Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity

Anaplastic thyroid carcinoma (ATC) is a rare, highly malignant thyroid tumor with dismal prognosis. Osteoclastic giant cell variant of ATC is extremely rare and is characterized by the presence of a large number of multinucleated giant cells resembling osteoclasts. We report here this unusual variant in a 67-year-old female with a history of long-standing goiter of 13 years duration. Histologically, many multinucleated osteoclast-like giant cells were seen accompanying the malignant spindle cell component. Despite extensive sampling, no evidence of differentiated thyroid malignancy could be elucidated

Expressions of Twist transcription factor and E-cadherin in anaplastic thyroid carcinoma and their relationship with the prognosis / 肿瘤研究与临床

Objective To investigate the expressions of Twist transcription factor and E-cadherin in anaplastic thyroid carcinoma and their correlation with the prognosis. Methods The clinicopathological data of 20 patients with anaplastic thyroid carcinoma in Shanxi Provincial Cancer Hospital from May 2016 to April 2018 were retrospectively analyzed. The expressions of Twist protein and E-cadherin protein in anaplastic thyroid carcinoma tissues and corresponding paracancerous tissues were detected by using immunohistochemistry. The relationship between the expressions of the two proteins and the clinicopathological features of the patients was analyzed, and the correlation among the expressions of the two proteins as well as the clinicopathological factors and the prognosis of the patients was analyzed. Results The positive expression rate of Twist protein in anaplastic thyroid carcinoma tissues was 65％ (13/20), while it was 20％ (4/20) in paracancerous tissues, and the difference was statistically significant (P= 0.004). The positive expression rate of E-cadherin in anaplastic thyroid carcinoma tissues was 60％(12/20), while it was 100％(20/20) in paracancerous tissues, and the difference was statistically significant (P = 0.001). There was a negative correlation between the expression of Twist protein and E-cadherin protein in anaplastic thyroid carcinoma (r=-0.685, P=0.001). The expression of Twist protein in anaplastic thyroid carcinoma was correlated with lymph node metastasis and TNM stage (both P< 0.05), while it had no correlation with gender, age and tumor diameter (all P> 0.05). The expression of E-cadherin protein in anaplastic thyroid carcinoma had no correlation with clinicopathological factors (all P> 0.05). The results of Kaplan-Meier survival analysis showed that lymphnode metastasis (P< 0.01), TNM stage (P = 0.002) and the expression of Twist protein (P = 0.017) were prognostic factors in patients with anaplastic thyroid carcinoma. Conclusions The expression of Twist transcription factor is upregulated in anaplastic thyroid carcinoma, and the expression of E-cadherin is downregulated. The expression of Twist protein is correlated with the prognosis of the patients. The epithelial-mesenchymal transition may be involved in the progress of anaplastic thyroid carcinoma.

Pleomorphic Adenoma of Breast:Â Study of a Common Tumor in an Uncommon Location

Pleomorphic adenoma occurs commonly in the major salivary glands but is uncommonly encountered in the breast. In both of these locations, the tumor is typically grossly circumscribed and has a ―mixed‖ histological appearance, being composed of myoepithelial and epithelial components amid a myxochondroid matrix. Pleomorphic adenoma of the breast is a rare, benign tumor accounting for 68 cases in the literature. It is most commonly seen in postmenopausal women. Here, we have reported a case of mammary pleomorphic adenoma in an asymptomatic 45-year-old woman which was preoperatively thought to represent a carcinoma on clinical and radiological grounds. It is the rarity of the tumor in the breast, rather than its histological appearance, that causes diagnostic difficulty.

Treatment outcomes of radiotherapy for anaplastic thyroid cancer

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare tumor with a lethal clinical course despite aggressive multimodal therapy. Intensity-modulated radiotherapy (IMRT) may achieve a good therapeutic outcome in ATC patients, and the role of IMRT should be assessed. We retrospectively reviewed outcomes for ATC treated with three-dimensional conformal radiotherapy (3D-CRT) or IMRT to determine the optimal treatment option and explore the role of radiotherapy (RT). MATERIALS AND METHODS: Between December 2000 and December 2015, 41 patients with pathologically proven ATC received RT with a sufficient dose of ≥40 Gy. Among them, 21 patients (51%) underwent surgery before RT. Twenty-eight patients received IMRT, and 13 received 3D-CRT. Overall survival (OS) and progression-free survival (PFS), patterns of failure, and toxicity were examined. RESULTS: The median follow-up time for survivors was 38.0 months. The median and 1-year OS and PFS rates were 7.2 months and 29%, 4.5 months and 15%, respectively. Surgery significantly improved the prognosis (median OS: 10.7 vs. 3.9 months, p = 0.001; median PFS: 5.9 vs. 2.5 months, p = 0.007). IMRT showed significantly better PFS and OS than 3D-CRT, even in multivariate analysis (OS: hazard ratio [HR] = 0.30, p = 0.005; PFS: HR = 0.33, p = 0.005). Significantly higher radiation dose could be delivered with IMRT than 3D-CRT (EQD210 66 vs. 60 Gy, p = 0.005). Only 2 patients had grade III dermatitis after IMRT. No other severe toxicity ≥grade III occurred. CONCLUSION: Patients with ATC showed better prognosis through multimodal treatment. Furthermore, IMRT could achieve favorable survival rates by safely delivering higher dose than 3D-CRT.

Clinical analysis of 21 cases of anaplastic thyroid carcinoma / 国际外科学杂志

Objects To investigate the therapeutic schemes and factors that influences survival of the patients with anaplastic thyroid carcinoma (ATC).Methods The clinical data of 21 cases with ATC admitted in First Affiliated Hospital of Zhengzhou University from Jan.2009 to Nov.2013 were analyzed retrospectively.Explored patients survival rates according to the age,the gender,the white cell count,the therapeutic scheme (surgery plus radiotherapy,surgery alone),the operation mode (radical surgery,palliative surgery).SPSS 21.0 software was used for statistical processing,and Kaplan-Meier was used to calculate the survival rate,the Log-Rank was uesd for the difference test.Results The overall survival rates of the 1-,3-and 5-year were 42.9％,28.6％,and 4.8％ respectively.A significant difference had been found in the 5-year survival rate between the group of surgery coupled with postoperative chemoradiotherapy(7.1％) and the group of surgery alone(0) (P ＜ 0.05).So it was the same between the group of radical surgery (8.3％) and the group of palliative surgery (0) (P ＜0.05).And a clear break point of the white blood cell count(1.0 × 1010/L) had demonstrated the significant difference of the 5-year survival rate between the groups of both sides,while the lower group (11.1％) could be much higher (P ＜0.05).Conclusions The prognosis of ATC is very poor,and the group the patients with higher white cell count (≥ 1.0 × 1010/L) can be even poorer.Compared with palliative surgery,radical surgery can improve the survival rate.Compared with surgery alone,surgery coupled with postoperative chemoradiotherapy can improve the survival rate signifantltly.

Expression of minichromosomes maintain protein 5, 7 in anaplastic thyroid carcinoma and its biological research / 中华内分泌外科杂志

Objective To cast light on the mechanisms governing anaplastic thyroid carcinoma (ATC) and to evaluate the minichromosomes maintain protein (MCM) 5 and MCM7 expression in human normal thyroid (NT),papillary thyroid carcinoma (PTC),and ATC samples,as well as in primary culture cells.Methods We tested the expression of MCM5,MCM7and PCNA in NT,PTC and ATC by immunohistochemistry.We used Western blot and Northern blot to test the expression of MCM5,and MCM7.ATC cells were transfected with MCM7 siRNA,and Western blot was used to examine the change of the expression of MCM7.Results In ATC samples,MCM5 had high expression in 65％ patients,and MCM7 had high expression in 73％ patients.The expression of MCM5 and MCM7 in NT and PTC samples were very low which can be ignored.In ATC cells,high MCM5 and MCM7 expression was paralleled by high levels of MCM2 and MCM6.Inhibition of MCM7 protein levels by small inhibitory duplex RNAs could reduce the rate of DNA synthesis in ATC cells.Conclusion MCM protein expression is upregulated in ATC and leads to excessive proliferation of ATC.

Clinical characteristics and prognosis of anaplastic thyroid carcinoma / 中华肿瘤杂志

Objective@#To investigate the clinical characteristics, treatment outcomes and prognostic factors in patients with anaplastic thyroid cancer.@*Methods@#Clinical data of 56 patients with anaplastic thyroid cancer at Zhejiang Cancer Hospital from January 2006 to June 2016 were retrospectively reviewed and followed up.@*Results@#Of the 56 patients, there were 24 male and 32 female. The median age was 65 years old. At diagnosis, 10 patients have different degrees of breathing difficulty; 8 patients have varying degrees of dysphagia, and 12 patients have hoarseness. Distant metastases were found in 23 patients at presentation. Patient staging was performed in accordance with the tumor-node-metastasis system as follows: stage ⅣA (n=19), stage ⅣB (n=14) and stage ⅣC (n=23). The median survival time of 56 patients was 4.5 months.The overall 1-year survival rate was 5.4%. Univariate analysis showed that radiotherapy and multimodality therapy were prognostic factors for 1-year overall survival (both of P<0.05). The overall 1-year survival rate of the patients who received precision radiotherapy was 16.7%, which was higher than who received the other radiation therapy (4.0%, P=0.040). Furthermore, the overall 1-year survival rate of the patients who received surgery combined with radiotherapy was 12.5%, which was higher than who received the other treatments(4.2%, P=0.040). Multivariate analysis indicated that radiotherapy was independently associated with improved survival (P=0.020).@*Conclusions@#Patients with anaplastic thyroid cancer should receive multimodality therapies combining surgery with radiotherapy. Radiotherapy is independently associated with improved overall survival. Notably, the precision radiotherapy that based on image guidance has a significantly beneficial impact on the prognosis of patients.

Rare Manifestations of Anaplastic Thyroid Carcinoma: the Role of BRAF Mutation Analysis

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.

The Role of Notch1 Signaling in Anaplastic Thyroid Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

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.

Thyroid leiomyosarcoma: presentation of two cases and review of the literature / Leiomiossarcoma da tireoide: apresentação de dois casos e revisão da literatura

Abstract Introduction: Leiomyosarcoma is a tumor which is rarely seen in the thyroid gland. The diagnosis may be difficult and the treatment is controversial. Objective: The objective of the study is to review the literature about a rare malignant disease of the thyroid gland which has high mortality. Methods: Two cases of thyroid leiomyosarcoma are presented and the previous 23 cases in the current literature are reviewed. Results: A total of 25 cases of thyroid leiomyosarcoma are reviewed; the most common complaint was rapidly growing anterior neck mass, and ten of the 25 patients had distant metastasis at the initial admission. Fifteen of the 25 patients died with the disease in the first 12 months after the diagnosis. Conclusion: The differential diagnosis of thyroid leiomyosarcoma is important and should be performed with other malignancies of the gland, especially with anaplastic carcinoma. The prognosis is poor and there is no consensus regarding the treatment.

Resumo Introdução: Leiomiossarcoma é um tumor raramente observado na glândula tireoide. O diagnóstico pode ser difícil e o tratamento é controverso. Objetivo: O objetivo do estudo foi revisar a literatura sobre um tumor raro da glândula tireoide que possui alto índice de mortalidade. Método: Dois casos de leiomiossarcoma da tireoide são apresentados, e os 23 casos anteriores relatados na literatura atual foram revisados. Resultados: Um total de 25 casos de leiomiossarcoma da tireoide foi revisado. A queixa mais comum foi o rápido crescimento de um tumor cervical anterior; 10 dos 25 pacientes apresentavam metástases distantes no momento da admissão. Quinze dos 25 pacientes foram a óbito nos primeiros 12 meses após o diagnóstico. Conclusão: O diagnóstico diferencial de leiomiossarcoma da tireoide é importante e deve ser feito com outras doenças malignas da glândula, especialmente carcinoma anaplásico. O prognóstico é ruim e não há consenso em relação ao tratamento.

CT features of anaplastic thyroid carcinoma / 实用放射学杂志

Objective To summarize the CT features of anaplastic thyroid carcinoma (ATC).Methods CT manifestations of 12 patients with ATC confirmed by surgery or biopsy were analyzed retrospectively.Results 1 1 (91.7%)patients had single lesion. The lesions appeared as low attenuation mass with cord-like,flocculent or patchy high attenuation areas.The lesions had mild to moderate enhancement in 1 1 cases (91.7%).Coarse calcifications were detected in 8 cases (66.7%),4 of them were incomplete rim or eggshell.11 cases (91.7%)showed invasion into adjacent structures,including trachea (6 cases,50%),esophagus (4 cases,33.3%),strap muscles (7 cases,58.3%),larynx (2 cases,1 6.7%),blood vessels (6 cases,50%).5 cases (41.7%)had tumor thrombus in the internal jugular vein.10 cases (83.3%)had lymph nodes metastasis.The enhancements of lymph nodes were divided into 3 types:mild homogeneous enhancement (4 cases,40%),mild enhancement with internal low-attenuation areas (7 cases,70%)and ring-like enhancement without internal enhancement (7 cases,70%).Conclusion CT features of ATC include low-density mass with cords,flocculent and patchy high-density areas,coarse calcification and mild to moderate enhancement,invasion to adjacent structure and lymph node metastasis with necrosis are common.

Importance of Regular Follow-Up Examination during Active Surveillance: a Case of Anaplastic Transformation of Papillary Thyroid Microcarcinoma

Because papillary thyroid carcinoma (PTC) is indolent and has an excellent prognosis, active surveillance, without immediate surgery, can be considered for small PTC. However, rarely, PTC can transform to anaplastic thyroid carcinoma (ATC), over a period of 5-20 years. We report 73-year-old man with rapid anaplastic transformation of a PTC. He was diagnosed with colorectal cancer, and a 1-cm-sized thyroid nodule was found incidentally and confirmed as PTC on fine-needle aspiration. He underwent transanal excision and chemotherapy for colorectal cancer. However, he was not concerned about the PTC, and no follow-up examination was performed. After 37 months, he suddenly noticed an enlarging neck mass, which was diagnosed as an ATC. Despite total thyroidectomy, locally advanced recurrence with lung metastasis developed, and he eventually died. Although PTC is indolent and progresses slowly in elderly people, it can transform to ATC. Therefore, during active surveillance in the elderly, follow-up examinations should be performed regularly.

Importance of Regular Follow-Up Examination during Active Surveillance: a Case of Anaplastic Transformation of Papillary Thyroid Microcarcinoma

Because papillary thyroid carcinoma (PTC) is indolent and has an excellent prognosis, active surveillance, without immediate surgery, can be considered for small PTC. However, rarely, PTC can transform to anaplastic thyroid carcinoma (ATC), over a period of 5-20 years. We report 73-year-old man with rapid anaplastic transformation of a PTC. He was diagnosed with colorectal cancer, and a 1-cm-sized thyroid nodule was found incidentally and confirmed as PTC on fine-needle aspiration. He underwent transanal excision and chemotherapy for colorectal cancer. However, he was not concerned about the PTC, and no follow-up examination was performed. After 37 months, he suddenly noticed an enlarging neck mass, which was diagnosed as an ATC. Despite total thyroidectomy, locally advanced recurrence with lung metastasis developed, and he eventually died. Although PTC is indolent and progresses slowly in elderly people, it can transform to ATC. Therefore, during active surveillance in the elderly, follow-up examinations should be performed regularly.

Diagnosis of anaplastic thyroid carcinoma on fine needle aspiration cytology – A rare case report.

Anaplastic thyroid carcinoma [ATC] is a rare highly malignant tumor that arises from the follicular cells of the thyroid gland. It accounts for 1% to 2% of all thyroid carcinomas and patients outcome. Patients often present at an advanced stage, making curative surgical resection not feasible. Recognizing the cytological finding of the ATC and making the prompt and proper cytological. diagnosis are helpful to determine the treatment plan for the patients who suffer with this entity.

Inhibitory Effects of Phosphatidylinositol 3-kinase Inhibitor LY29400 Combined with Indole-3-carbinol on the Proliferation of Human Anaplastic Thyroid Carcinoma FRO Cells / 中国药房

OBJECTIVE:To study the inhibitory effects of phosphatidylinositol 3-kinase (PI3K) inhibitor LY29400 (“LY”) combined with indole-3-carbinol (I3C) on the proliferation of human anaplastic thyroid carcinoma FRO cells. METHODS:RFO cells in logarithmic growth phase were divided into blank control group,I3C (250 μmol/L) group,LY (10 μmol/L) group and combination (I3C of 250 μmol/L + LY of 10 μmol/L) group,which were subject to 24,48 and 72 h drug action. MTT method was used to determine and calculate the inhibitory rates of the cells in all groups,flow cytometry assay to determine the apoptosis rates after 48 h action,Western blot method to determine the expressions of Capspase-3 proteins thereafter and immunohistochemi-cal method to determine the expressions of Bcl-2 and Bax thereafter. RESULTS:The inhibitory rate obviously increased with the ex-tension of drug action time,with statistical significance at each time point in combination group (P<0.05). Compared to I3C group and LY group,combination group had higher inhibitory rate,apoptosis rate and the expressions of Capspase-3 protein and Bax,and lower Bcl-2 expression and ratio of Bcl-2 to Bax,with statistical significance (P<0.01). CONCLUSIONS:LY com-bined with I3C has synergistic inhibitory effects on the proliferation of FRO cells by a mechanism which may be related to apopto-sis induced by down-regulating Bcl-2 expression,up-regulating Bax expression and activating Caspase cascade reaction.

A Case of Rhabdomyosarcoma Presenting a Rapidly Growing Thyroid Mass Showing Cytological Features Mimic Anaplastic Thyroid Carcinoma / 대한갑상선학회지

This is a case of a 30-year-old man who was referred to our hospital for evaluation of a rapidly growing tumor in the left thyroid gland. It was palpated 2 weeks ago. But it was growing fast. A 4x3 cm mass was palpated in the left thyroid gland. Our impression was anaplastic thyroid carcinoma. Computed tomography finding indicated a thyroid malignant tumor and cytology result suggested spindle cell neoplasm. A lower anterior neck mass was resected and final histopathological result turns out to be a rhabdomyosarcoma (RMS). Although cervical RMS is very rare in adults, it has to be included for the differential diagnosis for the rapidly growing mass at thyroid gland.

Anti-mitogenic effect of sorafenib and metformin on human anaplastic thyroid carcinoma cells / 中华内分泌代谢杂志

Objective To elucidate the effect of multi-kinase inhibitor sorafenib on anaplastic thyroid carcinoma cells in the presence or absence of metformin.Methods SW1736 and C643 cells were treated with sorafenib in the presence or absence of metformin for various periods of time.Cell viability was detected by MTT.Cell cycle and cell apoptosis were measured by flow cytometry.Caspase-3 activity was detected by colorimetric kit.Western blot was used to analyze pERK phosphorylation and cyclinD1 expression.Results Sorafenib inhibited the growth of anaplastic thyroid carcinoma cells and induced cell cycle arrest and cell apoptosis.The EC50 of sorafenib in SW1736 and C643 was 3.68 μmol/L and 4.87 μmol/L respectively.After sorafenib ± metformin treatment,the caspase3 activity was 131.5 ％ and 278.0％ (P＜0.01) in SW1736 cells,127.2％ and 196.6％ (P＜0.01) in C643 cells.On the molecular level,sorafenib inhibited the phosphorylation of ERK and decreased the expression of cyclinD1.Metformin amplified the growth inhibitory effect of sorafenib on anaplastic thyroid carcinoma cells.The cell viability was 0.76 ± 0.17 and 0.30 ± 0.04 (P＜0.01) in SW1736 cells,0.72 ± 0.09 and 0.34 ± 0.10 (P＜0.001) in C643 cells after 2.5 μmol/L sorafenib without or with 5 mmol/L metformin treatment.Conclusions The combination of sorafenib and metformin may be a potent strategy for the treatment of anaplastic thyroid carcinoma and other advanced cancers.

Acute pyelonephritis with anaplastic thyroid carcinoma producing granulocyte colony-stimulating factor

Paraneoplastic leukocytosis was defined as elevated white blood cell (WBC) levels caused by cytokines, likely produced by the tumor itself, without evidence of infection or myeloproliferative disease. We report a case of anaplastic thyroid carcinoma with leukocytosis caused by elevated production of granulocyte colony-stimulating factor (G-CSF) by the carcinoma. Initially, acute pyelonephritis (APN) was diagnosed and treatment for APN was ongoing, but the WBC count steadily increased to 68.8x10(9)/L. She was diagnosed with anaplastic thyroid carcinoma on her neck mass, and the serum concentration of G-CSF was found to be markedly increased at 1,010 pg/mL. In spite of supportive care, the patient's condition rapidly deteriorated and the patient died on day 23 of hospital stay. Leukocytosis without definite evidence of infection could be a paraneoplastic manifestation in patients with malignant tumors, and paraneoplastic leukocytosis may be related to poor prognosis.

Acute pyelonephritis with anaplastic thyroid carcinoma producing granulocyte colony-stimulating factor

Paraneoplastic leukocytosis was defined as elevated white blood cell (WBC) levels caused by cytokines, likely produced by the tumor itself, without evidence of infection or myeloproliferative disease. We report a case of anaplastic thyroid carcinoma with leukocytosis caused by elevated production of granulocyte colony-stimulating factor (G-CSF) by the carcinoma. Initially, acute pyelonephritis (APN) was diagnosed and treatment for APN was ongoing, but the WBC count steadily increased to 68.8x10(9)/L. She was diagnosed with anaplastic thyroid carcinoma on her neck mass, and the serum concentration of G-CSF was found to be markedly increased at 1,010 pg/mL. In spite of supportive care, the patient's condition rapidly deteriorated and the patient died on day 23 of hospital stay. Leukocytosis without definite evidence of infection could be a paraneoplastic manifestation in patients with malignant tumors, and paraneoplastic leukocytosis may be related to poor prognosis.

Aberrant L1 Cell Adhesion Molecule Expression in Cancer: In View of Proliferation, Migration and Invasion / 대한갑상선학회지

L1 cell adhesion molecule (L1CAM) is a 220-kDa type I membrane glycoprotein and is normally expressed in neuronal cells, endothelial cells, and renal epithelial cells. Recent clinical studies demonstrated aberrant L1CAM expression in various cancers, especially at the invasive area of cancers. L1CAM has a key role in tumorigenesis, tumor invasion, and it is associated with a poor prognosis of cancer. Anaplastic thyroid carcinoma (ATC) has a highly poor outcome and it is resistant to conventional treatment. In this review, I discuss the biological role of L1CAM in proliferation, migration, and invasion in the ATC.