Colloid Nodules Research Articles

2048: 3D US as a base for virtual surgery in thyroid mass

Objectives: To evaluate the role of 3D US in virtual surgery in planning operations of patients with thyroid nodules. Methods: Ninety-four patients were studied by 3D US mode; in 15 cases (four thyroid carcinomas, two adenomas, three colloid nodules, six multinodular goiter) virtual operation simulations were performed before surgery; 282 3D US reconstruction of anatomic structure and of thyroid nodules were created. Multiplanar reslicing and frontal images of thyroid nodules in consecutive lobe were studied. On comparison of frontal slices with intraoperative data topographic evaluation of nodules location in thyroid gland was worked up. Comparison of US results with intraoperative findings, final pathomorphology and fine-needle biopsy. Results: 3D US were accurate in detection of number, size and location of thyroid nodules and made influence on surgical decision. Preoperative evaluation of thyroid vascular anatomy and 3D multiplanar reconstruction of the nodules were of value for changing surgical management for thyroid resections and in rejecting necessity of operation. Results of virtual operation allowed to refuse surgery in three patients. Conclusions: Results of the investigation proved that computer processing and simulation of an optimal image as per segments allows to precise volume of affected and preserved tissues of thyroid gland or lobe and to perform operations in organ-preserving volume.

Changing Nodule Activity With Time on Tc-99m Pertechnetate Thyroid Scintigraphy

A patient with a diagnosis of malignant melanoma was found to have a multinodular goiter on routine examination. Thyroid function tests revealed normal free T4 and TSH levels. A multinodular goiter was confirmed by thyroid ultrasonography with the dominant nodule located at the isthmus. Tc-99m pertechnetate thyroid scintigraphy did not reveal nodule activity. Delayed imaging was performed for localization of the dominant nodule with a marker. Surprisingly, the nodule was found to be hyperactive. The nodule was normoactive on 1-131 thyroid scintigraphy. Fine needle aspiration biopsy confirmed a colloid nodule with follicular epithelial cells.

Specimen adequacy and diagnostic specificity of ultrasound-guided fine needle aspirations of nonpalpable thyroid nodules

Ultrasound-guided fine needle aspiration (USG-FNA) is a safe, effective, and dependable test used to assess thyroid nodules. However, the size of the lesion can adversely affect the outcome of the procedure. The aim of this study was to assess specimen adequacy and diagnostic specificity in USG-FNA of thyroid nodules measuring < or = 1.5 cm. A total of 219 thyroid FNAs were performed in a one year; 26 were obtained by pathologists, 139 by clinicians, and 54 by radiologists under ultrasound guidance. Of the 54 ultrasound-guided aspirates, 19 cases (35%) were performed on nodules < or = 1.5 cm (range 0.8-1.5 cm, mean 1.3 cm). Cytologic material from these 19 cases was reviewed along with corresponding available follow-up surgical material. Standard criteria for specimen adequacy and established morphologic criteria for diagnostic specificity were assessed in each case. All 19 cases met criteria for specimen adequacy, and in 17 cases (89%) specific cytologic diagnoses were made (cellular/adenomatous nodule--2 cases, colloid nodule--10 cases, Hashimoto's thyroiditis--4 cases, and papillary cystic carcinoma--1 case). The diagnoses were confirmed by surgical follow-up in six cases including the case of papillary carcinoma. One case diagnosed as suspicious for a papillary carcinoma subsequently was found to be a follicular adenoma by histology. In one case, a diagnosis of lymphocytic thyroiditis versus intrathyroidal lymphoid tissue was made (See Table I). In majority of cases of USG-FNA of nonpalpable thyroid nodules, adequate material may be obtained for a specific cytopathologic diagnosis.

Fine Needle Aspiration Cytology Of Thyroid Nodule(S): A Nigerian Tertiary Hospital Experience

Fine needle aspiration cytology (FNAC) of the thyroid has been used as an initial investigative procedure of thyroid nodule(s) in the Department of Histopathology, University of Maiduguri Teaching Hospital for 10 years (1995-2004). This study is aimed at evaluating our experience of FNAC and correlating with histologic diagnosis. A total of 69 patients with 51(73.9%) cases of benign, 18 (26.1%) cases of malignancy. There were four cases suspicious of malignancy, which were considered as malignant. The benign diseases include 34(49.3%) nodular colloid goiter; 6(8.7%) toxic goiter; 7(10.1%) follicular adenoma; 2(2.9%) cases each of Hashimoto's and subacute thyroiditis. The malignant cases were 10(14.5%) follicular carcinoma; 3(4.3%) cases each of medullary and papillary carcinomas, and 2 (2.9%) anaplastic carcinoma. The diagnostic accuracy is 94.2%, Sensitivity, 88.9%; Specificity, 96.1%; False Negative rate, 11.1% and false positive rate, 3.9%. In conclusion, FNAC of the thyroid nodule(s), is sensitive, specific, accurate and the initial investigation of thyroid diseases in our tertiary hospital. We therefore encourage our clinicians to embrace this investigative procedure in the management of our patients.

Thyroid cancer

The prevalence of nodular lesions of the thyroid gland (thyroid gland), according to various researchers, ranges from 3 to 7%]. The widespread introduction of ultrasound (ultrasound) in clinical practice, as well as the results of autopsy studies, showed that the prevalence of nodular lesions of the thyroid gland is much higher and is about 50%, especially at the age of over 50. In women, thyroid nodes are detected 2-4 times more often than in men. Children suffer from nodular lesions extremely rarely. The incidence of nodular goiter is directly proportional to age. The increase in the incidence of nodular goiter is approximately 0.1% per year at a young age and gradually reaches 2%. The prevalence of thyroid cancer (thyroid cancer) among nodular goiter, according to various authors, is from 1 to 6%. It should be noted that the prevalence in the population of nodular goiter is so high both in the regions of iodine deficiency and with normal iodine supply, but in the first case it is slightly higher. The incidence of thyroid cancer in absolute terms does not depend on the level of iodine supply. Thus, in a situation of a slightly higher incidence of banal nodular colloid goiter in the regions of iodine deficiency, the proportion of cancer among all cases of nodular goiter will be less. It is important to note that these data make it possible to equally use the results of studies on thyroid cancer obtained in regions with different iodine supply.

Human galectin-3 immunoexpression in thyroid follicular adenomas with cell atypia

Human galectin-3 (hgal-3) is a beta-galactoside binding protein involved in a number of physiological and pathological processes. Increasing hgal-3 immunoexpression has been reported in several human tumors, including thyroid carcinomas, but not in benign thyroid lesions. We analyzed the immunolocalization of hgal-3 in cell compartments of benign and malignant thyroid lesions. Hgal-3 immunoperoxidase reaction was carried out on 133 thyroid tissue samples obtained from 113 patients; 20 of these were normal (NT), 85 were benign thyroid lesions [20 colloid nodules (CN), 21 nodular hyperplasias (NH), 7 focal lymphocytic thyroiditis (FLT), 15 Hashimoto's thyroiditis (HT), 22 follicular adenomas (FA)], 25 differentiated carcinomas [15 papillary carcinomas (PC), 6 follicular carcinomas (FC) and 4 Hürthle cell carcinomas (HC)] and 3 anaplastic carcinomas (AC). Among the malignant thyroid lesions, hgal-3 was detected in 12/15 (80%) PC, 3/4 (75%) HC and in 4/6 (66.6%) FC, but in none of the 3 AC. Conversely, hgal-3 immunoexpression was absent in NT and in all benign thyroid lesions, but 1/15 HT and 10/22 (45.4%) FA. In the latter, hgal-3 was mostly expressed in microfollicular areas and in five of the six atypical FA. Hgal-3 cytoplasmic-perinuclear immunolocalization was observed in the majority of thyroid carcinomas and in more than half of the FA, theoretically suggesting an involvement of this protein in thyroid tumorigenesis throughout an antiapoptotic activity. Moreover, hgal-3 expression in FA might anticipate the likelihood of evolution of these benign lesions towards malignancy.

Proteomics reveals alterations in thyroglobulin expression and in the H2O2 detoxifying system in cold thyroid nodules

Szintigraphically cold thyroid nodules (CTN) are frequent findings in regions with iodine deficiency. While the presence of a CTN raises the possibility of thyroid cancer probably less than 3% of CTNs acutally represent malignancy. The molecular etiology of benign CTNs is still unresolved. We applied 2 D-gel electrophoresis in combination with MS analysis to define a protein fingerprint of CTNs as a pre-requiste to get further insights into their pathogenesis. 10 benign CTNs (colloid nodules and follicular adenoma) and corresponding normal thyroid tissue (ST) of the same patient were studied. The proteomics approach resulted in a protein resolution of ~ 1.500 spots/gel. Differential regulation of protein expression in CTN vs. ST was observed for 250 spots, which were subsequently identified by ESI-MS or FTICR. Proteins consistenly upregulated (>2fold) in CTNs fell into three major categories: 1. Cellular proliferation (amyloid precursor protein), 2. Tg trafficking (cathepsin B, PDI, HSP90, calreticulin, Tg fragments) and 3. H2O2 detoxifying system (peroxiredoxin 2 and 6, Glutathione S-transferase π, DJ-1). Western blot analysis for selective proteins e.g. APP, Cathepsin B and Tg was performed and verified the 2D-gel results.

Histopathologic pattern of thyroid disease.

Diseases of the thyroid are manifested by alteration in hormone secretion, enlargement of the thyroid gland (goiter), or both. The principal diseases of the thyroid gland are goiter (diffuse or nodular), hypo or hyperthyroidism, thyroiditis and neoplasms. The incidence and prevalence of these thyroid diseases in a given community are variable depending on various factors. Simple (non-toxic) goiter is extremely common throughout the world and is most prevalent in mountainous areas. The reported prevalance of goiter in Ethiopia varies between 18% and 30%. To review the histopathologic patterns of thyroid disease and their relationship with age and sex over a five year period. Tikur Anbessa teaching and referral hospital, Department of Pathology, Faculty of Medicine, Addis Ababa University. Retrospective analysis of five years biopsy material from patients with thyroid disease. Seven hundred and eighty consecutive patients with thyroid disease were included in the study. Six hundred and sixty (79%) were found to be non-neoplastic and 164 (21%) were neoplastic. Nodular colloid goiter (NCG) were found in 600 (76.9%) cases. Adenoma, carcinoma and thyroiditis accounted for 100 (12.8%), 64 (8.2%) and 16 (2.1%) cases respectively. Female to male ratio was 4.5:1. Eighty five point seven per cent of the thyroid diseases were found in the age group 20-59 years. Nodular colloid goiter is the most prevalent thyroid disease. Papillary carcinoma is the most frequent cancer seen in this series. Appropriate measures should be taken to reduce the iodine deficiency states in the diet to alleviate the social and medical consequences of the NCG. Similary clinical evaluation of goiter should be thorough, and use all means especially histopathologic study of the specimens to arrive at a definitive diagnosis as thyroid carcinoma is not uncommon.

Thyroid colloid nodules diagnosed by fine-needle aspiration: efficacy of suppression.

This study reviewed the accuracy of fine-needle aspiration biopsy (FNAB) and the efficacy of thyroid suppression for colloid nodules in our population to determine the utility of these two modalities on the decision to operate. A retrospective chart review of patients with colloid nodules diagnosed by FNAB from January 1993 to July 1995 was conducted. A 52-patient cohort underwent surgical management, and their needle aspirate cytologies and final pathologies were reviewed. A 7.7% false-negative rate in the detection of thyroid malignancy by FNAB was obtained. This is in keeping with data reported in the literature. Virtually no efficacy of hormonal suppression in our population was found. When the literature is reviewed and compared with the results of this study, the use of FNAB as a decision tool to operate is valid. The decision to operate based on the outcome of hormonal suppression, however, is not valid based on our results.

Proffered papers 14.00–15.00 Tuesday 16 September 2003 11 Galectin‐3 in thyroid nodules: a cytohistological correlation

Aim To assess sensitivity and specificity of galectin‐3 to identify malignant lesions of thyroid in cytological specimens.Methods Fifteen FNA biopsies with a histological correlation out of 392 have been considered suitable for immunostaining with galectin‐3. Galectin‐3 (mouse monoclonal antibody supplied by Novocastra Laboratories Ltd, Newcastle‐upon‐Tyne) primary antibody solution was used at a concentration of 1 : 400. Immunostaining was assessed using a score from 0 to 3 considering 0–1, negative and 2–3, positive.Results Four cases were cytologically reported as malignant (27%), five as suspicious (33%), six as benign (40%). Histologically, six were follicular adenomas, two hyperplastic nodules, three papillary carcinomas, two follicular carcinomas and one was a medullary carcinoma.Only in one case galectin‐3 immunostaining was positive in cytology, which resulted in histology to be a benign hyperplastic nodule. In histology, the galectin‐3 immunostaining was positive both in benign (three of nine) and malignant (three of six) nodules and negative in half of the carcinomas (three of six). Only in one case, galectin‐3 immunostaining was consistently positive both in cytology and histology (hyperplastic colloid nodule).Conclusion In our experience, galectin‐3 staining is poorly reproducible in cytological and histological samples and is of little help in the differential between malignant and benign lesions of the thyroid. Galectin score on cytology Cytological diagnosis Galectin score on histology Histological diagnosis 0 Follicular lesion 2 Benign hyperplasia nodule 0 Follicular neoplasm 1 Follicular adenoma 1 Papillary carcinoma 2 Papillary carcinoma 0 Follicular lesion 0 Follicular adenoma 0 Follicular lesion 0 Hyperplastic colloid nodule 0 Follicular lesion 2 Follicular adenoma 3 Atypical cells 2 Nodular hyperplasia 0 Follicular lesion 1 Follicular adenoma 0 No malignant cells 0 Follicular adenoma 3 Suspicious for malignancy 1 Follicular carcinoma 0 Follicular lesion 1 Follicular adenoma with papillary hyperplasia 0 Malignant cells? Papill. or med. carc. 0 Medullary carcinoma 0 Follicular lesion 3 Low grade minimal invasive follicular carcinoma 1 Papillary carcinoma 3 Papillary carcinoma 0 Suspicious for malignancy 0 Papillary carcinoma with Hurtle change

Changes in both size and cytological features of thyroid nodule after levothyroxine treatment.

We prospectively evaluated the effects of 12 months thyrotropin suppressive levo-thyroxine (L-T4) therapy in terms of changes in both thyroid nodule size and cytological features and considered whether thyroid nodule size changes actually resulted in (or were the result of) cytological changes. We studied 142 consecutive patients with benign 'cold' solitary thyroid nodules. For the purposes of the study, we divided our patients into three groups according to their initial cytological nodule classification as follows: group 1, including 88 colloid nodules (CN); group 2, including 30 hyperplastic nodules (HN); and group 3, including 24 adenomatous nodules (AN). The effects of TSH suppressive L-T4 treatment on both nodule volume and cytological characteristics were evaluated by ultrasonography and fine-needle aspiration (FNA) before and 12 months after the onset of therapy. Twelve months of TSH suppressive L-T4 treatment were effective in shrinking about one-third to one-quarter (31.8% CN, 26.7% HN and 25% AN) of thyroid nodules, irrespective of their initial cytological characteristics. Similarly, there was no difference in the prevalence of 'non-responders' (increasing nodules) to L-T4, which accounted for about one-fifth or less (20.5% CN, 13.3% HN and 20.8% AN) of all nodules. We found also that cytological features changed in 33.8% nodules after 12 months of L-T4 treatment. These changes were most commonly observed in HN and AN and consisted largely ( approximately 80%) of cytological characteristics resembling colloid features, not only in shrinking but also in stable nodules, thus indicating that cytology changes might be the very first indicator of nodule sensitivity to L-T4 therapy even in the continued absence of nodule shrinkage. When nodules were divided into three subgroups according to variations in size (shrinking, stable and increasing nodules), we observed that the distribution of the three cytological types showed a trend towards colloid lesions in shrinking nodules (chi2 3.8, P < 0.005) and towards an augmentation of hypercellular, adenomatous and suspicious characteristics in increasing nodules (chi2 3.6, P < 0.005). The frequency of shrinking nodules was not different between colloid, hyperplastic and adenomatous nodules. Repeat FNA should be advisable for thyroid nodules which increase in volume despite L-T4 therapy and might also provide useful information about nodule sensitivity to L-T4 treatment for both HN and AN, even where nodule size remains stable.

Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor.

Data on the expression of interleukin 6 (IL-6)/interleukin 6 receptor (IL-6R) in thyroid nodules is scarce. Based on our recent data of CD30 ligand (CD30L)/CD30 receptor (CD30) in these nodules and on the knowledge that this signal stimulates IL-6 production in non-thyroid neoplasms, we wanted to evaluate the immunocytochemical expression of these 2 ligand/receptor systems in a large archival series of paraffin-embedded specimens. These specimens included 6 normal thyroids and 130 thyroid nodules. Co-expression of IL-6 and IL-6R in the epithelial (follicular) cells was observed solely in CD30L/CD30 positive nodules: 5/15 (33%) oncocytic adenomas; 6/30 (20%) follicular adenomas which belonged to 2 variants (4/4 microfollicular toxic and 2/2 hyalinizing trabecular); 9/30 (30%) papillary thyroid cancers (PTC), all belonging to the conventional variant. In PTC the proportion of tumor epithelial cells that were IL6 positive was inversely correlated with the pTNM staging (r=-0.549, p=0.01). All 15 follicular cancers (FTC), all 6 anaplastic cancers (ATC) were IL-6/lL-6R negative; 14/15 FTC and 5/6 ATC were CD30L/CD30 negative. In another oncocytic adenoma, another 4 conventional PTC and another 7 non-conventional PTC CD30L/CD30 expression was associated to expression of IL-6 only. IL-6 staining associated to absent expression of CD30L and CD30 was observed in 7 follicular adenomas (all belonging to variants different from toxic and hyalinizing trabecular), 2 oncocytic adenomas, 5 of the 30 colloid nodules and 2 normal thyroids. Of the 6 tumors arising from the parafollicular C cells (medullary thyroid cancer, MTC), all 3 that had metastasized were CD30L/CD30/IL-6 positive and IL-6R negative; only IL-6 expression was lost in both the local and distant metastases. This finding matched the loss of IL-6 expression in one PTC metastasis. All 3 non-metastasized MTC were IL-6/IL-6R negative, and 1/3 was CD30L positive/CD30 negative. We conclude that only in a subset of both benign and malignant thyroid nodules the IL-6/IL-6R signal could be induced by the CD30L/CD30. IL-6 expression is related with aggressiveness in both PTC and MTC. In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30.

L-Thyroxin and potassium iodide therapy of nodular colloid euthyroid goiter

The article devoted to the L-Thyroxin and potassium iodide therapy of nodular colloid euthyroid goiter

Basedow disease. From subtotal to total thyroidectomy

Surgical treatment of Graves' disease is based on modern pathophysiolic understanding and adequate surgical tactic and technique. This is an audit from one institution about 81 consecutive, prospectively documented patients, undergoing subtotal (remnant < 6 g) or total thyroidectomy, by the technique of capsular dissection. Patients were female in 89%, aged 11-79 (median 35) years. They constitute 9% of all thyroid operations, i.e. 47% of those performed for hyperthyroidism. Indications were persistence and recurrence of disease, orbitopathy, large goiter, nodule formation, refusal of radioiodine, preconception control. Preoperative treatment was thyrostatic (97%), iodine (87%), propranolol (50%). During the study period use of total thyroidectomy increased from 0% to 87% (p < 0.0001), and the remnant size decreased from median 3.5 g to 0 g (p < 0.0001). Goiter weight was 20-255 g, median 70.28 (23%) patients had concomitant colloid or adenomatous nodules, 5 (6%) had an incidental microcarcinoma, and 3 (4%) had a clinical papillary or follicular carcinoma, 1 patient had a parathyroid adenoma. Mortality was 0; surgical morbidity was early postoperative haemorrhage (n = 2 (2.5%)), permanent nerve palsy (1 patient with recurrence after previous resection (1.2%; 0.6% of nerves at risk)); no case of permanent hypoparathyroidism occurred. Functional results: In 6 patients (8%; 15% of those with subtotal resection) recurrent hyperthyroidism developed, 1 month to 8 years postoperatively, necessitating reablative treatment (surgical in 2 instances). 1 further patient developed preclinical hyperthyroidism 11 years postoperatively. Postoperative thyroxine substitution was found to be inadequate in 16/73 (20%) patients, as demonstrated by suppressed or elevated TSH values. Recurrence-free survival at 10 years was 100% in patients with a remnant measuring < 3 g, vs. 55.8% in those with a remnant size > or = 3-6 g (p = 0.002). Ophthalmopathy improved in 33/47 (70%) and deteriorated in 5 (10%) patients postoperatively, independently of the procedure (total or subtotal). Extensive or total thyroidectomy is necessary for late recurrence-free survival.--Variation of the spontaneous remnant function may occur and contribute to inadequate substitution.--(Near) total thyroidectomy has a low morbidity and is considered the treatment of choice, also with the theoretical advantage of complete autoantigene removal.--Surgical progress is based on capsular dissection with fine preparatory operative technique.

Fas and Bcl-2 protein expression in thyrocytes of patients with nodular goiter.

The relative expression of the apoptotic protein Fas and the anti-apoptotic protein Bcl-2 were investigated in thyrocytes from patients with non-toxic nodular goiter (NTG, n=20) and Hashimoto's thyroiditis (HT, n=5), who underwent fine-needle aspiration biopsy for diagnostic reasons. On the basis of the clinical and cytological findings, the patients with NTG were sub-classified into the group of those with colloid nodules (n=9), degenerative nodules (n=6) and adenomatous nodules (n=5). Fine-needle biopsy aspirates were examined by immunocytochemistry for Fas and Bcl-2 expression, using specific monoclonal antibodies. For the evaluation of Fas and Bcl-2 immuno-reactivity, an expression index, based on the number of cells with positive staining, was used: grade 1 included samples with positive staining in <20% of cells; grade 2 included samples with 20-50% positive cells; and grade 3 included samples with >50% positive cells. Fas protein expression was generally low (grade 1) in patients with nodular goiter, in contrast to patients with HT, in whom high expression was detected (grade 3). Only in aspirates from degenerative nodules (four out of six), and in which lymphocytes were also present, was Fas expressed at an intermediate level (grade 2). On the other hand, Bcl-2 protein was differentially expressed among the nodule subtypes. It was low in colloid and degenerative nodules (grade 1) but high in adenomatous ones (grades 2 and 3). Bcl-2 expression was also low in patients with HT (grade 1). It is concluded that in comparison to HT, where there is up-regulation of Fas and down-regulation of Bcl-2 protein, Fas expression is low in human goiter, indicating low apoptotic activity. The regulation of Bcl-2 protein differs between adenomatous and colloid nodules, suggesting that this protein may play a role in the differentiation of thyroid nodules.

Follicular variant of papillary carcinoma: cytologic findings on FNAB samples-experience with 16 cases.

Between January 1, 1992 and December 31, 1997, a cytopathological diagnosis of follicular variant of papillary thyroid carcinoma (FVPC) was made on a series of 16 out of 18 patients with palpable nodules who underwent fine-needle aspiration biopsy (FNAB) in our Department. The results of aspiration biopsy were followed by histopathological examination of the surgically excised tissues. There were three false-negative aspirations (16.6%), of which two were probably bound to fine-needle sampling and one due to a mixture of benign and malignant cells which had originally gone unrecognized. The accuracy of the cytopathologic diagnosis in this variant was 88.8%. An analysis of the diagnostic cytopathological criteria was performed, which demonstrated the importance of both architectural features (monolayered and branching sheets, microacinar structures, and their combinations) and nuclear features (presence of nuclear grooves). Background -bound features were mainly represented by dense, nonfilamentous colloid. The cytopathologic findings in FVPC were compared to those found in a series of 10 usual papillary carcinomas (UPC) and 10 follicular neoplasms (FN). These latter had originally been diagnosed by FNAB and were subsequently classified histologically as follicular adenoma (n = 6), follicular carcinoma (n = 3), or adenomatoid colloid nodule (n = 1). Statistical evaluation was performed on the cytopathological findings in the three classes of lesions (FVPC, UPC, and FN) as to their presence and relative frequency or absence by using a nonparametric one-way ANOVA (Kruskall-Wallis) and, where necessary, a Mann-Whitney U test. Papillary cellular fragments and multinucleated giant cells (P < 0.005), nonfilamentous dense colloid, squamoid cells, and syncytia were significantly more represented in UPC than in FVPC (P < 0.05), while histiocytes were significantly more frequent in FVPC (P < 0.005). Other nuclear and/or background features were significant only in the distinction between papillary carcinomas as a group and FN. The cytological differential diagnosis of the FVPC is briefly discussed with relevance to the possible pitfalls caused by its peculiar cyto- and histomorphology.

Expression of CD30 ligand and CD30 receptor in normal thyroid and benign and malignant thyroid nodules.

Because the CD30 ligand (CD30L)/CD30 receptor (CD30) system is expressed in certain malignancies, but has not been studied in thyroid nodules, we investigated its immunohistochemical expression in 6 normal thyroids (NT) and 131 thyroid nodules: 28 colloid nodules (CN), 45 adenomas (15 oncocytic [OA], 30 follicular [FA]) and 58 carcinomas (15 follicular [FTC], 1 insular [ITC], 6 anaplastic [ATC], 30 papillary [PTC], and 6 medullary [MTC]). NT and CN expressed neither CD30L nor CD30 (CD30L-/CD30-). Forty percent of OA and 20% of FA showed epithelial coexpression of CD30L and CD30, and interstitial expression of CD30L, which was also observed in the surrounding normal tissue. Within malignancies, epithelial coexpression of CD30L and CD30 was observed in 7% of FTC, 33% of ATC, 67% of PTC, and 67% of MTC. Only PTC and MTC showed epithelial expression of CD30L in the perinodular tissue with similar frequency (80% PTC, 75% MTC). PTC and MTC had the highest proportion of CD30L+ or CD30+ cells, and together with OA, a thus far unreported nuclear location of CD30L. In PTC, the proportion of CD30L+ cells and the prevalence of nuclear location of CD30L correlated inversely and directly, respectively, with aggressiveness. In conclusion, CD30L/CD30 signaling is activated only past the colloid nodule stage, most frequently in an autocrine fashion.

Valor da repunção aspirativa na doença nodular benigna de tireóide

O presente estudo teve por objetivo verificar se um novo exame de punção aspirativa com agulha fina (PAAF) deve ser realizado em pacientes que já foram submetidos a tal procedimento e tiveram o diagnóstico citopatológico compatível com doença nodular benigna de tireóide. Quarenta e um pacientes com o diagnóstico clínico e laboratorial de bócio nodular foram submetidos a duas PAAFs, com intervalo mínimo de seis meses, e comparados quanto aos seus laudos e características citopatológicas. Além do resultado das punções, foram observadas as seguintes características (média±DP): idade= 44,3±13,1 anos; início do aparecimento do nódulo= 5,1±8,1 anos (mediana= 2,0 anos); volume nodular= 18,6±21,6ml (mediana= 9,6ml) e volume tireoidiano= 42,8±30,8ml (mediana= 33,5ml), ambos baseados na ecografia; captação de 131I em 24h= 13,2±5,4%; níveis de triiodotironina (T3)= 142,0±34,5ng/dl, de tiroxina (T4)= 8,6±1,5µg/dl, de hormônio tireoestimulante (TSH)= 1,7±1,0mUI/L e de tireoglobulina (TG)= 59,3±47,8ng/ml. O estudo demonstrou predominância do sexo feminino (40 de 41); nódulo misto (23 de 41) e frio (29 de 41), com padrão multinodular (23 de 41). Na avaliação citopatológica, o segundo laudo foi idêntico ao primeiro em 40 de 41 pacientes (97,6%), embora houvessem características citopatológicas distintas em 39 dos 41 pacientes estudados (95,1%), apontando para a própria heterogeneidade do nódulo colóide. Concluímos que a PAAF é um método diagnóstico seguro na doença nodular de tireóide. A não concordância nos detalhes citopatológicos das punções seqüenciais revela a grande heterogeneidade da morfologia do bócio colóide.

Thyroid carcinoma diagnosis based on a set of karyometric parameters of follicular cells.

In the works of various authors, performed with the help of morphometry, an assessment of cell changes was carried out, as a rule, by one sign of their atypia (e.g. area of cell nuclei). Moreover, the selective analysis of morphometric data for certain nosologic forms was performed. Such an approach allowed researchers to develop only additional diagnostic criteria of thyroid carcinoma. At the same time, the use of a set of quantitative signs of cell atypia as a criterion for tumor malignancy made it possible to improve oncologic diagnosis. In this study, which is a first step in the development of a quantitative approach to thyroid carcinoma diagnosis, a system of karyometric parameters was developed with the help of morphometry of cytologic material of patients with major nosologic forms of thyroid pathology (papillary and follicular carcinoma, follicular adenoma, autoimmune thyroiditis, and nodular colloid and diffuse toxic goiter). The significance of each parameter in thyroid carcinoma diagnosis was evaluated. Thyroid cells of autopsy, operative, and aspiration biopsy material were the object of the study. One hundred fifty-two preparations with histologically verified diagnosis were studied. Light morphometry was performed with the help of a semiautomatic computer analyzer of images. One hundred fifty thyroid nuclei were assessed in each preparation. Among many karyometric parameters, six were selected: mean area of thyrocyte nuclei, ratio of frequencies, and number of classes on histograms of distribution of their area, coefficient and a free term of the regression equation to a scattered diagram of perimeter and nuclear area, and the discriminant index. Boundary values of these parameters between the malignant and benign pathology were united into an expert system for thyroid carcinoma diagnosis. Clinical trials of the system were performed. On the basis of the obtained results, the informativity (accuracy, sensitivity, specificity) of its karyometric parameters was assessed. The formula for calculation of the weighting coefficient for each parameter was derived, the diagnostic index being determined by the sum of their values. An expert system was created based on a set of karyometric parameters reflecting the regularities of pathologic changes in thyrocyte nuclei with malignant and benign pathology. The informativity and weighting coefficients included into the system of parameters have been assessed, which made it possible to perform the probabilistic diagnosis of thyroid carcinoma.

Goiter and impairment of thyroid function in acromegalic patients: basal evaluation and follow-up.

We evaluated morphological, biochemical and cytological thyroid parameters in acromegalic patients, investigated before and after treatment for acromegaly. 28 acromegalics were investigated before and, in 18 cases, after 2-7 years of therapy. Fourteen patients were from areas of moderate iodine deficiency in Southern Italy. One patient underwent thyroidectomy before entering this study. 19 patients were euthyroid (FT4: 17.7 +/- 0.8 pmol/l and FT3 4.6 +/- 0.2 pmol/l), but TSH was undetectable in 5/19. Among them, TRH-stimulated TSH increase was absent/impaired or exaggerated/delayed in 9 and one cases, respectively. Decreased FT3 and/or FT4 values with low/normal TSH values were detected in 7 cases; TRH-stimulated TSH response was absent/impaired in 2 patients and exaggerated/delayed in another two. Increased free T4 and free T3 concentrations with undetectable TSH levels were found in one. Two euthyroid patients had high TPOAb levels. Goiter was diagnosed in 21 cases and nodules were found in 14/21. 99Tc scintiscan showed "cold" areas in 13/14 cases and a "hot" nodule in the hyperthyroid patient. Acromegalics from iodine deficient areas showed a not significant increase of prevalence of goiter (86 vs. 71 %) and of mean thyroid volume (35 +/- 7 vs. 28 +/- 4 ml, NS), compared to others. Thyroid volume (TV) did not correlate with GH, IGF-1 and TSH levels, the area under the curve of insulin-increase during OGTT, the age of patients or the duration of acromegaly. Fine needle aspiration biopsy (FNAB), performed in 11/14 patients with nodular goiter, showed colloid nodules in 8 cases, hyperplastic nodules in 2 and an adenomatous nodule in one. Neurosurgery, radiotherapy or medical treatment for acromegaly induced a significant decrease of mean GH and IGF-1 levels (21.5 +/- 8.5 vs. 12.9 +/- 9.6 ng/ml, p< 0.005 and 747 +/- 94 vs. 503 +/- 88 ng/ml, p < 0.02, respectively), but both GH and IGF-1 values normalized only in 3 cases. No significant variation of mean TSH levels was found. Although TV normalized in 3 patients, ultrasound evaluation showed a not significant decrease of mean TV and no changes in the diameter and number of nodules. FNAB was unchanged. Our results suggest that, despite no correlation between serum GH and IGF-1 levels and thyroid volume being found, a decrease in serum GH and IGF-1 levels has favourable effects on thyroid status.