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Value of aspiration cytology of the thyroid in metastatic disease.

Metastases may simulate primary malignant tumors of the thyroid, causing problems in the diagnosis and management of patients with a history of cancer. In the seven-year period of July 1978 through June 1985, 8 of 549 needle aspirates of the thyroid contained metastatic tumor, 6 of which were subsequently confirmed by histologic study. The primary sites of origin were the breast, kidney, colon and stomach as well as lymphoma. The cytologic features observed in the aspiration biopsy material from the six cases were characteristic of each of the primary tumors. Three of the patients had had prior resections of carcinomas (breast, colon and stomach) while in three patients the cytologic diagnosis of the thyroid aspirates led to the discovery of the primary tumor (kidney and two lymphomas). One case of lymphoma/leukemia and one case of previously biopsied lung carcinoma were confirmed on clinical grounds. It is of critical importance that primary thyroid neoplasms occurring in patients known to have primary tumors elsewhere be distinguished from disseminated tumors involving the thyroid. Our experience suggests that fine needle aspiration is of considerable value in this differential diagnosis. Needle aspirates of the thyroid are also of value in leading to the diagnosis of unsuspected nonthyroidal primary cancer.

Adult↗

Accumulation of thallium-201 in medullary thyroid cancer with negative serum calcitonin and carcinoembryonic antigens: a case report.

Thallium-201 (201Tl) scintigraphy has been used in the evaluation of thyroid neoplasm. Even though several authors have shown the usefulness of 201Tl scintigraphy in evaluating recurrent tumor of medullary thyroid cancer, the number of reports on primary thyroid cancer is limited. We presented a case of medullary thyroid cancer which showed 201Tl uptake in both early and delayed scans. This case had normal serum levels of calcitonin and carcinoembryonic antigen.

Calcitonin↗

Autoradiographical evidence for increased thyrotropin binding to autonomously functioning thyroid gland tissue.

The aim of this study was to quantify thyrotropin (TSH) binding to individual cells from autonomously functioning thyroid gland tissue (AFTT) in comparison with the corresponding non-autonomous cells. Cryostatic tissue sections from ten thyroid glands with autonomously functioning adenomas were incubated in 125I-labeled TSH. TSH-binding density (TBD) was visualized by means of autoradiography and quantified by means of reflection photometry. Eight out of ten specimens showed a significant (p less than 0.001), up to tenfold increase in TBD of AFTT cells. All ten specimens had a significantly increased number of TSH molecules bound per thyrocyte in comparison both with the corresponding non-autonomous cells and also with tissues from non-functioning thyroid neoplasms (n = 6). The increased TBD of AFTT persisted after transplantation onto nude mice. The paranodular tissue from thyroid glands with scintigraphically compensated adenomas showed in four out of six cases an increased TBD when compared with normal thyroid tissue. It can be concluded that AFTT possesses distinct cytoplasm membrane characteristics as evinced by TSH binding analysis. Increased TSH binding should be considered as a possible cause of metabolic hyperactivity of AFTT cells. The concomitant existence of functional autonomy in the paranodular tissue might lead to a false supposition of a compensated autonomous adenoma as revealed by scintigraphical evidence.

Adenoma↗

Assessing the need for frozen sections: still a valuable tool in thyroid surgery.

BACKGROUND: Since the development of fine-needle aspiration (FNA) there has been a trend away from frozen sections (FS) in the assessment of thyroid neoplasms. The objective of this study was to determine the role of FS in the surgical management of thyroid nodules in the presence of an adequate FNA biopsy finding. METHODS: Charts of patients who presented within a 3-year period for thyroid surgery were reviewed. Inclusion criteria consisted of both an adequate FNA and FS. RESULTS: Eighty-five patients met the inclusion criteria. Three lesions were benign, 71 were suspicious, and 11 were malignant with FNA. There were 66 deferred and 19 malignant diagnoses with FS. The overall accuracy for FNA and FS was 40% and 86%, respectively. When the FNA report was positive for malignancy, it was correct in 91% (10 of 11) of the cases. When the FNA report was suspicious, only 30% (21 of 71) had a malignant lesions. FS confirmed malignancy in 19 patients and deferred more extensive surgery in 66 patients with suspicious lesions. However, 18% of the deferred FS were found to be malignant on final pathology report. CONCLUSIONS: This study showed that there is a role for FS in the surgical management of thyroid nodules. Frozen sections can be useful when the FNA report is suspicious for malignancy; however, FS may be eliminated when the FNA report is positive for malignancy.

Adolescent↗

Thyroid cancer in the renal transplant population: epidemiological study.

BACKGROUND: The epidemiology of thyroid neoplasms in the renal transplant population has not been widely published. The present study compares the behaviour of thyroid cancer in the transplant cohort with that of the general population. It also documents the transplantation outcomes of patients with thyroid and non-thyroid cancers. METHODS: All recipients of renal grafts are registered with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Data were obtained from this institution and analysed using Microsoft Excel and Stata statistical software. Risk ratio, attributable risk, Mann-Whitney test, and the Kaplan-Meier survival probability were calculated. RESULTS: Between 1963 and 31 March 2002, 23 (0.22%) patients were diagnosed with thyroid cancer from a cohort of 10,689 renal transplant recipients. The median age in the renal-transplant thyroid cancer group was 48.2 years (range: 23-67 years), and there were 11 (48%) male patients, compared to 26% of thyroid cancer patients in the general population (P = 0.02). The median time to thyroid cancer diagnosis after transplantation was 68 months (range: 3-253 months) compared to 102 months (range: 3-363 months; P = 0.004) in non-thyroid cancers. Ten patients (43%) were found to have lymphatic metastasis, eight of whom presented at the time of primary diagnosis. The risk ratio (RR) was 5.2 (95% confidence interval: 2.0-16.6), with an attributable risk of 17.4 cases per 10,000. There were two cancer-related deaths resulting in a survival probability of 89% at 5, 10 and 15 years. CONCLUSIONS: There is a higher incidence of thyroid cancer and an altered sex distribution in the renal transplant population. A significant proportion presents with lymphatic metastasis requiring lymph node dissection and radioactive iodine treatment.

Adult↗

Hürthle cell medullary carcinomas of the thyroid gland.

Two medullary carcinomas of the thyroid (MCTs) composed entirely of Hürthle (oncocytic or oxyphilic) cells and containing follicular structures are described. Immunocytochemical analysis showed these tumours to be calcitonin-, carcino-embryonic antigen- and neuron-specific enolase-positive. The essence of this communication is twofold. Firstly, it highlights and draws attention to this unusual variant of MCT, which may be encountered at frozen section and misdiagnosed as a Hürthle cell tumour of follicular cell origin. Secondly, it undertakes a concise overview of the immunocytochemistry of Hürthle cell thyroid neoplasms and MCT.

Aged↗

Renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. A case report.

BACKGROUND: Renal cell carcinoma is an unpredictable tumor that can recur many years after the original diagnosis and metastasize to uncommon sites, including the thyroid gland. Differential diagnosis from primary thyroid tumor is often difficult both clinically and pathologically. We report a case of metastatic renal cell carcinoma in follicular adenoma of the thyroid gland. CASE: A 48-year-old woman presented with a 3-cm-diameter, palpable mass in the left lobe of the thyroid gland. The patient's history included removal of a left renal mass, which was conventional renal cell carcinoma. Fine needle aspiration cytology smears contained a few small clusters of polygonal cells with abundant, clear cytoplasm and irregular, hyperchromatic nuclei as well as bland-looking thyroid follicle cells and stromal cells. A papillary or follicular growth pattern was not detected. A cell block made from the aspirated sample was composed mainly of clear cells. By immunohistochemical stains, the clear cells were completely negative for TTF-1, thyroglobulin, calcitonin and inhibin while equivocally staining for cytokeratin, CD10 and galectin-3. The histologic diagnosis was renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. CONCLUSION: Renal cell carcinoma metastatic to the thyroid may masquerade as a primary thyroid neoplasm. A history of prior nephrectomy, the presence of unremarkable thyroid follicle cells, the absence of a papillary or follicular growth pattern and immunohistochemical study can help differentiating metastatic renal cell carcinoma from a primary thyroid lesion with clear cell change.

Adenoma↗

Immunohistochemical demonstration of ras p21 oncogene product in normal, benign, and malignant human thyroid tissues.

The p21 protein product of the cellular oncogene ras, designated ras p21, has been detected immunohistochemically in normal, benign and malignant human thyroid tissues. With the monoclonal antibody RAP-5 generated against a synthetic peptide corresponding to amino acid positions 10 to 17 of the ras p21 protein and an avidin-biotin-peroxidase complex (ABC), the expression of the ras p21 was evaluated in paraffin-embedded sections. Western blot analysis using fresh thyroid carcinoma tissue revealed double protein bands, one band was at molecular weight 21,000 and the other was a more rapidly migrating band at the molecular weight 17,500. Immunohistochemically, papillary adenocarcinomas of the thyroid showed moderate to intense stainings for ras p21 in most cases. Cytoplasmic and apical surface stainings were the most common patterns of immunoreactivity. Adenomas showed variable ras p21 positivity in cytoplasm and apical surface stainings of adenomas were negative to borderline in most cases. The cytoplasm of tissues of Hashimoto's thyroiditis, Graves' disease, and normal thyroid tissues was uniformly ras p21 positive, but the apical cell surface was nonreactive for ras p21 in all tissues. Judging from the findings obtained on this large series of normal, benign, and malignant thyroid tissues, the elevation of ras p21 may be a common event in thyroid neoplasm, and especially elevated ras expression in the apical cell surface may be characteristic to papillary carcinomas of the thyroid. This suggests that apical surface expression of ras p21 may be important in the development of thyroid carcinomas and be useful in differentiation of papillary adenocarcinoma.

Adult↗

Expression of the cadherin-catenin complex in well-differentiated human thyroid neoplastic tissue.

E-cadherin is a member of the cadherin family that plays a major role in epithelial integrity and tumorigenesis. Catenins are a group of cytoplasmic proteins that regulate the intracellular anchorage of cadherin and are required for the linkage between cadherin and the actin cytoskeleton. Loss of E-cadherin contributes to the pathogenesis in tumor invasion and gives a poor prognosis. In order to investigate the adhesion property of intercellular junctions in thyroid tumors, expression of alpha-,beta, and gamma-catenin should also be studied. A correlation between these molecular markers and malignancy would be useful as a preoperative diagnostic test for thyroid neoplasms. The expression of E-cadherin, alpha-, beta-, and gamma-catenin were studied in normal and neoplastic thyroid tissue by immunofluorescence microscopy and Western blot analysis. In the normal thyroid and in nodular goiter, and follicular adenoma, staining for E-cadherin, alpha-, beta-, and gamma-catenin was seen mainly at the lateral surface of epithelial cells in the follicle and the presence of these molecules was confirmed by Western blot analysis. Follicular carcinoma tissue stained positive for E-cadherin and alpha-catenin, but the results of beta- and gamma-catenin immunostaining were highly variable, with beta-catenin being absent in most follicular carcinomas (8/10) and gamma-catenin being absent in some follicular carcinomas (3/10). These results suggest that E-cadherin expression was not reduced during the pathogenesis of differentiated thyroid malignancies. Impairment of the cadherin-catenin complex at the cell junction may contribute to the malignant progression of differentiated thyroid neoplastic tissue.

Adult↗

Polo-like kinase 1 overexpression is an early event in the progression of papillary carcinoma.

Polo-like kinase 1 (PLK1) is one of the serine threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. We investigated PLK1 expression in various thyroid neoplasms in order to elucidate its physiological significance in thyroid carcinoma. Normal follicular cells only occasionally expressed PLK1. In follicular tumours and anaplastic carcinoma, PLK1 overexpression was not a common event and only 5.9% of follicular adenoma, 7.1% of follicular carcinoma, and 11.8% of anaplastic carcinoma overexpressed this protein. However, 43.7% of papillary carcinoma overexpressed PLK1. Polo-like kinase 1 overexpression was more frequently observed in smaller papillary carcinoma lesions, and 62.5% of microcarcinoma (ranging from 4 mm to 1.0 cm) and even 66.7% of incidental carcinoma (less than 4 mm) overexpressed it, whereas this phenomenon could only be seen in 20.0% of lesions larger than 4.0 cm. Furthermore, PLK1 overexpression was not related to cell-proliferating activity evaluated by Ki-67 labelling index, but it was inversely linked to UICC stage, extrathyroidal invasion, and the presence of poorly differentiated lesion as proposed by Sakamoto et al. These findings strongly suggest that, unlike other carcinomas previously studied, PLK1 does not act as a cell cycle regulator but plays a constitutive role in papillary carcinoma especially in the early phase, and may contribute to the malignant transformation of this carcinoma.

Blotting, Western↗

Mutation analysis of protein kinase A catalytic subunit in thyroid adenomas and pituitary tumours.

OBJECTIVE: The adenylyl cyclase system plays an important role in the control of both thyroid follicular and anterior pituitary cell function. Activating mutations affecting important pathway components such as the TSH receptor and Gsalpha occur in the majority of autonomously functioning thyroid nodules. Only a small proportion of other types of thyroid tumours, however, have been reported to harbour these mutations. Activating mutations of Gsalpha have been reported to occur in up to 40% of pituitary somatotroph adenomas. As the majority of cold thyroid nodules and pituitary tumours are unaffected by these mutations, we have investigated the possibility of activating mutations occurring in protein kinase A (PKA), which is another key component of the adenylyl cyclase pathway. DESIGN: Genomic DNA and cDNA were analysed for the presence of PKA Calpha mutations by allele-specific oligonucleotide hybridisation and single strand conformation polymorphism analysis. PATIENTS: A total of 171 tissue samples were investigated. These comprised 66 benign and 24 malignant thyroid neoplasms, 21 somatotroph adenomas, 35 non-functioning pituitary adenomas, 2 corticotroph adenomas, 1 malignant prolactinoma, and 22 normal pituitary tissue samples. RESULTS: No mutations of PKA Calpha were identified using either allele-specific oligonucleotide hybridisation or single strand conformation polymorphism analysis. CONCLUSIONS: It appears that PKA Calpha mutations at the codons investigated do not represent an oncogenetic mechanism in the development of thyroid and pituitary neoplasms.

Adenoma↗

Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor.

Data on the expression of interleukin 6 (IL-6)/interleukin 6 receptor (IL-6R) in thyroid nodules is scarce. Based on our recent data of CD30 ligand (CD30L)/CD30 receptor (CD30) in these nodules and on the knowledge that this signal stimulates IL-6 production in non-thyroid neoplasms, we wanted to evaluate the immunocytochemical expression of these 2 ligand/receptor systems in a large archival series of paraffin-embedded specimens. These specimens included 6 normal thyroids and 130 thyroid nodules. Co-expression of IL-6 and IL-6R in the epithelial (follicular) cells was observed solely in CD30L/CD30 positive nodules: 5/15 (33%) oncocytic adenomas; 6/30 (20%) follicular adenomas which belonged to 2 variants (4/4 microfollicular toxic and 2/2 hyalinizing trabecular); 9/30 (30%) papillary thyroid cancers (PTC), all belonging to the conventional variant. In PTC the proportion of tumor epithelial cells that were IL6 positive was inversely correlated with the pTNM staging (r=-0.549, p=0.01). All 15 follicular cancers (FTC), all 6 anaplastic cancers (ATC) were IL-6/lL-6R negative; 14/15 FTC and 5/6 ATC were CD30L/CD30 negative. In another oncocytic adenoma, another 4 conventional PTC and another 7 non-conventional PTC CD30L/CD30 expression was associated to expression of IL-6 only. IL-6 staining associated to absent expression of CD30L and CD30 was observed in 7 follicular adenomas (all belonging to variants different from toxic and hyalinizing trabecular), 2 oncocytic adenomas, 5 of the 30 colloid nodules and 2 normal thyroids. Of the 6 tumors arising from the parafollicular C cells (medullary thyroid cancer, MTC), all 3 that had metastasized were CD30L/CD30/IL-6 positive and IL-6R negative; only IL-6 expression was lost in both the local and distant metastases. This finding matched the loss of IL-6 expression in one PTC metastasis. All 3 non-metastasized MTC were IL-6/IL-6R negative, and 1/3 was CD30L positive/CD30 negative. We conclude that only in a subset of both benign and malignant thyroid nodules the IL-6/IL-6R signal could be induced by the CD30L/CD30. IL-6 expression is related with aggressiveness in both PTC and MTC. In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30.

Adenocarcinoma, Follicular↗

[Thyroid cancer: anatomy and pathologic histology].

Current pathological classifications of thyroid carcinoma only partially reflect the radical changes in our knowledge of these tumors, due to a large series of clinicopathological studies carried out over the past few years. Based on a critical review of this growing body of information concerning malignant thyroid neoplasms, a working formulation for clinical usage is proposed. This scheme has been adopted to classify 1339 consecutive cases of thyroid carcinoma observed at the Pathology Institute of the University of Florence between June 1966 and December 1993. The clinical implications of newer classification systems with regard to diagnosis, treatment and outcome of thyroid carcinoma are also discussed.

Adenocarcinoma↗

Primary papillary thyroid carcinoma presenting as cervical lymphadenopathy: the operative approach to the "lateral aberrant thyroid".

In contrast to a few follicles arranged in a wedge-shaped segment at the periphery of a lymph node, a significant amount of thyroid tissue in a cervical lymph node is considered evidence of metastatic thyroid carcinoma. In a consecutive series of 243 patients with papillary carcinomas, 52 presented with lateral cervical masses that proved to be lymph nodes with metastatic thyroid carcinoma, in the absence of readily palpable thyroid nodularity. The metastatic disease was demonstrated by excisional biopsy in 40 patients and fine needle aspiration cytology in 12 patients. Thirty-two (of the 52) underwent further diagnostic work-up, consisting of radionuclide scintigraphy and ultrasonography, with the demonstration of abnormalities consistent with a thyroid neoplasm in 75 per cent (24/32) of these patients. The remaining 20 patients had no additional studies except for chemical thyroid function evaluation. The operative treatment in all 52 patients was total thyroidectomy and unilateral or bilateral modified neck dissections, when extensive cervical adenopathy was encountered. Papillary thyroid carcinoma, ranging in size from 2 to 14 mm, was found in the lobe ipsilateral to the presenting cervical node metastasis, in all specimens. In addition, contralateral cervical lymph node metastases were found in five (10%) of these patients, with no evidence of thyroid carcinoma in the corresponding thyroid lobe. With a mean follow-up period of 9 years, all patients are alive with no evidence of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hürthle cell and/or apocrine-like changes.

BACKGROUND: We have recently observed that Hürthle cell tumours and papillary thyroid carcinoma with tumour cells showing decapitation of luminal portion of the cytoplasm (apocrine-like changes) display negative or decreased immunoreactivity for HBME. The purpose of this study is to correlate papillary thyroid carcinoma with positive and negative immunoreactivity for HBME with the histopathological features. METHODS AND RESULTS: Two hundred and five thyroid neoplasms including carcinoma and adenomas were grouped into Hürthle cell tumours, tumours with or without some features of Hürthle cells, tumours with apocrine-like changes and adenomas with or without limited nuclear features of papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma. All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma that have areas of limited nuclear features but not diagnostic for papillary thyroid carcinoma showed stronger immunostaining for HBME than their respective counterparts with Hürthle cell changes. All Hürthle cell tumours showed negative to focal reactivity. This decrease of reactivity for HBME was proportional to the levels of Hürthle cell changes. In addition, focal to extensive apocrine-like changes were seen in most Hürthle cell neoplasms and rarely seen in non-Hürthle cell neoplasms. Apocrine-like changes abolished or decreased HBME immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear features. Immunostaining for cytokeratin AE3 was not affected by Hürthle cell or apocrine-like changes. CONCLUSIONS: All papillary thyroid carcinomas without Hürthle cell or apocrine-like differentiation are reactive for HBME. Hürthle cell tumours and tumours with Hürthle cell or apocrine-like changes show negative or focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker for papillary thyroid carcinoma and tumours with limited nuclear features.

Adenoma, Oxyphilic↗

[Immunohistochemical studies of mononuclear cellular infiltrates of papillary, follicular and anaplastic thyroid cancers].

The mononuclear cellular infiltrate of thyroid neoplasms was examined by immunohistochemical techniques and compared to normal thyroid (control 1) and untreated Graves' disease tissue (control 2). Using a panel of monoclonal antibodies T-, B cells and macrophage antigens as well as the expression of activation-associated antigens and of MHC class II molecules were examined. In comparison to control 1 an increase of positive cells could be detected in carcinomas. This increase was significant for CD3+ and CD8+ T cells, for CD4+ macrophages and for HLA-DP+ cells in all types of carcinomas. In addition, in anaplastic carcinomas a significant increase of B cells, RM3/1+ macrophages, IL-2R+, ICAM-1+ and HLA-DQ+ cells was observed as well as of HLA-DR+ cells in follicular and of CD4+ T cells in papillary carcinomas. A comparison with control 2 revealed a significant increase of CD4+ cells (T cells and macrophages) in papillary and of CD8+ and RM3/1+ cells in anaplastic carcinomas. Our findings, an obvious increase of cell populations and of an upregulated expression of activation-associated antigens on these cells, indicated an immunological reaction caused by neoplastic thyrocytes. Further functional studies are however necessary.

Adenocarcinoma, Follicular↗

Radioiodine-associated thyroid cancers.

Numerous investigations document that exposure to low dose external therapeutic radiation leads to the development of benign and malignant thyroid neoplasms. There is considerable controversy, however, concerning whether radioactive iodine (131I) causes thyroid cancer. The aim of this investigation was to examine our experience and that in the literature related to this problem. From 1982 to March 1993 seven of 373 patients (1.9%) with thyroid cancer who were treated by one surgeon had a history of treatment with radioactive iodine for Graves' disease and toxic nodular goiter. Sixty-five patients have previously been reported in the literature from 1957 to present. Our patients (five women, two men) ranged in age from 26 to 80 years (mean 57 years). The interval between the exposure to the internal radiation and development of cancer ranged from 3 to 29 years (mean 11.4 years), and the mean age at the time of 131I treatment was 45 years (18-76 years). The therapeutic dose of 131I was 5 to 100 mCi (mean 25.3 mCi) in our patients. Two of our patients received 131I twice. The age of patients reported in the literature at the time of 131I treatment ranged from 7 to 74 years (mean 48 years). The mean therapeutic dose of 131I was 20.6 mCi (1.25-180.0 mCi) and the latent period was documented for a mean 8.7 years (0.25-28.0 years) in these patients. Three of 29 patients in the literature received 131I twice. Fine-needle aspiration cytology of thyroid nodules was positive for cancer in six of our patients (86%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular↗