Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells

OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hürthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P < .05). A higher incidence of malignancy was found in males, but the data did not reach statistical significance (P = .0586). CONCLUSION: Most of the follicular neoplasms revealed by FNAC were benign lesions. Low echo density on ultrasonography and male sex carried a higher risk of malignancy.     

Histopathological and immunohistochemical studies on medullary thyroid carcinoma

In order to study the multidifferentiation of medullary carcinoma of the thyroid gland (MCT), 24 cases of MCT were examined for the presence of immunoreactive calcitonin (CT), thyroglobulin (Tg), chromogranin A (CgA), somatostatin (SS), serotonin (5-HT), S-100 protein (S-100), neuron-specific enolase (NSE), vasoactive intestinal polypeptide (VIP), adrenocorticotrophin (ACTH) and neurofilament protein (NF) by using immunohistochemical ABC methods. Results showed that CT-immunoreactive cells were present in all tumors. Tg was present in three tumors. 23 cases contained CgA-immunoreactive cells. 14 tumors contained 5-HT-immunoreactive cells, 10 cases were immunoreactive to NSE and SS. 4 tumors contained VIP-immunoreactive cells and only one cases was positive for S-100. The demonstration of immunoreactivity for multiple antigens in 24 cases suggests that the origin of medullary thyroid carcinoma may originate from neuroectoderm cells potentially capable of producing numerous hormone substances. In addition, as the neoplastic cells in 12% of the tumors containing hormone substances as well as thyroglobulin, it is suggested that follicular epithelial differentiation and mixed medullary thyroid carcinoma may be more common than previously suspected. Recent studies indicate that mixed carcinoma of the thyroid may be derived from common stem cells in posterior branchia capable of differentiating into both follicular and parafollicular tumor cells.     

Endocrine therapy and after-care in thyroid gland carcinoma

The 10 year survival is excellent for stage I disease thyroid carcinoma. Survival decreases as a function of cancer invasion beyond the gland. Papillary and follicular cancers have longterm survival, but anaplastic cancers are lethal and survival is short. In differentiated carcinomas thyroidectomy and neck dissection are followed by radioiodine therapy to eliminate residual tissue and metastases. In case of papillary microcarcinomas a limited resection is justified. There is no need for radioiodine treatment. Thyroid hormones are given postoperatively in a high dose to suppress TSH. An increase of the tumor marker thyreoglobulin indicates the development of relapse or metastases. In medullary carcinoma basal or serum calcitonin levels after stimulation with pentagastrin-elicited are pathognomonic for a relapse. 25% of the medullary thyroid carcinomas are observed in families. Genetic screening is mandatory in patients with medullary carcinoma. Serum calcium values should be controlled to exclude safely hypoparathyroidism with certitude.     

S-100 protein is a differentiation marker in thyroid carcinoma of follicular cell origin: an immunohistochemical study

S-100 protein, a dimer of S-100 alpha and S-100 beta subunits (S-100 alpha and S-100 beta), is widely distributed in human tissue, and several papers describing S-100 protein expression in follicular cells of the thyroid have been published. In the present study, 105 cases of thyroid carcinoma (of which 96 were papillary, four follicular, two undifferentiated, and three medullary) were analyzed immunohistochemically for the expression of S-100 protein, S-100 alpha, S-100 beta, and thyroglobulin. In papillary carcinoma, 188 lesions were studied and classified into well differentiated types (56 papillary, 45 follicular) and poorly differentiated types (41 trabecular, four solid, eight squamoid, three tall, and one insular), because the histological structure of each tumor was heterogeneous. The percentage of lesions which expressed positively for S-100 protein and S-100 alpha, respectively, according to type were: papillary, 96 and 99%; follicular, 96 and 100%; trabecular, 95 and 100%; solid, 50 and 50%; squamoid, 50 and 75%; and tall, 33 and 100%. The insular type was negative for both. For papillary carcinoma, well differentiated lesions showed stronger S-100 alpha expression than poorly differentiated lesions. S-100 alpha expression was weaker in follicular and undifferentiated carcinoma than in papillary carcinoma. Medullary carcinoma also expressed S-100 alpha. S-100 beta was positive in lesions that expressed S-100 alpha strongly. Expression of S-100 protein and S-100 alpha protein correlated with thyroglobulin synthesis in the follicular cells. It was concluded that S-100 protein, mainly S-100 alpha, exists in thyroid follicular cells, that it exists in higher quantity in most of the well differentiated lesions but in lower quantity in poorly differentiated or undifferentiated lesions, and that S-100 protein, especially S-100 alpha, is a differentiation marker in carcinoma of thyroid follicular cell origin.     

Papillary and follicular thyroid carcinoma metastatic to the skin: a case report and review of the literature

Cutaneous metastases from thyroid cancers are rare. We report the case of an otherwise asymptomatic 81-year-old woman with an enlarging scalp lesion. Her solitary skin metastasis was the presenting feature of thyroid carcinoma. Routine histopathology of the lesion was notable for an atypical clear cell neoplasm. Immunohistochemistry was positive for thyroglobulin. Subsequent resection of the thyroid gland identified separate foci (< 1 cm) for both papillary and follicular carcinoma. Although such immunohistochemical staining has been used previously, it has never been reported to provide the definitive diagnosis for a solitary cutaneous metastasis from the thyroid. Previous tumors had anatomic features in a clinical context that permitted identification by routine light microscopy. Clear cell features found in the follicular focus of carcinoma in the thyroid suggest that it is the primary. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck.     

Coexistence of papillary and medullary carcinoma of the thyroid gland-mixed or collision tumour? Clinicopathological analysis of three cases

We present three thyroid carcinomas displaying medullary and papillary components. In two cases the papillary component was characterized by typical papillae with a fibrovascular core; in one a follicular variant of papillary carcinoma was found. The papillary component was dominant in two and the medullary in one case. One tumour showed clear-cut borders between the two components, the others displayed an intermingled pattern. Both tumour components were seen in lymph node metastases with immunostaining with antibodies to calcitonin, chromogranin A, carcinoembryonic antigen, other neuroendocrine markers and thyroglobulin. At least two of our cases are true mixed carcinomas probably arising from a common stem cell.     

Cerebral lesions of mature newborn due to perinatal hypoxia. I. Placental and umbilical cord pathology

We report the case of a patient with multiple endocrine neoplasia type three, which was first diagnosed by members of the department of Ophthalmology. He was found to have multiple mucosal neuromata and medullary thyroid carcinoma. The ocular components of this syndrome include visible corneal nerves, conjunctival neuromas, thickened lids, anterior displacement of the cilia and a "dry eye" syndrome. The major systemic components are medullary thyroid carcinoma and pheochromocytoma. It is important that the Ophthalmologist recognize the ophthalmic manifestations of this syndrome so that early diagnosis and treatment may be possible.     

Two-dimensional electrophoretic analysis of membranous protein from human thyroid tissues and cancer cell lines

Thyroid neoplasm is the most commonly encountered neoplastic disorder in endocrine clinics. Thyroid scan, ultrasonography, and fine needle aspiration cytology (FNAC) are used as diagnostic tools to differentiate a malignant nodule from a benign lesion. There are certain limitations and pitfalls in FNAC, especially in the diagnosing of follicular tumors. The lack of characteristic findings or a specific tumor marker are the most common problems in the preoperative diagnosis of thyroid follicular carcinoma. Although serum thyroglobulin level has been used as a tumor marker for post-operative, well-differentiated thyroid cancer, the assay cannot be used for preoperative diagnosis of thyroid carcinoma. In this study, various thyroid tissues and cancer cell lines including CGTH W-1, CGTH W-3, RO 82 W-1, SW 579 cell lines were used for the investigation of tumor markers. Specific spots were identified in the area near the 60 kDa molecular mass protein and isoelectric point (pI) 5.9 of the CGTH W-1 cell line. These spots could not be found in the papillary or anaplastic thyroid cancer cell lines. Another spot with a molecular weight of about 9.8 kDa with a low pI of 4.8 was present in the CGTH W-1 and RO 82 W-1 cell lines. This spot appeared to be a tumor marker of follicular cancer cells. This spot could not be found in the papillary and anaplastic cancer cell lines and other benign thyroid tissues. Specific proteins that were identified in this study may be useful as tumor markers for follicular thyroid carcinoma.     

Comparison of intraoperative cytology with frozen sections in the diagnosis of thyroid lesions

We retrospectively studied the usefulness of intraoperative cytology (IOC) and frozen section (FS) in the rapid diagnosis of 68 thyroid lesions. In 14 cases of papillary thyroid carcinoma, IOC correctly diagnosed 13 cases, while FS correctly diagnosed 11 cases. There was no significant difference in sensitivities, and both methods had similar specificities. In 21 cases of colloid nodule, IOC was slightly more sensitive than FS; IOC correctly diagnosed 16 cases, while FS correctly diagnosed 15 cases. However, the specificity of IOC was only 71%, but was 98% for FS. Of 17 follicular adenomas, FS diagnosed 16 as follicular neoplasms and misdiagnosed only 1 as a colloid nodule. By contrast, IOC misdiagnosed 9 follicular adenomas as colloid nodules, most of which were macrofollicular variants with abundant colloid. Of 11 follicular carcinomas, FS diagnosed all as follicular neoplasms, while IOC misdiagnosed 3 as colloid nodules. While IOC is not as accurate as FS in the diagnosis of colloid nodules and follicular neoplasms, it is highly sensitive and specific in the diagnoses of papillary carcinoma and performance of the technique is rapid and easy. In an intraoperative setting, IOC is a useful adjunct to FS in screening thyroid nodules for the presence of papillary carcinoma.     

Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.     

Thyroid paraganglioma: report of a case

A case of thyroid gland paraganglioma is reported in a 48-year-old woman with cold thyroid nodule. Review of the literature reveals only 4 cases of intrathyroidal paraganglioma but none of them have complete immunohistochemical study. The main differential diagnosis in this localization, namely medullary carcinoma and trabecular hyalinizing adenoma, are discussed.     

Pediocin N5p from Pediococcus pentosaceus: adsorption on bacterial strains

Oxyphilic cell (Hürthle cell) carcinomas of the thyroid gland, variant of follicular carcinoma, are more malignant than follicular non oxyphilic cell carcinomas with a similar size and degree of invasiveness. Gross features, microscopic features of oxyphilic, clear and bicolored cells carcinomas and diagnostic techniques are related with a differential diagnosis with papillary oxyphilic cell carcinoma.     

A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns

BACKGROUND: The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on Cancer programs, the NCDB offers a working example of voluntary, accurate, cost-effective "outcomes management" on a both a local and national scale. In addition, it is of particular value in capturing clinical information concerning rare cancers, such as those of the thyroid. METHODS: For the accession years 1985-1995, NCDB captured demographic, patterns-of-care, stage, treatment, and outcome information for a convenience sample of 53,856 thyroid carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition) stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma. Care patterns also are discussed. RESULTS: The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC staging failed to discriminate between patients with Stage I and II disease at 5 years. Total thyroidectomy +/- lymph node sampling/dissection represented the dominant method of surgical treatment rendered to patients with papillary and follicular neoplasms. Approximately 38% of such patients receive adjuvant iodine-131 ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more extensive surgery) failed to translate into compelling differences in survival for any subgroup with papillary or follicular carcinoma, but longer follow-up is required to evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied to papillary cases. Younger age appeared to influence prognosis favorably for all thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma. NCDB data also revealed that unusual patients diagnosed with undifferentiated/anaplastic carcinoma before age of 45 years have better survival. CONCLUSIONS: The NCDB system permits analysis of care patterns and survival for large numbers of contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care, evaluating prognostic models, generating new hypotheses, and overcoming the volume-related drawbacks inherent in the study of such neoplasms. [See editorial on pages 2434-6, this issue.]     

Oxygen parameters in the presence of hemoglobin H

Two cases of an unusual finding of capsular pseudoinvasion in follicular thyroid adenomas after fine-needle aspiration (FNA) procedures are reported. These capsular breaches were noted along the hemorrhagic needle track, which traversed the normal peripheral thyroid parenchyma into the lesions. A reparative reaction was seen at some points along one of the tracks. Histologic examination also showed extrusion of the tumor parenchyma through the capsular interruption in one case. Surgical pathologists should be aware of this rare complication of FNA of thyroid follicular adenomas as a differential diagnosis of minimally invasive (encapsulated) follicular carcinoma.     

Utility of fine-needle aspiration cytology and frozen-section examination in the operative management of thyroid nodules

Fine-needle aspiration cytology has a high sensitivity for the diagnosis of solitary thyroid nodules. Certain diagnoses involving follicular histologies often cannot be made with needle biopsy alone. The utility of frozen-section examination of thyroid nodules, with particular regard to those lesions with follicular histologies, is also limited. We examined the correlation of fine-needle aspiration cytology and frozen-section examination in solitary thyroid nodules to determine the contribution of frozen-section examination to the operation. We reviewed the fine-needle aspiration cytology, frozen-section examination, and final pathology of 100 consecutive patients undergoing thyroidectomy for a solitary solid thyroid nodule in an 4-year period. The diagnoses were classified as indeterminant, benign, or malignant. The utility and impact of the diagnosis from fine-needle aspiration or frozen section on the operative procedure performed was analyzed. Fine-needle aspiration cytology as a diagnostic test for thyroid nodules demonstrated an indeterminant rate of 23 per cent, with a diagnostic accuracy of 77 and 92 per cent for benign and malignant disease, respectively. In all patients with inaccurate benign diagnosis on fine-needle aspiration cytology, follicular neoplasm was misinterpreted for follicular adenoma or multinodular goiter. In comparing frozen-section results, the indeterminant, benign, and malignant rates were 7, 96, and 64 per cent, respectively. Of the 23 patients with indeterminant results on fine-needle aspiration cytology, the intraoperative frozen-section diagnosis on 4 patients was deferred to permanent section; 18 received accurate cytological diagnosis; and in 1 patient, carcinoma was missed. Overall, the decision about the extent of surgical thyroid resection was changed in only 2 patients based on the frozen-section results. Preoperative evaluation with fine-needle aspiration cytology can accurately and appropriately define the extent of thyroid surgery in most patients with a diagnosis of malignant neoplasm or benign disease. Intraoperative frozen-section examination may be helpful if fine-needle aspiration cytology results are inderminant and in cases of follicular histology as an adjunct for evaluation of the thyroid nodule, but overall, frozen section does not contribute to the management of the thyroid lesion at the time of surgery.     

Diagnosis of occult thyroid carcinoma by thyroid ultrasonography with fine needle aspiration cytology

OBJECTIVE: To assess the role of ultrasonography and fine needle aspiration cytology (FNAC) in preoperative diagnosis of patients with occult thyroid carcinoma (OTC). STUDY DESIGN: Data on 768 thyroid carcinoma patients receiving primary treatment at Chang Gung Medical Center were retrospectively reviewed. Of these patients, 97 had OTC. To detect small thyroid nodules early and define the characteristics of clinically palpable nodules, thyroid ultrasonography with FNAC were performed on 67 histopathologically proven OTC patients. Analysis for diagnostic value was done for ultrasonography and FNAC. RESULTS: In the 67 patients receiving ultrasonography with FNAC, 23 were preoperatively diagnosed as having papillary thyroid carcinoma and 1 as having follicular carcinoma. The tumor size of these 24 preoperative FNAC-proven OTC was 0.81 +/- 0.23 cm (mean +/- SD). In the remaining patients, 10 presented pictures suspicious for malignancy, with a mean tumor size 0.63 +/- 0.24 cm, and 33 (49.3%) were diagnosed as having benign thyroid lesions in preoperative FNAC. The tumor size in these 33 lesions was 0.58 +/- 0.24 cm. Fifty-seven of the 67 OTC patients received frozen sections. Thirty-eight papillary thyroid carcinomas and four follicular carcinomas were correctly diagnosed on frozen sections. CONCLUSION: Although the rate is not high, high-resolution ultrasonography and FNAC is the best approach to preoperative diagnosis for OTC patients today.     

The relevance of somatostatin receptors in thyroid neoplasia

111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).