Heart block

Malignant thymoma is a rare tumor that is associated with paraneoplastic syndrome. Myocarditis as a paraneoplastic syndrome has been rarely described. Reported herein is a young male patient with malignant thymoma and myocarditis as part of a paraneoplastic syndrome. This resulted in high-degree heart block and an asystolic cardiac arrest despite placement of a permanent pacemaker.

(CHEST 1999; 116:1135-1136)

Key words: advanced heart block; paraneoplastic syndrome; malignant thymoma

Abbreviation: CPK = creatinine phosphokinase

The thymus gland is very important to the normal development of the immune system, but its role in adults is not well understood. Malignant thymoma is an unusual disease process that typically affects middle-age adults. It is associated with a variety of paraneoplastic syndromes. This case describes a young male patient with malignant thymoma who developed myocarditis as part of a paraneoplastic syndrome. This subsequently lead to high-degree heart block, which has not been reported to have occurred as part of paraneoplastic syndrome.

CASE REPORT

The patient is a 17-year-old male who had been in previously good health until he presented to his local emergency department with a cough and upper respiratory tract symptoms. A chest radiograph revealed an anterior mediastinal mass. A CT scan revealed a large mass in the mediastinum. A thoracotomy was performed that revealed invasion of the mass into the right pleural space and evidence of pulmonary metastases. A biopsy was diagnostic for an invasive thymoma, mixed epithelial and lymphocytic type. The tumor was believed to be too extensive and invasive for resection. He was treated with six courses of VP-16, ifosfamide, and cisplatin. A follow-up CT scan revealed no change in the size of the mass.

Six months after completing chemotherapy, the patient was readmitted with cough, night sweats, and productive sputum, and he subsequently developed progressive respiratory distress that required a transfer to the ICU and intubation. He also developed transient heart block that resolved quickly and did not require temporary pacing. He had creatinine phosphokinase (CPK) elevations [is greater than] 10,000 U/L. A muscle biopsy was performed and was consistent with an inflammatory myositis. The CPK elevations were believed to be due to myocarditis. The myositis and myocarditis were believed to be a paraneoplastic manifestation of the thymoma, and treatment with IV immunoglobulins and prednisone was initiated. Eventually, tracheostomy placement and transfer to a chronic ventilatory Facility were required. He was successfully weaned from the ventilator at this facility; subsequently, he was maintained on prednisone and monthly chemotherapy with cyclophosphamide, adriamycin, and cisplatin.

Several months later the patient presented to the emergency department complaining of chest pain and dyspnea. A 12-lead ECG revealed anterolateral ST-segment elevations (see Fig 1) that were changed compared to prior ECGs. Emergency coronary angiography was performed and revealed normal coronary arteries. A subsequent echocardiogram revealed normal systolic performance of the left ventricle. Peak CPK was 10,870 U/L with 9.7% CPK-MB. He was presumed to have a recurrence of his myocarditis and was started on high-dose steroid therapy. He then developed 2:1 heart block with a heart rate around 50 beats/rain and a systolic BP of 100 to 120 mm Hg. As a precaution, the patient was transferred to the ICU for further monitoring. Several hours later, he progressed to 3:1 heart block (Fig 2), and a temporary pacemaker was placed with capture of the ventricle achieved at 0.5 MV. Subsequently, he was taken to the eleetrophysiology laboratory for permanent pacemaker placement. Because the procedure was believed to be risky, it was performed under general anesthesia. Initially, it was difficult to obtain adequate pacing thresholds, but eventually these were achieved and the patient was sent to recovery, where he developed ventricular tachycardia and was given a bolus of lidocaine. He then suddenly developed asystole with failure of the pacemaker to capture. A temporary pacemaker was reinserted but tidied to capture, and the patient died.

[Figures 1-2 ILLUSTRATION OMITTED]

DISCUSSION

The thymus gland is very important to the development of the immune system. Immature lymphocytes migrate to the thymus and undergo maturation there to become capable of recognizing antigen and generating an immune response. The absence or abnormal development of the thymus plays a role in the DiGeorge syndrome and in severe combined immunodeficiency. The gland undergoes atrophy in the adult, and its functional significance in the adult is unknown. Because of the central role of the thymus in the immune system, thymomas commonly result in immunologic manifestations, as will be discussed later.

About half of all tumors occurring in the anterior mediastinum originate from the thymus gland. Thymomas are classified according to their histologic appearance, and they are staged on the basis of the disease extent and invasiveness. Most thymomas (from 70 to 80%) have a benign appearance histologically, and when they do not invade surrounding structures, they are classified as benign. The malignant thymomas are classified into two different groups: (1) those with a histologically benign appearance, but with invasion into surrounding structures; and (2) those with a histologically malignant appearance. The latter are termed thymic carcinomas. Most tumors occur in adults; the mean age of patients at diagnosis is 45 to 50 years old.[1]

Most patients with thymoma are asymptomatic, and the tumors are discovered incidentally, often as a mediastinal mass on a chest radiograph. The most common symptomatic presentation is due to a paraneoplastic syndrome. Few carcinomas are associated with such a high rate of paraneoplastic syndrome. The most common is myasthenia gravis, which occurs in as many as half of all patients with thymoma. In many patients, the myasthenia improves with thymectomy.[2] Other common manifestations are hypogammaglobulinemia, anemia, and a variety of autoimmune disorders. The patient in this ease had myocarditis in association with thymoma, which is extremely unusual. In a series of 148 patients from the Mayo Clinic with thymoma, only 1 patient had myocarditis.[3]

The 10-year survival for patients with malignant thymoma ranges from 86 to 100% with stage I disease to 26 to 47% with stage IV disease. Stage I is a completely encapsulated mass; stage II refers to invasion into the capsule or surrounding fatty tissue. Stage III is the extension of the tumor into an adjacent organ such as the pericardium or great vessels, and stage IV refers to distant metastasis. Surgical resection, if possible, is the preferred method of treatment. Even with advanced stage of disease, surgical resection resulted in a 77% and 59% survival at 5 and 10 years, respectively, in one study.[1] Patients with complete resection did better than those with only a partial resection. Radiation therapy as an adjunct to resection is recommended for more advanced disease. It has not been until more recently that chemotherapy had been studied to treat unresectable disease. One study found a complete response rate of 68% and a partial response rate of 100% using a combination of cisplatin, vincristine, doxorubicin, and cyclophosphamide.[1] A larger trial studied a cisplatin, doxombicin, and cyclophosphamide combination and had an overall response rate of 50% and a median survival of just [is greater than] 3 years. The most common cause of death is intrathoracic progression of the thymoma (a myasthenic crisis). In one series, almost one fourth of patients died of unknown causes.[4]

This ease is unique in a number of respects. First, the young age of the patient is unusual, as most eases present in middle age. As stated above, there is only one other case report of a patient having myocarditis in association with malignant thymoma. This patient also suffered from rapidly progressive heart block that resulted in an asystolic arrest and death. Heart block has been described before in myocarditis, but never before as the result of a paraneoplastic syndrome. It is very possible that unrecognized myocarditis and heart block is a cause of death in patients with malignant thymoma who die of unknown causes. Heart block in eases of myocarditis seems to be directly related to myocardial necrosis and destruction of the conducting system, and those who develop heart block have evidence of more extensive necrosis than those who do not. Patients with myocarditis who develop conduction disturbances such as left bundle branch block have a worse prognosis than patients who do not.[5]

CONCLUSION

Heart block as a manifestation of a paraneoplastic syndrome is described for the first time. Clinicians who treat patients with these disorders should be more aware of myocarditis as paraneoplastic syndrome, and they should be alert to the possibility of the development of heart block. However, even in this ease with prompt recognition and institution of pacing, a fatal outcome could not be avoided.

REFERENCES

[1] Kohman L. Controversies in the management of malignant thymoma. Chest 1997; 112(suppl):296S-300S

[2] Morgenthaler T, Brown L, Colby T, et al. Thymoma. Mayo Clin Proc 1993; 68:1110-1123

[3] Lewis J, Wick M, Scheithauer B, et al. Thymoma: a clinico-pathologic review. Cancer 1987; 60:2727-2743

[4] Strollo D, Rosado de Christenson M, et al. Primary mediastinal tumors: Part 1. Tumors of the anterior mediastinum. Chest 1997; 112:511-522

[5] Morgera T, Di Lenarda A, Dreas L, et al. Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes. Am Heart J 1992; 124:455-467

COPYRIGHT 1999 American College of Chest Physicians
COPYRIGHT 2000 Gale Group