Interact CardioVasc Thorac Surg 2007;6:679-681. doi:10.1510/icvts.2007.151811
© 2007 European Association of Cardio-Thoracic Surgery
Case report - Transplantation |
Heart transplantation treatment for a malignant cardiac granular cell tumor: 33 months of survival
Javier Gualis*,
Yolanda Carrascal,
Luis de la Fuente and
Jose Ramón Echevarría
Cardiac Surgery Unit, Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 5 Valladolid, Spain
Received 8 January 2007;
received in revised form 29 June 2007;
accepted 3 July 2007
*Corresponding author. Tel.: +34 983 420 000; fax: +34 983 255305.
E-mail address: javgua{at}hotmail.com (J. Gualis).
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Abstract
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A malignant granular cell tumor is a high-grade sarcoma with a high rate of metastasis, local recurrence and short survival. We describe a patient who underwent orthotopic heart transplantation due to a metastatic unresectable malignant granular cell tumor. At thirty-three months following this procedure she is alive and free of recurrence.
Key Words: Transplantation; Granular cell tumor; Sarcoma
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1. Introduction
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Primary cardiac tumors are rare [1]. Only 25% are malignant [1, 2]. Granular cell tumors (GCTs), originally described by Abrikosoff in 1926 [3], are commonly benign Schwannian lesions, frequently multicentric [4]. Only occasionally, GCTs are malignant and, if so, cardiac involvement is extremely rare [5–7].
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2. Case report
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A 46-year-old woman presented to the Cardiac Surgery Department with a ten-month history of insidious progression of fatigue and dyspnea associated with gradual curtailment of activities (NYHA III/IV). Past history revealed that a malignant GCT located in the posterior region of the right thigh has been detected four years before. It was initially successfully treated by surgical excision but required reoperation and radiotherapy because of local recurrence seven months later.
On admission an electrocardiogram showed ST elevation in precordial leads. Echocardiography revealed septal hypertrophy and left ventricular anterior hypokinesia, related to extensive myocardial ischemia in perfusion study. Coronary angiography showed a large stenosis in the anterior descending coronary artery (>4 cm) and first diagonal with no atheromatosis. No lesion in the other coronary arteries was found. Magnetic resonance imaging (MRI) revealed an infiltrative 8 cm-diameter cardiac mass which extended to the left ventricle anterior wall and interventricular septum. Hypermetabolism shown in positron emission tomography (PET) 18F-deoxyglucose suggested a neoplastic origin. There was no evidence of tumor dissemination.
A percutaneous transluminal coronary angioplasty (PTCA) implanting three cover stent (Cypher) in anterior descending coronary artery was initially performed with suboptimal result. Heart transplantation (HT) was proposed as the only therapy available for a patient with previous sarcoma, unresectable cardiac tumor, short life expectancy and absence of metastatic disease. Standard orthotopic HT with tumor complete excision was performed 30 days after failed PTCA. Grossly, tumor infiltrated left ventricle free wall, atrioventricular and interventricular septum and epicardial fat surrounding left main coronary artery and anterior descending artery leading to stenosis and deformation in the left and right ventricular outflow tracts, aorta and pulmonary artery. Tumor implants were found in aortopulmonary fat, epicardium, subendocardial septum and ascending aortic adventitia (Fig. 1). Microscopically, the tumor presented five out of six malignant GCT characteristics described by Fanburg-Smith et al. [8]: necrosis, tumor cell spindling, vesicular nuclei with large nucleoli, high nuclear-to-cytoplasmic (N:C) ratio and pleomorphism. Mitotic activity (MA) was 2 mitoses/10 high-power fields at 200xmagnification (the sixth Fanburg criterion is MA>2 mitoses/10 high-power fields at 200xmagnification). GCTs are considered malignant if they satisfy at least three of the criteria. Immunohistochemical staining detected vimentin, enolase, S-100 protein, Ki 67<3% and p53<2%.
Postoperative recovery was uneventful. Immunosuppressive regimen is detailed in Table 1. The patient was discharged on postoperative day (POD) 10. Nine myocardial biopsies obtained during the first six months after transplantation showed Grade 0 in ISHLT (International Society of Heart and Lung Transplantation) classification. Thirty-three months after HT the patient remains asymptomatic, in NYHA functional class I. There is no clinical, echocardiographic or PET imaging evidence of tumor recurrence.
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3. Discussion
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GCTs are benign Schwannian lesions occurring in skin, subcutis, and mucosal surfaces and occasionally within skeletal muscle. They may be multicentrics and exhibit pleomorphism and mitotic activity [4]. Malignant GCTs are rare (1–2% of all GCT) [4]. Cardiac involvement is infrequent and generally the consequence of metastatic disease. We have not found in literature (Medline) any case of malignant cardiac GCT treated by HT [4–7].
Malignant GCTs are high-grade sarcomas with short survival and a high rate of local recurrence and metastasis. At three years of follow-up, mortality rates oscillate between 39% and 50%, local recurrence incidence is between 32% and 41%. Distant metastases involve up to 50–62% of patients [4, 7]. Survival in a malignant GCT is adversely affected by histological findings (tumor necrosis, vesicular nuclei and large nucleoli, and increased mitotic activity  2 mitosis/10 high-power fields at 200xmagnification), tumor size and older patient age. All these factors (except mitotic activity) are also related to development of metastases and only tumor size is related to local recurrence incidence. Immunohistochemical staining with Ki 67 values >10% and p53 immunoreactivity >50% are also adversely correlated to survival [4].
In our patient, all histological characteristics (except mitotic activity) led to the diagnosis of high-grade malignant tumor. Cardiac local infiltration, great tumor size (adversely affecting cardiac function) and the mentioned histological characteristics predicted a short life expectancy.
Diverse surgery techniques, such as cardiac autotransplantation, has been proposed as an alternative treatment in cardiac tumors. Class I ISHLT recommendations with regard to cancer, consider HT in patients with pre-existing neoplasm when tumor recurrence is low, based on tumor type, response to treatment and negative metastatic work-up [9]. These recommendations are respected in reference to a primary tumor located in the right thigh and HT is considered the only therapy available in a young patient with unresectable cardiac tumor, previous malignant GCT history, short life expectancy and absence of local extracardiac involvement or metastatic disease [9, 10].
Although limited survival rates in active malignancies from origins other than skin are considered absolute contraindication to HT, there are reports of patients being successfully transplanted with co-existing tumors or primary cardiac tumors. The limited number of cases does not permit to evaluate recurrence rate of malignancy or immunosuppressive treatment influence in primary tumor recurrence [9, 10]. No evidence has yet been provided that supports that the use of alternative therapeutics such as radio- or chemotherapy as an adjuvant treatment in malignant cardiac metastatic GCT. We decided to avoid its use because the tumor was completely resected and trials have shown no survival benefits. Accumulation of successful treatment in this type of disease may change the actual indication of HT.
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4. Conclusions
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Malignant cardiac granular cell tumor is a high-grade sarcoma that can benefit from heart transplantation in selected cases, without evidence of local tumor infiltration in resection borders after cardiac explantation (left atrium cuff, superior and inferior vena cavae or right atrium, and aortic root and pulmonary artery trunk), or metastatic disease. Cardiac transplantation in patients with active neoplasm is still in a stage of trial and cannot be recommended as a standardized and acceptable treatment for malignant cardiac tumor at this time. Nevertheless, some selected individuals, such as our patient, can benefit from this procedure.
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References
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Abstract
1. Introduction