Infiltration of differentiated thyroid carcinoma by proliferating lymphocytes is associated with improved disease-free survival for children and young adults

An immune response directed against thyroid cancer might be important in pr eventing metastasis and recurrence. This idea is supported by previous obse rvations showing that adults with autoimmune thyroiditis or lymphocytic inf iltration surrounding papillary thyroid carcinoma (PTC) have improved disea se-free survival. The long-term outcome for differentiated thyroid cancer i s even more favorable for children and young adults. If the immune response is important, we hypothesized that tumor-associated lymphocytes with a hig h proliferation index would be found in thyroid cancers from children and y oung adults and would be associated with improved disease-free survival. Us ing immunohistochemistry, we examined 39 childhood PTC, 9 follicular thyroi d carcinomas, 2 medullary thyroid carcinomas, 11 benign thyroid lesions, an d 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 vicin ity of thyroid cancers, but only 7 (18%) patients with PTC also had a diagn osis of autoimmune thyroiditis. Disease-free survival did not correlate wit h the presence or number of lymphocytes per high power field. In contrast, disease-free survival was significantly improved (P = 0.01) for thyroid can cers with the greatest number of Ki-67-positive lymphocytes per high power field. The number of lymphocytes per high powered field was greater for mul tifocal PTC (P = 0.023), and the number of proliferating lymphocytes was gr eatest 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 lym phocytes is associated with improved disease-free survival for children and young adults with thyroid cancer.