Mariusz Klencki

The usefulness of sonographic features in selection of thyroid nodules for biopsy in relation to the nodule's size.

OBJECTIVE To evaluate the efficacy of selected ultrasound (US) features of thyroid focal lesions useful for establishing indications for fine-needle aspiration biopsy (FNAB) with regard to the lesions size. METHODS US imaging features of 1141 thyroid nodules (shape, echogenicity, pattern of blood flow, presence of microcalcifications and the presence of other nodules in the thyroid) and their palpability were compared with the post-operative histopathological outcomes. The efficacy of the selected sets of the features was assessed for small nodules (SN)< or =15 mm and large nodules (LN)>15 mm, as well as separately for nodules< or =10 mm. RESULTS Logistic regression analysis showed that in SN hypoechogenicity (odds ratios, OR: 3.18), microcalcifications (OR: 19.12), solitary occurrence (OR: 3.29) and height-to-width ratio> or =1 (OR: 8.57) were independent risk factors for malignancy. The optimal set of small lesions that should be biopsied includes all lesions presenting at least one of the above-mentioned features (sensitivity 98%, specificity 44%). In the LN group, the selection criteria based on the shape of lesions and hypoechogenicity were less sensitive than in the SN group, but they allowed further reduction in the number of performed FNABs. Large nodules primarily selected for FNAB should be hypoechoic, more tall then wide or contain microcalcifications (sensitivity 84%, specificity 72%). CONCLUSIONS The obtained results provide rationale for using features from the US examination in selecting both small and large nodules for FNAB. In the case of LN, the usefulness of sonographic features is less sensitive, but more specific than in the case of SN.

The fine-needle aspiration biopsy efficacy of small thyroid nodules in the area of recently normalized iodine supply

OBJECTIVE To evaluate the incidence of focal lesions in the thyroid in the area of recently normalized iodine supply as well as to compare the efficacy of fine-needle aspiration biopsy (FNAB) of small (infracentimetric) and large thyroid lesions in this area. METHODS The outcomes of 13,646 ultrasound (US) examinations, 13,437 US-guided FNABs of the thyroid and 1694 results of post-operative histopathological examinations were analysed. RESULTS Infracentimetric nodules (INs < or = 10 mm) were revealed by US examinations in 43.5% of patients; in the majority of the cases (82.2%) INs were multiple. The percentage of revealed carcinomas by aspiration of INs is similar to that observed when large nodules (LNs > 10 mm) are examined cytologically. However, the efficiency of preoperative diagnosis of INs is lower than LNs with respect to both US selection of lesions for FNAB and the percentage of false negative results of FNAB (29.8 vs 5.4%, P<0.001). In post-operative histopathological examination, extrathyroidal extension of thyroid cancers was observed in nearly 30% of microcarcinomas. CONCLUSIONS In endemic or post-endemic areas, the efficiency of FNAB is lower in the case of small lesions than larger ones. In spite of this, the percentage of cytologically revealed carcinomas among small lesions is not lower than larger ones. Thus, it is particularly indicated to follow up small thyroid lesions with repeated US examinations in such areas.

Correlation between PCNA expression and AgNOR dots in pituitary adenomas.

Nucleolar organizer regions are segments of DNA associated with argyrophilic proteins (AgNORs). Our previous findings showed that the number, the area, and the intranuclear localization of AgNOR dots differ according to tumor aggressiveness and to the hormone-immunopositivity of pituitary adenomas. Proliferating cell nuclear antigen (PCNA) is a nuclear protein, whose expression is correlated with cell proliferation. The aim of the present paper was to examine PCNA-labeling indexes in pituitary adenomas and to correlate them with AgNOR dots in various immunohistochemical types of the tumors.Histological slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis. We found that the percentage of PCNA-positive cells did not differ significantly among examined groups of monohormonal adenomas. However, tumors immunopositive for α-subunit (α-SU) showed a significantly higher (p<0.05) PCNA index than adenomas immunonegative for that unit. PCNA index in recurrent tumors was significantly higher than in primary adenomas. There was a moderate positive correlation between the PCNA index and the mean area of AgNOR dots and a similar correlation between the PCNA index and the area of the biggest dot in the nucleus.The obtained results reveal that the PCNA indexes and estimated parameters of AgNOR dots differ according to tumor aggressiveness.

Food restriction enhances melatonin effects on the pituitary‐gonadal axis in female rats

Abstract: The effects of melatonin (25 μg s.c. daily in the late afternoon for 10 days) on the ovarian morphometry and the gonadotropin secretion were investigated in food‐restricted rats and rats fed ad libitum. In food‐restricted rats melatonin produced the significant decrease of the surface area of the ovary and of zona granulosa. Moreover, melatonin treatment of food‐restricted rats resulted in significant diminishment of the relative areas of Graafian follicles and zona granulosa estimated in relation to the ovary cross‐sectional surface area. On the other hand, melatonin did not produce significant alterations of the morphometric indices of the ovary in rats fed ad libitum. Melatonin administration was found to inhibit the effects of gonadoliberin on gonadotropin release in food‐restricted but not in normally‐fed rats. These findings suggest that food restriction sensitizes the pituitary‐ovarian axis to antigonadotropic melatonin action.

E-cadherin expression is more associated with histopathological type of thyroid cancer than with the metastatic potential of tumors

The aim of this study was to evaluate the relationship between abnormal expression of E-cadherin (E-CAD) and the extracapsular extension of tumors, lymph node involvement and the presence of metastasis in various types of thyroid cancers. Histopathological specimens of 35 benign thyroid lesions and 122 malignant tumors (papillary, follicular, poorly differentiated and undifferentiated cancers) were analyzed. E-CAD immunostaining intensity, its subcellular localization, homogeneity within lesion, and the relation of staining intensity between tumor and surrounding thyroid parenchyma were evaluated. The obtained results show that the variants of differentiated cancers with a poorer prognosis (i.e. tall cell and follicular variants of papillary cancer and widely invasive follicular cancers) present reduced intensity of E-CAD expression, its abnormal localization or heterogeneity of staining more frequently than classical papillary cancers and minimally invasive follicular cancers. However, the assessment of E-CAD expression does not allow the prediction of extrathyroidal growth of thyroid cancers.

Detrimental Effects of Increasing Iodine Supply: Iodine-Induced Hyperthyroidism, Following Iodine Prophylaxis

This chapter discusses the epidemiology and etiology of iodine-induced hyperthyroidism (IIH), which follows normalization of iodine supply. The thyroid gland seems to be well adapted to incidents of iodine intake in very high amounts. Still, there is evidence showing that increased intake of iodine may induce clinically relevant problems in some susceptible subjects. These effects are optimally identifiable at population level, as individual responses vary depending on many other factors that are difficult to control. One of the main undesirable consequences of increased iodine intake in a population is a higher incidence of hyperthyroidism. The elevated incidence of IIH, which follows normalization of iodine supply, is transient. The greater the iodine deficiency, the more numerous and clinically more difficult are the cases of hyperthyroidism, which occur after correction of the iodine supply. In fact, IIH, which follows iodine supply normalization, can be viewed as an outcome of iodine deficiency. The deeper the iodine deficiency, the more numerous and more difficult are the IIH cases, which occur after the correction of iodine supply. Also, children form the group that benefits the most from iodine prophylaxis. Some effects of prolonged iodine deficiency, such as the presence of autonomous nodules in the thyroid, seem to be irreversible.

Non-diagnostic cytological outcome of thyroid biopsy and the risk of thyroid malignancy.

This study assessed the incidence of neoplasms, including malignant tumors, in lesions within the thyroid gland from which non-diagnostic biopsy aspirates were obtained. An auxiliary goal of the study was an evaluation of the diagnostic efficacy of repeated biopsy in cases when the first biopsy was non-diagnostic. Thus, results of 4603 fine-needle aspiration biopsies (FNABs) were submitted to histopathological verification. The verification revealed the rate of malignancy at 7.1% for non-diagnostic biopsies, i.e., significantly higher (p<0.001) than that in cases FNAB-diagnosed as benign lesions (2.1%). Repeated biopsy, performed when inadequate material has been collected, seems to be less effective than the first biopsy (non-diagnostic specimens; 14.4% vs 8.9%; p<0.01). The occurrence of neoplasms in the goiter was significantly higher (p < 0.0001) in patients with non-diagnostic first FNAB than in those with diagnostic one (50.7% vs 33.5%, p<0.001). And again, in patients with two non-diagnostic FNABs, the occurrence of neoplasms was higher than that in patients with the second diagnostic cytology (63% vs 41.2%, p<0.05). According to our data, patients with non-diagnostic FNAB results should be very carefully monitored, especially when the repeated biopsy is either non-diagnostic again or not performed at all.

Silver-staining nucleolar organizer region quantification in pituitary adenomas

Nucleolar organizer regions (NORs) are segments of DNA, encoding for ribosomal RNA. They are associated with argyrophilic proteins and, thus, they can be localized through silver staining. A correlation has been shown between the number, the size, or the intranuclear localization of AgNORs, and the proliferative activity of cells. The aim of this study was to examine numerous features of AgNORs in pituitary adenomas and to relate them to immunohistochemical typing of tumor. Histologic slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis, supported by an AgNORmeter95 program. All the tumors were also immunocyto chemically characterized. We have found that gonadotropinomas, when compared with plurihormonal adenomas, revealed a lower proportion of nuclei with a single AgNOR and a higher percentage of marginal dots. Recurrent adenomas, when compared with primary adenomas, showed a higher proportion of nuclei with three AgNOR dots, a larger total area of dots in the nuclei, and a higher standard deviation of the AgNOR dot area in the nucleus. Adenomas immunopositive for prolactin, when compared with immunonegative ones, showed a larger mean area of the AgNOR dot, a larger area of the biggest dot in the nucleus, and a higher proportion of nuclei within a single dot. These results suggest that the estimated parameters of AgNOR dots differ according to tumor aggressiveness and to the hormone immunopositivity of pituitary adenomas.

The influence of fine-needle aspiration biopsy of the thyroid gland on the size of the examined nodule and its ultrasound image.

Introduction The aim of the study was to assess the influence of thyroid fine-needle aspiration biopsy (FNAB) on the size and ultrasound (US) features of the lesions and to examine whether the possible effects are persistent. Material and methods One hundred and fifty biopsied and 50 control thyroid nodules underwent two US examinations, 10-20 days and 8-10 weeks after the biopsy. The study took into account lesion volume alterations, both absolute and relative (with reference to its initial value), and the presence of US features of malignancy: hypoechogenicity, microcalcifications, internal blood flow, irregular or blurred margins and suspicious shape of the lesions. The analysis covered only those nodules which immediately after FNAB did not change their appearance owing to cyst fluid evacuation or intranodular hemorrhage. Results The increase of the lesion volume was more frequent in the group of biopsied lesions than the control one (58.0% vs. 24.0%, p < 0.0001) with the highest increase of 61.5%. The mean change percentage, however, was determined below 5% and a tendency of the lesions to resume their initial volume was noticeable. Neither a persistent increase in nodule volume of above 50% nor significant changes in the presence of malignancy suggestive US features were observed after FNAB. None of the biopsied nodules developed any microcalcifications, irregular or blurred margins, internal blood flow, or suspicious shape. Conclusions Fine-needle aspiration biopsy does not cause permanent changes in the US image of biopsied lesions, provided that the sampling technique is appropriate and there are no significant changes observed during the biopsy.

Usefulness of computer-aided karyometric examination in preoperative differentiation of Hürthle cell lesions.

We have previously reported that there is a significant difference in the mean size of thyrocyte nuclei among patients with nodular goiter, follicular adenoma, and follicular carcinoma. In the present study, we have examined karyometric parameters of Hürthle cells in smears collected from 41 patients with Hürthle cells adenomas, Hürthle cells carcinomas, nodular goiter, and lymphocytic thyroiditis. The karyometric evaluation was performed with the image analysis computer system—Karyometry Manager 1.2. We measured the mean volume, the mean intersection area, and the mean perimeter of 100 nuclei in each routine smear. We found that the sizes of Hürthle cell nuclei could be arranged in the ascending order from the nodular goiter, through lymphocytic thyroiditis to Hürthle cell neoplasms, but those differences did not reach a border of statistical significance. Diagn. Cytopathol. 1997; 17:255–257.