Measurement of vascularity as a diagnostic and prognostic tool for well differentiated thyroid tumours: comparison of different methods of assessing vascularity.
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AIMS: To determine whether the measurement of vascularity can be used to differentiate follicular adenomas from follicular carcinomas or to reflect the prognosis of follicular carcinomas and papillary carcinomas of the thyroid gland, and to compare four methods of assessing vascularity. METHODS: Tissue sections from 26 papillary carcinomas, 15 follicular adenomas, and 15 follicular carcinomas were stained with an antibody to CD34. A computerised image analysis system was used to calculate, for each tumour, mean endothelial areas and the mean endothelium to tumour epithelial nucleus area ratio from 10 systematically selected fields across one dimension of the tumour ("systematic field" analysis) or from the three most vascularised fields of the tumour ("hot spot" analysis). A European Organisation for Research on Treatment of Cancer (EORTC) prognostic index was calculated for each papillary carcinoma and follicular carcinoma. RESULTS: Significant differences in vascularity between the three tumour groups could only be shown by comparing mean endothelial area values measured from hot spots. While the hot spot median mean endothelial area of follicular carcinomas was significantly greater than that of follicular adenomas, there was a large overlap between the two groups. For follicular carcinomas, higher hot spot mean endothelial area values were related to worse prognosis as indicated by the EORTC prognostic indices. No association between vascularity and prognosis was found for the papillary carcinomas, regardless of the method of assessing vascularity. CONCLUSIONS: Measuring endothelial area from hot spots using a computerised image analysis system is a sensitive method of assessing the vascularity of thyroid tumours. While vascularity measurement cannot be recommended as a practical tool for differentiating between malignant and benign follicular tumours, the suggestion that vascularity may reflect prognosis for follicular carcinomas deserves further study. (+info)
Metastatic minimally invasive (encapsulated) follicular and Hurthle cell thyroid carcinoma: a study of 34 patients.
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Most studies that have examined minimally invasive, encapsulated, follicular carcinoma (FC) or Hurthle cell carcinomas (HCs) have contained only a few metastatic neoplasms. We studied 34 patients with a single, minimally invasive, metastatic FC or HC and compared them with 38 patients with similar, nonmetastatic FCs or HCs. The numbers of incomplete capsular penetration (neoplasm into but not through the capsule), complete capsular penetration (neoplasm through the capsule), and vascular invasion foci were quantified. The median number (three), range, and distribution of complete capsular penetration and vascular invasion foci were similar in the nonmetastatic and metastatic carcinomas. All of the metastatic FCs and HCs had at least one vascular invasion or complete capsular penetration focus. Sixty-two percent of the metastatic carcinomas had two to four complete capsular penetration foci, and 60% had two to four vascular invasion foci. Two metastatic neoplasms had incomplete capsular penetration but had one and two vascular invasion foci, respectively. One tumor had no vascular invasion but had four complete capsular penetration foci. No metastatic neoplasms had incomplete capsular penetration only. There were no differences in the number of vascular invasion or complete capsular penetration foci between metastatic and nonmetastatic FCs and HCs and between metastatic FCs and HCs. Most metastatic neoplasms had vascular space invasion and complete capsular penetration. The number of complete capsular penetration or vascular invasion foci was not associated with the initial site of metastasis or the interval between the surgery and the metastasis. (+info)
Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases.
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From 1977 through 1995, 1,013 thyroid carcinoma patients received treatment and were followed up at Chang Gung Medical Center in Taiwan. To evaluate the prognostic variables of papillary and follicular thyroid carcinomas with limited lymph node metastases, a retrospective review of these patients was performed. Of these patients, 910 had papillary or follicular thyroid carcinoma, and 119 patients were categorized as clinical stage 2 with limited neck lymph node metastases only at the time of diagnosis. The patients were categorized into two groups as no recurrence and local recurrence or distant metastasis at the end of 1997. After the operations, radioactive iodide (131I) treatments were performed in 114 patients and external radiotherapy for neck region or distant metastases in 18 patients. The median follow-up period of these patients was 5.4 years. Clinical variables were coded in our computer for statistical analysis. After the treatments, 93 patients remained disease-free; 10 were in stage 2; 5 in stage 3; and 11 aggravated to stage 4. Of the clinical variables, age, post-operative first 1311 uptake scans, and 1-month post-operative thyroglobulin levels revealed statistically significant differences between the group which improved and the group which did not. During the follow-up period, five patients died; three patients died of thyroid cancer and two died of intercurrent diseases. Patients with papillary thyroid carcinoma revealed a higher percentage of lymph node metastases. Although limited lymph node metastases did not influence survival rate, patients with poor prognostic factors need more aggressive treatment to avoid progression of the cancer. (+info)
Follow-up regimen of differentiated thyroid carcinoma in thyroidectomized patients after thyroid hormone withdrawal.
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For differentiated, nonmedullary thyroid carcinoma, postsurgical ablation of thyroid remnants and treatment of residual tumor and metastases with 131I is a potentially curative therapy. The aim of this study was to optimize the diagnostic protocol for the follow-up of thyroidectomized patients. METHODS: Two hundred fifty-four patients (187 females, 67 males; mean age, 45 y; range, 8-83 y) were studied retrospectively for a mean follow-up period of 2.7 y (range, 1-12.5 y). An evaluation study consisted of a low-dose 131I diagnostic procedure under hyperthyroid conditions (thyroid-stimulating hormone > 30 MicroU/mL), 201TI scintigraphy, and measurement of thyroglobulin (Tg) under hypothyroid conditions. A total of 254 preablation studies (1 study per patient) and 586 follow-up studies (average number of studies, 2.3 per patient) were evaluated. RESULTS: Before ablation, low-dose 131I screening was useful to estimate the size of the thyroid remnant. Low Tg levels (<10 pmol/L) indicated the absence of metastases. After ablation, undetectable Tg levels indicated the absence of tumor recurrence. When Tg levels were high (>10 pmol/L), local recurrence or metastases were always observed, providing the basis for additional high-dose 131I therapy. In these patients, 201TI imaging did not provide a significant contribution to patient management. In the case of autoantibodies against Tg, both low-dose 131I screening and 201TI scintigraphy may be advocated to allow an aggressive diagnostic work-up. CONCLUSION: Tg plays a key role in follow-up and in making decisions to treat patients with differentiated thyroid carcinoma. The role of 201TI imaging is very limited. In patients with negative low-dose 131I screening, 201TI scintigraphy can be considered when Tg is elevated or cannot be evaluated because of autoantibodies against Tg. Under such circumstances, administration of a therapeutic 131I dose without 201TI imaging can be considered. (+info)
Follicular thyroid cancer presenting initially with soft tissue metastasis.
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Follicular thyroid cancer rarely manifests itself as a distant metastatic lesion. We report a case of an otherwise asymptomatic 58-year-old woman with follicular thyroid cancer who initially presented with a soft tissue mass on the right scapular region. An incisional biopsy specimen of soft tissue metastasis showed thyroid follicular neoplasm. Upon this diagnosis, the thyroid gland was re-evaluated by ultrasound, which demonstrated a solitary, hypoechoic nodule in the right lobe. Ultrasonography guided fine-needle aspiration biopsy of the thyroid nodule confirmed follicular neoplasm and the diagnosis of metastatic follicular thyroid cancer was established. The patient refused any type of treatment and left hospital against medical advice. 2.5 years later the patient was admitted to the hospital with giant, sarcoma-like multiple soft tissue masses. On this admission, the serum thyroglobulin level was extremely elevated (3500 ng/ml) and she only accepted to receive chemotherapy. Epirubicin and cyclophosphamide were administered. She received three courses of chemotherapy and is alive with a stable disease after 3 months of follow-up. This case of follicular thyroid cancer is reported because of its uncommon initial presentation with soft tissue metastasis which spread to multiple areas as giant soft tissue masses during follow-up. (+info)
Expression of DNA topoisomerase IIalpha in thyroid neoplasia.
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Topoisomerase II (topo II) is an enzyme that affects replication, transcription, and chromosome segregation. It serves as a target for several useful antichemotherapeutic agents, such as etoposide (VP-16) and teniposide (VM26). Monoclonal antibody topo IIalpha (Clone JH2.7; Neomarkers, Union City, CA) specifically identifies the alpha isoform of topo II. Using this antibody in an immunohistochemical analysis, we studied differential expression of topo II in a variety of thyroid lesions. The topo II labeling index is defined as the number of topo II staining positive nuclei divided by the total number of tumor cells counted multiplied by 100. An average of 1,000 cells were counted in each case. The average labeling indexes for anaplastic carcinoma (7.8), tall cell variant of papillary carcinoma (4.8), follicular carcinoma (2.6), Hurthle cell carcinoma (3.4), and medullary carcinoma (2.4) were much higher than for papillary carcinoma (0.76), follicular adenoma (0.65), Hurthle cell adenoma (0.32), and normal thyroid (0.1). This study suggests that immunohistochemical analysis of topo II correlates with thyroid tumor histology; it is more frequently expressed in tumors that are associated with aggressive clinical behavior. It may help to define a role for anti-topoisomerase drugs in treatment of aggressive thyroid neoplasms. (+info)
Thyroid abnormality trend over time in northeastern regions of Kazakstan, adjacent to the Semipalatinsk nuclear test site: a case review of pathological findings for 7271 patients.
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From 1949 through 1989 nuclear weapons testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk and Pavlodar regions of Kazakstan. To investigate the possible relationship between radiation exposure and thyroid gland abnormalities, we conducted a case review of pathological findings of 7271 urban and rural patients who underwent surgery from 1966-96. Of the 7271 patients, 761 (10.5%) were men, and 6510 (89.5%) were women. The age of the patients varied from 15 to 90 years. Overall, a diagnosis of adenomatous goiter (most frequently multinodular) was found in 1683 patients (63.4%) of Semipalatinsk region, in 2032 patients (68.6%) of Ust-Kamenogorsk region and in 1142 patients (69.0%) of Pavlodar region. In the period 1982-96, as compared before, there was a noticeable increase in the number of cases of Hashimoto's thyroiditis and thyroid cancer. Among histological forms of thyroid cancer, papillary (48.1%) and follicular (33.1%) predominated in the Semipalatinsk region. In later periods (1987-96), an increased frequency of abnormal cases occurred among patients less than 40 years of age, with the highest proportion among patients below 20 in Semipalatinsk and Ust-Kamenogorsk regions of Kazakstan. Given the positive findings of a significant cancer-period interaction, and a significant trend for the proportion of cancer to increase over time, we recommend more detailed and etiologic studies of thyroid disease among populations exposed to radiation fallout from the SNTS in comparison to non-exposed population. (+info)
RET receptor expression in thyroid follicular epithelial cell-derived tumors.
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The RET proto-oncogene encodes a receptor tyrosine kinase for transforming growth factor-beta-related neurotrophic factors, which include GDNF and neurturin. The expression of RET proto-oncogene was detected in several tissues, such as spleen, thymus, lymph nodes, salivary gland, and spinal cord, and in several neural crest-derived cell lines. RET expression in the thyroid gland was reported to be restricted to neural crest-derived C cells. The presence of RET mRNA or protein has not yet been reported in thyroid follicular cells. We previously demonstrated the expression of oncogenic rearranged versions of RET in papillary thyroid carcinomas: tumors derived from thyroid follicular cells. To assess the expression of the normal RET proto-oncogene in follicular cells, we analyzed its expression in a panel of neoplasias originating from thyroid follicular epithelial cells: papillary carcinomas and both follicular adenomas and carcinomas. We also demonstrated the presence of RET normal transcripts in two follicular thyroid carcinoma lymph node metastases. Moreover, we found the presence of the RET/ELE1 transcript, the reciprocal complementary form of the oncogenic fusion transcript ELE1/RET, in a papillary thyroid carcinoma specimen expressing the RET/PTC3 oncogene, thus demonstrating that the RET promoter is active in those cells after rearrangement. Finally, we show that in a papillary carcinoma-derived cell line expressing the proto-RET receptor and the related GFRalpha2 co-receptor, GDNF treatment induced RET tyrosine phosphorylation and subsequent signal transduction pathway, indicating that RET could be active in thyroid follicular cells. (+info)