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.     

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.     

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.     

Electron Microscopic Study of Adenoid Cystic Carcinoma

This ultrastructural study is based on nine cases of adenoid cystic carcinoma arising from the salivary glands. Electron microscopically, the tumors consisted of five cell types: relatively differentiated intercalated duct cells, secretory cells, undifferentiated cells, cells of a squamous nature, and myoepithelial cells. Special attention was paid to the characteristic extracellular substances noted by light microscopic examination of these tumors. The hyaline material of the pseudocysts contained not only mucopolysaccharide granules but also fingerprintlike structures formed by replicated basement membrane. Some of these structures had a dense core, probably composed of mucopolysaccharide granules. Cell islands surrounded by elasticlike material also were found. The true lumina were usually filled with membranovesicular structures originating from fragments of the lining cells, mainly those with squamous differentiation. These membranovesicular structures included electron-dense rods, filamentous whorls, and structures displaying periodicity.     

Electron Microscopic and Immunohistochemical Analysis of Glomerular Deposits in Patients with Bronchogenic Carcinoma

Kidneys of 27 consecutive autopsied patients with bronchogenic carcinoma without clinical renal disease were studied by electron microscopy and immuno-histochemistry for the presence of glomerular deposits. Two patients had subepithelial electron-dense deposits compatible with immune complexes but failed to stain histochemically for immunoglobu-lin; most cases (19 of 27). including the two with complexes, demonstrated subendothelial deposition of fibrin. No tissue samples had histochemically detectable immunoglobulin. From this study it is suggested that renal immune complexes in lung cancer are rare.     

Immunohistochemical Demonstration of Epidermal Growth Factor Receptor and Ceruloplasmin in Thyroid Diseases

The expression of epidermal growth factor receptors (EGFR) and ceruloplasmin (CP) in thyroid diseases was investigated by immunohistochemical methods, and the results were compared with the expression of thyroglobulin (TG). Eighty eight surgical specimens of thyroid diseases, including follicular carcinoma (7 cases), papillary carcinoma (20 cases), follicular adenoma (29 cases), adenomatous goiter (10 cases), diffuse hyperplasia (20 cases) and chronic thyroiditis (2 cases), were studied. All cases of follicular carcinoma and 18 cases (90%) of papillary carcinoma expressed the EGFR immunoreaction in the cytoplasm with a moderate to strong staining intensity. A weak immunoreaction for EGFR was noted in some benign thyroid diseases. CP showed various degrees of positivity in all cases of follicular carcinoma and 19 cases (95%) of papillary carcinoma. The benign thyroid lesions were consistently negative for this antigen, not counting one case of Hiirthle cell adenoma. There was a positive correlation between EGFR and CP immunostaining intensity in thyroid carcinomas, representing higher expression of EGFR accompanied by a stronger staining intensity of CP. Except for two cases of papillary carcinoma, all cases showed immunoreaction for TG. The results indicate the enhanced expression of EGFR and CP in thyroid carcinomas. EGFR and CP thus appear to be valuable tools for differential diagnosis between benign and malignant thyroid neoplasms.     

An Immunohistochemical Study of Calcitonin–containing Cells in Benign and Malignant Thyroid Lesions

Parafollicular cells (C-cells) in benign and malignant thyroid lesions were studied immunohistochemically with a polyclonal anti-calcitonin (CT) antibody. The C-cells were seen most frequently in the middle third of the lateral lobes in the thyroid gland of normal individuals and patients with Graves' disease and chronic thyroiditis, although in the latter the number of such cells was significantly decreased (p< 0.05). In adenomatous goiter, C-cells were present in nodular lesions from an early stage of nodule development (frequency about 19%), whereas in the later stage these cells were rarely observed inside type 1 nodules, which were generally characterized by an admixture of follicles with considerably different sizes. However, C-cells were not observed inside type 2 nodules, which were composed of similar-sized follicles, or in the parenchyma of 56 cases of benign and malignant thyroid tumors. These findings suggest that since C-cells are present in nodular lesions, the histogenesis of adenomatous goiter is quite different from that of follicular adenoma; thyroid neoplasms generally contain no C-cells in the parenchyma. Acta Pathol Jpn 40: 187-192, 1990.     

Mixed Medullary-Follicular Thyroid Carcinoma : Molecular Evidence for a Dual Origin of Tumor Components

Mixed medullary-follicular carcinomas (MMFCs) are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. The histogenetic origin and possible molecular mechanisms leading to MMFCs are still unclear. To address these questions, we have isolated the two histological components of 12 MMFCs by (laser-based) microdissection, analyzed them for mutations in the RET proto-oncogene and allelic losses of nine loci on six chromosomes, and studied the clonal composition of MMFCs in female patients. Our results provide strong evidence that the follicular and medullary components in MMFCs are not derived from a single progenitor cell, because the seven tumors amenable for analysis consistently exhibited a different pattern of mutations, allelic losses, and clonal composition. We also demonstrate that follicular structures in MMFCs are often oligo/polyclonal and more frequently exhibit hyperplastic than neoplastic histological features, indicating that at least a subset of MMFCs are composed of a medullary thyroid carcinoma containing hyperplastic follicles.     

甲状腺球蛋白测定与131I全身显像在甲状腺乳头癌复发监测中的意义

探讨甲状腺球蛋白(Tg)和131I全身显像(131I-WBS)在甲状腺乳头癌(PTC)复发监测中的意义. 30例PTC患者术后6周,行131I(3.7GBq)首次清除残留甲状腺组织治疗,6个月后再给予131I 治疗1次,治疗中同时测定Tg和进行131I-WBS.结果表明,在首次清除残留甲状腺组织治疗时,显像发现淋巴、肺及骨转移6例,其余转移灶于6个月治疗时发现,有3例患者(10%)Tg测定在正常范围,而131I-WBS出现转移灶,4例患者(13.3%)Tg测定异常,而131I-WBS正常.Tg测定和131I-WBS可作为诊断PTC有无转移的重要指标,二者监测复发应联合应用,可互相补充.     

Reduplicated Basal Lamina in Clear-Cell Carcinoma of the Ovary: An Immunohistochemical and Electron Microscopic Study

Clear-cell carcinomas of the female genital tract are uncommon tumors that usually arise in the ovary, cervix, or vagina. The objectives of the present study were to examine the immunohistochemical and ultrastructural characteristics of 18 of these tumors and to determine whether any distinctive features were present at the different locations. The fine structure of the neoplastic cells was similar at the several sites but there was a striking difference in the appearance of the basal lamina. Prominent reduplication of the basal lamina was seen in all 7 ovarian carcinomas, whereas it was mild in 3 and absent in 7 of the cervico-vaginal tumors. The distribution of eosinophilic hyaline material in hematoxylin/eosin sections and of immunohistochemical staining for type IV collagen and laminin correlated with the ultrastructural observations. Reduplication of the basal lamina has been observed in a number of epithelial neoplasms and viewed as a criterion of differentiation, but there is currently no evidence that its presence influences the prognosis of clear-cell carcinomas of the ovary.     

Primary Fibrosarcoma of the Liver Immunohistochemical and Electron Microscopic Studies

An autopsy case of primary fibrosarcoma occurring in the liver of a 75-year old female is presented. The tumor, arising from the lateral upper portion of the right lobe, measured 14 cm in greatest dimension. Light microscopy of the tumor revealed homogeneous, spindle-shaped cells with abundant collagen fibers showing a classic herringbone pattern. Immunoreactive vimentin was found in the tumor cells. Electron microscopically, the tumor cells were rich in rough endoplasmic reticulum without a basement membrane, and were surrounded by large amounts of collagen fibers. The fibroblastic character of the tumor cells was suggested by light and electron microscopy. This may be the first reported case of primary hepatic fibrosarcoma examined by immunohistochemistry and electron microscopy. Acta Pathol Jpn 39: 814 820, 1989.     

Effects of Synthetic Salmon Calcitonin on C Cells of the Thyroid

The effects of long term administration of synthetic salmon calcitonin (TZ-CT) on thyroid C cells of rats were evaluated immunohistochemically and electron microscopically. Low dose (0.075, 0.75 and 7.5 IU/kg/day) administration caused no significant changes in the C cell population, whereas high doses (30 and 120 IU kg day) caused C cell suppression. The area ratio of C cells to total cells in the thyroid was measured on sections immunoperoxidase stained for calcitonin. The average C cell ratio was compared among the experimental groups. This mor-phometric analysis of the high-dose and control groups confirmed the differences in C cell populations statistically (30 IU/kg vs. control, pgO.05; 120 IU/kg vs. control, p ≦ 0.05). The suppressive effect of TZ CT on C cells was reversible after cessation of administration for one month. Electron microscopic examination on the C cells in the high dose groups revealed no particular ultrastructural differences. These results may suggest a negative feedback mechanism on C cells by exogenous CT. Acta Pathol Jpn 39: 545-550, 1989.     

血清CEA、 Tg联合检测在甲状腺良、恶性肿瘤中的临床价值

目的 探索血清CEA、Tg联合检测在甲状腺良、恶性肿瘤中的临床价值.方法 采用化学发光法分别检测经病理证实的68例分化型甲状腺癌(DTC)术前和手术联合131I清甲治疗后、65例甲状腺腺瘤、55例正常对照的CEA、Tg水平,并将结果应用SPSS13.0软件进行统计学分析.结果 术前DTC组的CEA水平明显高于腺瘤组(P＜0.05)、Tg水平与腺瘤组差异无统计意义(P ＞0.05);DTC组患者手术联合131I清甲治疗后的Tg水平有显著性下降(P＜0.05);术后Ⅰ和Ⅱ期DTC患者的Tg、CEA水平明显低于Ⅲ和Ⅳ期的(P＜0.05).结论 血清CEA、Tg联合检测对手术及131I清甲治疗后DTC患者的治疗效果及预后判断有较大价值,CEA检测对确诊中晚期的DTC患者有辅助诊断作用.     

Immunohistochemical, Electron Microscopic, and Immunoelectron Microscopic Features of Plasmacytoma of the Thyroid with Amyloid Deposition

A rare case of primary plasmacytoma of the thyroid with amyloid deposition is reported. The tumor consisted of diffuse proliferation of atypical plasma cells showing IgG lambda-type monoclonal growth. Amyloid deposition with focal giant cell reaction was also observed. Bone marrow aspiration and systemic skeletal radiographic surveys revealed no evidence of multiple myeloma and myelomatosis. Radial arrangement of amyloid bundles was observed ultrastructurally. By immunoelectron microscopic examination, δ chain was detected in the amyloid fibrils and rough endoplasmic reticulum of the tumor cells. Our findings suggest the following: amyloid fibrils originate from monoclonal light chains produced by tumor cells, and histiocytes contribute to amyloid deposition as well as to giant cell reaction in extramedullary plasmacytoma.     

Mixed Epithelial and Stromal Tumor of the Kidney: Preliminary Immunohistochemical and Electron Microscopic Studies of the Epithelial Component

Mixed epithelial and stromal tumor of the kidney is a rare biphasic tumor composed of cysts and tubules embedded in the spindle cell stroma. Although the histogenesis of this tumor is unknown, it has been proposed that both components of the tumor, i.e., stromal and epithelial, are neoplastic. The authors report preliminary immunohistochemical and electron microscopic studies of the epithelial component from one case of a typical, benign, mixed epithelial, and stromal tumor of the kidney. In this study, some tubules showed positivity for proximal, while others showed positivity for distal, nephron immunomarkers. By electron microscopy, some tubules had features of proximal tubular epithelium, while other tubules had features of the loop of Henle (thin segments). The authors believe that in a benign tumor such morphologic heterogeneity is inconsistent with neoplastic proliferation. Therefore, they postulate that in mixed epithelial and stromal tumor of the kidney the tubules are entrapped rather than neoplastic. Additional studies are needed to address this issue and electron microscopy should play a significant role in this process.     

Mixed Epithelial and Stromal Tumor of the Kidney: Preliminary Immunohistochemical and Electron Microscopic Studies of the Epithelial Component

Mixed epithelial and stromal tumor of the kidney is a rare biphasic tumor composed of cysts and tubules embedded in the spindle cell stroma. Although the histogenesis of this tumor is unknown, it has been proposed that both components of the tumor, i.e., stromal and epithelial, are neoplastic. The authors report preliminary immunohistochemical and electron microscopic studies of the epithelial component from one case of a typical, benign, mixed epithelial, and stromal tumor of the kidney. In this study, some tubules showed positivity for proximal, while others showed positivity for distal, nephron immunomarkers. By electron microscopy, some tubules had features of proximal tubular epithelium, while other tubules had features of the loop of Henle (thin segments). The authors believe that in a benign tumor such morphologic heterogeneity is inconsistent with neoplastic proliferation. Therefore, they postulate that in mixed epithelial and stromal tumor of the kidney the tubules are entrapped rather than neoplastic. Additional studies are needed to address this issue and electron microscopy should play a significant role in this process.     

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

INTRODUCTION:

Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored.

PURPOSE:

To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended.

METHOD:

Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations.

RESULTS:

The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6–15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene.

CONCLUSION:

Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were highly useful for diagnosing s-medullary thyroid carcinoma. The rate of complete patient recovery was low, and none of the parameters analyzed were useful predictors of the thyroid tumor size. Our findings support previous recommendations for routine serum calcitonin evaluation and immunostaining analysis involving single thyroid nodules.     

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).     

Thyroid Carcinoma in Japan and the West: Similarities and Differences

Geographic or ethnic differences in the incidence of thyroid carcinoma, as well as in the histologic distribution of thyroid carcinoma between Japan and Western countries, have been described but are still unclear. The recent establishment of histologic criteria for the diagnosis of thyroid carcinoma by the WHO committee has facilitated the comparison of clinicopathological data of patients with thyroid carcinoma all over the world. The aim of the present review article is to clarify the epidemiological and clinicopathological differences of thyroid carcinoma between Japan and Western countries. We found recently no significant differences in the incidence, mortality, and histologic distribution of thyroid carcinoma between Japan and Western countries; this was contrary to our expectation. This is likely attributable to westernization of the Japanese diet, standardized medical levels, and international standardization of histologic criteria of thyroid carcinoma.