The biological characteristics and chemosensitivity of anaplastic thyroid carcinoma transplanted into nude mice

Three xenografts established from three patients with anaplastic thyroid carcinoma were investigated for their biological characteristics and chemosensitivity. The histological and immunohistochemical findings of these tumors were almost the same as those of the original tumors. Although the growth rate of each xenograft was constant, the tumor doubling time varied from 4.8 per 9.0 days, and the labeling indexes, determined using bromodeoxyuridine pulse labeling, varied from 11.4 to 25.1 per cent. The chemosensitivity tests were performed according to the Battle Columbus Laboratories Protocol, with adriamycin, cyclophosphamide, cisplatin, mitomycin C and tegafur administered intraperitoneally to tumor-bearing nude mice in maximum tolerable doses. Tumors with slower growth rates tended to be sensitive to more drugs. Furthermore, cyclophosphamide showed antitumor effects against all the tumors tested. Althouth previous treatments of the original tumors may have affected the results, our results suggest that a more suitable chemotherapy for anaplastic thyroid carcinoma could be developed.     

Derangement of the E-cadherin/catenin complex is involved in transformation of differentiated to anaplastic thyroid carcinoma

BACKGROUND: Anaplastic thyroid cancer arises, or transforms, from pre-existing differentiated thyroid cancer. E-cadherin functions as a cell-cell adhesion molecule that complexes with catenin proteins for function. The objective of this study was to evaluate the change in E-cadherin/beta-catenin expression in the transformation of differentiated to anaplastic thyroid carcinoma. METHODS: A tissue microarray was constructed from 12 anaplastic thyroid tumors and their adjacent associated differentiated foci. Immunohistochemistry was used to evaluate tumor expression of E-cadherin and beta-catenin. RESULTS: There was decreased expression of E-cadherin and beta-catenin by the anaplastic tumors when compared with the differentiated thyroid tumors from which they evolved. The expression of E-cadherin and beta-catenin was 92% and 67%, respectively, by the differentiated thyroid carcinoma, and 17% and 50%, respectively, by the anaplastic tumors. CONCLUSIONS: This report shows that derangement of the E-cadherin/catenin complex is associated with the transformation of differentiated into anaplastic thyroid carcinoma.     

Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21

OBJECTIVE: To analyze the clinicopathologic features of a large cohort of patients with insular or anaplastic carcinomas treated at a single institution. SUMMARY BACKGROUND DATA: Insular and anaplastic carcinomas of the thyroid, although uncommon, have more aggressive clinical behavior than well-differentiated carcinomas of the thyroid. In the literature, the incidence and features of these carcinomas have not been fully characterized. METHODS: The authors reclassified 740 primary thyroid carcinomas diagnosed and treated between January 1, 1954, and December 30, 1998, to select those with features that met the histologic criteria of insular or anaplastic carcinoma. The clinicopathologic features of these carcinomas were studied and compared. The expression of p53 and p21 in these tumors was analyzed by immunohistochemistry. RESULTS: Twenty-two patients (5 men, 17 women) with insular carcinoma and 38 patients (7 men, 31 women) with anaplastic carcinoma were found. Patients with insular carcinomas were younger (mean age 45 vs. 70 years) and had smaller tumors than those with anaplastic carcinomas (mean diameter 5 vs. 8 cm). Insular carcinomas were commonly mislabeled as other histologic subtypes, whereas anaplastic carcinomas might be overdiagnosed on pathologic examination. A history of longstanding goiter (>10 years) was noted in 27% of patients with insular carcinoma and 24% of patients with anaplastic carcinomas. Concomitant well-differentiated carcinomas of the thyroid were noted in 59% of patients with insular carcinoma and 39% of patients with anaplastic carcinoma. In anaplastic carcinomas, 13% of patients had concomitant insular carcinoma. Calcification or bone was noted in the stroma of 23% of patients with insular carcinomas and 47% of those with anaplastic carcinomas. The 10-year survival rates for patients with insular carcinoma and anaplastic carcinoma were 42% and 3%, respectively. Distant metastases were seen in 32% of patients with insular carcinoma and in 47% of patients with anaplastic carcinomas. In both types of carcinomas, metastatic tumors were often seen in bone and lung. Distant metastases were noted in a variety of organs in anaplastic carcinomas. In insular carcinoma, neither p53 nor p21 expression was present. In anaplastic carcinoma, p53 and p21 expression was identified in 69% and 3%, respectively. Concomitant expression of p53 and p21 was noted in one tumor. CONCLUSIONS: Insular carcinoma and anaplastic carcinoma had distinctive clinicopathologic features, and recognition of these histologic variants is important for better management of these tumors in the future. p53 overexpression might have a role in dedifferentiation from insular carcinoma to anaplastic carcinoma.     

Expression of Vascular Endothelial Growth Factor and Presence of Angiovascular Cells in Tissues from Different Thyroid Disorders

Background

Vascular endothelial growth factor (VEGF) is involved in tumor angiogenesis and other pathophysiological processes.

Materials and methods

We studied the localization of VEGF in human thyroid tissues to clarify its involvement in proliferative processes in a variety of thyroid disorders. Immunohistochemical analysis using purified rabbit polyclonal anti-human VEGF or anti-human CD34 antibody and a streptavidin–biotin peroxidase complex detection system was performed on 58 tissue specimens from 53 patients with different thyroid disorders and 5 normal thyroid glands.

Results

Vascular endothelial growth factor was not detected in normal thyroid follicular cells. However, some thyroid tumor cells expressed VEGF in the cytoplasm (papillary carcinoma, 10/18; follicular carcinoma, 1/3; medullary carcinoma, 2/2; follicular adenoma, 3/11; adenomatous goiter, 2/4). In benign follicular adenoma and adenomatous goiter, weak expression of VEGF was found in small areas of the tumor, whereas in malignant thyroid tumors, it was strongly expressed in many cells. However, VEGF was not expressed in anaplastic carcinoma, malignant lymphoma, or Graves’ disease. Angiovascular cells stained with CD34 antibody in tissues from different thyroid disorders reflected statistically significant differences in papillary carcinoma, follicular adenoma, and Graves’ disease compared with normal thyroids, and such cells showed a trend toward increases in medullary carcinoma and adenomatous goiter. In contrast, low vascularity was observed in anaplastic carcinoma, malignant lymphoma, and follicular carcinoma.

Conclusions

Because VEGF probably functions as a hypoxia-inducible angiogenic factor, overexpression of this mediator, concomitant with hypervascularity, may be induced more strongly in malignant thyroid tumors, which need more oxygen to proliferate, than in benign follicular tumors. However, neither VEGF nor CD34 was expressed in anaplastic thyroid carcinoma, which is an extremely poorly differentiated malignant tumor. CD34 but not VEGF was expressed in the hyperplastic thyroid tissues of Graves’ disease composed of nontransformed cells. Thus, the expression of VEGF concomitant with CD34 is suggested to reflect both the transformation and differentiation state of malignant tumors.     

Divergent histology in the primary and metastatic lesions of thyroid carcinoma

The metastatic lesions of malignant diseases tend to present similar histological findings as the primary tumor. However, thyroid carcinoma is one of the malignancies which may be an exception to this rule. We have reviewed 61 consecutive autopsies of thyroid cancer patients at the Ito Hospital and Kawasaki Medical School Hospital during a period between 1969-1982. Fifty-five of 61 cases of thyroid carcinoma were found to have metastatic spreads beyond the thyroid. The uniform pathological findings were present in 5 of 9 papillary adenocarcinomas, 14 of 15 anaplastic carcinomas, and 1 of two squamous cell carcinoma and one epidermoid carcinoma. The remaining 36 patients were found to have different histological findings in metastatic lesions from the primary tumor. The histological types in coexisting metastases varied from one lesion to the other; the primary tumor was adenocarcinoma, but one of the metastases was anaplastic and the others showed adenocarcinoma or its combination. Those histological divergence in the primary tumor and metastases can be considered as the results of anaplastic or squamous cell transformation from adenocarcinoma. Such alteration of the histological findings in thyroid carcinoma calls for the reassessment of the therapeutic strategy.     

Molecular evidence of anaplastic transformation in coexisting well-differentiated and anaplastic carcinomas of the thyroid

Anaplastic thyroid cancer is a rare but nearly universally fatal tumor. Epidemiologic data suggest that many anaplastic thyroid carcinomas arise from transformation of preexisting or coexisting well-differentiated thyroid carcinomas. At the molecular level, the mutations responsible for the anaplastic transformation are incompletely understood, although the mutational events are thought to involve tumor suppressor genes. To examine transformation from a well-differentiated thyroid carcinoma to anaplastic carcinoma, we studied coexisting well-differentiated (Hürthle cell and papillary carcinoma) and anaplastic tumors with a molecular genotyping panel of tumor suppressor genes associated with thyroid neoplasia. The patterns of allelic loss in our results showed that the majority of cases have a core of conserved mutations in the two morphologically distinct areas and substantial increases in mutation rates in the anaplastic components.     

Thyroid disorders. Part III: neoplastic thyroid disease.

This paper is part III of the series on thyroid disorders. Thyroid tumors are the most common endocrine neoplasms. Most of these tumors are benign hyperplastic or colloid nodules or benign follicular adenomas. However, 5% to 10% of the lesions that come to medical attention are carcinomas. A major clinical challenge is establishing which nodules are hyperplastic, benign, or malignant. History, clinical findings, ultrasonography, and fine-needle aspiration biopsy are the mainstays for diagnosis. There are 3 main histologic types of thyroid cancer: differentiated, medullary, and anaplastic. Differentiated lesions are subdivided into papillary, follicular, and Hurthle cell carcinomas. In addition, primary lymphoma may occur in the thyroid gland and other cancers may metastasize to the thyroid. An important neoplastic syndrome, multiple endocrine neoplasia type 2 (MEN2), involves medullary carcinoma of the thyroid gland. In 2002 there were 10 cases of thyroid cancer per 100 000 population. During the past 10 years the rate of thyroid cancer has been increasing 5% per year. The overall 10-year survival for papillary carcinoma is 80% to 90%, follicular carcinoma 65% to 75%, and medullary carcinoma 60% to 70%. The prognosis for anaplastic carcinoma is very poor and 5-year survival is rare. The dentist by inspection and palpation of the neck in the area of the thyroid gland may detect single or multiple lesions that may be benign or malignant. Patients with identified nodules or enlarged thyroid glands should be referred for diagnosis and treatment. Patients with thyroid cancer will benefit from the early detection and treatment of their lesions as early detection can lead to a cure or prolongation of their life.     

Oncogenic emergency and treatment in thyroid disease

The urgent treatment of thyroid disease is mainly considered to be that of thyroid neoplasia, especially malignant thyroid tumors. The clinical symptoms produced by malignant neoplasia are acute respiratory failure caused by tumor compression and/or invasion of the trachea. Massive bleeding caused by tumor invasion of the major vessels also requires emergency therapy. In general, thyroid cancer has a favorable prognosis in patients with well-differentiated papillary carcinoma, which makes up more than 90% of thyroid malignancies. However, anaplastic carcinoma, undifferentiated papillary carcinoma, and malignant lymphoma originating from the thyroid sometimes require urgent therapy to save lives. Anaplastic carcinoma that is basically transformed from well-differentiated papillary carcinoma shows rapid growth and invades the surrounding tissue to produce tracheal obstruction. Repeated postoperative recurrences in patient with papillary carcinoma suggest undifferentiated carcinoma that eventually becomes the same endostage as anaplastic carcinoma. Radical surgery is needed in such cases initially, although making a differential diagnosis between well- and undifferentiated carcinoma is extremely difficult. Urgent treatment of these diseases consists of ensuring that the airway remains open to improve quality of life, but does not include radical treatment. Stent insertion is one adequate method for the urgent treatment of respiratory disturbance caused by tumor compression. Malignant lymphoma frequently develops from Hashimoto's thyroiditis. Immediately after making an accurate pathologic diagnosis, chemotherapy and/or radiation therapy are effective in reducing enlarged goiters rather than surgical management.     

The coexistence of anaplastic and papillary carcinomas of the thyroid: a case presentation and literature review

Papillary carcinomas of the thyroid are the most common malignant growth affecting the thyroid, currently representing 60-65 per cent of malignant thyroid neoplasm. Although the etiology of this neoplasm is unknown, they are thought to be related to neck irradiation, adenoma transformation, and Hashimoto thyroiditis. Papillary carcinomas are usually purely papillary but occasionally have areas of histologically different neoplasm, most commonly follicular. Overall, these carcinomas represent an indolent group of neoplasm and have an excellent prognosis. The occurrence of an anaplastic area in a papillary carcinoma represents the dedifferentiation of the primary neoplasm. This is an extremely rare occurrence and is considered to have negative prognostic significance. The purpose of this presentation is to discuss an unusual clinical case of a coexisting anaplastic and papillary carcinoma of the thyroid, diagnosed by fine needle aspiration (FNA) analysis presenting in a 67-year-old African-American woman. Evaluation and treatment will be discussed.     

Identification of molecular markers altered during transformation of differentiated into anaplastic thyroid carcinoma

HYPOTHESIS: A change in tumor expression profile will be observed during the transformation of differentiated into anaplastic thyroid carcinoma. DESIGN: Cohort study. SETTING: Population-based sample (British Columbia). PATIENTS: Sequential archival cases of anaplastic thyroid cancer with an adjacent associated differentiated thyroid cancer focus, and with available paraffin blocks, that had been diagnosed and treated in British Columbia during a 20-year period (12 cases; January 1, 1984, through December 31, 2004) were identified through the provincial tumor registry for tissue microarray construction. MAIN OUTCOME MEASURE: Significant associations between marker staining and tumor pathologic diagnosis (differentiated vs anaplastic) were determined with contingency table and marginal homogeneity tests. A classifier algorithm was also used to identify useful and important molecular classifiers. RESULTS: Overall, there were 3 up-regulated and 5 down-regulated markers when comparing the anaplastic carcinoma with associated differentiated thyroid cancers. Contingency table statistics identified 5 markers (thyroglobulin, Bcl-2, MIB-1, E-cadherin, and p53) to be significantly differentially expressed by the anaplastic and differentiated tumor foci. These 5 markers and 3 others (beta-catenin, topoisomerase II-alpha, and vascular endothelial growth factor) were significant when evaluated using the marginal homogeneity test. Clustering and classification analysis based on these same 8 markers readily separated differentiated and anaplastic thyroid tumors with a high degree of accuracy. CONCLUSION: The markers we observed to change during thyroid tumor progression may not only show promise as molecular diagnostic or prognostic tools but also warrant further study as potential targets for treatment of disease.     

Anaplastic Thyroid Carcinoma: Expression Profile of Targets for Therapy Offers New Insights for Disease Treatment

Background Anaplastic thyroid cancer is an endocrine malignancy. Its rare and rapidly lethal disease course has made it challenging to study. Little is known regarding the expression by anaplastic tumors of molecular targets for new human anticancer agents that have been studied in the preclinical or clinical setting. The objective of this work was to evaluate the expression profile of anaplastic thyroid tumors for molecular targets for treatment. Methods Of the 94 cases of anaplastic thyroid cancers diagnosed and treated in British Columbia, Canada over a 20-year period (1984–2004), 32 cases (34%) had adequate archival tissue available for evaluation. A tissue microarray was constructed from these anaplastic thyroid tumors and immunohistochemistry was utilized to evaluate expression of 31 molecular markers. The markers evaluated were: epidermal growth factor receptor (EGFR), HER2, HER3, HER4, ER, PR, uPA-R, clusterin, E-cadherin, β-catenin, AMF-R, c-kit, VEGF, ILK, aurora A, aurora B, aurora C, RET, CA-IX, IGF1-R, p53, MDM2, p21, Bcl-2, cyclin D1, cyclin E, p27, calcitonin, MIB-1, TTF-1, and thyroglobulin. Results A single tumor with strong calcitonin expression was identified as a poorly differentiated medullary carcinoma and excluded from the study cohort. The mean age of the anaplastic cohort was 66 years; 16 patients (51%) were females, and the median patient survival was 23 weeks. A wide range in molecular marker expression was observed by the anaplastic thyroid cancer tumors (0–100%). The therapeutic targets most frequently and most strongly overexpressed by the anaplastic tumors were: β-catenin (41%), aurora A (41%), cyclin E (67%), cyclin D1 (77%), and EGFR (84%). Conclusions Anaplastic thyroid tumors exhibit considerable derangement of their cell cycle and multiple signal transduction pathways that leads to uncontrolled cellular proliferation and the development of genomic instability. This report is the first to comprehensively evaluate a panel of molecular targets for therapy of anaplastic thyroid cancer and supports the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors, which may offer new hope for individuals diagnosed with this fatal thyroid malignancy.     

Flow cytometric DNA analysis of thyroid carcinoma

Abnormal DNA content has been considered as an additional criterion for determining the biological behavior of a tumor. Flowcytometric DNA analysis was done on 121 patients with thyroid carcinoma encountered during the period between 1975 and 1987. Tumor tissues were sampled from paraffin-embedded blocks and the histology of thyroid carcinoma found to consist of 91 papillary, 23 follicular, 2 medullary, 1 squamous cell and 4 anaplastic carcinomas. The incidence of aneuploidy in thyroid carcinoma was 7.4 per cent (9 patients) while that of diploidy was 92.6 per cent (112 patients). The aneuploid specimens consisted of 6 papillary, 1 follicular, 1 medullary and 1 anaplastic carcinomas and, of 4 anaplastic carcinoma patients with subsequent death within 6 months, only 1 was aneuploid. As an indicator of proliferative potential, S-phase fraction (SPF) was also determined by flow cytometry, but this could not be used as an independent prognostic factor. The aneuploid patients showed a significantly decreased survival rate (p<0.01). Thus, although DNA measurement proved useful for predicting the survival of aneuploid patients, there is some discrepancy between DNA content and the biological behavior of the tumor.     

Solitary fibrous tumor of the thyroid gland: report of seven cases.

Solitary fibrous tumor is a soft tissue neoplasm initially described in the pleura but subsequently reported in a wide variety of locations. The clinical behavior is usually benign, but the existence of aggressive cases has been documented both in the pleura and in extrapleural sites. In this report clinical and pathologic features of seven solitary fibrous tumors of the thyroid gland are presented. Patients' ages ranged from 43 to 64 years (mean 52 years), and tumor sizes varied from 2 to 6 cm. Grossly, the tumors were white-tan and well circumscribed. Microscopically, there was a variegated, wavy, storiform, hemangiopericytic or desmoid-like arrangement of spindle cells. Trapped thyroid follicles within the tumor and peripheral jagged tumor infiltration among follicles were common. There was immunohistochemical reactivity for CD34, CD99, and bcl-2, and ultrastructural analysis of one tumor was consistent with a fibroblastic lineage. The differential diagnosis included other benign and malignant mesenchymal tumors of the thyroid, spindle cell follicular adenoma, Riedel's thyroiditis, the spindle cell, and paucicellular variants of anaplastic carcinoma, papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma, and the spindle epithelial tumor with thymus-like differentiation. The cumulative data of 13 cases (comprised of the seven present cases and the six previously reported) suggest a benign clinical behavior for thyroid SFT.     

Flow cytometric DNA analysis of thyroid carcinoma

Abnormal DNA content has been considered as an additional criterion for determining the biological behavior of a tumor. Flowcytometric DNA analysis was done on 121 patients with thyroid carcinoma encountered during the period between 1975 and 1987. Tumor tissues were sampled from paraffin-embedded blocks and the histology of thyroid carcinoma found to consist of 91 papillary, 23 follicular, 2 medullary, 1 squamous cell and 4 anaplastic carcinomas. The incidence of aneuploidy in thyroid carcinoma was 7.4 per cent (9 patients) while that of diploidy was 92.6 per cent (112 patients). The aneuploid specimens consisted of 6 papillary, 1 follicular, 1 medullary and 1 anaplastic carcinomas and, of 4 anaplastic carcinoma patients with subsequent death within 6 months, only 1 was aneuploid. As an indicator of proliferative potential, S-phase fraction (SPF) was also determined by flow cytometry, but this could not be used as an independent prognostic factor. The aneuploid patients showed a significantly decreased survival rate (p less than 0.01). Thus, although DNA measurement proved useful for predicting the survival of aneuploid patients, there is some discrepancy between DNA content and the biological behavior of the tumor.     

Biologic considerations and operative strategy in papillary thyroid carcinoma: arguments against the routine performance of total thyroidectomy

Reasons cited for the routine performance of total thyroidectomy in patients with papillary thyroid carcinoma include: fear of multicentric neoplastic foci causing local recurrence and death; risk of anaplastic transformation of unresected multifocal microscopic carcinoma; toxicity of high-dose radioactive iodine to ablate normal thyroid remnants; and lack of reliable criteria for grading malignancy and identifying patients at high risk. However, autopsy studies have detected microscopic foci of papillary thyroid cancer as incidental findings in up to 24% of patients dead of other diseases. The prevalence of anaplastic transformation of papillary thyroid carcinoma as determined from reports in the literature is less than 1%. A retrospective investigation of 90 patients with papillary thyroid carcinoma derived from the Swedish National Cancer Registry showed no complications from radioiodine ablation of postoperative thyroid remnants in 45 patients. Retrospective analysis of the DNA content of tumors at the time of the initial operation showed a significant difference between a group of 10 patients who died of recurrent and metastatic papillary thyroid carcinoma and a group of 16 patients alive at least 10 years after operation despite distant metastases or recurrent cancer in the thyroid bed and/or cervical lymph nodes. The risk of permanent hypoparathyroidism is higher in patients after total thyroidectomy without apparent improvement in survival rates when compared with less extensive resections. Therefore it is proposed that the criteria for total thyroidectomy in patients with papillary thyroid carcinoma be limited to: tumors that clinically involve both lobes of the thyroid gland, extracapsular spread of cancer requiring enbloc resection, and reoperations where scarring prevents accurate delineation of the extent of the tumor. By differentiating patients at high risk for death from papillary thyroid carcinoma from patients at low risk, the measurement of DNA content may decrease the need for routine total thyroidectomy.     

Rare malignant tumors of the thyroid

The incidence of rare malignant tumors of the thyroid is about 4 cases/100,000 people and represent only 1.8% of all the thyroid cancers. When we talk about "rare" tumors, obviously, we do not refer to the most frequent cancers (papillary, follicular), or less frequent tumors (medullary, anaplastic), but to some types of thyroid tumors that have been almost always sporadically observed. Mucoepidermoid carcinoma and squamous carcinoma have been described in the literature. They present occasional papillary formation so that, according to some authors, could be considered as variants of the papillary carcinoma. Teratoma is another rare tumor which in the paediatric age is benign, but its prognosis could be unfavourable because it causes an important respiratory distress, while in the adult it presents a very aggressive clinical course like the anaplastic carcinoma. Lymphoma is the most frequent of the "rare" tumors of the thyroid (1-5% of all the thyroid cancers). It arises often in a setting of a long history of goitre and Hashimoto thyroiditis. Fine-needle aspirate is important to make diagnosis and to start a correct treatment which allows a 5-year survival up to 85% in the favourable cases.     

甲状腺未分化癌和甲状腺乳头状癌超声成像特征的对比研究

目的结合疾病病理特点,探讨甲状腺未分化癌和甲状腺乳头状癌超声成像特征的差异。 方法选取2010年1月至2015年6月在本院接受治疗并经病理证实为甲状腺未分化癌的患者12例为观察组,另选取同期经病理证实为甲状腺乳头状癌的患者35例为对照组,观察两组患者临床特征和超声特征。 结果女性患者所占比例大,观察组患者病灶平均直径大于对照组,纵横比<1的比例高于对照组,且观察组病灶微钙化程度高、血流少不规则、超声回声更不均匀、边界更为模糊,以上差异均有统计学意义（P<0.05）。两组患者超声特征中病灶形态、囊性变、回声、被膜受侵的对比差异无统计学意义。 结论甲状腺癌患者以女性为主,未分化癌患者病灶纵横比一般都<1且具有微钙化程度高、血流少不规则、超声回声更不均匀、边界更为模糊的特点,值得临床参考。     

Retrospective evaluation of the efficacy of regional endolymphatic polychemotherapy in kidney cancer depending on the histologic structure of the tumor

An attempt was made to differentiate the prognosis for patients with various histological patterns of renal cell carcinoma subjected to adjuvant regional endolymphatic polychemotherapy from those patients who were not. A total of 90 patients were allocated to 3 groups: the first group consisted of those persons for whom a 4-component endolymphatic therapy with 5-fluorouracil, cyclophosphamide, methotrexate, thiotepa was employed; the second group (25 patients) was administered the same preparations intravenously; the third-group patients (25 subjects) were those who after surgery were not given drugs at all. Tumor biopsy specimens were studied in detail histologically and 3 carcinoma patterns were distinguished: clear cell, granular cell and anaplastic carcinoma. The number of mitotic figures per 1,000 tumor cells was defined as well. The life-span of all anaplastic carcinoma patients was less than 5 yrs. Three-year survival was the most common in first group patients with clear cell or granular cell carcinomas. Five-year survival in patients with granular cell carcinoma was 50 per cent in the first and 11.1 per cent in the second group, while in those with clear cell carcinoma it was relatively equal in all groups. The total five-year survival rate was 40 per cent in group I, 20 per cent in group II and 16 per cent in group III. The results obtained were indicative of a higher effect of adjuvant endolymphatic polychemotherapy versus intravenous treatment. As better results were in those with granular cell carcinoma than in patients with clear cell carcinoma, tumor histological pattern be considered before the adjustment of cytostatic dosages and disease prognostication.     

Anaplastic thyroid carcinoma: risk factors and outcome.

Anaplastic thyroid carcinoma, in contrast to well-differentiated thyroid carcinoma, has a dismal prognosis, and little progress has been made in improving survival for this disease. We reviewed our experience during a 23-year period to identify risk factors and possible methods to improve outcome. Between 1966 and 1989, 340 patients with thyroid carcinoma underwent operation. Of these, 17 (5%) were undergoing operative treatment of anaplastic or undifferentiated thyroid carcinoma. The female/male ratio was 3.5:1, and mean age at presentation was 63 years. The most common presenting symptoms included neck mass, voice change, or dysphagia. Unusual presentations included symptomatic bradycardia from compression of the vagus nerve and superior vena cava syndrome. Four patients had a history of well-differentiated thyroid carcinoma. Nine patients had been diagnosed or treated in the past for "goiter" or a neck mass, and four patients had concurrent differentiated thyroid carcinoma associated with the anaplastic tumor. Thus 13 (76%) of 17 patients had a previous thyroid disorder, benign or differentiated malignant, and eight (47%) of 17 patients had previous or concurrent differentiated thyroid carcinoma. At the time of presentation, six patients had unilateral true vocal cord paralysis. At operation, 14 patients had local extension of the tumor and four required tracheostomy. Only five of 12 patients showed response to postoperative radiation therapy. Overall median survival was 12 months, and 13 (76%) of 17 patients died. The two patients alive longer than 12 months had only small foci of anaplastic carcinoma in association with well-differentiated carcinoma. Anaplastic thyroid carcinoma is a locally and systemically aggressive disease, with long-term survival seen only in those with well-localized anaplastic tumor. The major risk factor in this series is a history of previous benign or malignant thyroid disease. Because of this, a more aggressive approach to thyroid masses may be warranted. Long-standing goiters or benign nodules should be followed carefully and considered for resection if they grow or do not respond to medical therapy, and total thyroidectomy for malignant disease may obviate the subsequent development of anaplastic carcinoma. This method of early diagnosis and resection of abnormal thyroid tissue seems to be the only method currently available to improve the nearly uniform fatality of this disease.     

Anaplastic Thyroid Carcinoma Survival

Anaplastic thyroid carcinoma is a rare, highly malignant tumor of elderly people. The purpose of this retrospective study was to characterize the patient population and to detect a potential subgroup with better prognosis or any intervention that would be useful. From 1967 through 1994 a total of 33 anaplastic thyroid carcinomas were operated on at the Second Department of Surgery, Helsinki University Central Hospital. There were 26 females and 7 males with mean age of 66.0 years (range 36–89 years). At the time of diagnosis 16 of 33 patients had distant metastases, and 32 of 33 of the tumors had invaded the thyroid capsule. Disease-specific survival was 9.7% (95% confidence interval from 2.0% to 25.9%) at 1 year using the product limit survival analysis. In the stepwise Cox proportional hazards regression model, local resectability (p= 0.0002), presence of distant metastases at diagnosis (p= 0.0014), radiotherapy (p= 0.014), and radioiodine ablation (p= 0.039) were independent prognostic factors. We concluded that even though statistically significant, independent, prognostic factors can be found the survival of the patients with the best prognostic characteristics is still poor. Only one patient, who had an anaplastic carcinoma focus within an encapsulated follicular thyroid carcinoma, survived in this series. At present there seems to be no surgical treatment that would be efficient for treating symptomatic anaplastic thyroid carcinoma.