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Association Between Thymoma and Second Neoplasms
To the Editor: In our review of cases of thymoma,1 we discovered several patients with multiple neoplasms. These patients were not necessarily treated with radiation therapy or found to have a history of myasthenia gravis, suggesting that the association between thymoma and cancer may be intrinsic and not due to treatment or thymoma-associated conditions.
Methods
A total of 136 patients with a histologic diagnosis of thymoma were evaluated.1 Additional malignancies were recorded through chart review, corresponding physician notes, and the hospital tumor registry.
Results
Additional neoplasms were noted in 38 patients (28%). Fourteen patients had at least 3 unrelated neoplasms. No histologic subtype of thymoma was more strongly associated with additional neoplasms. Six patients with additional neoplasms never underwent thymic resection.
Forty-six patients received radiation or chemotherapy for their thymoma. Among these, 16 (35%) developed second neoplasms. This rate did not differ significantly from the incidence in those who did not receive adjuvant treatment (22/90 [25%]; P = .20). Conversely, of the 38 patients with additional neoplasms, 16 received radiation therapy. Among radiation therapy recipients, second tumors developed outside the radiation fields more often than within them. In several cases, the other neoplasms were diagnosed shortly before or at the same time as the thymoma.
Of 67 patients with thymoma-related immunological disorders (myasthenia gravis, red cell aplasia, hypogammaglobulinemia), 16 (24%) developed additional neoplasms. This was similar to the rate in the group without immunological disorders (31%; P = .36). Six additional patients with thymoma whose pathologic materials were unavailable for review also were found to have multiple neoplasms (Table 1). Including these patients, the proportion with second malignancies reached 31%.
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Table. Distribution of Neoplasms in Patients With a History of Thymoma (N = 44)*
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Comment
Evidence linking thymoma with other neoplasms is provided by the clinical literature. One study found second malignancies in 21% of 146 patients with thymoma2 and a 1974 review of the literature revealed a second malignancy incidence of 17%.3 Since these reports did not describe treatments, the possibility of treatment-induced malignancies not be excluded.
An analysis of patients with myasthenia gravis without thymoma who underwent thymic resections revealed no increase in second malignancies.4 However, patients with myasthenia and thymoma who underwent resection had an observed-to-expected malignancy ratio of 3:42, suggesting surgical resection of the thymus per se cannot account for the high cancer incidence. This finding also agrees with our observation that myasthenia gravis (or its treatment) is not an independent risk factor for neoplasia.
The fact that the additional neoplasms usually developed outside the radiation therapy ports, along with their timing (often before or shortly after radiation therapy), makes it unlikely that these represent radiation-induced malignancies.
The number of patients with 3 or more primary neoplasms was high. This strong oncogenic tendency among patients with thymoma is confirmed by a review detecting a third neoplasm in 33% of patients with a history of thymoma and a hematologic neoplasm.5
Although medical texts routinely describe the association of thymoma with myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia, the "forgotten association" between thymoma and cancer is of greater clinical significance. Our data suggest that this association may be intrinsic; these are true second cancers rather than cancers secondary to treatment. Awareness of this increased risk should lead to appropriate surveillance.
AUTHOR INFORMATION
Acknowledgment: We gratefully acknowledge and appreciate the assistance of Anne Kammer of the Johns Hopkins Tumor Registry.
James S. Welsh, MS, MD;
Kirsten Bass Wilkins, MD;
Rennae Green, MD;
Gregory Bulkley, MD;
Frederic Askin, MD;
Marie Diener-West, PhD;
Steven P. Howard, MD, PhD
The Johns Hopkins Medical Institutions
Baltimore, Md
1. Wilkins KB, Sheikh E, Green R, et al. Clinical and pathologic predictors of survival in patients with thymoma. Ann Surg. 1999;230:562-572.
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2. Souadjian JV, Silverstein MN, Titus JL. Thymoma and cancer. Cancer. 1968;22:1221-1225.
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3. Souadjian JV, Enriquez P, Silverstein MN, Pepin JM. The spectrum of diseases associated with thymoma: coincidence or syndrome? Arch Intern Med. 1974;134:374-379.
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4. Masaoka A, Yamakawa Y, Niwa H, et al. Thymectomy and malignancy. Eur J Cardiothorac Surg. 1994;8:251-253.
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5. Friedman HD, Inman DA, Hutchison RE, Poiesz BJ. Concurrent invasive thymoma and T-cell lymphoblastic leukemia and lymphoma: a case report with necropsy findings and literature review of thymoma and associated hematologic neoplasm. Am J Clin Pathol. 1994;101:432-437.
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Letters Section Editors: Phil B. Fontanarosa, MD, Deputy Editor; Stephen J. Lurie, MD, PhD, Fishbein Fellow.
JAMA. 2000;283:1142-1143.
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