We report 3 cases of intrathyroidal epithelial thymoma, a clinicopathologic entity distinct from squamous cell carcinoma of the thyroid. Two patients are long-term survivors among 5 postoperative patients with squamous cell carcinoma of the thyroid. One has been free from the disease for 17 years, and the other with local recurrence died of an unrelated disease 18 years after the surgery. The diagnosis in these 2 was corrected to intrathyroidal epithelial thymoma following a review of the histological findings. These 2 tumors consisted of tumor cell nests resembling poorly differentiated squamous cell carcinoma surrounded by many lymphocytes. Features discriminating thymoma from squamous cell carcinoma included the lack of foci of anaplastic carcinoma and papillofollicular tumor, which are seen in squamous cell carcinoma of the thyroid. Two of the 3 patients with squamous cell carcinoma died within 1 year. We have found recently another case of thymoma.The present observations indicate that: thymoma can arise in the thyroid gland presumably from aberrant thymic tissue, mimicking squamous cell carcinoma; and the prognosis of thymoma is favorable. Therefore, it is important to discriminate thymoma from squamous cell carcinoma of the thyroid, which is usually fatal.We had the opportunity to observe 3 patients with intrathyroidal epithelial thymoma and 3 with squamous cell carcinoma of the thyroid. To our knowledge, there has been no previous reports of epithelial thymoma in the thyroid gland. Squamous cell carcinoma rarely occurs in the thyroid gland, and is

Ninety-five patients with papillary thyroid carcinoma (PTC) who received primary surgical treatment in 1983 at Kuma Hospital and were followed until 1992 were the subjects of this study. Initial therapy was tumor resection for 5 patients, lobectomy for 23 patients, total thyroidectomy with unilateral modified neck dissection for 60 patients, and total thyroidectomy with bilateral modified neck dissection for 7 patients. Clinical stage at diagnosis was as follows. Class I included 28 patients with intrathyroidal disease, class II included 60 patients with positive cervical lymph nodes, and class II included 7 patients with tumor invasion into tissue outside of the thyroid gland. Recurrence of the tumor was evaluated according to lymphocytic infiltration in the thyroid gland. Group A consisted of 36 patients with PTC associated with lymphocytic infiltration, 26 with infiltration surrounding the tumor, 3 with infiltration inside of the tumor, and 7 with both. Group B consisted of the remaining 59 patients with PTC with no lymphocytic infiltration. There were no differences in age, sex, initial tumor size, or initial treatment between groups A and B. Antithyroglobulin antibody and/or antimicrosomal antibody were positive in 16 patients from group A and 4 patients from group B (P < 0.001). Class I included 14 patients from each group, class II included 22 patients from group A and 38 patients from group B, and class III included 7 patients, all from group B. Recurrence of the tumor was found in only 1 group A patient (2.8%), but in 11 patients of group B (18.6%). The percentage of patients free from recurrence over the 10 yr of follow-up in group A was significantly higher than that in group B (by Cox-Mantel test, P < 0.01). The time between initial treatment and recurrence was 2-10 yr. In comparing the clinical stage at the time of initial treatment, recurrence was found in 1 class II patient from group A (4.5%) and in 1 class I (7.1%), 6 class II (15.8%), and 4 class III (57.1%) patients from group B. No patients died during the 10 yr of follow-up. In conclusion, 1) lymphocytic infiltration surrounding the tumor or inside the tumor in PTC might be of use as a means for predicting a favorable prognosis; and 2) class II or class III patients with no lymphocytic infiltration had a high rate of recurrence.

The HLA DRB1*08032 allele was strongly associated with susceptibility to methimazole-induced agranulocytosis, suggesting that cellular autoimmunity may be involved in its development.

Graves' disease may result eventually in hypothyroidism in approximately 5-20% of patients. In a few such patients hypothyroidism was associated with TSH-blocking antibodies, but whether the frequency of TSH-blocking antibodies in such patients is as high as it is (21%) in patients with primary myxedema is not known. This study was undertaken to determine the presence of various immunoglobulins [TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies (TSAb), and TSH-blocking antibodies] in 26 patients with Graves' disease who developed hypothyroidism from 0.5-10 yr or more after discontinuation of antithyroid drug therapy. Eight of the 26 patients (31%) had TSH-blocking antibodies, 16 (61%) had TSAb, and 14 (54%) had thyroid hormone binding inhibitor immunoglobulins. Thyroid needle biopsies were performed in 9 patients. Three of 5 patients who had subclinical hypothyroidism had chronic lymphocytic thyroiditis, and all had positive TSAb titers. Three patients had the fibrous variant of chronic lymphocytic thyroiditis; their TSAb values were 902%, 431%, and 1290%. One patient had follicular hyperplasia. We conclude that TSH-blocking antibodies may account for hypothyroidism in approximately one third of patients with Graves' disease who were previously treated with antithyroid drugs, and that autoimmune thyroiditis is comparable for the hypothyroidism in the remaining two thirds of Graves' disease patients.

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.

We studied the effect of therapy with 0.1 mg/day T4 for 3 months on goiter size in 49 patients with solitary thyroid nodules. The nodule volume in 18 patients (responders) decreased by more than 50%. In this group the mean serum thyroglobulin (Tg) levels decreased significantly (from 425 to 61 micrograms/L; P less than 0.01). In the nonresponders the mean serum Tg levels did not change significantly (145 vs. 250 micrograms/L). The mean serum T4, free T4, free T3, and rT3 concentrations increased significantly in both groups during T4 therapy, serum T3 levels did not change, and serum TSH decreased. These findings demonstrate that serum Tg levels decrease when T4 therapy is effective. Thus, serum Tg measurements may prove a useful indicator of the efficacy of T4 therapy in patients with solitary nodules.

Periodic paralysis (PP) is a well recognized although rare and peculiar complication of thyrotoxicosis, especially among Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked to certain immunogenetic factors, and increased frequency of certain HLA antigens has been found in patients with Graves' disease. This study was, therefore, undertaken to determine HLA haplotypes in Japanese men with thyrotoxic periodic paralysis (TPP). HLA typing in 35 TPP patients and 263 normal men and women demonstrated highly significant increases (P less than 0.01) in HLA-A2, Cw3, and DRw8 in the TPP patients. In comparing TPP patients with thyrotoxic men who did not have PP, the frequency of DRw8 antigen was 2.5-fold greater in patients with PP than in those without it (62.8% vs. 28.6%). The data suggest that the HLA-DRw8 gene itself may play a significant role in the susceptibility to TPP among Japanese men.

SUMMARYHashimoto's ihyroiditis (HT) and lymphoma are sometimes diffieult to distinguish belween. Moreover, lymphoma sometimes develops in a thyroid gland from pre-existing HT. Ofien-or largeneedlc biopsy usually distinguishes between ihem; the specimen may be examined hislotogically and subjected to immunohislochcmlslry. Another possible method of examination is finc-nccdie aspiration hiopsy (FNAB). The cells obtained may be evaluated cylologically, and subjected lo flow cytometry. using various antibodies. In this study, anti-kappa and anti-lambda antibodies are especially important, as a gross predominance of kappa or lambda B lymphocytes infiliraiing the thyroid is evidence for a B cell moniKlone. In this sludy. 15 patients were selected bcxause of Iheir rapidly growing goitres. They all underwent FNAB. Five had cytology typical of HT, and no evidence of monoclonality on flow cyiomeiry. They were diagnosed as HT without further hisiopaihology. The remaining 10 patients had cytology suspected of lymphoma. or evidence of monoclonality on flow cylotiielry, or both. These patients underwent open-or largc-needlc biopsy. Only three of them were diagnosed hisiopaihologically as lymphoma; the other seven were diagnosed histopathologically asHT. making 12 cases of HT in all. Five of the.sc 12 cases, and one of the three cases of lymphoma showed flow cyiometrical evidence of monoclonality; thus evidence of monoclonality from FNAB, while interesting, does not necessarily serve to differentiate between HT and lymphoma. Furthermore, ihc immunohistochcmical assessment of monoclonalily did not correlate with the flow cytomelrical assessment. Follow-up evidence will be required lo discover whether those patients with a B cell monoclone in their HT are the ones who develop a lymphoma.