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PubMed2006

Thyroid disease associated with exposure to the Nevada nuclear weapons test site radiation: a reevaluation based on corrected dosimetry and examination data.

BACKGROUND: A study was begun in 1965 to 1966 to determine whether children exposed to radioactive iodine from nuclear weapons testing at the Nevada Test Site from 1951 through 1962 were at higher risk of thyroid disease. In 1993, we reported that among those examined in 1985 to 1986 (Phase II) there was an association between radiation from the Nevada Test Site and thyroid neoplasms. METHODS: We reevaluated the relationship between exposure to Nevada Test Site fallout and thyroid disease using newly corrected dose estimates and disease outcomes from the Phase II study. A prospective cohort of school children 12 to 18 years old living in Utah, Nevada, and Arizona was first examined for thyroid disease in 1965 to 1966 and reexamined in 1985 to 1986. In the Phase II report, 2497 subjects formed the basis for this analysis. Thyroid disease, including thyroid neoplasms and thyroiditis, was expressed as cumulative incidence and risk ratios (RRs) with a dose-response expressed as excess risk ratio (ERR/Gy). RESULTS: The RR between thyroid radiation dose in the highest dose group and thyroid neoplasms increased from 3.4 (in the earlier analysis) to 7.5. The RR for thyroiditis increased from 1.1 to 2.7 with an ERR/Gy of 4.9 (95% confidence interval = 2.0 to 10.0). There were too few malignant thyroid neoplasms to estimate risk. CONCLUSIONS: Persons exposed to radioactive iodine as children have an increased risk of thyroid neoplasms and autoimmune thyroiditis up to 30 years after exposure.

Adolescent↗
PubMed1986

Enzyme histochemistry and thyroid neoplasia.

The authors have examined the enzyme histochemical staining of surgically removed human thyroid tissue in an attempt to identify markers that might be useful in the histopathologic diagnosis of thyroid neoplasms. Fresh thyroid glands and other tissues were fixed in cold (4 degrees C) 4% paraformaldehyde and embedded in glycol methacrylate. Forty-two specimens were studied in thin sections, which gave excellent histologic detail and enzyme preservation. Cytologic detail was similar to that in Papanicolaou-stained smears, with good definition of nuclear inclusions and grooves, particularly in cases of papillary carcinoma. The enzyme histochemical reactions studied were as follows: adenosine triphosphatase, alkaline and acid phosphatases, alpha-naphthyl acetate esterase, and 5'-nucleotidase. Thyroid epithelial cells and the benign neoplasms derived from them were typically positive for 5'-nucleotidase, alpha-naphthyl acetate esterase, and acid phosphatase, and negative for adenosine triphosphatase and alkaline phosphatase. Staining for adenosine triphosphatase was present in papillary and follicular carcinomas and was seen in benign glands only under certain circumstances such as Graves' disease. The adenosine triphosphatase reaction therefore appears to be helpful in distinguishing between benign and malignant neoplasms derived from thyroid epithelium in humans and may be a useful adjunct to routine morphology.

5'-Nucleotidase↗
PubMed2004

Latency period of thyroid neoplasia after radiation exposure.

OBJECTIVE: To determine the temporal sequence for developing benign and malignant thyroid neoplasms after radiation. SUMMARY BACKGROUND DATA: Therapeutic radiation is associated with thyroid neoplasms in humans and animals. Some question whether thyroid cancers develop de novo or from benign thyroid neoplasms. Little information, however, is available concerning the time to development of benign and malignant thyroid neoplasms after radiation exposure. METHODS: We retrospectively analyzed the records of 171 consecutive patients who had a history of exposure to radiation and were treated surgically at University of California, San Francisco-affiliated hospitals for thyroid neoplasms between 1960 and 1999. RESULTS: There were 66 men and 105 women aged 9 to 80 years (mean, 47.0 years). One hundred patients had benign and 71 had malignant tumors (58 papillary cancers, 10 follicular cancers, 1 Hurthle cell cancer, 1 medullary cancer, and 1 carcinosarcoma). The mean latency period for benign tumors was longer than that for malignant lesions (mean, 34.1 and 28.4 years, P = 0.018; median, 38.0 years and 30.0 years, P = 0.001). Follicular carcinomas developed sooner (mean, 20.5 years; median, 20 years) than did follicular adenomas (mean, 35.3 years; median, 36.5 years; P = 0.003, P = 0.0009). Patients with papillary thyroid cancers presenting as occult papillary cancers (<1 cm) and as a dominant nodule had similar latency periods (mean, 34.0 and 28.0 years P = 0.29; median, 37.5 and 30.5 years, P = 0.09), respectively. CONCLUSION: Although there could be selection bias regarding referral of patients, our data document that malignant thyroid tumors after radiation exposure, including follicular carcinomas, present earlier than do benign thyroid tumors. Occult and manifest papillary thyroid cancers present at about the same time interval after radiation exposure. Our findings question whether benign thyroid neoplasms progress to malignant thyroid neoplasms and that most occult thyroid cancers do not progress to malignant thyroid cancers in radiation-exposed patients.

Age Factors↗
PubMed1983

Characterization of the thyrotropin receptor-adenylate cyclase system in neoplastic human thyroid tissue.

Experiments were performed to determine whether the TSH receptor-adenylate cyclase (AC) system in benign and malignant thyroid neoplasms differs from the TSH receptor-AC system in normal thyroid tissue removed from the same patients. TSH binding and AC assays were performed using the same in vitro conditions. TSH binding was rapid, reversible, saturable, and hormone specific in particulate fractions from both normal and neoplastic thyroid tissue. A positive correlation existed between the equilibrium constants for [125I]bovine ([125I]bTSH) TSH binding and the concentration of TSH required to activate AC, suggesting that binding sites were coupled to AC in neoplastic thyroid tissue. Mean values for dissociation constants (Kd1 and Kd2), capacity (site 2), as determined by Scatchard analysis, and nonspecific binding (NSB) for the TSH receptors were lower in neoplastic thyroid. Some normal thyroid tissue appeared to lack a high affinity site, and some tumors lacked a low affinity binding site. Hormone specificities (bTSH, human (h) TSH, hLH, hFSH, hGH, hACTH, and glucagon) in normal thyroid and neoplastic tissue were virtually identical. hFSH, hACTH, hGH, and glucagon failed to inhibit [125I]bTSH binding or stimulate AC in either normal or neoplastic thyroid tissue, whereas hLH inhibited [125I]bTSH binding and stimulated AC, but required 10- to 100-fold higher concentrations than hTSH or bTSH. The specific binding and NSB of [125I]bTSH in both normal and neoplastic thyroid tissue was highest at pH 7.0 and lowest at pH 8.3. In contrast to bTSH binding, TSH stimulation of AC was lowest at pH 7.0 in both normal and neoplastic tissues and highest at pH levels of 7.5-8.0. TSH binding and TSH stimulation of AC activity were highest in the absence of NaCl and decreased progressively as the salt concentration was increased in both normal and neoplastic thyroid tissues. Increasing the sucrose concentration and, thus, the osmolarity of the system had a minimal effect on the binding of [125I]bTSH. Preincubation with ammonium sulfate did not significantly influence binding. Basal AC activity and the AC response to TSH were greater in neoplastic thyroid than in normal tissues. These studies demonstrate that changes in salt concentration and pH affect the TSH receptor-cyclase system in a comparable fashion in normal and neoplastic thyroid tissues. The discriminatory properties of the TSH receptor are also maintained in thyroid neoplasms. Thyroid tumors, however, have a higher affinity for TSH and display a greater AC response to TSH than normal thyroid tissue.

Adenylyl Cyclases↗
PubMed1993

Immunohistochemical identification of receptors for epidermal growth factor in tumor endothelium may be affected by cross-reactivity to blood group A antigen.

It has been reported that endothelium in malignant glioma stains with a commercial antibody raised against the receptor for epidermal growth factor (EGFr) on A431 cells (clone 29.1). In this report, this antibody was used to study the immunohistochemical expression of EGFr in benign and malignant ovarian, mid-gut carcinoid, and thyroid neoplasms using the avidin-biotin-peroxidase complex technique. Eighteen of the 37 ovarian neoplasms, 4 of the 10 thyroid neoplasms, and 14 of 28 mid-gut carcinoid tumors expressed strong and distinct endothelial staining, whereas staining results of the remaining tumors were negative. The endothelial nature of the staining was verified by staining serial sections with Ulex europaeus agglutinin-I. The staining was independent of that obtained with an antibody raised against a synthetic peptide consisting of residues 985 to 996 from the cytoplasmic domain of EGFr (clone F4). All positive staining occurred in patients determined to be of blood groups A or AB, whereas samples from patients with blood groups B or O were negative. Immunoabsorption of the antibody with centrifuged erythrocytes from a blood group A donor, but not from a blood group B donor, abolished the positive staining. The data indicate that positive staining of tumor endothelium with this antibody is due to cross-reactivity with blood group A antigen. The results obtained challenge the validity of previously performed immunohistochemical studies in which monoclonal antibodies raised against the EGFr of A431 cells have been used, and in which the epitope for the monoclonal antibody has not been determined.

ABO Blood-Group System↗
PubMed2004

Oncocytic parathyroid adenoma: problem in cytological diagnosis.

Parathyroid lesions, which may occur within the thyroid, may clinically simulate thyroid nodules. Fine-needle aspiration (FNA) of these presumably "thyroid nodules" can lead to misinterpretation of cytomorphological findings because of similarities in cytological features of neoplastic and nonneoplastic parathyroid and thyroid lesions. This might be true especially for oncocytic parathyroid adenomas and parathyroid adenomas with prominent oncocytic component that, although rare, tend to be large and often are associated with minimal hyperparathyroidism. We report two cases of this type of clinically "silent" parathyroid adenomas that on FNA were diagnosed as Hurthle cell thyroid neoplasm.

Adenoma, Oxyphilic↗
PubMedDate not supplied

Functional parathyroid carcinoma. Cytology, histology, and ultrastructure of a case.

A case of a functional parathyroid carcinoma that recurred 1 year after being resected is presented. The clinical and laboratory data and the histologic structure are presented with confirmatory electron microscopy. The preoperative aspiration biopsy showed findings suggestive of parathyroid carcinoma although simultaneous core biopsy results were reported as parathyroid adenoma. The differential cytologic diagnosis with thyroid neoplasms is discussed.

Adenoma↗
PubMed1981

Pulsatile sternal tumor: report of three cases and a review of the literature.

At our institution, 3 patients with pulsatile sternal tumor have been seen. Although ascending aortic aneurysm frequently is high on the list of differential diagnoses, the likelihood that this tumor is metastatic from either a primary renal or thyroid neoplasm is overwhelming. Of the 15 patients reported, 11 had metastases from a primary renal cell carcinoma, including all 3 of our patients. There were 2 patients with primary myeloma, the only histologically proved primary pulsatile sternal tumor. From the surgical standpoint, only the patient with metastatic renal cell carcinoma has a chance of cure. With the recent report of 2 5-year survivors and our own experience of 1 patient with a long asymptomatic interval following resection of the primary kidney tumor and the secondary sternal metastasis, the attitude of hopelessness for these patients should be challenged and an aggressive approach considered.

Adult↗
PubMed2004

Overexpression of urinary plasminogen activator (uPA) protein and mRNA in thyroid carcinogenesis.

OBJECTIVE: Urinary plasminogen activator (uPA), a protease, is one of the critical components of tumor invasion and metastasis. Its expression in thyroid carcinoma and potential role in thyroid tumorigenesis are unknown. The objective of this study was to determine whether uPA is differentially expressed in benign and malignant thyroid tumors. DESIGN: uPA expression was evaluated by immunohistochemistry (IHC) in 20 thyroid tumors (six classic papillary thyroid cancers (PTC) and three tall cell variants (TCV) and 11 adenomas). To validate IHC results, in situ hybridization was performed on both adenomas and cancer tissues to explore the expression of uPA at the mRNA level. The Fisher exact test was used to compare protein as well as mRNA expressions in adenomas and thyroid cancer. RESULTS: Intense granular cytoplasmic staining for uPA was observed in five of nine (56%) of thyroid cancers: 2/6 classic PTC (33%) and all tall cell variant PTC. Furthermore, uPA mRNA expression was found in the malignant thyroid epithelium but not in adjacent normal thyroid follicles or the stromal elements. None of the adenomas expressed uPA (P = .008). uPA staining was absent in histologically normal follicles adjacent to malignant thyroid follicles. CONCLUSIONS: uPA is expressed in thyroid carcinoma but not in benign adenomas or normal adjacent follicles. The selective expression of uPA in thyroid carcinoma provides evidence that uPA is useful in distinguishing benign and malignant thyroid neoplasms. More importantly, uPA may represent molecular target for therapeutic treatment of this malignancy.

Adenocarcinoma, Papillary↗
PubMed1999

Tumor-to-tumor metastasis to follicular variant of papillary carcinoma of thyroid.

OBJECTIVE: To describe and document tumor-to-tumor metastases in the thyroid gland. METHODS AND RESULTS: In this series we describe 3 cases of tumor-to-tumor metastasis in which the recipient tumor was a follicular variant of papillary thyroid carcinoma. The donor tumors and sites were small cell carcinoma of the lung, neuroendocrine carcinoma probably of pancreatic origin with initial presentation as liver metastasis, and clear cell carcinoma of the kidney with metastasis to liver and pancreas. The donor tumor cells infiltrated the substance of the follicular variant of papillary thyroid carcinoma, the nontumorous thyroid parenchyma, and the lymphovascular spaces. Small cell carcinoma and neuroendocrine carcinoma showed positive reactivity for neuroendocrine markers and were negative for thyroglobulin and calcitonin. The follicular variant of papillary thyroid carcinoma showed positivity with thyroglobulin and cytokeratin 19. CONCLUSIONS: Although tumor-to-tumor metastases in thyroid gland are exceedingly rare, one should be aware of this phenomenon as the metastatic lesion may simulate a thyroid primary. History of a previous tumor and immunohistochemical stains can be helpful in distinguishing between primary and metastatic thyroid neoplasms.

Adenocarcinoma, Clear Cell↗
PubMed1998

Immunohistochemical staining for bcl-2 and mcl-1 in intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) and cervical thymic carcinoma.

Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE), a rare thyroid neoplasm, was recently shown to be immunoreactive for CD5, providing immunophenotypic evidence of previously postulated thymic differentiation. To assess whether ectopic malignant neoplasms with thymic differentiation display other markers associated with thymic carcinoma, we studied five cases of ITET/CASTLE, two cases of cervical thymic carcinoma, and one case of cervical thymoma for bcl-2 and mcl-1 immunoreactivity. Both of these antiapoptosis proto-oncogenes have been reported to be expressed by the majority of true thymic carcinomas but only a minority of thymomas. All of the five cases of ITET/CASTLE, both CD5-positive cervical thymic carcinomas, and one CD5-negative cervical thymoma were immunoreactive for bcl-2, as were 10 (91%) of 11 thymic carcinomas arising in the thymus, in contrast to 6 (25%) of 24 benign and invasive thymomas arising in the thymus. Similarly, all of the five cases of ITET/CASTLE, both cervical thymic carcinomas, but not the cervical thymoma, were immunoreactive for mcl-1, as were 9 (90%) of 10 thymic carcinomas, in contrast to 6 (33%) of 18 benign and invasive thymomas. We conclude that dual immunoreactivity for bcl-2 and mcl-1 is a feature of malignant neoplasms with thymic differentiation in general, both within the thymus and at ectopic sites.

Adult↗
PubMed2000

Metalloproteinase-9 immunoexpression and angiogenesis in thyroid follicular neoplasms: relation to clinical and histopathologic features.

BACKGROUND: Thyroid follicular neoplasms (adenoma and carcinoma) may pose considerable difficulties to the differential diagnosis. Because such a distinction is not possible at fine-needle aspiration, surgery is often necessary. Clinical information such as age, sex, and node size is important in case of suspected carcinoma. Follicular carcinoma is characterized by capsular invasion, vascular invasion, and metastatic dissemination mainly by the hematogenic pathway. This invasion depends on collagen degradation in capsule and in subendothelial basement membrane. Collagen degradation has been widely researched in the angiogenesis process and in the hematogenic dissemination mechanism. In this study, we performed clinical and histopathologic assessment of 74 follicular neoplasms, as well as immunohistochemical reactions for CD-34 protein to estimate angiogenesis and for metalloproteinase-9, an enzyme that degrades type IV collagen. METHODS: The research was carried out retrospectively in 74 patients who had surgery and were followed up at HC-FMUSP and IBCC. Clinical, histologic, and immunohistochemical variables were compared among the groups of follicular neoplasms and a control group of 36 patients with colloid goiter. RESULTS: No significant statistical difference was found between patients with follicular adenoma and thyroid follicular carcinoma concerning sex (p =.092), age (p =.098), thyroid node size (p =.426), vascularization (p =.388), and immunostaining intensity for metalloproteinase-9 (p =.055). The proportion of immunoreactive cells for metalloproteinase-9 in follicular carcinoma cases was higher than that observed in follicular adenoma cases (p <.001). Patients in more advanced stages of carcinoma were more than 45 years old (p =.006), presented extensive invasion (p <.001), had less vascularization (p =.046), and a had higher proportion of immunoreactive cells for metalloproteinase-9 (p <.001). CONCLUSIONS: The proportion of immunoreactive cells for metalloproteinase-9 in follicular carcinoma was higher than that observed in follicular adenoma, with a significant statistical difference (p <.001). This method must be developed to apply in material obtained by fine-needle aspiration to differentiate follicular adenoma from carcinoma.

Adenocarcinoma, Follicular↗
PubMed1998

Expression of p27kip1 and Ki-67 in benign and malignant thyroid tumors.

Thyroid neoplasms represent a broad spectrum of tumors with different biologic behaviors. The majority of these tumors can be readily diagnosed by characteristic histopathologic features, but the distinction between follicular adenomas and follicular carcinomas can be difficult. Recent studies with cell cycle proteins such as p27kip1 (p27), a cell cycle inhibitory protein, and Ki-67, a proliferation marker, suggest that these markers might be useful in predicting the behavior of various neoplasms. We analyzed 95 thyroid lesions (16 follicular adenomas, 23 follicular carcinomas, 22 papillary carcinomas, 27 anaplastic carcinomas, plus 7 non-neoplastic thyroids [NNTs], used as a control group) for expression of p27 and Ki-67 by immunostaining. The distribution of immunoreactivity was analyzed by quantifying nuclear staining in each case without knowledge of the diagnosis or outcome. Clinical history and follow-up information were obtained by chart review. There were significant differences in the expression of p27 between follicular adenomas (labeling index [LI] = 47.9+/-5.6) and follicular carcinomas (LI = 15.7+/-2.0). Papillary carcinomas (LI = 11.6+/-3.0) and anaplastic carcinomas (LI = 9.4+/-1.7) had p27 LIs similar to that of follicular carcinomas; the NNT group had the highest p27 LI (74.1+/-4.9). The Ki-67 LI of anaplastic carcinomas (57.6+/-3.8) was more than threefold greater than that of any other group. Logistic regression showed that p27 was effective in distinguishing follicular adenomas from follicular carcinomas (P = .0056) and that Ki-67 could also distinguish follicular adenomas from follicular carcinomas (P = .0060). Analysis of follicular carcinomas with and without metastases showed significantly higher expression of Ki-67 in patients with metastases (P = .0019). These results indicate that antibodies to p27 and Ki-67 might be useful in distinguishing between thyroid neoplasms that are difficult to diagnose by the usual histopathologic criteria.

Adenocarcinoma, Follicular↗
PubMed2005

Flow pattern and vascular resistive index as predictors of malignancy risk in thyroid follicular neoplasms.

OBJECTIVES: The purpose of this study was to evaluate whether flow pattern and resistive index (RI) are useful parameters for distinguishing benign from malignant thyroid follicular neoplasms (FNs). METHODS: Eighty-six thyroid nodules that underwent sonographically guided fine-needle aspiration and were diagnosed as cases of FN were evaluated by power and duplex Doppler sonography. Pathologic correlation was available for all nodules. The flow pattern seen via power Doppler examination was ranked for each nodule on a scale of 0 to 4, in increasing flow order. For each nodule, the RI value was considered the average of 1 to 3 values obtained with different flow signals. RESULTS: Ten nodules (11.63%) were malignant (3 follicular carcinomas, 5 follicular variants of papillary carcinoma, and 2 papillary carcinomas). Fourteen nodules (16.27%) were adenomas, and 62 (72%) were non-neoplastic nodules. The average RI in non-neoplastic nodules was 0.588 (P < .001, chi(2) test): 0.662 in adenomas and 0.763 in malignant nodules. None of the nodules had flow pattern type 0. Flow patterns 1 and 2 (peripheral flow only or predominantly) were present in 58 non-neoplastic nodules (93.5%), 10 adenomas (71.4%), and 2 malignant nodules (20%). Flow pattern type 3 (predominantly central flow) was present in 7 malignant nodules (70%), 4 adenomas (28.6%), and 4 non-neoplastic nodules (6.5%). Only 1 nodule, a papillary carcinoma, had flow pattern type 4 (internal flow only). CONCLUSIONS: In FNs, there were significant positive associations between predominantly central flow and malignancy and between predominantly peripheral flow and benign disease (P < .0001, Fisher exact test). However, power Doppler characteristics could not be used to rule out malignancy because 20% of malignant nodules had predominantly peripheral flow. For predicting malignancy, an RI cutoff of 0.75 had good accuracy, specificity, and negative predictive value but had low sensitivity and positive predictive value (respectively, 91%, 97%, 92%, 40%, and 67%). Resistive index values in non-neoplastic nodules were lower than in adenomas and malignant nodules (P < .001, chi(2) test).

Adenoma↗
PubMed1998

Na+/I- symporter distribution in human thyroid tissues: an immunohistochemical study.

Antipeptide antibodies raised against the carboxyl-terminal region of the human sodium/iodide (Na+/I-) symporter (hNIS) were used to investigate by immunohistochemistry the presence and distribution of the hNIS protein in normal thyroid tissues, in some pathological nonneoplastic thyroid tissues, and in different histotypes of thyroid neoplasms. In normal thyroid tissue, staining of hNIS protein was heterogeneous and limited to a minority of follicular cells that were in close contact with capillary vessels. In positive cells, immunostaining was limited to the basolateral membrane. In contrast, in Graves' disease the majority of follicular cells expressed the hNIS protein. In autoimmune thyroiditis, the number of hNIS-positive cells, was similar to that found in normal tissue. These positive cells were found essentially close to lymphocytic infiltrates. This observation supports the concept of hNIS as an autoantigen. In diffuse nodular hyperplasia, hNIS staining was heterogeneous, but the number of hNIS-positive cells exceeded that found in normal tissue. In well differentiated follicular or papillary carcinoma, the number of hNIS-positive cells was significantly lower than in normal tissue. In poorly differentiated follicular carcinoma, the number ofhNIS-positive cells was less than that found in well differentiated carcinoma, or there were no positive cells. Interestingly, in all of these thyroid tissues, the number of follicular cells exhibiting TSH receptor (TSHR) immunoreactivity was greater than the number ofhNIS-positive cells. As hNIS expression appears to be related to TSHR stimulation, the decreased number of TSHR-positive cells in cancers may contribute to the reduced capacity of neoplastic cells to concentrate iodide. In one patient with a follicular cancer with an absence of hNIS immunostaining, the total body 131I scan showed no uptake in metastatic tissue. In three cancers with positive hNIS cells, the 131I scan showed uptake in lymph node metastases. This suggests that immunodetection of hNIS could predict radioiodine uptake in thyroid cancers.

Carrier Proteins↗