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Infiltration of Differentiated Thyroid Carcinoma by Proliferating Lymphocytes Is Associated with Improved Disease-Free Survival for Children and Young Adults¹

Departments of Pediatrics (S.G., A.P., A.F., C.F., G.L.F.) and Pathology (R.C.), F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814; Departments of Pediatrics and Clinical Investigation, Walter Reed Army Medical Center (C.A.D.), Washington, D.C. 20307-5001; and Endocrinology Service, Memorial Sloan Kettering Cancer Center (R.M.T.), New York, New York 10021

Address all correspondence and requests for reprints to: Gary L. Francis, M.D., Ph.D., Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814. E-mail: gfrancis{at}usuhs.mil

An immune response directed against thyroid cancer might be important in preventing metastasis and recurrence. This idea is supported by previous observations showing that adults with autoimmune thyroiditis or lymphocytic infiltration surrounding papillary thyroid carcinoma (PTC) have improved disease-free survival. The long-term outcome for differentiated thyroid cancer is even more favorable for children and young adults. If the immune response is important, we hypothesized that tumor-associated lymphocytes with a high proliferation index would be found in thyroid cancers from children and young adults and would be associated with improved disease-free survival. Using immunohistochemistry, we examined 39 childhood PTC, 9 follicular thyroid carcinomas, 2 medullary thyroid carcinomas, 11 benign thyroid lesions, and 2 normal thyroid glands for the presence of lymphocytes (leukocyte common antigen) and lymphocyte proliferation (proliferating cell nuclear antigen, Ki-67). The majority of PTC (65%) and follicular thyroid carcinomas (75%) from children and young adults contained lymphocytes in the immediate vicinity of thyroid cancers, but only 7 (18%) patients with PTC also had a diagnosis of autoimmune thyroiditis. Disease-free survival did not correlate with the presence or number of lymphocytes per high power field. In contrast, disease-free survival was significantly improved (P = 0.01) for thyroid cancers with the greatest number of Ki-67-positive lymphocytes per high power field. The number of lymphocytes per high powered field was greater for multifocal PTC (P = 0.023), and the number of proliferating lymphocytes was greatest for PTC with regional lymph node involvement (30.5 ± 12.3 vs. 6.8 ± 5.0; P = 0.047). We conclude that proliferation of tumor-associated lymphocytes is associated with improved disease-free survival for children and young adults with thyroid cancer.

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