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PubMed1994

Differentiation of thyroid neoplasms by evaluating epithelial membrane antigen, Leu-7 antigen, epidermal growth factor receptor, and DNA content.

The expression of epithelial membrane antigen (EMA), Leu-7 antigen, epidermal growth factor receptor (EGFr), and deoxyribonucleic acid (DNA) content in 40 thyroid nodules was investigated to identify those factors that might differentiate these lesions or correlate to their prognosis. There were 22 carcinomas (16 papillary, 4 follicular, 1 anaplastic, 1 medullary) and 18 benign lesions prospectively obtained between 1989 and 1993. Patients' charts were reviewed to establish a database of known clinical prognostic indicators. Expression of EMA and Leu-7 was significant in malignant lesions when compared to benign lesions (P < 0.02 and P < 0.001). EMA was expressed significantly more frequently by follicular carcinomas than by follicular adenomas (P < 0.03). Leu-7 antigen was expressed by all papillary carcinomas. Neither of these antigens showed any association with known clinical prognostic indicators. EGFr expression neither differentiated benign from malignant lesions nor correlated with prognostic factors. The presence of aneuploidy correlated with poor tumor differentiation (P < 0.02), but did not distinguish benign from malignant lesions. These results suggest that EMA expression may be useful for confirming malignancy in follicular neoplasms and that the expression of Leu-7 antigen can assist in distinguishing papillary carcinoma from benign lesions with pseudopapillae.

Adolescent↗
PubMed1994

Fine-needle aspiration of thyroid follicular neoplasm: diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47.

BACKGROUND: We previously demonstrated that thyroid peroxidase (TPO) immunocytochemistry with monoclonal antibody 47 can help to differentiate benign (staining score, 80% or more) from malignant (staining score, less than 80%) thyroid nodules on fine-needle aspiration (FNA) samples. In the present study we assessed the use of TPO immunocytochemistry in the cytologic diagnosis of thyroid follicular neoplasms. METHODS: A total of 109 histologically proven follicular tumors were studied. There were 60 microfollicular adenomas, 23 atypical adenomas, 17 oncocytic adenomas, and 9 follicular carcinomas. Adequate preoperative FNA samples were available in all cases. TPO immunocytochemistry was performed on one half of the slides. RESULTS: The staining score was less than 80% in all follicular carcinomas, whereas it was 80% or more in 68 of 100 benign tumors. There was no false negative and 32 false positives for diagnosis of malignancy. The false positives were 10 microfollicular adenomas, 13 atypical adenomas, and 9 oncocytic adenomas. TPO immunocytochemistry has a sensitivity of 100% and a specificity of 68% for screening of follicular cancer. CONCLUSIONS: TPO immunocytochemistry with monoclonal antibody 47 on FNA samples is a highly sensitive and fairly specific method to distinguish benign from malignant follicular neoplasms. This technique can help to reduce the number of surgical procedures for benign thyroid nodules without increased risk of overlooking malignancy.

Antibodies, Monoclonal↗
PubMed2004

[Surgical tactics in thyroid nodular neoplasms associated with chronic autoimmune thyroiditis].

There were analyzed the results of surgical treatment of 628 patients with different thyroid nodular neoplasms combined with autoimmune thyroiditis, who were operated in the surgical department of the Mandryka Central Military Clinical Hospital in 1989-2001. The use of organ-preserving operations is substantiated by the necessity of maximal decrease of the post-operative complication level and preservation of thyroid hormonogenic function. Resection with node removal within the limits of healthy tissues is substantiated by the results of analysis of morphologic structure of nodular neoplasm and adjacent thyroid tissue. The analysis of repeated operations has shown that the etiology and morphologic structure of nodular neoplasm (but not the volume of operation) play the main role in the pathogenesis of relapse development.

Chronic Disease↗
PubMed1998

Polymerase chain reaction-based microsatellite polymorphism analysis of follicular and Hürthle cell neoplasms of the thyroid.

Follicular and Hürthle cell carcinomas of the thyroid cannot be differentiated from adenomas by either preoperative fine needle aspiration or intraoperative frozen section examination, and yet there exist potentially significant differences in the recommended surgical management. We examined, by PCR-based microsatellite polymorphism analysis, DNA obtained from 83 thyroid neoplasms [22 follicular adenomas, 29 follicular carcinomas, 20 Hürthle cell adenomas (HA), and 12 Hürthle cell carcinomas (HC)] to determine whether a pattern of allelic alteration exists that could help distinguish benign from malignant lesions. Alterations were found in only 7.5% of informative PCR reactions from follicular neoplasms, whereas they were found in 23.3% of reactions from Hürthle cell neoplasms. Although there were no significant differences between follicular adenoma and follicular carcinoma, HC demonstrated a significantly greater percentage of allelic alteration than HA on chromosomal arms 1q (P < 0.001) and 2p (P < 0.05) by Fisher's exact test. The documentation of an alteration on either 1q or 2p was 100% sensitive and 65% specific in the detection of HC (P < 0.0005, by McNemar's test). In conclusion, PCR-based microsatellite polymorphism analysis may be a useful technique in distinguishing HC from HA. Potentially, the application of this technique to aspirated material may allow this distinction preoperatively and thus facilitate more optimal surgical management. Consistent regions of allelic alteration may also indicate the locations of critical genes, such as tumor suppressor genes or oncogenes, that are important in the progression from adenoma to carcinoma. Finally, this study demonstrates that Hürthle cell neoplasms, now considered variants of follicular neoplasms, differ significantly from follicular neoplasms on a molecular level.

Adenocarcinoma↗
PubMed1993

The usefulness of computer-aided karyometric examination in preoperative differentiation of follicular neoplasms of the thyroid gland.

Fine-needle aspiration biopsy (FNAB) is the most important procedure in preoperative diagnosis of thyroid neoplasms. However, routine cytological examination is insufficient for differentiation between follicular adenoma and follicular carcinoma. Therefore, we decided to assess the usefulness of karyometric analysis in the examination of aspirates from these neoplasms. Morphometric analysis was performed with the use of the computer system for karyometric measurements--"Karyometry Manager" ver. 1.2. We examined cytological smears derived from 26 patients. In 10 of them a nodular goitre was diagnosed in both cytological and histopathological examinations. In the other 16 patients, "follicular neoplasms" were found in cytological examination. These proved to be follicular adenomas (8 cases) and follicular carcinomas (8 cases) on histopathological examination. The following morphometric parameters were measured in 100 nuclei per smear: volume, intersection area, perimeter, convexity coefficient and shape coefficient. We found that: 1) the mean volume and the mean intersection area of thyrocyte nuclei from follicular carcinomas were significantly (p < 0.001) greater than those of nuclei from adenomas or nodular goitres; 2) the mean perimeter of thyrocyte nuclei from follicular carcinomas was significantly greater than the mean perimeter of thyrocyte nuclei from follicular adenomas (p < 0.025) and nodular goitres (p < 0.001); 3) the mean nuclear area of thyrocytes from follicular adenomas was significantly greater than that of thyrocytes from nodular goitres (p < 0.05). Our results show that karyometric analysis can be useful in cytological differentiation of follicular neoplasms.

Adenocarcinoma, Follicular↗
PubMed1992

Hurthle cell neoplasms of the thyroid gland revisited.

Hurthle cell tumours (benign and malignant) have been regarded as lesions with uncertain biological behaviour. However recent clinico-pathological studies have shown that they should be categorized as benign or malignant on the basis of capsular and/or vascular invasion, like other differentiated thyroid neoplasms. The fact that the tumours are composed of Hurthle cells is irrelevant. Currently, histological parameters do not seem to predict biological behaviour of Hurthle cell carcinomas.

Adenoma↗
PubMed1996

Encapsulated columnar-cell neoplasms of the thyroid. A report of four cases suggesting a favorable prognosis.

Four encapsulated thyroid neoplasms with columnar-cell features were studied. The patients were a 29-year-old man and three women aged 42, 60, and 83 years. The tumors measured from 1.2 to 8.0 cm in maximum dimension. All were completely surrounded by a thick capsule; three demonstrated invasion into the capsule (but no farther), whereas one (from the 60-year-old woman) did not. In addition to columnar-cell areas, all the neoplasms had areas with follicular and solid growth, in varying proportions. Although the growth pattern in the columnar-cell zones was usually papillary, nuclear characteristics of papillary carcinoma were not present in these areas or elsewhere. Follow-up on the four patients was 112, 51, 112, and 29 months, respectively, and none had any evidence of recurrence or metastasis. The findings suggest that encapsulated columnar-cell thyroid tumors have a much more favorable prognosis than those that are unencapsulated and invasive into adjacent thyroid or extrathyroid tissue.

Adult↗
PubMed1984

Follicular neoplasms of the thyroid. A study of 44 cases followed for a minimum of 10 years, with emphasis on differential diagnosis.

Forty-four follicular thyroid neoplasms followed for a minimum of 10 years are presented. The cases were divided into four categories: follicular adenoma (19 cases), encapsulated follicular carcinoma (7 cases), invasive follicular carcinoma (11 cases), and the follicular variant of papillary carcinoma (7 cases). The former two tumor types were distinguished by the presence of capsular invasion in encapsulated follicular carcinoma (which was defined as lacking extension into the surrounding thyroid) and by the frequent thinness of the capsule in follicular adenoma, while the latter two (which both infiltrated adjacent thyroid or extrathyroid tissue) were separated primarily on the basis of the tendency toward vesicular and hypochromatic nuclear staining in the follicular variant of papillary carcinoma, but with consideration of a number of other factors in addition. No patient with follicular adenoma had any further difficulty after removal of the lesion. Metastasis to cervical lymph nodes occurred in five cases of the follicular variant of papillary carcinoma, but there were no distant metastases or deaths due to tumor. By contrast, three patients with encapsulated follicular carcinoma and nine with invasive follicular carcinoma died of tumor, and all of these had distant metastasis (most often to bone). Local recurrence was seen only in invasive follicular carcinoma (six cases).

Adenocarcinoma↗
PubMed1987

Encapsulated papillary neoplasms of the thyroid. A study of 14 cases followed for a minimum of 10 years.

Fourteen cases of encapsulated papillary thyroid neoplasm in which extracapsular extension was not observed and a minimum of 10 years follow-up was available are herein presented. The cases were divided into three categories: encapsulated papillary carcinomas (five cases), which had cytologic features typical of papillary thyroid carcinoma (vesicular or indented nuclei) and an entirely or predominantly thick capsule with capsular invasion; encapsulated papillary neoplasms of undetermined malignancy (seven cases), in which the cytologic features were also typical of papillary carcinoma but the capsule was predominantly thin (less than 0.1 mm thick) or was thick without capsular invasion; and follicular adenomas with papillae (two cases), which resembled follicular adenomas cytologically (rounded, stippled nuclei and Hürthle cell change) but contained a significant number of papillary structures (both cases had an entirely or predominantly thin capsule). The only evidence of malignant behavior in the entire series was a cervical lymph node metastasis in one case of encapsulated papillary carcinoma; the "encapsulated papillary neoplasms of undetermined malignancy" were so labeled because other authors have reported "encapsulated papillary carcinomas without capsular invasion" and it was therefore thought that the malignant potential of this category is as yet best considered undefined.

Adenocarcinoma↗
PubMed1994

Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm.

Thyroid carcinoma has been described as occurring more frequently than expected in association with familial adenomatous polyposis. The histology of these cases has not been described in detail, although the reported cases were usually diagnosed as papillary carcinoma. We now report the pathological features of four cases of thyroid carcinoma associated with familial adenomatous polyposis, and review the findings in the literature. The tumours in these four cases were all of follicular cell origin as shown by thyroglobulin immunohistochemistry. In three they were multifocal. The tumours showed some features of papillary carcinoma--grooved nuclei and papillary architecture, but these were not consistent. They also showed features that were unusual for papillary carcinoma--a cribriform pattern and solid areas with spindle cell component. Commonly the tumours combined both patterns. A review of the reported cases of thyroid cancer associated with familial adenomatous polyposis showed that they also were commonly multifocal and occurred predominantly in young women. When the histology was adequately reported or illustrated it was, in most instances, consistent with the findings in our own cases. We therefore suggest that these thyroid tumours form a distinct type with some unusual features. Clearly it is likely that the APC gene is associated with their pathogenesis, and that other factors contribute to the predominantly female incidence in this as in sporadic tumours. Six of 63 reported cases showed metastasis or died from thyroid carcinoma. In a number of cases the tumours presented before the familial adenomatous polyposis was recognized. The findings of these unusual histological features in a thyroid tumour, and particularly of multicentricity, should alert the pathologist to the possibility of familial adenomatous polyposis with its implications for family screening. The tumours are often well demarcated but, because of the multicentricity, total thyroidectomy should be advocated.

Adenocarcinoma, Follicular↗
PubMedDate not supplied

Proton magnetic resonance and human thyroid neoplasia. II: Potential avoidance of surgery for benign follicular neoplasms.

Thyroid cancer is rare, but many thyroidectomies continue to be performed simply to exclude a diagnosis of malignancy. The purpose of this study was to determine the potential financial savings associated with the use of proton magnetic resonance analysis of follicular neoplasms. Proton magnetic resonance spectroscopy was performed on tissue obtained at the time of surgery from 98 consecutive solitary or dominant thyroid nodules. Fine-needle biopsies were also performed on operative specimens, and the tissues assessed by proton magnetic resonance; these spectra were then compared with those obtained from tissue specimens. An estimate of potential savings was obtained by comparing the magnetic resonance data with the indications for surgery and pathology on all patients having thyroidectomy over a 10-year period. Proton magnetic resonance spectroscopy was able to distinguish between normal thyroid tissue and invasive thyroid cancer with 100% specificity. Benign follicular adenomas fall into two groups: 44% having a spectral pattern comparable with normal thyroid, and the remaining 56% demonstrating an altered spectral pattern more comparable to the malignant magnetic resonance profile. Proton magnetic resonance spectroscopy on fine-needle biopsy specimens produced spectra similar to those from tissues from the same patient. From a fine-needle biopsy specimen, proton magnetic resonance spectroscopy can identify a group of benign follicular adenomas with spectral profiles akin to those of normal thyroid cells, thus avoiding the need for unnecessary surgical excision. The potential savings in one surgical unit alone were over $1 million in 10 years.

Adenocarcinoma, Follicular↗
PubMed1993

Thyroid-stimulating hormone activates phospholipase C in normal and neoplastic thyroid tissue.

BACKGROUND: Thyroid-stimulating hormone (TSH) stimulates thyroid growth through two signal transduction pathways: the G protein-adenylate cyclase system and the G protein-phospholipase C (PLC) system. The adenylate cyclase system has been studied extensively, but there is little information available concerning PLC activity in thyroid neoplasms. METHODS: Human thyroid membranes were incubated for 30 minutes at 37 degrees C in the presence or absence of bovine TSH (300 mU/ml). PLC activity was assayed by liberation of inositol phosphates from the enzymatic hydrolysis of tritiated phosphatidylinositol bisphosphate. Fifty-six tissues were assayed (normal, 23; multinodular goiter, 5; follicular adenoma, 9; and differentiated thyroid cancer, 19 [9 low risk and 10 high risk]). RESULTS: TSH significantly increased PLC activity in normal, benign, and most malignant thyroid neoplasms. Although there were no differences in basal or TSH-stimulated PLC activity between the groups of normal thyroid, multinodular goiter, follicular adenoma, or the cancers, one half of the high-risk cancers had an aberrant PLC response. CONCLUSIONS: This is the first demonstration that TSH stimulates PLC activity in normal and neoplastic human thyroid tissue. Aberrant TSH-stimulated PLC activity was present in half of the aggressive thyroid neoplasms.

Enzyme Activation↗
PubMed2004

The utility and limitation of thyroid transcription factor-1 protein in primary and metastatic pulmonary neoplasms.

Thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor expressed in the thyroid and lung. The clinical utility and limitation of TTF-1 in primary or metastatic carcinomas of the lung have not been previously studied in detail. We examined TTF-1 expression in 510 primary lung and 107 metastatic neoplasms. TTF-1 was detectable in 4/99 (4%) squamous cell carcinomas, 169/176 (96%) solitary adenocarcinomas, 34/34 (100%) multifocal adenocarcinomas, 1/1 (100%) signet ring cell carcinoma, 16/20 (80%) mucinous adenocarcinomas, 23/23 (100%) nonmucinous bronchioloalveolar carcinomas, 19/36 (53%) small cell carcinomas, and 39/44 (89%) sclerosing hemangioma. TTF-1 was absent in all eight carcinoids, three atypical carcinoids, 23 pleomorphic carcinomas, 25 lymphoepithelioma-like carcinomas, the sarcomatous component of one pseudomesotheliomatous carcinoma, and one mesothelioma. In four combined small cell carcinomas and 12 adenosquamous carcinomas, TTF-1 expression was only demonstrated in the adenocarcinoma component. There were 78 TTF-1 non-immunoreactive metastatic cases from 22 livers, 20 colorectums, 10 breasts, six nasopharynx, four larynx, four ovaries, three salivary glands, three esophagus, two adrenal glands, two kidneys, one bile duct, and one endometrium. TTF-1 was also detected in all 10 cervical lymph nodes, seven brain, and 6/7 (86%) bony tissues of 24 patients with metastatic carcinomas of unknown primary site, but it was absent in 125 patients with metastatic carcinomas other than lung origin in cervical lymph nodes, brain, and bony tissues. These results indicate the clinical usefulness and limitation in certain primary and metastatic lung neoplasms.

Adenocarcinoma↗
PubMed2005

Characterization of thyroid 'follicular neoplasms' in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application.

The distinction of benign from malignant follicular thyroid neoplasms remains a difficult task in diagnostic fine-needle aspiration cytology, and some discrepant results have been reported for the individual immunocytochemical markers of malignancy proposed so far. The aim of this study was to test if the combined use of a panel of markers could improve the diagnostic accuracy in the preoperative cytological evaluation of 'follicular neoplasms' in an attempt to reduce the number of thyroidectomies performed for benign lesions. The immunocytochemical expression of galectin-3, HBME-1, thyroperoxidase, cytokeratin-19 and keratan-sulfate was retrospectively analyzed in 125 consecutive fine-needle aspiration samples (cell blocks) of indeterminate diagnoses of 'follicular thyroid neoplasm', and compared with their corresponding surgical specimens, including 33 follicular carcinomas, 42 papillary carcinomas and 50 follicular adenomas. Statistical analysis on each marker confirmed that galectin-3 and HBME-1 were the most sensitive (92% and 80% respectively) and specific (94% and 96% respectively) molecules. The use of these two markers sequentially in non-oncocytic lesions (testing HBME-1 as a second marker whenever galectin-3 proved negative) increased the sensitivity and specificity up to 97% and 95% respectively. In oncocytic lesions, HBME-1 proved to be less sensitive, and the sequential combination of galectin-3 and cytokeratin-19 reached 100% of both specificity and sensitivity. Our data showed that, as compared with the use of single markers, the sequential combination of two markers represents the most accurate immunohistochemical panel in managing patients with a fine-needle aspiration biopsy diagnosis of 'follicular neoplasms', especially in otherwise controversial categories such as oncocytic tumours. The combination of three or more markers did not substantially improve the diagnostic accuracy of the test.

Adenocarcinoma, Follicular↗
PubMed1979

Neoplasms and pigmentation of thyroid glands in F344 rats exposed to 2,4-diaminoanisole sulfate, a hair dye component.

2,4-Diaminoanisole sulfate was fed at dietary levels of 0.12% (low dose) or 0.5% (high dose) to groups of 50 male and 50 female inbred F344 rats for 78 weeks. By 107 weeks after the initial exposure, 58% of the male rats and 42% of the female rats administered the high dose had thyroid neoplasms, whereas only 7--8% of the controls developed them. Follicular cell carcinomas were the primary type of neoplasm induced. None of the controls had these tumors. The carcinomas, which were papillary, cystic, or solid, were highly invasive but did not metastasize. A brown pigment was present as granules primarily in thyroid follicular cells in all exposed rats. The amount of pigment as determined by an image-analyzing computer revealed that the cross-sectional area occupied by the pigment granules and the optical density of the granules were dose related.

Adenocarcinoma↗