Anaplastic thyroid carcinoma (ATC) is difficult to distinguish from other cancers, especially when its pathological features are atypical for ATC or when the tumor is totally undifferentiated and occurs after a considerable lapse of time, in an area remote from the original site of the tumor. Here, we present two patients (68-year-old man and 56-year-old woman) with rare manifestations of ATC, which were initially thought to be other malignancies. Immunohistochemical tests, using various markers, failed to provide information about the origin of these tumors. However, both patients had a history of papillary thyroid carcinoma (PTC) from several years ago and BRAF mutations were observed in the undifferentiated tumors, as well as in the previous PTCs. Therefore, we could make a diagnosis of ATC derived from PTC. As such, BRAF mutation analysis may serve as a useful tool for ATC diagnosis in challenging ATC cases.
Diagnosis ; Humans ; Immunohistochemistry ; Middle Aged ; Thyroid Carcinoma, Anaplastic* ; Thyroid Neoplasms

Anaplastic thyroid carcinoma (ATC) is a rare disease that shows very aggressive behavior. Most ATCs arise from pre-existing thyroid carcinomas. However, anaplastic transformation occurring in metastatic cervical nodes is extremely rare. We report herein on 3 cases of anaplastic transformation of metastatic lateral cervical lymph nodes from primary papillary thyroid carcinoma (PTC), which happened long after the initial surgical treatment. All the patients died of disease within 4 months in spite of aggressive treatment for the lesions. Our experience supports that appropriate lymph node dissection is mandatory at the time of initial surgery even for differentiated thyroid carcinomas.
Humans ; Lymph Node Excision ; Lymph Nodes* ; Rare Diseases ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms*

This report concerns a 71-year-old female with long standing untreated toxic multinodular goiter (TMG) coexisting with anaplastic thyroid carcinoma who presented with progressive shortness of breath and easy fatigability. Thyroid function tests showed suppressed TSH and elevated FT4 and FT3. Anti-thyroid hormone drugs were started. Thyrotropin receptor antibody was negative. A thyroid scan revealed both hot and cold nodules and fine needle aspiration biopsy (FNAB) of the thyroid gland showed colloid nodule. Chest CT scan imaging revealed an enlarged thyroid gland with the right lobe compressing the trachea. Patient underwent total thyroidectomy, final histopathology showed Anaplastic thyroid carcinoma. Our case is interesting from a pathophysiologic perspective,since it suggests that TMG can potentially transform into an aggressive form of thyroid carcinoma. High index of suspicion in patients with TMG with other risk factors for malignancy requires careful evaluation to detect cancer.

Human ; Female ; Aged ; Goiter ; Immunoglobulins, Thyroid-stimulating ; Receptors, Thyrotropin ; Thyroid Carcinoma, Anaplastic ; Thyroid Hormones ; Thyroid Neoplasms ; Thyroid Nodule ; Thyroidectomy ; Hyperthyroidism

BACKGROUND: Tumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment. METHODS: Total 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups. RESULTS: The mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ²=0.432, P=0.013). CONCLUSION: Increased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.
Antibodies ; Biomarkers ; Diagnosis ; Humans ; Macrophages* ; Receptors, CXCR* ; Receptors, CXCR4* ; Thyroid Carcinoma, Anaplastic* ; Thyroid Gland ; Tumor Microenvironment

PURPOSE: The Notch signaling pathway is widely expressed in normal, reactive, and neoplastic tissues; however, its role in thyroid tissues has not been fully elucidated. Therefore, this study was conducted to characterize the expression of the Notch signaling pathway in papillary thyroid cancer (PTC) cells and anaplastic thyroid cancer (ATC) cells. MATERIALS AND METHODS: Expression of activated Notch1 in ATC and PTC paraffin-embedded tissues was determined by immunohistochemistry. The small interfering RNA techniquewas employed to knock down Notch1 expression in ATC and PTC cell lines. RESULTS: The expression of activated Notch1 was higher in ATC cases than in PTC cases. Inhibition of Notch1 significantly reduced proliferation and migration of ATC cells, but not PTC cells. In addition, inhibition of Notch1 in ATC cells significantly reduced the expression of key markers of epithelial-mesenchymal transition and cancer stem cells. Conversely, changes in the expression of these proteins were not observed in PTC cells. CONCLUSION: The results of this study suggest that Notch1 expression plays different roles in tumor progression in ATC and PTC cells. We also found that Notch1 expression was significantly related to the highly invasive or proliferative activity of ATC cells.
Cell Line ; Epithelial-Mesenchymal Transition ; Immunohistochemistry ; Neoplastic Stem Cells ; RNA, Small Interfering ; Thyroid Carcinoma, Anaplastic* ; Thyroid Gland ; Thyroid Neoplasms

Riedels thyroiditis is a rare variant of thyroiditis that is characterized by replacement of the normal thyroid parenchyma by extensive fibrosis. Typically, the thyroid is diffusely involved and a painless, hard anterior neck mass shows clinical features similar to those of anaplastic thyroid carcinoma, that is, a rapidly enlarging, hard, fixed thyroid mass and symptoms such as dysphagia, dysphonia, and dyspnea. We encountered a case of Riedels thyroiditis in a 41-year-old female patient with a longstanding benign thyroid nodule for 6 years; she subsequently presented with a rapidly growing, hard, fixed, thyroid mass mimicking anaplastic thyroid cancer. The clinical features were indistinguishable from those of anaplastic transformation, but open biopsy excluded anaplastic thyroid cancer. After surgery, the final diagnosis of Riedels thyroiditis was made based on typical microscopic findings and immunohistochemical studies. We have reported this case and reviewed the related literature.
Adult ; Biopsy ; Deglutition Disorders ; Diagnosis ; Dysphonia ; Dyspnea ; Female ; Fibrosis ; Humans ; Neck ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Nodule ; Thyroiditis*

The incidence of thyroid cancer is growing the fastest among all cancers in the United States, especially in women. The number of patients with thyroid neoplasm is part of an even larger number of patients who often need to undergo an operation to exclude a cancer diagnosis. While differentiated thyroid cancer (papillary thyroid cancer and follicular thyroid cancer) accounts for most cases of thyroid cancer and has a relatively good prognosis, effective treatments for patients with de-differentiated and anaplastic thyroid cancer are still gravely needed. Despite progress in the identification of genetic changes in thyroid cancer, the impact of aberrant epigenetic alterations on thyroid cancer remains to be fully elucidated. Understanding of the roles of epigenetic changes in thyroid cancer could open new opportunities for the identification of innovative molecular targets for novel treatment modalities, especially for anaplastic thyroid cancer for which treatment is very limited. This article briefly reviews the studies that exemplify the potential for and promise of using epigenetic regulators in the treatment of thyroid cancer.
Diagnosis ; Epigenomics* ; Female ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; Humans ; Incidence ; Prognosis ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms* ; United States

Differentiated thyroid cancer of follicular cell origin (DTC) is a fascinating tumor because of its varying aggressiveness. Luckily most patients with these cancers, despite regional metastasis, can be cured by surgical resection, radioiodine ablation and thyrotropin (TSH) suppression therapy. Unfortunately some patients with well differentiated thyroid cancer that fail to respond to conventional treatment and also patients with poorly differentiated thyroid cancers or anaplastic thyroid cancers are not successfully treated by this combined therapy. These tumors unfortunately may grow rapidly, invade adjacent structures and spread to other parts of the body. During the dedifferentiation process, these carcinomas lose thyroid specific gene expressions including the ability to take up and organify radioiodine and to make thyroglobulin (Tg). The methods used to treat patients with DTC are therefore usually not effective in these patients. These tumors also usually fail to respond to alternative treatment with external radiation or systemic cancer chemotherapy. We therefore need to develop new treatments for these unfortunate patients. Recent advances in molecular and cellular biology make it possible to develop new therapeutic approaches to thyroid cancer. Genes related with thyroid specific functions are also promising targets for cancer therapy. Redifferentiation therapy targets thyroid specific genes in order to restore thyroid specific differentiated function and thus to make these tumors respond to conventional therapy. Redifferentiating agents and gene therapy using thyroid specific genes have been studied for this purpose. Most of therapeutic approaches described here have been established effects in vitro but have not yet been used clinically. Careful clinical trials and analyses should be performed.
Drug Therapy ; Gene Expression ; Genetic Therapy ; Humans ; In Vitro Techniques ; Neoplasm Metastasis ; Thyroglobulin ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyrotropin

Medullary thyroid cancer (MTC) accounts for 5% to 10% of all thyroid cancers, and originates from the parafollicular or C-cells of the thyroid gland. More than 50% of patients present with a thyroid mass and up to 75% of these patients have locoregional lymph node metastasis at the time of diagnosis. The neuroendocrine C-cells of the thyroid gland secrete calcitonin, a relatively accurate tumor marker for MTC. Plasma basal and stimulated calcitonin measurements have been used to screen patients who are at risk of developing MTC and indispensable for the detection of residual MTC after initial surgical treatment. The overall survival rate of patients with MTC is intermediate to that of patients with differentiated thyroid cancer and anaplastic thyroid cancer. Postoperative radioiodine ablation therapy, chemotherapy and radiation therapy are generally ineffective. Surgical resection, therefore, remains the only definite treatment for patients with MTC. Unfortunately, residual MTC as indicated by elevated plasma basal or stimulated calcitonin levels is common even after apparent complete initial surgical resection. We present a case of metastatic MTC in the anterior mediastinum with review of the literatures.
Calcitonin ; Diagnosis ; Drug Therapy ; Humans ; Lymph Nodes ; Mediastinum* ; Neoplasm Metastasis ; Plasma ; Survival Rate ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms*

Thyroid tumors display an intriguing biological diversity from benign follicular adenomas to lethal anaplastic carcinomas. Thyroid tumorigenesis is becoming better understood. Benign follicular adenomas are frequently associated with mutation of the thyrotrophin receptor, G alpha s or RAS. Although confirmatory studies are necessary, the present knowledge concerning the similarity in gene expression profiling between follicular adenomas and follicular carcinomas supports the progression of adenoma to carcinoma sequence. Four major genetic aberrations in follicular cellderived thyroid carcinomas such as papillary, follicular, and Hurthle cell carcinomas include mutations of BRAF or RAS, and chromosomal rearrangement of RET/papillary thyroid tumor or PAX8/peroxisome proliferator-activated receptor gamma. Differentiated thyroid carcinomas of follicular cell origin dedifferentate to poorly differentiated or anaplastic thyroid carcinomas through mutation of p53 and CTNNB1. Familial nonmedullary thyroid carcinomas are heterogenous in genetic profiling, but some genes have been investigated as candidates for causative genetic aberration. Ret mutations can cause medullary thyroid carcinomas. A genotype- phenotype relationship helps to decide prophylactic thyroidectomiesin family members of hereditary medullary carcinomas such as MENIIa or MENIIb. Primary thyroid lymphomasare closely related with Hashimoto's thyroiditis. Recent novel and promising findings include additional abnormalities in the regulation of microRNA expression, polymorphisms associated with thyroid cancer susceptibility and epigenetic changes. A newly proposed fetal cell carcinogenesis hypothesis explains more about thyroid tumorigenesis than classical multi-step carcinogenesis model, but is not yet firmly supported by evidence. Future studies need to uncover new molecular mechanisms in thyroid tumorigenesis and to provide novel therapeutic targets for thyroid carcinomas.
Adenoma ; Biodiversity ; Carcinogenesis* ; Carcinoma ; Carcinoma, Medullary ; Epigenomics ; Gene Expression Profiling ; Humans ; MicroRNAs ; Phenotype ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroiditis ; Thyrotropin