Thyroid Specimens Research Articles

So you think your mother is always looking over your shoulder?—She may be in your shoulder!

So you think your mother is always looking over your shoulder?—She may be in your shoulder!

Dipeptidyl peptidase IV expression in thyroid cytology: retrospective histologically confirmed study.

Fine needle aspiration cytology (FNAC) of the thyroid gland is a well-established method. However, it has inherent limitations, especially in the diagnosis of follicular and oncocytic tumours and in distinguishing between nuclear atypia in colloid goitre with regressive changes and cystic papillary carcinoma. The aim of our study was to evaluate dipeptidyl peptidase IV (DPP IV) as a marker of malignancy in FNAC. We tested 254 thyroid specimens (intraoperative imprint smears) for DPP IV. The sensitivity was 71%, the specificity was 96%, and the diagnostic accuracy was 93%, respectively, with a threshold of 50% of positive cells. To the best of our knowledge it is the largest histologically confirmed study reported in the literature. We suggest the assessment of DPP IV as an adjunct diagnostic marker of malignancy in thyroid specimens suspicious of papillary carcinoma. However, the value of the marker in follicular lesions is very limited.

Simian virus 40-like sequences from early and late regions in human thyroid tumors of different histotypes.

Simian virus 40 (SV40) sequences were investigated in human thyroid tumors of different histotypes, Graves' disease thyroid specimens, normal thyroid tissues, and peripheral blood mononuclear cells (PBMC) of healthy donors. Specific SV40 large T antigen (Tag) sequences were detected, by PCR and filter hybridization, in human thyroid tumors with a frequency ranging from 66% in papillary thyroid carcinomas (PTC) to 100% in anaplastic thyroid carcinomas (ATC). SV40 was revealed in 60% and 100% of normal thyroid tissues adjacent to PTC and ATC, respectively, but in only 10% of control normal thyroid tissues (NTT) from patients affected by multinodular goiter. Thyroid tissues from patients affected by the Graves' disease were found to be SV40 positive with a frequency of 20%. In agreement with previous investigations, the presence of SV40 sequences was detected in 25% of PBMC of healthy individuals. SV40 Tag mRNA was detected by RT-PCR, whereas the viral oncoprotein was revealed by immunohistochemistry with a specific monoclonal antibody. The high prevalence of SV40 footprints in human thyroid tumors indicates that the oncogenic virus may participate as a cofactor in the onset/progression of specific human thyroid cancers. Detection of SV40 sequences in NTT adjacent to thyroid cancers suggests that the viral infection may spread from transformed cells to normal cells surrounding the tumor. The presence of the SV40 footprint in PBMC implies that blood cells are vectors of the virus in other tissues of the host.

Using technetium 99m tetrofosmin parathyroid imaging to detect parathyroid adenoma and its relation to P-glycoprotein expression

Background. The purpose of this study was to retrospectively evaluate technetium 99m tetrofosmin (Tc-TF) uptake in parathyroid adenomas and compare the results with their expression of multidrug resistance-mediated 170-kDa P-glycoprotein (Pgp). Methods. Twenty patients with larger parathyroid adenomas (> 1.5 g) and the other 40 patients with smaller parathyroid adenomas (0.5-1.5 g) underwent early and delayed (10-minute and 2-hour) Tc-TF parathyroid imaging before operation. In this retrospective study, immunohistochemical analyses were performed on multiple nonconsecutive sections of the 40 parathyroid adenomas and 40 normal control specimens (20 normal parathyroid glands and 20 normal thyroid specimens) to detect Pgp expression. Results. The Tc-TF parathyroid image accurately localized 17 larger and 16 smaller parathyroid adenomas, but not the remaining 3 larger and 4 smaller adenomas. The 17 larger and 16 smaller parathyroid adenomas with significant Tc-TF uptake on the delayed 2-hour parathyroid images revealed negative Pgp expression, but the 3 larger and 4 smaller adenomas without significant Tc-TF uptake, as well as 20 normal parathyroid glands and 20 normal thyroid specimens, revealed positive Pgp expression. Conclusions. Not only the size of parathyroid adenomas, but Pgp expression also limited the sensitivity of Tc-TF parathyroid image to localize parathyroid adenomas before the operation. (Surgery 2002;132:456-60.)

Using technetium 99m tetrofosmin parathyroid imaging to detect parathyroid adenoma and its relation to P-glycoprotein expression

Background. The purpose of this study was to retrospectively evaluate technetium 99m tetrofosmin (Tc-TF) uptake in parathyroid adenomas and compare the results with their expression of multidrug resistance-mediated 170-kDa P-glycoprotein (Pgp). Methods. Twenty patients with larger parathyroid adenomas (> 1.5 g) and the other 40 patients with smaller parathyroid adenomas (0.5-1.5 g) underwent early and delayed (10-minute and 2-hour) Tc-TF parathyroid imaging before operation. In this retrospective study, immunohistochemical analyses were performed on multiple nonconsecutive sections of the 40 parathyroid adenomas and 40 normal control specimens (20 normal parathyroid glands and 20 normal thyroid specimens) to detect Pgp expression. Results. The Tc-TF parathyroid image accurately localized 17 larger and 16 smaller parathyroid adenomas, but not the remaining 3 larger and 4 smaller adenomas. The 17 larger and 16 smaller parathyroid adenomas with significant Tc-TF uptake on the delayed 2-hour parathyroid images revealed negative Pgp expression, but the 3 larger and 4 smaller adenomas without significant Tc-TF uptake, as well as 20 normal parathyroid glands and 20 normal thyroid specimens, revealed positive Pgp expression. Conclusions. Not only the size of parathyroid adenomas, but Pgp expression also limited the sensitivity of Tc-TF parathyroid image to localize parathyroid adenomas before the operation. (Surgery 2002;132:456-60.)

Intrathyroidal fetal microchimerism in Graves' disease.

During pregnancy, fetal cells are known to reach the maternal circulation and infiltrate a variety of tissues (fetal microchimerism). Although the presence of such cells has the potential to modulate the maternal immune response to both self antigens and fetal alloantigens, the degree of their influence remains unclear. The hyperthyroidism of Graves' disease frequently abates during pregnancy and exacerbates after childbearing. Thus, we have hypothesized that fetal cells in the maternal circulation and tissues may influence this decrescendo to crescendo pattern of autoimmune thyroid disease. Part of this hypothesis was tested using an ELISA-PCR for the detection of DNA for a male-specific gene, sex-determining region Y. The sensitivity of this assay was the equivalent of approximately 1 male cell among 10(5) female cells. We initially examined paraffin-embedded thyroid tissues and detected male cells in 4 of 20 female Graves' thyroid specimens, but not in 6 of 6 female adenoma specimens. Using frozen thyroid tissue specimens, an additional 6 of 7 Graves' disease samples demonstrated intrathyroidal fetal microchimerism, whereas 1 of 4 female samples with thyroid nodules showed male cells. The greater detection of the sex-determining region Y gene in frozen female thyroid tissues was probably due to DNA fragmentation in the paraffin-derived samples. In summary, we demonstrated that intrathyroidal fetal microchimerism was common and profound in female patients with Graves' disease. Thus, fetal male cells are valid candidates for modulating autoimmune thyroid disease in pregnancy and postpartum.

Incidence of inadvertent parathyroid removal during thyroidectomy.

To assess the incidence of unintentional parathyroid removal during routine thyroidectomy and to identify factors that might predict patients at high risk. Retrospective review of case records. Data analyzed for incidental finding of parathyroid gland(s) in the thyroidectomy specimen and postoperative temporary or permanent hypocalcemia. The clinical records of 220 patients undergoing thyroidectomies between January 1997 and October 1999 were reviewed. Pathology reports were screened for information on the presence of parathyroid tissue along with the thyroid specimen. Operative reports were reviewed to exclude the possibility of intentional parathyroid gland removal. Case records were scrutinized to determine whether the patient developed symptomatic hypocalcemia postoperatively. Nine percent of the 220 patients were found to have had inadvertent removal of parathyroid tissue. The majority of patients (95%) had two or less parathyroid glands in their specimens. The size and histological nature of the thyroid lesion were not predictive of inadvertent parathyroid removal. Of the 25 repeat operations for recurrent or persistent malignancy, 5 (20%) were found to have unintentional parathyroid removal compared with 15 (7.71%) of 195 primary thyroidectomy cases (P <.05). Nineteen percent of patients who had tracheoesophageal groove node dissection had an incidental parathyroid in their specimen compared with 7% who did not undergo tracheoesophageal groove node dissection (P = .04). None of the patients with unintentional parathyroid gland removal developed either temporary or permanent postoperative hypocalcemia. Inadvertent excision of a parathyroid gland(s) occurred in 9% of patients undergoing thyroidectomy in our experience. Reoperative thyroid surgery and tracheoesophageal node dissection were associated with a significantly higher risk of inadvertent parathyroid gland excision. Inadvertent parathyroidectomy did not result in symptomatic temporary or permanent hypocalcemia postoperatively.

Study in China on Ingestion and Organ Content of Trace Elements of Importance in Radiological Protection

To improve knowledge of the ingestion and organ content of calcium, cesium, iodine, potassium, strontium, thorium, and uranium that have a high priority in radiological protection, a total diet and organ content studies was conducted. The total diet study used the market basket sample method with representative sampling. For the organ content specimens of muscle, skeleton, liver, kidney, lung, and thyroid were collected during autopsies of normal, healthy adult accidental death victims. The concentration of above stated elements in the diet and organs were analyzed by nuclear and nuclear-related techniques with strict quality assurance measures. The results are presented in the paper and compared with previous national and international data and the parameters of current International Commission on Radiological Protection (ICRP) Reference Man. The study provided a new and reliable database for setting the parameters for the Chinese reference man and the reference Asian man. It also facilitated the study on biokinetics behavior of their radiation counterparts in human body and helped in the realistic assessment of their internal radiation doses.

Detection and characterization of RANK ligand and osteoprotegerin in the thyroid gland.

Receptor activator of NF-kappaB (RANK) ligand (RANKL) and osteoprotegerin (OPG) play essential roles in bone metabolism and immune responses. RANKL activates RANK, which is expressed by osteoclasts and dendritic cells (DC), whereas OPG acts as its decoy receptor. The role of RANKL and OPG in thyroid physiology is unclear. Northern analysis revealed pronounced OPG mRNA levels in normal human thyroid. By contrast, RANKL mRNA levels were most abundant in lymph node and appendix, and low in the thyroid. In the human thyroid follicular cell line XTC and in primary human thyroid follicular cells, OPG mRNA levels and protein secretion were upregulated by interleukin (IL)-1beta (33-fold), tumor necrosis factor (TNF)-alpha (eightfold), and thyrotropin (TSH) (threefold). RANKL mRNA was stimulated in XTC by IL-1beta and TNF-alpha, but inhibited by TSH. Conditioned medium harvested from IL-1beta-treated XTC (containing high concentrations of OPG) inhibited RANKL-induced CD40 upregulation and cluster formation of DC. OPG mRNA levels were three times more abundant in surgical thyroid specimens of Graves' disease as compared to other thyroid diseases. Our data suggest that RANKL and OPG are produced in the thyroid gland by thyroid follicular cells, are regulated by cytokines and TSH, and are capable of modulating dendritic cell functions. Thus, these cytokines may represent important local immunoregulatory factors involved in the pathogenesis of autoimmune thyroid diseases.

Papillary Microcarcinoma of the Thyroid

Objective To investigate the biological behavior, clinical characteristics, diagnosis and therapy of papillary thyroid microcarcinoma(PTMC). Methods The clinical data of 89 cases with PTMC treated and confirmed by pathology from 1985 to 2002 were retrospectively analyzed. Results All patients were followed-up from 5 to 196 (mean 68.9) months. Five cases suffered recurrence and are alive. PTMC was found in 38 cases incidentally from thyroid specimens removed for supposed benign disease, another 51 cases were doubtful of cancer before operation and were identified by biopsy. Upper and mid deep cervical lymph nodes and tracheoesophageal fold lymph node were more commonly involved in 40 cases with lymph node metastasis. The frequency of lymph node metastasis among primary tumor in upper third, middle third and lower third lobe were not different significantly. Lymph node metastasis in cases of multifocal cancer in the affected lobe or of both lobes was significantly higher than in monofocal cancer in uni-lobe. The primary tumor size(≤5 mm,5 mm) had a significant influence on the frequency and distribution of cervical lymph node metastasis. The local recurrent rate in palpable lymph node group was significantly higher than the non-palpable lymph node group. Conclusions Careful palpation, B type ultrasonography, exploratory operation and frozen section are very important factors to heighten diagnosis of PTMC. We believe that PTMC could be divided into two subsets: with the former of non-aggressive behaviors treated by conservative surgery, and the later of a potentially aggressive clinical course treated by a more aggressive procedure.

Fine needle aspiration biopsy cytology in thyroiditis - With mention on FNA in different setting

The cytopathologic characteristics as seen in fine needle aspirate smears of 50 thyroiditis patients were reviewed, with emphasis on pitfalls. Fortyeight patients were female and only 2 patients were males. Of these, 46% were in 4th decade of life. Fifty two percent came within a period of 6 months of illness of which 46.15% were hypothyroid at presentation. The cytologic diagnoses were as follows : Hashimotos thyroiditis (H.T.) 13; lymphocytic thyroiditis (L.T.) 11; subacute thyroiditis 2; acute thyroiditis 1; and suspicious benign lesions 23. Thirty patients were operated. Twenty three erroneous diagnoses were uncovered by (i) repeat FNA in 3 cases (ii) smear examination by single senior cytopathologist in 8 cases and (iii) histopathological examination of operated thyroid specimen in 12 cases. Prerequisites for accurate cytological diagnosis is adequate and representative sample. Cytodiagnostic pitfalls occured mainly in cases of H.T. Examination of FNA slides of suspicious thyroiditis cases by single senior cytopathologist was the key factor in achieving diagnostic accuracy. The ease of doing FNA and its diagnostic accuracy mandate continued use of FNA in the diagnostic management of patients with thyroidits.

Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study

Some so-called autoimmune diseases in women might be alloimmune and represent a chronic graft-versus-host response attributable to transplacentally acquired fetal cells. Thyroid disease is more common in women than men, and post partum exacerbation of thyroiditis is common. Our aim was to investigate whether there is an association between fetal cell microchimerism and thyroid disease in women. Surgical specimens were obtained from 29 women who underwent thyroidectomy for various thyroid disorders. Control specimens were taken from clinically and histologically normal thyroids obtained at necropsy from eight women who died from unrelated conditions. Medical records and pregnancy histories were reviewed. Fluorescence in-situ hybridisation analysis was done with probes specific for X and Y chromosomes. Slides were examined with a fluorescence microscope to detect the presence of male cells-with one X and one Y signal in the nucleus-among maternal cells containing two X signals. Male cells were seen in thyroid sections from 16 patients but not in those from controls (p=0.01). Male cells (1-165 per slide) were seen individually or in clusters in all thyroid diseases and were not restricted to inflammatory thyroid diseases. In one patient with a progressively enlarging goitre, we noted fully differentiated male thyroid follicles closely attached to and indistinguishable from the rest of the thyroid. Our findings suggest a relation between fetal cell microchimerism and thyroid disease. Furthermore, fetal stem cells might be capable of differentiation into mature thyroid follicles in their mothers with favourable environmental and developmental factors.

Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings

The major factor to influence localization of parathyroid adenomas is tumor size. P-glycoprotein (P-gp) expression in parathyroid adenomas has been considered to be an another possible factor to influence localization of parathyroid adenomas because false-negative studies have been reported with large tumors and true-positives reported with very small tumors in previous studies. The aim of this study was to characterize Tc-99m MIBI uptake and retention by parathyroid adenomas and to correlate this with cell surface expression of P-gp. Sixteen patients with parathyroid adenoma (larger than 1.5 gm) underwent dual-phase (10min and 2hr) Tc-99m MIBI parathyroid image immediately before parathyroid exploration. Tissues were obtained from normal and abnormal parathyroid glands and from the thyroid gland. Immunohistochemistry (IHC) was obtained with monoclonal antibodies to identify P-gp expression in all tissues. All of the 16 parathyroid adenomas and 32 normal control specimens (16 normal parathyroid and 16 normal thyroid specimens) were submitted for P-gp detection by IHC. The dual-phase Tc-99m MIBI parathyroid image accurately localized 14 parathyroid adenomas, but not the remaining 2 adenomas. The 14 parathyroid adenomas with significant Tc-99m MIBI uptake in delayed 2hr images revealed negative P-gp expression, but the 2 adenomas without significant Tc-99m MIBI uptake, as well as normal parathyroid and normal thyroid specimens, revealed positive P-gp expression when evaluated by IHC. Not only the size of parathyroid adenomas, but also significant P-gp expression limited the sensitivity of dual-phase Tc-99m MIBI parathyroid image to localize parathyroid adenomas before operation.

Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients.

Total (or near-total) thyroidectomy (TT) is considered by many as the most adequate treatment for papillary thyroid carcinoma (PTC). In patients who have undergone lobectomy, the necessity of performing a completion thyroidectomy (CT) is still discussed. The aim of this retrospective study was to evaluate tumor bilaterality in patients initially treated with partial thyroidectomy for PTC and who then underwent CT. We studied 182 patients treated with CT after lobectomy and/or isthmectomy for PTC diagnosed from 1969-1998. Mean age at diagnosis was 40+/-14.5 years and mean interval between partial thyroidectomy and CT was 19.8+/-56.8 months. At CT, 80 of 182 patients (44%) had one or more foci of tumor in the remaining thyroid lobe, always of the same papillary histotype, associated with ipsilateral lymph node metastases in 22 cases. In addition, 10 patients with no tumoral foci in the thyroid specimen had evidence of lymph node metastases. The rate of bilateral tumor was not different when patients were analyzed according to the classification of "low-" or "high-risk." Among several clinical features, the presence of lymph node metastases at the first surgical treatment and time interval between first treatment and CT were correlated with higher frequency of bilaterality (p = 0.033 and p = 0.044, respectively). The postsurgical 131I whole-body scan revealed the presence of persistent lymph node metastases or diffuse micronodular lung metastases in 7 and 6 patients, respectively. In conclusion, PTC was frequently bilateral in our series and this bilaterality was independent from the "low-" or "high-risk" classification. On these bases, we believe that PTC should be treated with TT when diagnosed before surgery and submitted to CT, if partial surgery was the initial intervention.

Evidence of fetal microchimerism in Hashimoto's thyroiditis.

Fetal microchimerism, the engraftment of fetal progenitor cells into maternal tissues, has been implicated in the etiology of autoimmune diseases. We used PCR analysis to determine whether microchimerism occurred in the thyroid glands of female patients suffering from Hashimoto's disease and thus may be involved in its etiology. PCR amplification was performed from thyroid gland specimens using primers unique to a Y-chromosomal sequence (SRY gene) and primers for a sequence that is Y/X-chromosomal homologous except for a 6-bp deletion in the X-chromosomal sequence (amelogenin). Microchimerism was detected in 8 of 17 Hashimoto patients, but in only 1 of 25 controls (nodular goiters). Both groups were of similar age and had comparable numbers of pregnancies and numbers of sons. All individuals with microchimerism had given birth to at least 1 son. Our results show that microchimerism is significantly more common in Hashimoto patients than in patients suffering from nodular goiter. We therefore suggest that microchimerism might play a role in the development of Hashimoto's disease, although we cannot completely eliminate the hypothesis that microchimerism is just an "innocent bystander" in a process triggered by other mechanisms.

Immunohistochemical detection of somatostatin receptor types 1-5 in medullary carcinoma of the thyroid.

We have analysed the distribution of the five somatostatin receptors (sst1-5) by immunohistochemistry in a large retrospective series of 51 medullary carcinoma of the thyroid (MCT) specimens and correlated the pattern of sst expression with expression of somatostatin (SRIF) peptide, tumour pathology and clinical outcome. Immunohistochemistry was performed with rabbit polyclonal antipeptide antibodies directed against the extracellular domains or cytoplasmic tail of human (h) sst1-5. SRIF immunoreactivity was investigated in parallel paraffin sections. Eighty-five percent of the tumours were positive for one or more sst, localized to both tumour cells as well as surrounding peritumoural structures, especially blood vessels. Forty-nine percent of the tumours were positive for sst1, 43% for sst2, 47% for sst3, 4% for sst4, and 57% for sst5. Fifty-one percent of tumours expressed one or two sst subtypes; 33% were positive for three or more sst isoforms. All five sst receptors were detected in only two cases. Tumours expressing octreotide sensitive subtypes (sst2,3,5) accounted for 75% of the series. 50% of the tumours co-expressed SRIF suggesting tumour cell regulation by endogenous SRIF via paracrine/autocrine circuits. There was no correlation between sst1-5 expression and age, sex, tumour size or stage, histological type or clinical outcome. Simultaneous analysis of primary tumour and lymph node metastases revealed a similar pattern of sst immunoreactivity indicating that sst expression is not modified in the course of disease progression. With the exception of sst4, medullary carcinoma of the thyroid display a rich but heterogeneous expression of sst subtypes. Immunohistochemical typing of sst receptor expression using specific antireceptor antibodies represents an ideal approach for characterizing sst subtype expression in medullary carcinoma of the thyroid for optimizing receptor targeted diagnosis and therapy with somatostatin analogs.

Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer

Background. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies. Several recent reports have documented over expression of VEGF in papillary thyroid cancer. We hypothesized that increased expression of VEGF would be associated with either an increased risk of recurrence or a decreased recurrence-free survival in papillary thyroid cancer. Methods. Immunohistochemistry was used to detect VEGF expression in archival paraffin-embedded surgical thyroid specimens from 96 subjects with papillary thyroid cancer. Results. VEGF expression was detected in 98% (94/96) of the samples, predominantly of slight-to-moderate intensity in the majority of malignant cells. However, the specific finding of a diffuse pattern of intense immunostaining for VEGF was detected significantly more often than less intense, patchy immunostaining patterns in subjects with distant metastasis at diagnosis (63% versus 15%, P =.005), local recurrence (58% versus 13%, P =.001), and distant recurrence (83% versus 14%, P =.001). Furthermore, this specific pattern of diffuse, intense VEGF expression was associated with a significantly shorter recurrence-free survival than other staining patterns (P =.007). Conclusions. These data demonstrate that the immunohistochemical pattern of VEGF staining in the initial surgical specimen is strongly associated with the incidence of local and distant metastasis in papillary thyroid cancer. (Surgery 2001;129:552-8.)

Thyroid cytology and the risk of malignancy in thyroid nodules: importance of nuclear atypia in indeterminate specimens.

Fine needle aspiration (FNA) cytology is the best test for malignancy in thyroid nodules. However, cytologic interpretation of FNA specimens is often difficult, especially in the presence of indeterminate microfollicular cytologic patterns, which are thought to suggest follicular neoplasm (adenoma or carcinoma). To assess the risk of malignancy associated with specific cytologic patterns, we correlated preoperative FNA cytologic patterns (n = 484 reports including repeat aspirations) with final histological diagnoses for 368 surgical thyroid specimens obtained during the period 1994-1998. The overall prevalence of malignancy in the surgical specimens was 31% (113 cancers, including 96 papillary and 9 follicular carcinomas). For nodules with benign FNA cytologic diagnoses of nodular goiter and chronic thyroiditis there was a low risk of malignancy (6/99, or 6.1%). Nodules with indeterminate cytologic patterns in the absence of nuclear atypia (i.e., microfollicles without nuclear atypia) had a similarly low malignancy risk (3/46, or 6.5%). In contrast, 31/52 nodules with cytologic nuclear atypia consistent with follicular neoplasm were malignant (60%), including specimens with or without microfollicular cytology. Nodules with frankly malignant cytologic patterns were almost invariably cancer (54/55), and cytologic diagnoses of papillary carcinoma were confirmed at surgery in all 49 cases. These results indicate that indeterminate microfollicular cytologic patterns in the absence of nuclear atypia are associated with a low risk of malignancy, at least in this series. This finding suggests that many nodules with such microfollicular cytology might be managed conservatively with observation. In contrast, cytologic nuclear atypia consistent with a follicular neoplasm confers a high risk of cancer. In addition, frankly malignant cytologic diagnoses, especially papillary carcinoma, are highly reliable, and thus may be used as a guide for planning surgery appropriate for thyroid cancer.

Histological changes of thyroid tissues in patients with liver cirrhosis.

Alterations in thyroid hormone regulation and metabolism, such as low serum T3 and T4 with normal TSH, are frequently noted in liver cirrhosis, but few morphological studies have ever been done on thyroid tissue in liver cirrhosis. In this study we analyzed the histological changes of thyroid tissue in the patients with liver cirrhosis. Specimens of thyroid gland obtained from autopsies in 16 cirrhotic patients were examined, and compared with those of two control groups. Control group I consisted of 7 patients with diabetes mellitus and control group II, 12 patients who died from sudden onset of cardiovascular problems. We measured follicular diameter and epithelial width on light micrographs of the central portion of thyroid specimens. We graded the degree of colloid vacuole, lipofuscin deposition in follicular epithelia, regenerative reaction and perivascular fibrosis in 10 consecutive light microscopic fields of the specimen. In the cirrhotic group, mean follicular diameter and epithelial width were significantly shorter and thinner, respectively, than those in the two control groups. Perivascular fibrosis was more prominent in the cirrhosis group than in the controls. These findings suggest that thyroid glands in patients with liver cirrhosis have the characteristic features of hypoactivity.

Differential reactivity for galectin-3 in Hürthle cell adenomas and carcinomas.

Hürthle cell carcinomas behave as the most aggressive variant of differentiated thyroid carcinoma of follicular origin, with frequent recurrences and higher morbidity. Its differential diagnosis with Hürthle cell adenoma remains a problem for the clinician and for the pathologist. The vertebrate lectins, galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation in thyroid neoplasms. Galectin-3, a beta-galactoside binding protein, has been recently found to be highly expressed in papillary and follicular carcinomas. The current study was undertaken to investigate immunohistochemical reactivity for galectin-3 of thyroid specimen tissues with Hürthle cell adenomas (n = 14) and carcinomas (n = 17), follicular (n = 14) and papillary (n = 11) carcinomas, colloid goiter (n = 30), Hashimoto's thyroiditis (n = 11), follicular adenoma (n = 9), and normal thyroid tissues (n = 18). Follicular (78.5%) and papillary (82.0%) carcinomas were frequently reactive for galectin-3, more often when some H rthle cells were present. There was no galectin-3 immunostaining in any of the specimens from Hashimoto's thyroiditis, colloid goiters or normal thyroid samples, whereas only one case of follicular adenoma was found positive (11.1%). By contrast, galectin-3 immunostaining in Hürthle cell carcinomas was significantly higher (59%) than in H rthle cell adenomas (7.1), p < 0.05). These results suggest that galectin-3 may potentially serve as a marker in difficult differential diagnosis cases involving Hürthle cell adenomas and Hürthle cell carcinomas.