Cystic Medullary Thyroid Carcinoma: Report of a Case with Morphological and Clinical Correlations

Cystic lesions of the thyroid are common findings. Although many thyroid cysts are of benign, some cases of hemorrhagic degenerative changes occur in neoplastic nodules, mostly follicular neoplasms and papillary carcinomas. The occurrence of hemorrhagic changes in medullary carcinomas has never been documented with aspirative cytological and histological pictures to the best of our knowledge. A case of medullary thyroid carcinoma with a large central hemorrhagic cyst is described, and the literature regarding the pathogenesis of this regression and the occurrence of cystic neoplasms in the thyroid is reviewed.     

Follicular thyroid lesions coexisting with Hashimoto's thyroiditis: incidence and possible sources of diagnostic errors

Our objectives were to study the types and incidence of thyroid follicular lesions coexisting with Hashimoto's thyroiditis (HT), the pitfalls in their cytodiagnosis, and the effect on management. All cases of HT diagnosed by fine-needle aspiration (FNA) and/or histology over a 7-yr period were retrospectively studied. HT coexisted with follicular adenoma (FA) in 6 cases, follicular variant of papillary carcinoma (FVPC) in 1 case, and goitrous nodule (GN) in 2 cases. The overall incidence rates of thyroid neoplasm and goitrous nodules coexistent with HT were 15% and 3.5%, respectively. A preoperative FNA diagnosis was available in 10 histologically proven cases of HT. A false-positive diagnosis of follicular neoplasm (FN) that led to unnecessary thyroidectomies was given in 3 cases. In 2 of these, the cytological diagnosis was HT with the possibility of coexisting FN, and in the third case, the cytological finding of HT was misinterpreted as FN. The main causes of these diagnostic pitfalls were the presence of hyperplastic follicular cells with nuclear pleomorphism, a paucity of lymphoid cells in burned-out HT, and lack of ones exposure. Nuclear pleomorphism was observed in none of the follicular adenomas. FNA diagnosed accurately the coexisting lesions in 6 cases; 3 FA, 1 FVPC, and 2 GN, but it did not sample HT. In one case, FNA diagnosed correctly both HT and the coexisting FA. Therefore, the presence of a coexistent neoplasm or goitrous nodule reduced the chances of sampling HT by 85.7%, with no false-negative results. Indeed, aspiration on and around the thyroid nodule helps in sampling HT. However, HT may dominate the smear and obscure neoplasia. This can be avoided if the procedure is performed by the pathologist and the aspiration is done on the nodule only. The overlapping cytological features of FN and HT were the main causes of false-positive results. This can be reduced by avoiding the diagnosis of FN in the presence of follicular-cell pleomorphism and/or moderate to excessive numbers of lymphoid cells, provided proper aspiration technique is maintained.     

TMA与TGA检测对甲状腺疾病的临床诊断价值

根据174例疑诊患者的TMA、TGA，T3，T4放射免疫测定结果及其临床表现进行诊断，结果表明桥本氏甲状腺炎和甲亢所占的比例(分别为38．51％及31．61％）显著高于甲减和亚急性甲状腺炎(分别为6．32％和4．02％)，P＜0．05。甲减患者TGA TMA的阳性率（81．82％)显著高于甲亢(50．91％)，桥本氏甲状腺炎(50．75％)及亚急性甲状腺炎(57．14％)，P＜0．05。单项抗体阳性者以TMA较TGA为多。本文结果提示在甲状腺疾病中TMA，TGA的阳性结果存在相互重叠现象，与T3、T4联检并结合临床表现进行综合分析有助于甲状腺疾病的鉴别诊断并正确指导治疗。     

Use of serum-free hormonally defined media to evaluate the effects of growth factors and inhibitors on proliferation of estrogen-responsive mammary and pituitary tumor cells in culture

Summary Serum-free defined media have been developed for assay of the mitogenic effects of growth factors on human MCF-7, human T-47D, and mouse COMMA-D mammary cells as well as for identification of mitogens and inhibitors of GH₄C₁ rat pituitary tumor cell growth. These lines were shown to grow in vivo in response to a variety of hormones including estrogens and thyroid hormones. With mammary cells, complete hormonally and nutritionally defined media were established that supported continuous passage at 50 to 90% of the serum stimulated rate. The strategy used to measure mitogens for mammary cells was to identify nutritional conditions where the growth rate was reduced greatly without impairing the response to picomolar to nanomolar concentration of growth factors. The effects of polypeptide growth factors and tissue extracts were estimated by their addition to basal medium and measuring cell number increases or labeled thymidine incorporation into DNA. In a variation of this methodology, the MTW9/PL2 rat mammary cells were used to identify secreted autocrine growth factors; nutritionally defined conditions were sought for growth of these rat cells in the complete absence of exogenous growth factors. The factors secreted into the medium were detected by bioassays with COMMA-D or MCF-7 mammary cell lines. The effects of growth factors-inhibitors on pituitary cells were measured by a related method; the GH₄C₁ cells were grown at less than optimal rates in a defined medium designated TRM-1. Addition of mitogens to TRM-1 stimulated pituitary cell growth whereas addition of inhibitors caused reduced levels of growth. The methods described in this report offer new means of assaying growth factors-inhibitors for a range of mammary and pituitary tumor cells.     

Immunostaining of galectin-3 and CD44v6 using fine-needle aspiration for distinguishing follicular carcinoma from adenoma

To evaluate the clinical applicability of galectin-3 and CD44 variant 6 (CD44v6) immunostaining in fine-needle aspiration cytology (FNAC) of thyroid follicular tumors, 79 cytological specimens (35 follicular carcinomas and 44 follicular adenomas) were studied. The positive rates of galectin-3 and CD44v6 were 89 and 74% in follicular carcinoma, respectively, and 25 and 30% in follicular adenoma, respectively. There were no significant correlations between the expression of galectin-3 or CD44v6 in follicular carcinoma and characteristics such as capsular invasion, vascular invasion, metastasis, or tumor size. Positive staining of either galectin-3 or CD44v6 resulted in a diagnostic sensitivity of 97% and a specificity of 52% for follicular carcinoma among follicular tumors. Immunostaining of galectin-3 or CD44v6 using cytological specimens can provide independent information on conventional morphological findings of cytology to distinguish follicular carcinoma from adenoma.     

Effect of potassium iodide and perchlorate on the secretion of thyroid hormones

The effect of potassium iodide and perchlorate was studied on parameters characterizing the secretion of thyroid hormones: the cyclic AMP level in the thyroid gland tissue and the number of intracellular colloid drops during stimulation with thyroid hormones. Excess of iodide was shown to depress these indices whereas perchlorate prevented the inhibitory effect of iodide. The results support the view that the adenylate-cyclase system of the thyroid gland is sensitive to the organic iodine concentration. Excess of iodide evidently reduces the ability of perchlorate to affect its concentration in the gland, so that the process of organification of iodine and the secretion of thyroid hormones are maintained at the optimal level.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 653–655, December, 1978.     

不同年龄组儿童甲状腺测量值及其变化的研究

调查了90具童尸用状腺的基本形态,可分四型。其中以甲状腺由两侧叶及峡部组成者为最多,占50.22%。测量了甲状腺各部的长、宽、厚。分年龄组进行了数据的统计学处理,并计算出儿童与成人甲状腺各部相应值的百分比。结果显示:小儿甲状腺侧叶的长度和宽度在幼儿期(1—3岁)就已发育近成人的一半。随着年龄的增长,甲状腺各部的均值逐渐增加。除各部的宽度以及锥体叶的长度外,各相邻两组间同项均数的比较,经双侧T检验发现差异具有高度显著性(P<0.01)。     

Adhesion molecule expression in Graves'' thyroid glands; potential relevance of granule membrane protein (GMP-140) and intercellular adhesion molecule-1 (ICAM-1) in the homing and antigen presentation processes.

To assess the potential role of adhesion molecules in the pathogenesis of Graves' disease, we examined the expression of several of these adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1) and granule membrane protein-140 (GMP-140), in sections of Graves' thyroid glands and control thyroids, using immunohistochemical techniques. Up-regulated expression of GMP-140 was frequently observed on endothelial cells (EC) of post-capilliary venules in all Graves' thyroids examined, compared with an occasional weak staining on EC control glands. Some capillary EC around thyroid follicles (perifollicular EC) were strongly positive for GMP-140 in the Graves' thyroids in contrast to a negative staining on the same structures in the control glands. In addition, there was a correlation between the reactivity and frequency of GMP-140 expression on EC and the severity of mononuclear cell (MNC) infiltration in the Graves' thyroids. The expression of ICAM-1 was up-regulated on perifollicular EC and EC of small venules in some thyroids of both Graves' and control groups. Conversely, no significant expression was observed on any type of EC for both endothelial-leucocyte adhesion molecule-1 (ELAM-1) and VCAM-1. However, dendritic-like cells, present within lymphocytic infiltrates, were positive for VCAM-1 in most of the Graves' thyroids examined, especially in those with a severe lymphocytic infiltration. Thyrocytes were constantly negative for the expression of all four adhesion molecules investigated. These data suggest that GMP-140, as well as ICAM-1, could play an important role in the initiation of MNC infiltration in Graves' disease. ELAM-1 and VCAM-1 appear not to be relevant for the migration of MNC from the blood vessels into the target gland, although VCAM-1 expression on dendritic-like cells might play an additively tissue-selective role in autoantigen presentation and subsequent elicitation of autoimmune phenomena.     

Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema

The expression of two autoimmune thyroid diseases, GD and idiopathic myxoedema, is associated with antibodies to the thyroid-stimulating hormone (TSH) receptor. Thyroid stimulating antibodies (TSAb) in GD are TSH agonists and cause hyperthyroidism as well as goitre, whereas thyroid stimulation blocking antibodies (TSBAb) in idiopathic myxoedema are TSH antagonists and cause hypothyroidism and thyroid atrophy. We investigated the effect of antibodies to TSH receptor on Fas-mediated apoptosis of thyroid epithelial cells (thyrocytes). Human IgG was isolated from healthy donors, patients with GD and idiopathic myxoedema. Human thyrocytes were obtained from surgical specimens. Thyrocytes were cultured in the presence or absence of human IgG with or without interferon-gamma (IFN-γ) or IL-1β for a specified time. After incubation, we examined the level of cAMP in cultured supernatants and both Fas and Bcl-2 expression on thyrocytes. In addition, we examined anti-Fas-mediated apoptosis of thyrocytes. Fas expression on thyrocytes was significantly down-regulated by Graves' IgG and TSH, although idiopathic myxoedema IgG did not affect Fas expression on thyrocytes. Idiopathic myxoedema IgG abrogated the effect of TSH on both cAMP production and inhibition of Fas expression on thyrocytes. Treatment of thyrocytes with IL-1β or IFN-γ caused a marked augmentation of Fas expression on thyrocytes. The increase of Fas expression of thyrocytes induced by IL-1β or IFN-γ was significantly suppressed in the presence of TSH or Graves' IgG. Anti-Fas-induced apoptosis of thyrocytes was observed in thyrocytes treated with IL-1β or IFN-γ, but was markedly inhibited in the presence of TSH or Graves' IgG. Furthermore, idiopathic myxoedema IgG abrogated most of the inhibitory effect of TSH on Fas-mediated apoptosis of thyrocytes treated with IL-1β or IFN-γ. Bcl-2 expression of thyrocytes did not change after stimulation with TSH, Graves' IgG, idiopathic myxoedema IgG, IL-1β or IFN-γ. These results suggest that TSAb found in Graves' patients may be potentially involved in the development of goitre by inhibition of Fas-mediated apoptosis of thyrocytes. In addition, TSBAb inhibit the action of TSH and increase the sensitivity toward Fas-mediated apoptosis of thyrocytes, inducing thyroid atrophy seen in patients with idiopathic myxoedema.     

Insular component as a risk factor of thyroid carcinoma

Forty-four thyroid carcinomas with an Insular component (JC) were reviewed from 2457 tumors diagnosed as papillary (PC) or follicular carcinoma (FC). These tumors were classified as FC with an IC (FCIC; 30 cases) and PC with an IC (PCIC; 14 cases). Both tumors were composed of solid cell nests in some areas and had a tendency toward a characteristic nuclear size: FCIC had a small nucleus and PCIC contained a nucleus of an Intermediate type or a large nucleus similar to that of PC, although there were numerous tumors with an exceptional nuclear size. The mean age and tumor diameter were the highest and largest in FCIC, respectively, followed by PCIC. Among the 44 cases, 17 patients died of the disease, two were alive with the disease and 18 were alive without the disease. From 13 clinicopathological factors, the presence of an IC, age, non-encapsulation, tumor size, vascular invasion and necrosis were found to be independent variables for actual prognosis of FC and PC based on univariate analysis followed by multtvariate analysis. The results of the present study indicate that the presence of an IC is an independent aggressive prognostic factor for patients with PC and FC.