[Medical-industrial expertise in thyroid neoplasms].
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BACKGROUND: Fine-needle aspiration biopsy (FNAB) is the most reliable diagnostic tool for thyroid nodules. A difficult cytologic diagnosis may be supported by an immunocytochemical study. The efficacy of a panel made up of RET, HBME-1, and Galectin-3 antibodies was evaluated in smears processed by thin-layer cytology (TLC). DESIGN: Thyroid FNABs (n = 99) with both conventional (CS) and thin-layer cytology (TLC) smears were studied. The cases were diagnosed as follows: 5 benign lesions (BL), 13 papillary carcinomas (PC), and 81 follicular proliferations (FP). The category of FP was divided into three subgroups according to nuclear features of follicular cells: Follicular neoplasm (FN NOS), oxyphilic follicular neoplasm (OFN), and follicular lesion with nuclear pleomorphism (FLWNP). Immunostains for HBME-1, Galectin-3, and RET were carried out on TLC slides. RESULTS: Among 49 cases undergoing surgery, all 10 PC and 2 BL were histologically confirmed, whereas 15 out of 37 FP (40.5%) were malignant. The complete immunocytochemical panel (ICCP) was positive in 9 of 10 malignancies (90%) and negative in both BLs. Out of 37 FP, the ICCP yielded positive in 15 cases (4 benign, 11 malignant) and negative in 11 (all benign). In the FLWNP subgroup, the ICCP was positive in 11 (84.6%) and negative in 2 histologically benign cases. CONCLUSION: The combined panel of antibodies and the nuclear pleomorphism of follicular cells were effective in distinguishing between thyroid nodules requiring surgery from thyroid nodules requiring just follow-up.
Plasma thyroglobulin (Tg) was determined by radioimmunoassay in 219 patients with differentiated carcinoma of the thyroid gland after treatment by total thyreoidectomy and at least 2 131I therapies with a total of 170 mC. Of 145 patients without residual thyroid tissue and a negative whole body scan, 6 patients exhibited significant Tg levels. It remains unclear whether these individuals will develop recurrency later on. Of 23 patients with proven metastases, 14 had extremely high Tg concentrations of greater than 1000 ng/ml. In 6 cases Tg was between 20 and 280 ng/ml and in 3 individuals Tg levels below 10 ng/ml were measured. The reason for low Tg concentrations in some patients with proven metastases is unknown. At present plasma Tg measurements therefore cannot be recommended as substitution for whole body scanning. However, plasma Tg is an important additional parameter in the follow-up of patients with differentiated carcinoma of the thyroid.
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A retrospective analysis of 19 follicular adenomas, 12 minimally invasive follicular carcinomas and 3 widely invasive follicular carcinomas of the thyroid was performed on 5-microm-thick Feulgen-stained paraffin sections by means of a semiautomatic system for picture analysis. The major aim was to assess the potential of multiparameter karyometry for separation of the first two tumour types. Sixteen planimetric and densitometric features were defined in each case on 200-300 randomly selected nuclei and processed by a number of uni- and multivariate statistical methods. Despite predominantly significant ANOVA results a substantial overlap between tumour groups limited the practical usefulness of any karyometric feature alone. Factor and cluster analyses indicated independence of planimetric and densitometric parameters from each other, which was of crucial importance in finding an optimal subset of variables for discriminant analysis. The classification rule derived from the latter procedure was checked by the "jack-knife" method, by classification of 3 widely invasive cancers and by hierarchical tumour clustering. Sensitivity and specificity of the model for detection of malignancy were 100% and 94.7%, respectively. A multivariate karyometric approach, when applied correctly, can be a useful tool for differentiation between follicular adenomas and minimally invasive follicular carcinomas of the thyroid.
OBJECTIVE: To develop a computer-assisted image analysis procedure for quantitation of neovascularization in formalin-fixed paraffin-embedded specimens of thyroid gland tissue from dogs with and without thyroid gland neoplasia. SAMPLE POPULATION: 47 thyroid gland carcinomas, 8 thyroid gland adenomas, and 8 specimens of thyroid tissue from dogs without thyroid gland abnormalities (normal). PROCEDURE: Serial tissue sections were prepared and stained with antibodies against human CD31 or factor VIII-related antigen (factor VIII-rag). The areas of highest vascularity were identified in CD31-stained sections, and corresponding areas were then identified in factor VIII-rag-stained sections. Image analysis was used to calculate the total vascular density in each section, and neovascularization, expressed as a percentage, was determined as the absolute value of the total vascular density derived from factor VIII-rag-stained sections minus the vascular density derived from CD31-stained sections. RESULTS: Mean vascular density of thyroid gland carcinomas derived from CD31-stained sections was significantly greater than density derived from factor VII I-rag-stained sections. This incremental difference was presumed to represent degree of neovascularization. However, significant differences were not detected between vascular densities derived from CD31 and factor VIII-rag-stained sections for either normal thyroid gland tissue or thyroid gland adenomas. No significant correlations were found between vascular density in thyroid gland carcinomas and survival time following surgery. CONCLUSION AND CLINICAL RELEVANCE: A computer-assisted image analysis method was developed for quantifying neovascularization in thyroid gland tumors of dogs. This method may allow identification of dogs with tumors that are most likely to respond to treatment with novel antiangiogenesis agents.
Formalin fixed paraffin sections of previously resected surgical specimens and ethanol fixed stamped samples of newly obtained specimens from patients with thyroid neoplastic lesions were investigated for the presence of cytokeratin by the help of avidin-biotin peroxidase complex (ABC) method using anticytokeratin monoclonal antibody PKK-1. The result showed that PKK-1 reacted only to a large cell variant of anaplastic carcinoma of the thyroid and not to a small cell type. Therefore this method appears not to be useful for differentiation between small cell carcinoma and lymphoma. The differentiation between papillary carcinoma and follicularly growing tumor was possible by this method because the former reacted to PKK-1 at a high rate, whereas most of the latter were negative to it. Freshly prepared stamped samples showed a better reaction to the monoclonal antibody, and thus this technique appears to be applicable to an aspiration biopsy cytology.
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Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only S of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extra thyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.
The thiroidian tumor with Hürtle cells represents a rare clinical form of thyroid neoplasia and has a particular biological behavior. Tumors included in this category are those in which more than half of the cell population is made up of Hürtle cells. We present the case of a 58 years old woman with a recidivant oncocitic adenoma, four years after a subtotal bilateral thyroidectomy. The pathological examination using HE, van Gieson, AgNOR stains, the positive imunoreaction for thyreoglobulin LSAB and the ultrastructural examination established the definitive diagnosis. The surgical treatment is the main therapeutic measure and must be performed under oncological curative principles: lobectomy for the benign forms and total thyroidectomy for the malignant ones. The malignant potential is higher than for other well differentiated thyroidian carcinomas.
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