Latency period of thyroid neoplasia after radiation exposure

Abstract

Objective: To determine the temporal sequence for developing benign and malignant thyroid neoplasms after radiation.

Summary background data: Therapeutic radiation is associated with thyroid neoplasms in humans and animals. Some question whether thyroid cancers develop de novo or from benign thyroid neoplasms. Little information, however, is available concerning the time to development of benign and malignant thyroid neoplasms after radiation exposure.

Methods: We retrospectively analyzed the records of 171 consecutive patients who had a history of exposure to radiation and were treated surgically at University of California, San Francisco-affiliated hospitals for thyroid neoplasms between 1960 and 1999.

Results: There were 66 men and 105 women aged 9 to 80 years (mean, 47.0 years). One hundred patients had benign and 71 had malignant tumors (58 papillary cancers, 10 follicular cancers, 1 Hurthle cell cancer, 1 medullary cancer, and 1 carcinosarcoma). The mean latency period for benign tumors was longer than that for malignant lesions (mean, 34.1 and 28.4 years, P = 0.018; median, 38.0 years and 30.0 years, P = 0.001). Follicular carcinomas developed sooner (mean, 20.5 years; median, 20 years) than did follicular adenomas (mean, 35.3 years; median, 36.5 years; P = 0.003, P = 0.0009). Patients with papillary thyroid cancers presenting as occult papillary cancers (<1 cm) and as a dominant nodule had similar latency periods (mean, 34.0 and 28.0 years P = 0.29; median, 37.5 and 30.5 years, P = 0.09), respectively.

Conclusion: Although there could be selection bias regarding referral of patients, our data document that malignant thyroid tumors after radiation exposure, including follicular carcinomas, present earlier than do benign thyroid tumors. Occult and manifest papillary thyroid cancers present at about the same time interval after radiation exposure. Our findings question whether benign thyroid neoplasms progress to malignant thyroid neoplasms and that most occult thyroid cancers do not progress to malignant thyroid cancers in radiation-exposed patients.

FIGURE 1. Latency and age of exposure in benign and malignant thyroid neoplasms. A, White diamonds show benign thyroid tumors and black squares show malignant tumors. B, Each histogram represents the mean ± SD. There is no difference between mean and median. The patient's number was shown in the parenthesis. Latency of benign thyroid tumors is longer than that of malignant thyroid tumors (P = 0.018).

FIGURE 2. Latency and age of exposure in follicular and Hürthle cell neoplasms. A, White diamonds show follicular and Hurthle cell adenomas and black squares show follicular and Hürthle cell carcinomas. B, Each histogram represents the mean ± SD. There is no difference between mean and median. The patient's number was shown in the parenthesis. FA; follicular adenoma, FC; follicular carcinoma. HA: Hürthle cell adenoma, HC: Hürthle cell carcinoma. Latency of malignant & Hurthle cell cancer is shorter than that of benign tumors.

FIGURE 3. Latency and age of exposure in occult and dominant papillary thyroid carcinomas. A, White diamonds show occult papillary thyroid carcinomas and black squares show dominant papillary thyroid carcinomas. B, Each histogram represents the mean ± SD. There is no difference between mean and median. The patient's number was shown in the parenthesis. Two patients are unknown because they had surgery at other medical centers. PC oc; occult papillary carcinoma, PC dominant; dominant papillary carcinoma. Latency of dominant or manifest papillary thyroid cancers is the same as that of occult papillary cancers (P = 0.29).

FIGURE 4. Latency and age of exposure in external radiation. One hundred and fifty-two patients were exposed external radiation. A, White diamonds show low dose exposure, gray squares show medium dose exposure and black triangle show high dose exposure. Low dose is below 2000 rads, medium dose is between 2000 rads and 4000 rads, and high dose is higher than 4000 rads. B, Each histogram represents the mean ± SD. There is no difference between mean and median. Latency of low dose radiation exposure is longer than that of medium and high dose radiation exposure (P < 0.01). In the subgroup of low dose radiation exposure, latency of benign thyroid tumors is longer than that of malignant thyroid tumors (P = 0.01) and latency of malignant follicular tumors is shorter than that of benign follicular tumors (P = 0.001).

FIGURE 5. Correlation between tumor size, DeGroot classification and latency. A, White diamonds show the maximum diameter of benign thyroid tumors except multinodular goiters and black squares show the maximum diameter of malignant thyroid tumors. B, Each histogram represents the mean ± SD. The number of patient is shown in the parenthesis. Seven patients are unknown because they had surgery at other medical centers. There is no correlation between tumor size or tumor aggressiveness and time till clinical treatment.