[Thyroid function and neoplasms of the breast. Study of the behavior of thyroid function tested with radioactive iodine in 24 cases of malignant breast neoplasms].
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Hurthle cells are found in thyroid neoplasms and in reactive nodules in thyroiditis or goitrogenic processes. Cytometric studies have evaluated Hurthle cell neoplasms but not their reactive counterparts. DNA content of Hurthle cells in 22 cases of autoimmune thyroiditis was measured by flow cytometry and image content of Hurthle cells in 22 cases of autoimmune thyroiditis was measured by flow cytometry and image processing using nuclei extracted from paraffin-embedded tissue after microdissection of the Hurthle cell nodules. All 22 autoimmune thyroiditis Hurthle cell nodules were diploid, including 16 without associated neoplasms and six with associated malignant neoplasms (four papillary carcinomas, one follicular carcinoma and one follicular adenoma with papillary carcinoma). Concordance between flow cytometry and image processing was 100%. These findings indicate that the markedly atypical Hurthle cells in autoimmune thyroiditis are diploid by DNA quantitation. This suggests that atypia in Hurthle cells due to reactive or neoplastic processes may be differentiated by quantitative DNA analysis.
BACKGROUND: Surgical strategy in patients with thyroid cancer (TC) infiltrating the aerodigestive system is controversial. This study was undertaken to examine the long-term results of cervical evisceration (CE). PATIENTS AND METHODS: Since 1995, 14 consecutive patients with advanced TC underwent total laryngectomy (LE, n = 6) or esophagolaryngectomy (ELR, n = 8). Patients with unusual thyroid neoplasms or metastases to the thyroid (n = 3) were excluded. For esophageal reconstruction, free jejunal grafts (n = 6) and gastric tubes (n = 2) were used. RESULTS: Procedure-related morbidity and mortality were 42% and 14%, respectively. ELR was associated with a significant higher frequency of complications and reoperations compared with LE. Twelve-month and 30-month survival rates were 73% and 55%, respectively; 85% of the patients were satisfied with the surgical results. There were no long-term problems concerning food intake in the ELR patients. Two ELR patients were able to learn a substitutive voice. CONCLUSIONS: Cervical evisceration in patients with TC is associated with significant perioperative morbidity and mortality requiring careful patient selection. Regarding long-term survival, local tumor control, and patient's satisfaction, however, CE should be taken into account in suitable patients with advanced TC.
Hürthle cell carcinomas behave as the most aggressive variant of differentiated thyroid carcinoma of follicular origin, with frequent recurrences and higher morbidity. Its differential diagnosis with Hürthle cell adenoma remains a problem for the clinician and for the pathologist. The vertebrate lectins, galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation in thyroid neoplasms. Galectin-3, a beta-galactoside binding protein, has been recently found to be highly expressed in papillary and follicular carcinomas. The current study was undertaken to investigate immunohistochemical reactivity for galectin-3 of thyroid specimen tissues with Hürthle cell adenomas (n = 14) and carcinomas (n = 17), follicular (n = 14) and papillary (n = 11) carcinomas, colloid goiter (n = 30), Hashimoto's thyroiditis (n = 11), follicular adenoma (n = 9), and normal thyroid tissues (n = 18). Follicular (78.5%) and papillary (82.0%) carcinomas were frequently reactive for galectin-3, more often when some H rthle cells were present. There was no galectin-3 immunostaining in any of the specimens from Hashimoto's thyroiditis, colloid goiters or normal thyroid samples, whereas only one case of follicular adenoma was found positive (11.1%). By contrast, galectin-3 immunostaining in Hürthle cell carcinomas was significantly higher (59%) than in H rthle cell adenomas (7.1), p < 0.05). These results suggest that galectin-3 may potentially serve as a marker in difficult differential diagnosis cases involving Hürthle cell adenomas and Hürthle cell carcinomas.
INTRODUCTION: The role of fine-needle aspiration (FNA) and frozen section (FS) in the management of thyroid neoplasms continues to generate considerable controversy. We reviewed our recent experience to determine the clinical utility of FNA and FS in our surgical management and intraoperative decision-making. METHODS: All patients who had operations for thyroid disease between January 1996 and June 1999 were identified in our prospective database. Completion and incidental thyroidectomies were excluded. Data obtained from the pathology files included FNA, FS, and the final histologic diagnosis. RESULTS: Five hundred sixty-four patients, including 409 women (73%), with a median age of 50 years (range, 6-94) were identified, of whom 293 (52%) had cancer diagnosed on permanent sections. Three hundred twenty-nine patients (58%) had evaluable FNA, of which 91 (28%) were benign, 94 were malignant (28%), and 144 (44%) were suspicious (46% of these were malignant on final). Frozen section was performed in 397 (70%) patients; of these samples, 170 (43%) were found to be benign, 106 (27%) were malignant, and 121 (30%) were deferred (46% malignant on final). Fine-needle aspiration positively identified 51% of confirmed malignancies; 13% of patients with malignancy had a benign FNA result. Total thyroidectomy was performed in 64% of malignant tumors and 29% of benign thyroid disease (P < .001). Logistic regression revealed no association of extent of surgery with FNA results. A frozen section positive for malignancy was associated with total thyroidectomy (P < .001, RR 6 [CI 3-10]), and a negative frozen section report was associated with lobectomy (P < .05, RR 0.5 [CI 0.3-0.96]). Frozen sections results altered the preoperative plan in only 29 patients (5%). CONCLUSION: Results of preoperative FNA had no direct impact on the selection of the surgical procedure in this selected cohort. Intraoperative FS added very little to surgical management. The majority of thyroid operations at this institution are planned and performed based on known prognostic factors and intraoperative findings.
We report a patient with unilateral thyroid carcinoma, who developed hyperfunction of the thyroid gland during the metastatic progression of the thyroid carcinoma. Concurrently with this event, TSI increased and it is suggested that the differentiated aggressive metastatic thyroid neoplasm had initiated the autoimmune disorder leading to TSI production and thus to hyperplasia and hyperfunction of the thyroid resulting in hyperthyroidism.
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Thyroid cancer includes three types of carcinomas classified as differentiated thyroid carcinomas (DTC), medullary thyroid carcinomas, and undifferentiated carcinomas (UTC). DTC and medullary thyroid carcinomas generally have a good prognosis, but UTC are usually fatal. Consequently, there is a need for new effective therapeutic modalities to improve the survival of UTC patients. Here we show that NF-kappa B is activated in human thyroid neoplasms, particularly in undifferentiated carcinomas. Thyroid cell lines, reproducing in vitro the different thyroid neoplasias, also show basal NF-kappa B activity and resistance to drug-induced apoptosis, which correlates with the level of NF-kappa B activation. Activation of NF-kappa B in the DTC cell line NPA renders these cells resistant to drug-induced apoptosis. Stable expression of a super-repressor form of I kappa B alpha (I kappa B alpha M) in the UTC cell line FRO results in enhanced sensitivity to drug-induced apoptosis, to the loss of the ability of these cells to form colonies in soft agar, and to induce tumor growth in nude mice. In addition, we show that FRO cells display a very low JNK activity that is restored in FRO-I kappa B alpha M clones. Moreover, inhibition of JNK activity renders FRO-I kappa B alpha M clones resistant to apoptosis induced by chemotherapeutic agents. Our results indicate that NF-kappa B plays a pivotal role in thyroid carcinogenesis, being required for tumor growth and for resistance to drug-induced apoptosis, the latter function very likely through the inhibition of JNK activity. Furthermore, the strong constitutive NF-kappa B activity in human anaplastic thyroid carcinomas, besides representing a novel diagnostic tool, makes NF-kappa B a target for the development of novel therapeutic strategies.
The existence of angiosarcoma of the thyroid gland and its relation to angiomatoid carcinoma have been debated. The authors reviewed eight angiomatoid thyroid neoplasms. Controls consisted of six sarcomatoid thyroid carcinomas without angiomatoid features and an angiosarcoma metastatic to the thyroid gland. All eight angiomatoid neoplasms consisted of epithelioid cells with prominent eosinophilic cytoplasm lining vascularlike spaces. All eight expressed vimentin. Four tumors were predominantly angiosarcomalike neoplasms, based on staining for factor VIII-related antigen (three of four), CD31 (four of four), CD34 (one of four), and Ulex europaeus I lectin (four of four); they lacked epithelial markers other than cytokeratin (two of four). Four tumors were designated as angiomatoid carcinomas, based on staining for multiple epithelial markers: cytokeratin (four of four), epithelial membrane antigen (three of four), thyroglobulin (three of four). Three angiomatoid carcinomas also expressed or labeled with one or more vascular markers: CD34 (one of four), CD31 (two of four), Ulex europaeus I lectin (one of four), factor VIII-related antigen (one of four). The metastatic angiosarcoma to the thyroid gland labeled for factor VIII-related antigen, vimentin, CD31, and with Ulex europaeus I lectin. It did not express CD34. The six sarcomatoid carcinomas without angiomatoid features stained for cytokeratin (four of six), epithelial membrane antigen (one of six), and vimentin (six of six). None labeled for thyroglobulin, factor VIII-related antigen, CD31, CD34, or with Ulex europaeus I lectin. Angiomatoid carcinomas of the thyroid gland exhibit both epithelial and endothelial features. "Angiosarcoma" may represent the extreme in this spectrum of endothelial differentiation. All tumors behaved in a similar clinical fashion characterized by persistent local disease, widespread metastases and poor prognosis.
Parafollicular cells (C-cells) in benign and malignant thyroid lesions were studied immunohistochemically with a polyclonal anti-calcitonin (CT) antibody. The C-cells were seen most frequently in the middle third of the lateral lobes in the thyroid gland of normal individuals and patients with Graves' disease and chronic thyroiditis, although in the latter the number of such cells was significantly decreased (p less than 0.05). In adenomatous goiter, C-cells were present in nodular lesions from an early stage of nodule development (frequency about 19%), whereas in the later stage these cells were rarely observed inside type 1 nodules, which were generally characterized by an admixture of follicles with considerably different sizes. However, C-cells were not observed inside type 2 nodules, which were composed of similar-sized follicles, or in the parenchyma of 56 cases of benign and malignant thyroid tumors. These findings suggest that since C-cells are present in nodular lesions, the histogenesis of adenomatous goiter is quite different from that of follicular adenoma; thyroid neoplasms generally contain no C-cells in the parenchyma.
Thyroid nodules are found in 5% to 10% of the population. While these nodules carry only a 5% to 10% risk of malignancy, tests that complement fine-needle aspiration (FNA) cytology in preoperative diagnosis and risk stratification are lacking. Telomerase is a ribonucleoprotein polymerase with activity found in many malignant tissues, but absent from most normal adult tissue. In this study, we have investigated telomerase activity in 24 thyroid tumors, 14 matched adjacent thyroid tissues, and 3 chronic thyroiditis tissue samples. Using a telomeric repeat amplification protocol (TRAP) assay on frozen tissue, telomerase activity was detected in 11 of 20 thyroid carcinomas, including 10 of 14 papillary carcinomas and a Hurthle cell carcinoma. Telomerase activity was not detected in 4 benign adenomas, 3 follicular carcinomas, or a single case each of medullary and anaplastic thyroid carcinoma. Telomerase activity was detected in 3 of 14 samples of adjacent thyroid tissue from patients with thyroid tumors. Interestingly, all 3 cases of adjacent thyroid tissue that tested positive had a moderate to marked degree of chronic inflammation. In addition, 3 of 3 samples from chronic thyroiditis specimens tested positive for telomerase activity. When tumor invasiveness (vascular and/or capsular) was compared with telomerase activity in papillary carcinomas, only 1 of 4 telomerase-negative tumors was invasive, while 6 of 10 of telomerase-positive tumors were invasive. Moreover, 6 of 7 invasive papillary carcinomas had telomerase activity. In summary, this is the first report of telomerase activity in thyroid tissue and nodules. This activity was detected in a large percentage of papillary thyroid carcinomas, but not benign adenomas, follicular carcinomas, or most normal thyroid tissue. Telomerase activity may also correlate with tumor invasiveness. Further studies will focus on larger numbers of tumors, metastatic tissue, and undifferentiated carcinomas, as well as application of this assay to products from fine-needle aspirates as a potential diagnostic and prognostic marker in thyroid neoplasms.
In this case-control study we describe how often thyroid cancers and occult cancers are diagnosed or not diagnosed by fine-needle aspiration (FNA) in patients with thyroid nodules and a family history of nonmedullary thyroid cancers (FNMTC). Our hypothesis is that patients with thyroid nodules and a family history of FNMTC seem to be similar to patients with thyroid nodules and a history of exposure to low-dose therapeutic radiation. Both have been reported to have multifocal thyroid neoplasms and malignant tumors are common. Cytological examination may therefore be less accurate. From 1979 to 1996, 27 patients from 24 families with FNMTC were examined histologically after a preoperative cytological examination in all of them. A positive cytology examination was defined when biopsy documented thyroid cancer. It was interpreted as a false-negative study when a benign diagnosis was made and thyroid cancer was present anywhere within the thyroid, including in areas sampled or not sampled by FNA and not palpable preoperatively. A randomized control group, matched for age and gender, contained 27 patients with papillary thyroid cancer without familial disease. In our study group, 25 patients were treated with total thyroidectomy, including 7 with neck dissection, and 2 by thyroid lobectomy. At final histological examination 17 of 27 patients (63%) in this study group had multiple nodules and 25 of 27 (92.6%) had thyroid cancer. Thyroid cancer was diagnosed by FNA in 22 of 25 patients (88%), with 3 (12%) false-negative biopsies due to sampling errors (thyroid cancer not in the index nodule), versus 1 (3.7%) false-negative biopsy in the control group. Two patients in the study group with benign nodules were accurately diagnosed. In patients with false-negative biopsies and a history of FNMTC, the cancer was situated in one or more small nodules. Only one cancer was occult (< 1.0 cm). One-third of the patients in our study group (33%) had a history of radiation; 44% of the irradiated group had a single nodule; 56% had multiple nodules. In the control group, 9 of 27 patients (33%) also had a history of radiation; 33% of the irradiated group had a single nodule, 67% had multiple nodules. In conclusion, the reliability of FNA in patients with FNMTC appears to be less accurate than it is for other patients because of the high incidence of multifocal thyroid cancer and coexistence of benign nodules. Patients with thyroid nodules and a family history of thyroid cancer are more likely to have thyroid cancer and because they also have more coexistent benign nodules, they must be followed closely or treated with total or near-total thyroidectomy.
A 16-year-old girl presented with a palpable thyroid nodule which was found to be functioning autonomously by radioiodine (123I) scintigraphy. After needle biopsy proved non-diagnostic, surgical excision showed the nodule to be Hürthle cell carcinoma. Functional thyroid nodules are rarely malignant, thyroid carcinoma is rare in childhood, and Hürthle cell carcinoma is a rare thyroid neoplasm, so the presence of these three rare conditions in one patient makes it a very unusual case.
Treatment for Hodgkin's disease (HD) is associated with a variety of thyroid abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neoplasms. Due to the small sample size and short follow-up time of most published studies, it has been difficult to appreciate the full extent of the problem and to characterize the interaction between various patient and treatment variables. To overcome these limitations we have assessed thyroid status in 1,791 (959 males) HD survivors from among 13,674 participants in the Childhood Cancer Survivor Study, a cohort of 5-yr survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. Survivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a median of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subjects were treated with radiation (median dose of radiation to the thyroid, 3,500 cGy; range, 0.37-5,500 cGy). Control data were available from 2,808 (1,346 males) sibling controls. Thirty-four percent of the entire cohort has been diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compared to sibling controls. Increasing dose of radiation, older age at diagnosis of HD, and female sex were all independently associated with an increased risk of hypothyroidism. Actuarial risk of hypothyroidism for subjects treated with 4,500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism was reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than the incidence reported by the controls. Thyroid dose of 3,500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid nodules was 27 times (P < 0.0001) that in sibling controls. Female sex and radiation dose to the thyroid of 2,500 cGy or more were independent risk factors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagnosed in 20 survivors, which is 18 times the expected rate for the general population. After taking into account the possibility that some of the relative risk estimates may be exaggerated due to ascertainment bias, abnormalities of the thyroid are still extremely common in young adult survivors of childhood HD, particularly among females treated with high doses of radiation to the neck.
This immuno-histochemical description of thyroglobulin synthesis in human thyroid carcinomas is based on the analysis of 72 malignant thyroid neoplasms and about 100 cases of thyroid adenomas and other diseases of the thyroid gland. In our experience immuno-histochemistry has been an invaluable diagnostic adjunct to light microscopy for three reasons: 1) as an approach to a functional classification of thyroid carcinomas, 2) as an aid in the differential diagnosis of thyroid carcinomas of follicle cell type from tumors of other origins, 3) as an aid in the functional classification of non-cancerous thyroid tissue. In the field of metastasizing thyroid carcinoma this immuno-histochemical approach combined with a morphometrical method may enable accurate identification of patients for whom radioiodine therapy is appropriate.
BACKGROUND: Epidemiologic data suggested that the differentiated thyroid carcinoma was affected by sex hormones, especially estrogen. METHODS: The authors have immunohistochemically studied estrogen receptors (ER) in papillary thyroid carcinoma in women. Two anti-ER monoclonal antibodies, D5 and H222, were used. The authors then investigated the responsiveness to estrogen of thyroid neoplasms using primary culture of surgically resected thyroid tissues. The proliferative activity of cultured cells was measured by the bromodeoxyuridine (BrdU) labeling index (LI). RESULTS: Twenty-six percent of the specimens (18/70) showed positive staining with D5, but only 5.6% of the specimens (2/36) showed positive staining with H222. The BrdU LI of ER-positive papillary thyroid carcinoma increased with the addition of estradiol. CONCLUSIONS: These findings indicate that estrogen may affect the proliferation of ER-positive papillary thyroid carcinoma.
The authors and others believe that surgery (thyroidectomy) is underused in the treatment for patients with Graves' disease. It is the most rapid and consistent method of making the patient euthyroid; it avoids the possible long-term risks of radioactive iodine; and it provides tissue for histologic examination. Children, young women, pregnant women, and patients with coexistent thyroid nodules are ideal candidates for thyroidectomy. It also is the treatment of choice for patients with Graves' ophthalmopathy. Patients should be rendered euthyroid before thyroidectomy. Although the operation is technically more difficult than operating on patients with nontoxic goiter or thyroid neoplasms because of the vascularity of the thyroid gland, this difference is small, and the complication rates are low. The authors recommend the Hartley-Dunhill operation (total thyroidectomy on one side and subtotal thyroidectomy on the other side, leaving about 4 to 5 g of thyroid tissue) for most patients and total thyroidectomy for patients with Graves' ophthalmopathy. In patients with recurrent or persistent thyroid cancer who fail to respond to surgery and radioactive iodine ablation, immunosuppressive therapy should be considered.
Surgery is still today the first choice treatment in the thyroid neoplasm. The authors examined 37 patients with thyroid cancer out of 389 thyroidal operation performed in the period 1982-85 at the Institute of Surgical Pathology II and Surgical Clinic of University of Bari. The pro-operation screening was scintigraphy, US study and needle biopsy. In 23 case, with positive cytology examination and/or clinical malignancy the performed operation was total extracapsular thyroidectomy. Other nine patients underwent lobectomy and in 2 cases the operation chosen was sub-total strumectomy completed by thyroidectomy after histologically proved malignancy. The laterocervical lymphadenectomy was done only in the case of nodes involvement. Operative mortality was 0 and post-operative stay was about 6 days. The extracapsular total thyroidectomy is the first choice operation for cancer. Nevertheless recently some Authors proposed less destructive operation in the small differentiated type cancers with good results.