C Cell Carcinoma of the Thyroid Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immuno-histochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma. Acta Pathol Jpn 39: 393-399, 1989.     

Follicular Carcinoma Associated with Minocycline-Induced Black Thyroid

Grossly evident black pigmentation of the thyroid has been observed in a number of patients, most of whom have a history of chronic ingestion of minocycline. In the majority of reported cases, no thyroid dysfunction or lesion has been noted, although rare instances of papillary carcinoma have been described. We describe a patient with a history of chronic, minocycline ingestion, who presented with a neck mass of recent onset. Histologic examination of the thyroid revealed diffuse pigment deposition, typical for that seen in association with minocycline ingestion. Also present was a 3.2-cm follicular neoplasm with capsular and vascular permeation, consistent with minimally invasive follicular thyroid carcinoma. This represents the first report of follicular carcinoma associated with minocycline-induced black thyroid (MIBT).     

Squamous Differentiation in Thyroid Carcinoma With Special Reference to Histogenesis of Squamous Cell Carcinoma of the Thyroid

Squamous differentiation of thyroid carcinoma was studied clinicopathologically and immunohistochemically in 29 autopsy cases. Tumor cell nests with squamous differentiation (CNSD), which histologically resembled squamous cell carcinoma, were found in 6 cases (20.7%). All of these 6 cases with CNSD had areas of undifferentiated carcinoma, representing 31.6% of 19 cases with undifferentiated carcinoma, and all but one case also showed coexisting papillary carcinoma. The CNSD were histologically associated with undifferentiated carcinoma in 5 cases, and with papillary carcinoma in one case; the CNSD were occasionally intermingled with these types of carcinoma, and there were findings suggesting a histological transition between the CNSD and undifferentiated carcinoma or papillary carcinoma. Immunohistochemistry revealed that all the CNSD were reactive with antibodies for keratin and vimentin, whereas thyroglobulin and desmin were not expressed. It was concluded that the CNSD examined here were most probably due to extensive squamous differentiation (squamous metaplasia) in undifferentiated carcinoma and papillary carcinoma. In addition, the present results may explain the fact that cases diagnosed solely as squamous cell carcinoma sometimes show a prognosis similar to that of undifferentiated carcinoma, and may well represent extensive squamous differentiation in such tumors rather than true squamous cell carcinoma of the thyroid. Acta Pathol Jpn 39: 306 312, 1989.     

Palliative Radiation in Primary Squamous Cell Carcinoma of Thyroid: A Rare Case Report

Primary squamous cell carcinoma of the thyroid is an extremely rare neoplasm with aggressive behavior. Until date, only around 60 cases have been reported in the literature. Primary treatment of the patient is radical surgery. With optimum treatment survival is not more than 6 months in this aggressive malignancy. However in our patient surgery it was not possible because of unresectability of the mass due to encroachment of major vessels. Hence, we have delivered radiotherapy alone, with which effective palliation could be achieved and patient is leading a good quality-of-life for last 1 year.     

Columnar Cell Carcinoma of the Thyroid: MIB-1 Immunoreactivity as a Prognostic Factor

We report a case of columnar cell carcinoma of the thyroid. A 47-year-old Japanese man had a nonencapsulated thyroid mass that infiltrated the surrounding tissues extensively. Seventeen months after thyroidectomy he died of respiratory failure resulting from tracheal invasion. An autopsy showed distant metastases to the liver, lung, esophagus, and pancreas. Histologically, the thyroid mass consisted of tall columnar atypical cells with marked nuclear stratification. About one-fifth of tumor cells were immunopositive for MIB-1. The MIB-1 positive index of our case was extremely high, compared with that of ordinary papillary carcinoma. This case indicates that biological growth activity in columnar cell carcinoma may be similar to that of undiferentiated carcinoma of the thyroid, since the MIB-1-positive index is close to each other.     

22例儿童甲状腺癌临床病理分析

为探讨儿童甲状腺癌的临床病理特点、预后相关因素,回顾性总结了22例儿童甲腺状癌患者的临床病理特征及预后.结果显示,22例经病理组织学检查证实为儿童甲状腺癌的患者中,有4例为术前穿刺标本病理诊断为甲状腺癌,18例为术中病理冰冻切片诊断为甲状腺癌.22例均行手术切除治疗,其中19例为乳头状癌,2例为滤泡癌,1例髓样癌,淋巴...     

Mixed Medullary-Follicular Carcinoma of the Thyroid Immunohistochemical and Electron Microscopic Studies

A case of mixed medullary follicular carcinoma of the thyroid is reported. Grossly, the tumor was a solid, grayish white, well circumscribed mass without lymph node metastasis. Microscopically, the tumor showed both medullary and follicular areas. The follicular areas occupied discrete portions of the tumor, and were considered to be neoplastic. Tumor cells in the medullary area were polyhedral or spindle-shaped. There was no amyloid deposition within the tumor. Immunohistochemically, tumor cells in the medullary area were positive for calcitonin and negative for thyroglobulin. Some cells lining the follicles were positive for thyroglobulin. By electron microscopy, two types of tumor cell were observed. One type contained numerous cytoplasmic secretory granules, whereas the other type had few granules and showed a prominent rough endoplasmic reticulum. These findings suggested that this mixed medullary follicular carcinoma of the thyroid presented neoplastic changes within a common cell lineage.     

Carcinoembryonic Antigen and Nonspecific Cross-reacting Antigen in Medullary Carcinoma of the Thyroid

Carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) were studied immunohisto-chemically in formalin fixed, paraffin embedded tissues of 73 cases of medullary carcinoma of the thyroid (MTC) using 2 polyclonal antibodies (CEA antisera cross-reactive with or without NCA), 3 monoclonal antibodies recognizing epitopes only on CEA, and one monoclonal antibody against NCA. The staining patterns of the 5 antibodies against CEA in MTCs were not different, and they reacted with 86.3% of all cases. With regard to the effects of fixatives on the staining patterns, samples fixed with formalin or 4% paraformaldehyde demonstrated CEA immunoreactivity in both the cell membrane and cytoplasm. In Bouin fixed tissue, the immunoreactivity was predominant on the cell membrane, whereas cytoplasmic positivity predominated in alcohol fixed specimens. Thus the difference in fixatives used in previous studies does not appear to be a major reason for the difference in the reported incidence of CEA positive MTCs. It is concluded that CEA is still a useful tumor marker for MTC and that it is detectable only in thyroid tumors originating from C cells, as seen in our series. The epitope defined by monoclonal antibody F106 88, present only on NCA, was found in 42.5% of all cases (49.2% of CEA positive MTCs). The NCA immunoreactivity was located in the tumor cell cytoplasm as globular aggregates, which were also labeled for CEA.     

The Pathology of Medullary Carcinoma of the Thyroid: Review of the Literature and Personal Experience on 62 Cases

The aim of the present review is to analyze the numerous pathological patterns of medullary carcinoma of the thyroid (MCT) and discuss the problems of differential diagnosis with other thyroid and nonthyroid tumors. In addition, morphological parameters and phenotypic features were related to the clinical outcome. The recent literature was reviewed and compared with the features of 62 MCTs observed at our institution. The most common patterns of growth are trabecular, alveolar, and spindle cells, but MCT can mimic virtually all other primary thyroid tumors and some nonthyroid neoplasms. This heterogeneity has no proven implications for prognosis, but is of relevance for diagnostic purposes, as the differential diagnosis of MCT can be difficult in nonclassical cases. In agreement also with the literature data, no relationship between histopathological parameters and outcome was found in our series, although clinically aggressive tumors had a more advanced stage at presentation. Immunocytochemical demonstration of calcitonin is apparently the only valid criterion for a correct typing of MCT. Chromogranin A is an additional sensitive marker of MCT and parallels calcitonin expression in the majority of cases.     

Lung Carcinoma Metastatic to Microfollicular Adenoma of the Thyroid A Case Report

A 75-year-old woman with lung adenocarcinoma in whom autopsy revealed metastasis to microfollicular adenoma of the thyroid is described. A thyroid tumor specimen from this patient was initially interpreted as representing primary encapsulated follicular carcinoma of the thyroid associated with a component of poorly differentiated carcinoma of follicular cell origin. The widespread involvement of the lungs and other sites was also interpreted as metastases from the poorly differentiated carcinoma component within the encapsulated follicular carcinoma of the thyroid. Subsequent meticulous histologic examination revealed that the thyroid tumor was a microfollicular adenoma, and that the component of poorly differentiated carcinoma within it was the same as the lung carcinoma. Immunohistochemical investigation revealed that the poorly differentiated carcinoma cells within the thyroid tumor were stained positively with polyclonal and monoclonal antibodies against carcinoembryonic antigen (CEA) and negative for thyroglobulin and calcitonin. The carcinoma cells from the lungs and other sites also showed positive staining for CEA. These findings support the view that the component of poorly differentiated carcinoma was a metastatic lesion from the primary lung carcinoma to the microfollicular adenoma of the thyroid. The present study emphasizes that attention should be directed to thyroid metastasis, even if it is within a thyroid primary neoplasm.     

Diffuse Sclerosing Variant of Papillary Carcinoma of the Thyroid Report of Three Cases

Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 consecutive malignant tumors of the thyroid gland retained in the surgical pathology files of Kanazawa University Hospital over the last 10 years. The tumors were characterized by diffuse involvement of one or both lobes of the thyroid, dense fibrosis, papillary carcinoma with marked squamous metaplasia and abundant psammoma bodies, heavy lymphocytic infiltration and extensive lymphatic permeation. In two cases, the neoplasms showed more aggressive regional lymph node metastases and local invasion; the patient in the first case underwent surgery three times after initial radical surgery because of regional lymph node recurrences, and the second case showed direct invasion of the thyroid tumor to the larynx and distant metastasis to the lungs. Although the number of examined cases was small, the findings suggest that the diffuse sclerosing variant type has a less favorable prognosis and should be differentiated from papillary carcinomas with excellent prognosis.     

ER、PR及其相应拮抗剂与甲状腺癌的相关性研究进展

雌激素受体(ER)、孕激素受体(PR)在甲状腺癌中的异常表达说明性激素受体在甲状腺癌的发病机制中起重要作用.ER、PR通过经典的基因途径及非基因途径对甲状腺癌的发生、发展及生物学特征产生重要影响.性激素受体拮抗剂抑制甲状腺癌细胞增殖作用的研究,将为甲状腺癌的治疗提供新的选择方案.     

Combined "Mixed Medullary-Follicular" and "Papillary" Carcinoma of the Thyroid with Lymph Node Metastasis

We report a case of combined “mixed medullary-follicular” and “papillary” carcinoma of the thyroid that occurred in a 44-yr-old Japanese woman. The grossly single 3 cm tumor was histologically composed of both mixed medullary-follicular carcinoma and papillary carcinoma, which abutted against each other with a clear border between two components. Immunohistochemically, the component of medullary carcinoma was positive for calcitonin and carcinomebryonic antigen (CEA), and the follicular carcinoma and papillary carcinoma components were positive for thyroglobulin. Lymph node metastasis was also noted. The patient has been alive without recurrence for 20 yr. To the best of our knowledge, this is the first reported case in the literature. We report this unique case of thyroid carcinoma and review related thyroid malignancies.     

IL-17和IL-35水平与甲状腺癌关系的Meta分析

目的 探讨白细胞介素(interleukin,IL)-17和IL-35水平与甲状腺癌的关系.方法 应用计算机检索PubMed、中国知网和万方数据库自200年1月至2016年12月关于IL-17和IL-35水平与甲状腺癌关系的临床对照试验.按纳入和排除标准选择文献,提取数据.采用Stata12.0软件对纳入文献进行Meta分析.结果 纳入文献5篇,样本量409例.与对照组比较甲状腺癌患者IL-17水平明显增加[WMD=6.31, 95%CI(5.89, 6.73)],而IL-35水平明显减低[WMD=-8.52, 95%CI(-9.40, -7.63)],其差异均具有统计学意义(P均<0.05).结论 现有证据表明IL-17和IL-35水平与甲状腺癌的关系密切,其可为甲状腺癌的诊断、治疗和预后提供依据.     

Effects of Dietary Iodine on Chemical Induction of Thyroid Carcinoma

Effects of dietary iodine on the induction of thyroid carcinoma using N-nitrosobis(2 hydroxypropyl)amine (BHP) were studied. Male Wistar rats were fed with an iodine-adequate diet (IAD group), an iodine-rich diet (IRD group) and an iodine-deficient diet (IDD group), respectively, until the time of sacrifice. From the 2nd experimental month, animals were injected with BHP once a week for 10 weeks. In the IAD and IRD groups, benign nodules and papillary carcinoma were found. The incidence of rats with benign nodules was 100% in both groups and animals with papillary carcinoma in the IAD and IRD groups comprised 33% and 29%, respectively. The area of the thyroid gland occupied by nodular lesions was much narrower in the IRD group than in the IAD group. In the IDD group, the thyroid showed marked enlargement due to multiple nodular proliferation of follicle cells. The incidence of rats with carcinoma was 100%, and not only papillary but also follicular carcinoma and one pulmonary metastasis were found. As the iodine content of the diet decreased, the nodular lesions increased in width and number, and the incidence of carcinoma in rats became higher. These effects of dietary iodine are probably related to the goitrogenic and/ or promoting effects of TSH. Acta Pathol Jpn 40: 705-712, 1990.     

Familial Non-Medullary Thyroid Carcinoma: An Update

Familial thyroid cancer can arise from follicular cells (familial non-medullary thyroid carcinoma (FNMTC)) or from the calcitonin-producing C-cell (familial medullary thyroid carcinoma). This is usually a component of multiple endocrine neoplasias (MEN) IIA or IIB, or as pure familial medullary thyroid carcinoma syndrome. The genetic events in the familial C-cell-derived tumors are known and genotype–phenotype correlations are well established. In contrast, the case for a familial predisposition of non-medullary thyroid carcinoma is only now beginning to emerge. Although the majority of papillary (PTC) and follicular thyroid carcinomas (FTC) are sporadic, familial tumors account for over 5% of cases. The presence of multifocal papillary carcinoma is a common feature of FNMTC. The familial follicular cell-derived tumors or non-medullary thyroid carcinomas encompass a heterogeneous group of diseases, including diverse syndromic-associated tumors and non-syndromic tumors. Based on clinico-pathologic findings, FNMTC is divided into two groups. The first includes familial syndromes characterized by a predominance of non-thyroidal tumors, such as familial adenomatous polyposis (FAP), PTEN hamartoma tumor syndrome (PHTS), Carney complex type 1, and Werner syndrome. The second group includes familial syndromes characterized by a predominance of NMTC, such as pure familial (f) PTC with or without oxyphilia, fPTC with papillary renal cell carcinoma, and fPTC with multinodular goiter. Some characteristic morphologic findings should alert the pathologist of a possible familial cancer syndrome, which may lead to further molecular genetic evaluation.     

RET Proto-Oncogene and Thyroid Cancer

TheRET proto-oncogene has not only conclusively been identified as responsible for the three subtypes of the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN-2) but also shown to be involved in the molecular evolution of sporadic medullary and papillary thyroid carcinoma as well as Hirschsprung’s disease. A variety of recent studies have elucidated the pathophysiological mechanisms leading to neoplastic disease and we now understand that dominant activating germline mutations lead to MEN-2A, MEN-2B, and familial MTC; somatic mutations to sporadic medullary thyroid carcinoma;RET rearrangements to papillary thyroid carcinoma; and inactivating alterations to Hirschsprung's disease. The clinical significance, however, ofRET alterations especially in sporadic thyroid tumors is still controversial and therapeutic concepts in MEN-2 gene carriers only start to emerge. This article is a short summary of the recent findings on the structure and physiology of theRET proto-oncogene and its role in familial and sporadic thyroid cancer. This article was presented in part at the Endocrine Pathology Society Companion Meeting of the USCAP in Orlando, FL, March 1, 1997.     

Renal Cell Carcinoma Metastatic to the Thyroid Gland: A Comparative Molecular Study Between the Primary and the Metastatic Tumor

A case of renal cell carcinoma metastatic to the thyroid gland is presented. The thyroid tumor showed typical features: clear cells arranged in nets with a prominent sinusoidal vascular pattern. The histologic appearance was identical to the renal tumor removed 6 yr before. A comparative molecular study between the primary and the metastatic tumor showed a common profile with a loss of heterozygosity at identical loci on chromosome 3, which provided further support to the metastatic nature of the thyroid tumor. However, the frequent existence of allele losses on chromosome 3p in both renal cell carcinomas and primary thyroid follicular carcinomas rest some force from such a molecular approach to the differential diagnosis of thyroid tumors that contain a predominant population of clear cells.