The thyroids from 101 consecutive autopsies from Finland were subserially sectioned at 2-to 3-mm intervals. From 36 thyroids, 52 foci of occult papillary carcinoma (O K) were found, giving a prevalence rate of 35.6%. the highest reported rate in the world. The rate was higher, although not significantly, in males (43.3%) than in females (27.1%), but it did not correlate to the age of the patients. Twenty-six glands contained one tumor focus and ten glands contained two to five tumor foci. Only a minority of the smallest tumors can be detected with the method used. The probable number of O K s over 0.15 mm in diameter was calculated to be about 300 in this material. The tumor diameter varied from 0.15 mm to 14.0 mm, with 67% of tumors under 1.0 mm. The smallest tumors were usually circumscribed and were composed almost solely of follicles. Imrger tumors had more papillary structures and were often invasive. Fibrosis and, in the largest O K s , lymphocytic reaction were seen around the invasive islands. All tumors were positively stained for thyroglohulin and all but one of the tumors stained positively for epidermal keratin. OPC appears to arise from follicular cells of normal follicles. Apparently the great majority of the tumors remain small and circumscribed and even from those few tumors that grow larger and become invasive O K s only a minimal proportion will ever become a clinical carcinoma. According to the study, OPC can be regarded a s a normal finding which should not be treated when incidentally found. In order to avoid unnecessary operations it is suggested that incidentally found small O K s (less than 5 mm in diameter) were called occult papillary tumor instead of iarcinoma. Cuncer 56531-538, 1985. HYROID CARCINOMA is not a common disease; its T incidence rates range in different countries from 0.5 to 10 per lo5 persons.' In most countries, papillary carcinoma is the most common histologic type that comprises about 40% to 70% of all cases.'-5 Its incidence rates in the Scandinavian countries vary between 0.4 and 3.4 per 10' persons.6 Although papillary carcinoma is not common compared to many other human cancers, the prevalence rate of occult papillary carcinoma (O K) has been reported to be high, varying between 5.6% and 28.4% in several systematical autopsy studies.'-' '
The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.
Familial nonmedullary thyroid cancer (FNMTC) is a clinical entity characterized by a phenotype more aggressive than that of its sporadic counterpart. Families with recurrence of nonmedullary thyroid cancer (NMTC) have been repeatedly reported in the literature, and epidemiological data show a very high relative risk for first-degree relatives of probands with thyroid cancer. The transmission of susceptibility to FNMTC is compatible with autosomal dominant inheritance with reduced penetrance, or with complex inheritance. Cases of benign thyroid disease are often found in FNMTC kindreds. We report both the identification of a new entity of FNMTC and the mapping of the responsible gene, named "TCO" (thyroid tumors with cell oxyphilia), in a French pedigree with multiple cases of multinodular goiter and NMTC. TCO was mapped to chromosome 19p13.2 by linkage analysis with a whole-genome panel of microsatellite markers. Interestingly, both the benign and malignant thyroid tumors in this family exhibit some extent of cell oxyphilia, which, until now, had not been described in the FNMTC. These findings suggest that the relatives of patients affected with sporadic NMTC with cell oxyphilia should be carefully investigated.
Thyroid carcinoma has been described as occurring more frequently than expected in association with familial adenomatous polyposis. The histology of these cases has not been described in detail, although the reported cases were usually diagnosed as papillary carcinoma. We now report the pathological features of four cases of thyroid carcinoma associated with familial adenomatous polyposis, and review the findings in the literature. The tumours in these four cases were all of follicular cell origin as shown by thyroglobulin immunohistochemistry. In three they were multifocal. The tumours showed some features of papillary carcinoma--grooved nuclei and papillary architecture, but these were not consistent. They also showed features that were unusual for papillary carcinoma--a cribriform pattern and solid areas with spindle cell component. Commonly the tumours combined both patterns. A review of the reported cases of thyroid cancer associated with familial adenomatous polyposis showed that they also were commonly multifocal and occurred predominantly in young women. When the histology was adequately reported or illustrated it was, in most instances, consistent with the findings in our own cases. We therefore suggest that these thyroid tumours form a distinct type with some unusual features. Clearly it is likely that the APC gene is associated with their pathogenesis, and that other factors contribute to the predominantly female incidence in this as in sporadic tumours. Six of 63 reported cases showed metastasis or died from thyroid carcinoma. In a number of cases the tumours presented before the familial adenomatous polyposis was recognized. The findings of these unusual histological features in a thyroid tumour, and particularly of multicentricity, should alert the pathologist to the possibility of familial adenomatous polyposis with its implications for family screening. The tumours are often well demarcated but, because of the multicentricity, total thyroidectomy should be advocated.
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