Relation between estrogen receptor and malignancy of thyroid cancer

The relationship between the histological grade of dedifferentiation of thyroid cancer and estrogen receptors (ER) was examined immunohistochemically. Thyroid cancers were from postmenopausal females of almost the same mean age (69-73 years old) and within the same period of time (1974-1983). ER immunoreactivity located in the nucleus of the epithelium was found in all 6 well differentiated papillary cancers, and 5 of them (83.3%) showed ER-immunoreactive (ER-IR) cells amounting to 20 or more per visual field (x 100) under a light microscope. Of the 6 cases of poorly differentiated papillary cancer, 5 (83.3%) had 1-19 ER-IR cells per visual field. ER-IR cells were negative in 5 out of 6 cases (83.3%) of anaplastic cancers. Thus, the number of ER-IR cells tended to decrease with the degree of atypism of thyroid cancer (P less than 0.001).     

An immunohistochemical study of estrogen receptors in thyroid carcinoma

Estrogen receptors immunoreactivity (ER-IR) has been examined in 64 cases of human thyroid carcinomas. ER-IR was found to be located in the nucleus of cancer cells and was detected in 30 (57.7%) of 52 papillary carcinomas that were examined. Eleven cases showing a good number of ER-IR positive cancer cells revealed a lowered EORTC index of under 65, and no ER-IR was found in 12 anaplastic carcinomas. These findings indicate that ER-IR might generally bear a similar reciprocal relationship to the malignancy of a thyroid carcinoma.     

New developments in the diagnosis and treatment of thyroid cancer

Answer questions and earn CME/CNE Thyroid cancer exists in several forms. Differentiated thyroid cancers include those with papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from those of differentiated thyroid tumors. Genetic testing and newer adjuvant therapies have changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, workup, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. CA Cancer J Clin 2013;63:373‐394. ^©2013 American Cancer Society, Inc.     

Descriptive Epidemiology of Thyroid Cancers in Togo

Background: The purpose of this study was to provide epidemiological and histological data of thyroidcancers in Togo. Materials and Methods: This was a retrospective cross-sectional study of cases of thyroidcancers diagnosed from 2000 to 2014 (15 years) at the pathology laboratory of the Sylvanus Olympio TeachingHospital of Lomé. All cases of review of a thyroid sample (biopsies, surgical specimens) were collected from thedata records of that laboratory. Results: Thyroid cancers represented 1.1% (7930cases) of all cancers registeredduring the study period. Mean age was 45.4±0.3 years and the proportion of females was 78.3%. We identified92.4% carcinomas and 7.6% lymphomas. Carcinomas were well differentiated in 80 cases and were dominatedby the papillary type (47 cases). Metastasis was observed in 13% of patients. The pTNM classification evaluatedin 18 cases showed a predominance of grade I (13 cases). Lymphomas were dominated by lymphoma diffuse largeB-cell (5 cases). Conclusions: This study is the first global standard for thyroid cancer pathology in Togo. Thehigh frequency of follicular form suggests an unrecognized iodine deficiency. The improvement of the technicalplatform of the LAP (immunohistochemistry) will increase the diagnosis of rare forms of thyroid cancer.     

Genetic Aspects of Familial Thyroid Cancer

Familial thyroid cancer is rare, accounting for <10% of thyroid cancer cases. Activating germline point mutations in the RET proto‐oncogene are associated with multiple endocrine neoplasia types 2A, 2B, and familial medullary thyroid cancer (FMTC)—around 3% of thyroid cancer cases. Familial papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) have been identified as a distinct group of familial thyroid cancers. Sporadic nonmedullary thyroid cancer (NMTC) accounts for ～90% of all thyroid cancers—about 6% of NMTCs are familial (FNMTC). Although multiple endocrine neoplasia types 2A and 2B and FMTC are well characterized, very little is known about the genetic predisposition to PTC and FTC. In this paper, the genetic types of FMTC and FNMTC are reviewed and the clinical features and screening are outlined.     

Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults

Purpose The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase (TP) inside target tissues. 5-FU interferes with DNA synthesis by blocking thymidylate synthase (TS) but is inactivated by dihydropyrimidine dehydrogenase (DPD). Favorable enzyme profiles (high TP and low DPD) generate high intratumor levels of 5-FU that are effective against many tumors, especially those with low TS. Capecitabine has not been tested against thyroid cancers, and it is not known to what extent thyroid cancers express TP, TS or DPD.Methods To test this, we determined TP, TS and DPD in 19 thyroid cancers from young patients (14 papillary, 4 follicular, 1 medullary) by immunohistochemistry. After approval by the Human Use Committee, the intensity of TP, TS, and DPD staining was determined by two independent examiners and graded (absent=0 to intense=3) with >90% concordance.Results TS was detected in 7/19 cancers (37%), TP in 14/19 cancers (74%) and DPD in 14/19 cancers (74%). In six tumors, TP was more intense that DPD, suggesting capecitabine sensitivity. Only five tumors failed to express TP but four of these expressed DPD, suggesting capecitabine resistance. Overall, 6/19 tumors (32% of the total) had a favorable expression profile, and all of them were papillary cancers.Conclusions We conclude that the majority of differentiated thyroid cancers (74%) express TP and low levels of TS (63% undetectable). The results support the hypothesis that capecitabine is activated in the majority of differentiated thyroid cancers and that 32% have favorable expression of all three enzymes (TP, TS, and DPD).The opinions or assertions contained herein are the personal views of the authors and are not to be construed as official or to reflect the opinions of the Uniformed Services University of the Health Sciences, The Department of the Army, or The Department of Defense.     

A report of six cases of familial papillary thyroid cancer.

AIMS: Familial occurrence of papillary thyroid cancer is uncommon. The purpose of this study was review our own experience in a series of 267 papillary thyroid cancers. METHODS: We analysed the clinical records of 267 consecutive patients operated on for papillary thyroid cancer (PTC) in our hospital between June 1980-March 2000. RESULTS: We identified a family history in three families (6 patients), which results in a 2.25% familial papillary thyroid carcinoma (FPTC) rate. Pathology findings revealed that the tumour was multifocal and bilateral in 2 patients. Lymph-node metastases were found in 4 patients. They are all alive with a mean time of follow-up of 74.3 months (range 2-120). CONCLUSIONS: We recommend that patients with familial disease should be treated according to the disease stage and other risk factors, similar to those with sporadic differentiated papillary thyroid cancer. We encourage the further reporting and pedigree analysis to identify patients affected by FPTC.     

甲状腺癌合并呼吸困难的处理

1980～1988年共治疗甲状腺癌合并呼吸困难10例,手术切除8例,切除率80％,无手术死亡。因纵隔广泛受累,仅切检后放、化疗和术中探查,发现癌块包绕颈动脉,未能切除,仅切检并狭窄平面下气管切开各1例,切除例剔除气管受累处:气管壁洞穿性缺损直径0.5cm 3例,均行气管造口;气管后间隙残留癌灶行狭窄平面下气管切开1例。切除例中,5例术后分别健在6年,5年半、5年、3年和1年半;2例于术后1、2年内死亡;1例2年后失访。未切除2例中,1例带瘤生存6月,另1例6月后死亡。提倡在无手术禁忌情况下争取较彻底切除。     

Parental cancer and risk of papillary and follicular thyroid carcinoma.

In a population-based case-control study in the Uppsala-Orebro Health Care Region of Sweden, the histories of cancer among parents of 517 histologically confirmed cases of papillary and follicular carcinoma and of a similar number of sex- and age-matched controls were compared. The parental history of cancer was compiled through information from death certificates and from the nationwide Cancer Register. The incidence of malignancies in a cohort of parents of cases of thyroid cancer was also compared with the incidence in the whole Swedish population. A maternal history of cancer was more common among women with follicular carcinoma than among their controls (OR 2.11, 95% CI 0.96-4.67). Parents of probands with papillary carcinoma had an increased risk of thyroid cancer (OR 4.25, 95% CI 1.16-10.89), and mothers of probands with follicular carcinoma had an increased risk of stomach cancer (OR 3.65, 95% CI 0.99-9.35) compared with the general population. Cancer of the lung, breast, and pancreas were less common than in the general population. Familial cases of thyroid cancer were not limited to the papillary type. An inheritable pattern of carcinogenesis is possible for certain differentiated non-medullary thyroid cancers, but shared environmental exposures may also explain the parent-child associations of cancer in this study.     

新疆地区907例甲状腺癌回顾性分析

目的：探讨新疆地区人群甲状腺癌的发病特点。方法：收集新疆医科大学第一附属医院2003年1月-2013年12月甲状腺癌患者病例资料907例，用SPSS 22.0及Microsoft Excel 2007软件分析新疆地区人群甲状腺癌的发病趋势及性别、年龄和族别差异。分析方法采用χ²检验，检验水准α=0.05。结果：2003-2013年间，甲状腺癌的构成比呈上升趋势；甲状腺癌的病理类型主要为乳头状癌（90.96%）；患者男女人数比例1∶2.88，其构成比具有性别差异（P < 0.05），男女发病年龄高峰均为40～49岁，女性病例增加程度高于男性；甲状腺癌的组织类型在汉族与维吾尔族间分布不同（P < 0.05），乳头状癌在汉族患者中的比例（93.77%）高于维吾尔族（83%）。结论：过去10年当中该院收治甲状腺癌患者逐年增多，女性患者增加人数多于男性，男、女性甲状腺癌的高发年龄均为40~49岁，乳头状癌是主要的病理类型，病理类型的分布在汉族和维吾尔族之间存在差异。     

分化型甲状腺癌患者的临床特点及预后分析

目的 分析分化型甲状腺癌患者的临床特点及预后影响因素.方法 收集147例分化型甲状腺癌患者的临床资料,包括一般资料、手术方法、术后基本情况及临床特征,采用Logistic回归模型分析分化型甲状腺癌患者预后的影响因素.结果 147例分化型甲状腺癌患者中,单侧发病95例,双侧发病52例;单发59例,多发88例;91.16％...     

Prospective study of body mass index,physical activity and thyroid cancer

Increased body size and physical inactivity are positively related to risk of several cancers, but only few epidemiologic studies have investigated body‐mass index (BMI) and physical activity in relation to thyroid cancer. We examined the relations of BMI and physical activity to thyroid cancer in a prospective cohort of 484,326 United States men and women, followed from 1995/1996 to 2003. During 3,490,300 person‐years of follow‐up, we documented 352 newly incident cases of thyroid cancer. The multivariate relative risks (RR) of thyroid cancer for BMI values of 18.5–24.9 (reference), 25.0–29.9 and ≥30 kg m^?2 were 1.0, 1.27 and 1.39 [95% confidence interval (CI) = 1.05–1.85]. Adiposity predicted papillary thyroid cancers (RR comparing extreme BMI categories = 1.47; 95% CI = 1.03–2.10) and, based on small numbers, suggestively predicted follicular thyroid cancers (RR = 1.49; 95% CI = 0.79–2.82) and anaplastic thyroid cancers (RR = 5.80; 95% CI = 0.99–34.19). No relation with BMI was noted for medullary thyroid cancers (RR = 0.97; 95% CI = 0.27–3.43). The positive relation of BMI to total thyroid cancer was evident for men but not for women. However, the test of interaction (p = 0.463) indicated no statistically significant gender difference. Physical activity was unassociated with thyroid cancer. The RRs of total thyroid cancer for low (reference), intermediate, and high level of physical activity were 1.0, 1.01 and 1.01 (95% CI = 0.76–1.34, p for trend = 0.931), respectively. Our results support an adverse effect of adiposity on risk for developing total and papillary, and possibly follicular thyroid cancers. Based on only 15 cases, adiposity was unrelated to medullary thyroid cancers. Physical activity was unrelated to total thyroid cancer.     

结节性甲状腺肿合并甲状腺癌诊治分析

目的　总结结节性甲状腺肿合并甲状腺癌的诊治经验。方法　回顾性分析 2 3例结节性甲状腺肿合并甲状腺癌的临床资料。结果　同期手术治疗结节性甲状腺肿患者 83 6例 ,合并甲状腺癌 2 3例 ( 2 .75 % ,2 3 /83 6)。病理检查结果示 :灶性癌变 3例 ,微小癌变 8例 ,乳头状癌 11例 ,乳头状癌并滤泡状癌 1例。所有患者均行术中快速冷冻病理检查 ,并根据病理检查结果采取不同的手术方式 ,术后长期服用甲状腺素片。结论　结节性甲状腺肿临床中常见 ,但并发甲状腺癌诊断困难 ,多为分化好的乳头状癌。结节性甲状腺肿的手术指征应放宽 ,术中快速冷冻病理检查有利于选择正确的手术方式 ,使治疗合理有效     

直肠癌ER／PE受体表达及预后关系的病理学分析

 本文应用石蜡切片免疫组化PAP法，回顾性观察了61例直肠中分化管状腺癌组织ER、PR表达情况。ER(+)/PR(+)为42.6%；ER(-)/PR(-)为57.4%。ER/PR的存在表明该癌组织具有了依赖性激素的特性。ER(+)/PR(+)者的中位生存期为4.5年，一、三、五年生存率为88.5%、53.9%、38.5%，均高于ER(-)/PR(-)者的生存率。　ER(-)/PR(-)者的中位生存期为2.4年，一、三、五年生存率为65.7%、42.8%、28.6%。表达阳性与阴性两者的生存期有明显差异(P<0.01)。检测ER/PR受体亦可做为判定预后的指标之一。本实验证实ER、PR表达与年龄、性别以及LNM之间无明显差异(P>0.05)。     

分化型甲状腺癌再次手术临床分析

目的:探讨分化型甲状腺癌再次手术的原因、时机及对策。方法:对5年来收治的甲状腺手术后病理证实为分化型甲状腺癌,需要再次手术治疗的30例临床病理资料进行回顾性分析。结果:24例再次手术的原因为将分化型甲状腺癌误诊为甲状腺良性病变,手术切除范围不够,4例原因为分化型甲状腺癌术后复发,2例原因为131I治疗前的甲状腺清除。结论:分化型甲状腺癌的误诊是造成甲状腺癌再次手术的主要原因,应强调术中快速冰冻病理检查在甲状腺手术中的常规应用。     

Second primary malignancies in thyroid cancer patients

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.     

Histological validation of diagnoses of thyroid cancer among adults in the registries of Belarus and the Ukraine

In order to evaluate the diagnostic reliability of the thyroid cancers listed in adult registries from the Ukraine and Belarus, a histological review was organised of 327 randomly selected thyroid carcinoma cases diagnosed between 1980 and 1999. A final diagnosis was reached at a 5-day consensus conference by six pathologists who met around a multiheaded microscope. The study concluded with a comparison between the final diagnosis and the initial diagnosis. The pathologists agreed with the initial diagnosis of malignancy in 286 cases (88%). A final diagnosis of papillary, follicular or medullary thyroid carcinoma was reached in 86, 4, and 6% of the cases respectively. In 2.8% of the cases reviewed, diagnostic discrepancies persisted. The percentage of agreement between the final diagnosis and the initial diagnosis was 93%, with a weighted kappa-statistic of 0.61 (confidence interval 95% (CI(95%)): [0.45-0.77]). In all, 89% of the 286 confirmed cancer cases were in agreement for the type of cancer, with a kappa-statistic of 0.56 (CI(95%): [0.43-0.69]). The level of agreement differed according to cancer categories, with concordance rates of 94, 40 and 33% for papillary, follicular and medullary thyroid carcinomas respectively. The low prevalence of follicular thyroid carcinomas in the adult population studied calls for further exploration. The discrepancies and classification difficulties encountered were analysed.     

Immunohistochemical detection of estrogen receptors in paraffin sections of human thyroid tissues.

The optimal demonstration of estrogen receptor binding in thyroid tissues was made under conditions of 10% protease in 50 mM Tris-HCl buffer (pH 7.6) for 10 min as the pretreatment digestion step, incubation of primary antibody (ER-ICA monoclonal kit; Abbott Laboratories) at 37 degrees C for 2 h and incubation of secondary antibody (ABC kit; Vector) at 37 degrees C for 40 min. Thyroid tissues used for assessing the reaction were 17 cases of goiter, 25 adenoma cases, 27 cases of papillary carcinoma, 14 cases of follicular carcinoma and 10 latent cancer cases. Incidences of positive estrogen receptor reaction were 22% (11/51) for all thyroid cancers, 20% (5/25) for the thyroid adenomas and 59% (10/17) for goiters. 15% (4/27) of papillary carcinomas, 21% (3/14) of follicular carcinomas and 40% (4/10) of latent cancers proved positive, the estrogen receptor reaction being limited to the nuclei of thyroid follicular/papillary type cells.     

Cytologic features of aggressive variants of follicular-derived thyroid carcinoma

Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive thyroid cancer subtypes is sometimes challenging and subject to increased interobserver variability. This review deals with the cytological features of such tumors including aggressive variants of papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. These malignancies fall into 2 groups based on their cytomorphology: those that exhibit distinct microscopic features (eg, nuclear findings typical of classical papillary thyroid carcinoma or marked anaplasia) and those that present with more subtle cytologic features (eg, nuclear pseudostratification, “soap bubble” nuclei, supranuclear or subnuclear cytoplasmic vacuoles, rosette-like structures, hobnail cells). We review the literature regarding these aggressive thyroid cancers and highlight important phenotypic characteristics that can be useful for their diagnosis based on fine needle aspiration.     

Quantification of thyroglobulin messenger RNA by in situ hybridization in differentiated thyroid cancers. Difference between well-differentiated and moderately differentiated histologic types

Thyroglobulin messenger RNA (mRNA) was located and quantified in tissue sections of differentiated human thyroid cancers by in situ hybridization using cloned complementary DNA probes. The cells of the well-differentiated follicular and papillary forms contained similar levels of thyroglobulin mRNA, corresponding to about 2000 copies per cell. In contrast, cells of moderately differentiated thyroid cancers contained about two to three times less thyroglobulin mRNA. It was also found that thyroglobulin mRNA was present almost exclusively in polyribosomes under the form of heavy polyribosomes actively synthesizing thyroglobulin. It is suggested that in situ hybridization method allows localization of specific mRNA in differentiated thyroid cancers and correlation with the level of differentiation of the cells.