Background-Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. Aims-To determine the significance of histological findings of patients with malignant polyps. Methods-Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67 months). Results-Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16 (42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. Conclusion-As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems suYcient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk. (Gut 1998;43:669-674)

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Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.

Recently, an impressive increase in malignant thyroid tumours has been observed among children less than 15 years of age living in the Republic of Belarus at the time of the nuclear accident of Chernobyl in 1986. More than half of these patients lived in the region of Gomel, nearest to Chernobyl. Because of the very short time interval between the accident and the tumour occurrence an independent review of the available histopathological material was done. Out of 101 cases diagnosed as thyroid cancers, we reviewed slides of 93 cases and agreed the diagnosis of malignancy in 92.5%. Of these tumours 96.5% were papillary carcinomas, 61.5% were moderately or poorly differentiated. Extrathyroidal extension was observed in 60.5%, regional lymph node metastases in 74% and distant metastases in 7%. One of the patients died from lung metastases. Our results confirm that the neoplasms increasingly diagnosed between 1986 and 1991 among children of this region are thyroid carcinomas. In addition, we correlate several histopathological findings with sex and age of the patients and other parameters, and compare the results with data from other studies.

Thyroid glands from 215 patients, aged 19 to 88 years, without known thyroid disease, were serially sectioned at 2-3 mm intervals and microscopically examined for occult disease. Glands were normal in 32.5%, while nodules were observed in 60% and adenomas in 13%. Carcinomas were found in 20 cases (9.3%): occult papillary carcinomas in 19 (8.8%) and one medullary carcinoma. No carcinomas were found in the thyroids of 15 patients less than 40 years of age. There were no significant differences in frequency of occult carcinomas between female and male patients and, for patients over 40 years, with increasing age. Of the 19 papillary tumours more than one focus was found in six cases (a total of 28 foci). The diameter of 27 of these tumours was less than or equal to 5 mm (96.4%), with one exception (diameter 6.3 mm). These findings were compared with those obtained in 86 thyroid glands of children surgically resected for carcinomas between 1986 and 1991. Only 10 of these tumours (11.6%) were less than or equal to 1 cm. These tumours, however, were significantly larger than the occult papillary carcinomas and their morphological features were quite different. Our results are discussed with regard to the possible role of factors other than irradiation due to the nuclear accident at Chernobyl, and the observed sharp numerical increase of thyroid carcinomas in children of the Republic of Belarus after this event.

The various isoforms of transforming growth factor-beta (TGFbeta) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFbeta in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFbeta expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFbeta in benign multinodular goiter. In the present study, we therefore analyzed the expression of TGFbeta1, TGFbeta2, and TGFbeta3 in normal thyroid tissue, multinodular goiters and papillary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGFbeta isoforms was barely detectable. However, in the carcinomas, almost all epithelial cells displayed immunoreactivity for the three TGFbeta isoforms. In the nodules from multinodular goiters, all 3 isoforms were found to be expressed although the immunolocalization of the 3 proteins was highly variable. TGFbeta-immunostaining was found in scattered clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles. TGFbeta-positivity was present in spite of immunostaining for proliferating cell nuclear antigen (PCNA), a marker for actively proliferating cells. In conclusion, this study shows that thyroid carcinomas and benign tumors express the TGFbeta1, TGFbeta2, and TGFbeta3 isoforms. In contrast to the abundant and homogeneous expression in differentiated thyroid carcinomas, TGFbeta expression displays a highly variable interfollicular and intrafollicular pattern in multinodular goiters, suggesting an important role of TGFbeta isoforms in tumorigenesis of thyroid cells.

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