ultrastructural Pathol 1997; 12: 221–233. 5 Lucarelli G, Galimberti M, Polchi P et al. Bone marrow transplantation in patients with thalassemia. New Engl J Med 1990; 322: 417–421. 6 Lucarelli G, Clift RA, Galimberti M et al. Marrow transplantation for patients with thalassemia. Results in class 3 patients. Blood 1996; 87: 2082–2088. 7 Morrisoy JF, Campeti FL, Mahoney EB, Yu PN. Right atrial myxoma: report of 2 cases and review of the literature. Am Heart J 1963; 66: 4–10. 8 Kabbani S, Cooley DA. Atrial myxoma: surgical considerations. J Thorac Cardiovasc Surg 1973; 65: 731–736. 9 Hanson EC, Gill CC, Razavi M, Loop TD. The surgical treatment of atrial myxomas. Clinical experience and late results in 33 patients. J Thorac Cardiovasc Surg 1985; 89: 298–302. 10 Hannah H, Eisemann G, Hiszcznsky JR et al. Invasive atrial myxoma: documentation of malignant potential of cardiac myxomas. Am Heart J 1982; 104: 881–883. 11 Rankin LI, De Sousa AL. Metastatic atrial myxoma presenting as intracranial mass. Chest 1978; 74: 451–452. 12 Pastakia B. Malignant atrial myxoma presenting as intracranial mass. Chest 1979; 75: 531–532. 13 Pochis WT, Wingo MW, Cinquegrani MP, Sagar KB. Echocardiographic demonstration of rapid growth of a left atrial myxoma. Am Heart J 1991; 122: 1781–1784. 14 Roudaut R, Gosse P, Dallocchio M. Rapid growth of a left atrial myxoma shown by echocardiography. Br Heart J 1987; 58: 413–416. 15 Malekzadeh S, Roberts WC. Growth rate of left atrial myxoma. Am J Cardiol 1989; 64: 1075–1076.

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