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Anaplastic thyroid carcinoma, thyroid lymphoma, and secondary metastasis to the thyroid gland are uncommon thyroid malignancies. They represent significant challenges for the surgeon owing to difficulties in diagnosis, aggressive biology, and the infrequency of their presentation. An awareness and appreciation of multimodality treatment strategies is essential for their management.
A male patient with clinical and radiographic evidence of cretinism was found to have T3 thyrotoxicosis. The cause was thought to be a well-differentiated follicular carcinoma of the thyroid. Although the disease was not documented, the patient probably had long-standing hypothyroidism. Untreated primary thyroid failure accompanied by high serum thyroid stimulating hormone (TSH) may be carcinogenic to the thyroid. The association of thyroid abnormalities and male breast carcinoma is discussed.
Three marine invertebrate FITC-labelled lectins, CNL, GCL, and GSL, isolated respectively, from the sponges Chondrilla nucula, Geodia cydonium, and the hexacoral Gerardia savaglia, were used as potential diagnostic tools for different breast tumors. The lectins vary in their carbohydrate binding properties: GSL is D-mannose specific, GCL and CNL D-galactose specific. GSL labels most investigated types of malignant tissues distinctively, while the results with CNL and GCL are less consistent. The well known D-mannose specific lectin, concanavalin A, also binds to tumor tissues, but with much lower intensity than GSL.
Thyroid carcinoma derived from the thyroid hormone-producing follicular epithelium is the most common thyroid malignancy. While the morphologic diagnosis of conventional papillary thyroid carcinoma is simple, thyroid tumors with a follicular pattern are sometimes a diagnostic challenge. It is in the latter group of thyroid neoplasms that ancillary diagnostic tests such as immunohistochemistry may be of great help. Furthermore, while most differentiated thyroid carcinomas have an excellent prognosis, a subset of these tumors may progress to a poorly or undifferentiated phenotype indicating an aggressive biologic behavior that may lead to systemic spread and death. Application of immunohistochemistry to identify a subset of thyroid carcinoma that may progress to a biologically aggressive phenotype may help in the management of patients with thyroid carcinoma. This review discusses the role of immunohistochemistry in the diagnosis and progression of thyroid carcinoma is discussed.
Thyroid disease is comparatively prevalent, and it is important to perform careful palpation of the anterior neck when patients are first examined. In this paper, the latest data on and clinical characteristics of the epidemiology of thyroid carcinoma are described. According to Japanese cancer statistics, in 1996, the number of cases of thyroid carcinoma was 1,390 men and 5,437 women. The female to male ratio was 3.91: 1. The crude rate of thyroid carcinoma per 100,000 population was 2.3 men and 8.5 women. The age-adjusted incidence rate showed a gradual increase with age, and the peak of the age-adjusted incidence rate was over 80 years old among men, and from 70 to 80 years old among women. According to the Japanese Thyroid Cancer Registration Committee, from 1977 to 1999, papillary thyroid carcinoma accounted for more than 85% (30,256) of thyroid carcinomas among 35,312 patients. Medullary thyroid carcinoma (1.4%) and anaplastic thyroid carcinoma (1.6%) were rare. The female to male ratio of thyroid carcinoma was 6.1: 1. Registration was made in accordance with the general rules issued by the Japanese Society of Thyroid Surgery. According to the vital statistics, mortality related to thyroid carcinoma among all cancer-related deaths was 0.23% among men (411) and 0.76% among women (887) in 2000. The female to male ratio of mortality was 2.16: 1. The peak of mortality was from 70 to 80 years old among men, and from 80 to 90 years old among women. Most patients with differentiated thyroid carcinoma had a low mortality rate, but anaplastic carcinoma had a poor prognosis. Lung and bone were the main distant metastatic sites, and respiratory insufficiency was the most common specific fatal condition.
Thyroid carcinomas represent only 1% of all human malignancies, but more than 90% of endocrine tumors. It can be histologically divided into papillary, follicular, anaplastic or medullary thyroid carcinomas. Here we report the genetic causes of the development of these tumors. For papillary thyroid carcinoma formation of fused genes of tyrosine kinases (RET proto-oncogene, NTRK1 proto-oncogene and met proto-oncogene) with other genes is typical. They can activate these kinases and induce mutation in BRAF gene. The presence of PAX8/PPARgamma fused gene and ras mutations are important in the development of follicular thyroid carcinoma. Anaplastic thyroid carcinoma derives from the dedifferentiation of papillary and follicular carcinomas as a consequence of mutation or loss of heterozygozity in p53 gene. Medullary thyroid carcinoma comes from parafollicular C-cells, where point somatic and germ-line mutations (in familial form of medullary thyroid carcinoma or in multiple endocrine neoplasia type 2) in the RET proto-oncogene determine its development. Identification of these specific genetic alternations for each type of carcinoma can contribute to precision of the diagnosis, explanation of the origin of carcinomas, establishment of prognosis of the disease or in future as a tool for the target gene therapy.
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Thyroid carcinoma has a unique biologic behavior characterized by early spread to regional lymph nodes and occasional extrathyroidal soft tissue extension but a low incidence of distant metastasis and infrequent disease-related death. Therefore, controversy exists over the proper extent of thyroidectomy and regional lymph node dissection in patients with differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). The modest disease-specific mortality makes it unlikely that the extent of surgery will ever be the subject of a prospective randomized trial. Although more extensive cervical surgery may have only a limited effect on the duration of survival in patients with DTC, it may significantly improve quality of life by minimizing cervical recurrence. The high rates of cervical recurrence in patients with DTC and MTC have alerted physicians to the importance of fine-needle aspiration biopsy and ultrasonography for the diagnosis, preoperative staging, and follow-up of thyroid cancer. In patients with MTC, death caused by disease is uncommon in the absence of radiographically evident distant metastasis at the time of thyroidectomy. Cervical recurrence is even more common with MTC, and the need for compartment-oriented lymphadenectomy is accepted as standard surgical treatment to minimize disease recurrence. Postoperatively, calcitonin (CT) levels can be used to guide clinical management, but basal CT levels should not be used to direct the timing of prophylactic thyroidectomy in affected high-risk patients with familial MTC.
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Thyroid carcinomas are the most frequent endocrine malignancies. Complications may arise from an established malignancy and these may lead to the initial clinical presentation or cause subsequent problems. In this case report two elderly patients with differentiated and undifferentiated thyroid carcinomas who suffered unusual medical complications are described. The incidence and treatment of thyroid carcinoma is discussed and the importance of fine needle aspiration of thyroid nodules and the recognition of iodine containing radiographic contrast media in the causation of iodine induced thyrotoxicosis is highlighted.
Thyroid carcinoma is the first symptom in some patients with familial adenomatous polyposis (FAP). We evaluated the cellular localization of beta-catenin in thyroid carcinomas associated (n = 4) or not associated (n = 173) with FAP, since loss of functional protein of the adenomatous polyposis coli (APC) gene leads to nuclear accumulation of beta-catenin in adenomas and carcinomas of the FAP colon. Immunoreactive beta-catenin was demonstrated at the cell membrane of glandular cells of the non-neoplastic thyroid and non-FAP carcinomas. On the other hand, cytoplasmic and nuclear accumulation of beta-catenin is specific to FAP-associated papillary carcinomas. The abnormality in the APC / beta-catenin pathway is thus also important in FAP-associated thyroid carcinoma, and beta-catenin immunohistochemistry is a feasible screening method to identify occult FAP in young patients with thyroid tumors.
Thyroid carcinoma is the most frequent endocrine malignant neoplasm even if a rare occurrence (0.5%-1.0%) of all human malignant tumors. Primary differentiated (papillary and follicular) forms represent over 90% of the total. Since recurrence of thyroid carcinoma can occur even after several years, patients must undergo a life-long follow-up. Thyroglobulin, being organ-specific, plays a major role as tumor marker and it is used essentially in the monitoring and follow-up of patients with differentiated thyroid carcinoma, both during L-thyroxine suppressive therapy and when it is discontinued or after recombinant TSH administration. The presence of antithyroglobulin antibodies masks the real value of thyroglobulin and therefore, at the same time, antithyroglobulin antibodies should always be determined.
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.
Thyroid glands obtained from patients in southeastern Canada, northeastern Japan, southern Poland, western Colombia, and from Japanese living in Hawaii were serially step-sectioned and examined microscopically using identical techniques and diagnostic criteria. The prevalence of occult papillary thyroid carcinoma was significantly higher in Japan (28.4%) and in Hawaiian Japanese (24.2%) when compared with Canada (6%), Poland (9.1%), and Colombia (5.6%). The carcinomas were all papillary except for a single follicular lesion from Colombia. There was no significant sex prevalence. Most of the patients were between 40 and 79 years of age, but there was no particular predominant decade. Only the Colombian series had a large number of younger patients, and they showed a slightly lower prevalence of occult carcinomas before age 40. Most papillary thyroid carcinomas grow slowly and probably remain occult for the life of the patient.
Thyroid carcinoma usually presents as an asymptomatic thyroid nodule. Thyroid cancer may show microscopic vascular invasion; however, internal jugular vein tumor thrombus is a rare complication of thyroid cancer. A unique case of internal jugular vein tumor thrombus associated with thyroid carcinoma is presented and discussed.
The medical records of 38 dogs with thyroid neoplasia that were treated by surgical excision of the tumor, or had an incisional biopsy performed as a diagnostic procedure, were reviewed. Of the 38 dogs, 21 (55%) had resectable tumors, whereas 17 (45%) had an incisional biopsy as the tumors were nonresectable. All dogs had an initial diagnosis of thyroid carcinoma. The type of carcinoma was confirmed in 33 dogs by histological and immunohistochemical examination. Twelve dogs (36%) had medullary thyroid carcinoma, and 21 dogs (64%) had thyroid adenocarcinoma. Of the 12 dogs with medullary thyroid carcinoma, 10 (83%) had resectable tumors. Of the 10, three (30%) had at least a 1-year survival. None had radiographic evidence of metastasis at the time of surgery. Of the 21 dogs with thyroid adenocarcinoma, 11 (52%) had resectable tumors. Of the 11 dogs, five (45%) had at least a 1-year survival. Three dogs had radiographic evidence of metastasis at the time of surgery. Of 10 dogs with nonresectable thyroid adenocarcinoma, two dogs (20%) had at least a 1-year survival. In the dogs in this study, medullary thyroid carcinoma was more prevalent than previously reported. Most of the medullary thyroid carcinomas were well circumscribed and resectable. Medullary thyroid carcinoma may possess gross and histological characteristics of a less malignant nature when compared with other thyroid carcinomas.
Thyroid carcinomas are fairly uncommon and include disease types that range from indolent localised papillary carcinomas to the fulminant and lethal anaplastic disease. Several attempts to formulate a consensus about treatment of thyroid carcinoma have resulted in published guidelines for diagnosis and initial disease management. Multimodality treatments are widely recommended, although there is little evidence from prospective trials to support this approach. Surgical resection to achieve local disease control remains the cornerstone of primary treatment for most thyroid cancers, and is often followed by adjuvant radioiodine treatment for papillary and follicular types of disease. Thyroid hormone replacement therapy is used not only to rectify postsurgical hypothyroidism, but also because there is evidence to suggest that high doses that suppress thyroid stimulating hormone prevent disease recurrence in patients with papillary or follicular carcinomas. Treatment for progressive metastatic disease is often of limited benefit, and there is a pressing need for novel approaches in treatment of patients at high risk of disease-related death. In families with inherited thyroid cancer syndromes, early diagnosis and intervention based on genetic testing might prevent poor disease outcomes. Care should be carefully coordinated by members of an experienced multidisciplinary team, and patients should be provided with education about diagnosis, prognosis, and treatment options to allow them to make informed contributions to decisions about their care.
Thyroid carcinoma represents the most frequent endocrine tumor. Recent reports have documented an increase in the incidence of thyroid cancer. Its incidence varies geographically around the world from 0.9/ 100,000 men and 2.4/100,000 women in Great Britain to 8.8/100,000 men and 18.2/ 100,000 women in Hawaii. Radiation exposure has been strongly implicated as an aetiological factor. The greatest risk occurs with acute exposure to X and/or gamma rays, with a linear dose response curve, while the risk is inversely related to age at exposure with a latent period of 5-20 years. Together with irradiation, other factors (iodine, alcohol and calcium diet intake, hyperthyroidism, Hashi-moto's thyroiditis, Gardner syndrome, Cowden syndrome, pharmaceutical agents, hormonal factors, occupational exposure, activation of cellular oncogenes) have been associated with the risk of thyroid cancer. In prevention a policy should include regulations and methods for avoiding radiation exposure of the thyroid and for preventing nutritional deficiency and excess of iodine. Besides, early and continuous suppressive therapy of all patients affected by non-toxic goiter or treated previously with thyroidectomy, and a screening of medullary thyroid carcinoma (MTC) using pentagastrin stimulation test and restriction fragment length polymorphism analysis, in subjects with a familial history of MTC, are of paramount importance to prevent thyroid cancer.