Anaplastic carcinoma of the thyroid.

BACKGROUND: Anaplastic thyroid carcinoma, albeit rare, is one of the most aggressive human tumors, with a dismal prognosis. METHODS: Twenty-eight patients with anaplastic thyroid carcinoma were identified during the past 30 years to evaluate its clinicopathologic features and to document our experience in management. Potential risk factors for survival time were analyzed. RESULTS: The usual presentation was that of a rapidly enlarging neck mass. Distant metastases were present in 50% of patients on presentation. Palliative resection was performed in 16 patients. The median survival was 38 days, and the 2-year survival rate was 4%. Among factors analyzed, patients selected for surgical resection, absence of distant metastases at presentation, young age, and tumor size <6 cm were associated with an increased survival time. Concomitant well-differentiated thyroid carcinoma and p53 overexpression were present in 12 of the 22 and 13 of the 19 specimens, respectively. CONCLUSIONS: Patients with anaplastic carcinoma of thyroid have a dismal prognosis heralding imminent death. Surgical ablation followed by adjuvant therapy can provide palliation for selected patients only.     

Anaplastic giant cell thyroid carcinoma.

Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of making radio-iodine therapy possible.     

Anaplastic carcinoma of the thyroid. Our experience]

Nineteen patients, 12 females and 7 males, with mean age of 66 years, with anaplastic carcinoma of the thyroid, were treated between 1976 and 1990. At diagnosis, in 4 patients disease presented as intraglandular mass, in 11 as infiltration of the adjacent structures and as distant metastases in 4 cases. A preceding history of goiter was found in 7 patients. Total thyroidectomy was performed in 9 patients, subtotal thyroidectomy in 1 and a diagnostic biopsy only in 4 cases. All patients received external radiotherapy (4000-6000 rads). Median global survival was 6 months with no difference between patients receiving thyroidectomy plus RT or biopsy plus RT. All patients died of tumor except 1 who is alive and free of disease at 120 months. Combination modality treatment of anaplastic carcinoma of the thyroid represent, at times, a rational palliative therapeutic approach, even if, in selected patients with early intraglandular disease, total surgery may represent a curative therapy.     

Anaplastic carcinoma of the thyroid: A 24-year experience

Background. Anaplastic carcinoma of the thyroid gland is a lethal entity; few patients live more than 12 months following diagnosis. We retrospectively reviewed the experience with this entity at our cancer institute and identified a subgroup of patients with complete resection who have a 60% 5-year survival. Methods. Twenty-one cases of anaplastic carcinoma of the thyroid gland were analyzed retorspectively with respect to prognostic factors influencing survival. This represents 2.7% of 771 cases of thyroid cancer seen at our institution from 1968 to 1992. The median age at presentation was 65.1 years; male/female ratio was 1:1.1; and the most common symptom was a rapidly enlarging neck mass (76%). Results. Estimated 5-year survival was 10% (median: 4.5 months). Tumor size less than 6.0 cm (p = .004) and female gender (p = .02) were significant prognostic factors. Five patients who underwent complete resection had an estimated 5-year survival of 60% (median: 131 months). Four of these patients had postoperative radiotherapy with or without sequential chemotherapy. Two of these patients survived more than 10 years, and a third remains alive without disease at 26 months. Conclusions. Complete resection and multimodality therapy result in long-term survival for a subgroup of patients with anaplastic thyroid carcinoma. © 1995 Jons Wiley & Sons, Inc.     

Differentiated carcinoma of the thyroid gland

Local recurrence at the stump of resection was examined with regard to stage of disease and extent of resection in patients with papillary and follicular carcinoma of the thyroid treated during the 23-year period from 1956 to 1979. The overall recurrence rate was 8.3% in both papillary and follicular carcinoma. In papillary carcinoma, total lobectomy is indicated for tumors<2 cm in diameter and subtotal thyroidectomy for pT-3 tumor stage, whereas total thyroidectomy should be performed for tumors ≧ 5 cm in diameter and for pT-4 tumor stage. On the other hand, in follicular carcinoma, total lobectomy is performed for tumors<2 cm in diameter, but subtotal thyroidectomy is the treatment of choice for those ≧ 2 cm in diameter and for pT-2 or more advanced tumor stage. Total thyroidectomy is not indicated for most patients with follicular carcinoma.     

Papillary carcinoma of the thyroid gland

Papillary thyroid cancer is after ovarian cancer the most frequent malignant disease of the endocrine system and because of this fact, early detection and appropriate surgical treatment is essential. Radical surgical treatment lower the risk of the disease relapse and postoperative adjuvant therapy with radioiodine is possible as well as postoperative follow up with thyreoglobulin measurement. If the total thyroidectomy is performed in highly specialized institution the risk of postoperative complications is acceptable and therefore is the treatment of choice for papillary thyroid cancer. Only the patients with occult papillary thyroid cancer can be treated with hemithyroidectomy. In our series of 410 patients the majority of the patients (85.12%) were in the early phase of the disease and the degree of successfully performed radical surgery for papillary thyroid cancer was very high (tumor reduction was performed in only 1.46% of cases).     

Medullary carcinoma of the thyroid gland

Nine cases of medullary carcinoma of the thyroid gland (MTC) are reported. Four of the carcinomas were of the familial type. Five of the patients were men and four were women. Patient age ranged from 23 to 66 years, with a mean age of 40 years. The median age of the four patients with the familial MTC was 32 years. A total or a subtotal thyroidectomy was performed in four and five patients, respectively, associated with a modified neck dissection in six patients with involved cervical lymph nodules. An underlying pheochromocytoma of the left adrenal was excised in one patient prior to thyroidectomy. In all cases the parathyroid glands were identified, and in two cases of familial MTC, in which they were grossly enlarged, the parathyroid glands were removed. Four patients died as a result of their disease within 3 years, whereas patients are well 4 to 12 years after surgery. The best chance of cure lies in early diagnosis and an aggressive surgical removal of the primary tumor and any cervical metastases.     

Secondary carcinoma of the thyroid gland

When the cervical tumor mimics thyroid carcinoma, some cases are shown to be the primary carcinoma of other site. Four cases of secondary thyroid carcinoma, of which primary sites are adjacent organ, are studied. The characteristics of histology are squamous cell carcinoma. Squamous cell carcinoma of which primary organ seems to be thyroid often discloses metastatic neoplasm originated from the adjacent organs. Since chronically inflammatory lesion is recognized concurrently, abnormal thyroid is suggested to be congenial soil for malignant growth. Our experience indicates that the secondary carcinoma due to direct extension should be considered on diagnosing squamous cell carcinoma of the thyroid.     

Follicular carcinoma of the thyroid gland

Follicular thyroid cancer is the second most common thyroid malignancy. This tumor has a predisposition for hematogenous dissemination an extra thyroid spread. Accurate cytological diagnosis of follicular thyroid cancer is not possible and this fact highlights the necessity for surgical treatment of any suspicious thyroid nodule. Aggressiveness of this tumor is greater than in the case of papillary thyroid cancer and it is the reason for radical surgical treatment of follicular thyroid cancer. Total thyroidectomy facilitates later adjuvant therapy with thyroid hormones and radioiodine. This procedure improves the outcome and the risk of relapse. Results of our study clearly demonstrate that diagnosis of follicular thyroid cancer in us is established in the early phase of the disease (78.57%), but the significant number of the patients (21.43%) is still in the advanced phase of the disease.     

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 (undifferentiated) thyroid carcinoma (ATC)

BACKGROUND: Old age, reduced general condition and far advanced tumor stage associated with poor prognosis induced the belief that, apart from verifying the diagnosis of anaplastic thyroid carcinoma (ATC) by biopsy, no additional surgery would be justified. However, in some cases, an ultraradical approach was recommended in order to improve the quality of life and survival. METHODS: These are the results of a retrospective analysis involving 120 patients subjected to restricted radical surgery (excising as much as possible of the tumor and local metastases, foregoing ultraradical removal of vital organs such as esophagus, larynx and trachea). RESULTS: Irrespective of the surgical approach used, 6+/-2% of the patients were alive after 5 years (median survival time: 3.1 months). Patients without tumor residues (R0-resections; extending to soft tissue only; Kaplan-Meier estimate - cumulative survival 15+/-5%) had a significantly better prognosis than patients with tumor residues (R1/R2-resections; no patient survived 5 years; P<0.001). Tumor morphology (spindle cells, giant cells, mixed cells) or differentiated parts of the tumor as well as lymph-node involvement had no statistically significant impact on the prognosis. CONCLUSIONS: In ATC, the objective should be to remove as much of the carcinoma as possible (in the ideal case, a thyroidectomy); if lymph nodes are affected, neck dissection should be the goal, if possible (restricted radical approach, improving quality of life). Ultraradical surgery to include segmental resection of larynx, trachea or esophagus do not seem to be indicated, as prolonged survival is questionable and quality of life is certainly diminished.     

Squamous cell carcinoma of the thyroid gland

We present the clinical manifestations and details of treatment and outcome for eight patients with squamous cell cancer arising in the thyroid gland, which is a rare entity. All patients had advanced disease, with primary tumors invading adjacent structures (the trachea, esophagus, and major vessels). In two patients, pulmonary metastases were also present. Six patients died 6 months or less after diagnosis, five from the effects of local disease. Transient palliation was obtained in four patients who underwent partial excision (three patients) and radical radiotherapy (one patient). Two patients remained free of disease at last follow-up more than 4 years after gross total tumor resection and radical radiotherapy and were presumably cured. One patient treated by partial resection and radical radiotherapy died from other causes 17 months later. His disease status was unknown. Complete excision with postoperative radiotherapy may be curative, and debulking followed by external irradiation may provide short-term palliation. Patients with unresectable tumors are best managed by supportive measures only unless a truly effective chemotherapeutic regimen is developed for squamous cell cancer of the head and neck.     

Clear cell carcinoma of the thyroid gland

Clear cell carcinoma is a rare variant of thyroid cancer, histologically related to the well-differentiated thyroid malignancies. The purpose of this paper is to discuss data collected from the English literature and to present three additional cases. In two of the three cases presented, thyroglobulin levels were extremely high after thyroid ablation. Both cases presented metastasis to lung and bone with significant I131 uptake. It seems that, when compared to the well-differentiated carcinomas of the thyroid gland, clear cell carcinoma has a more aggressive clinical course. Initial radical surgery is the treatment of choice for this kind of neoplasm and I131 should always be considered for the treatment of its metastasis.     

Medullary carcinoma of the thyroid gland.

Out of the discovery of concurrent multiple endocrine neoplasms has evolved the concept of multiple endocrine adenomatosis (MEA1 and MEA2). Medullary carcinoma of the thyroid gland is the most constant facet of MEA2 and is derived from C-cells of the neural crest. These cells, resembling parafollicular cells of lower animals, elaborate calcitonin which acts as a sensitive signal of the presence of the tumor. Ninety per cent of MCT occurs sporadically; in 10% the tumor presents as an atuosomal dominant trait. Other endocrinopathies, especially pheochromocytomas, are present in 70% of cases. The lesions are "cold" on iodine radioisotope scan. On microscopic examination, the appearance of amyloid is characteristic. Regional lymph node metastasis occurs early. The tumor deserves appropriate aggressive management. Surgical therapy should begin early and vigorously with the minimum procedure being total thyroidectomy. Frequent lymph node metastasis speaks for the need for regional neck dissection extended into the superior mediastinum. The search for, and the treatment of, the frequently associated endocrinopathies is essential. Pheochromocytoma must be suspected and eradicated before treatment of the thyroid tumor. A genetic workup should be included.     

Secondary carcinoma of the thyroid gland.

Two patients are described who presented with clinically solitary thyroid nodules which were found to be due to metastatic disease from the kidney and colon respectively. Removal of the solitary metastatis in one patient resulted in disease-free survival for over 5 years.     

Anaplastic thyroid carcinoma in ecuador: analysis of prognostic factors

The highest incidence of anaplastic thyroid carcinoma (ATC) has been reported in countries with endemic goiter, such as in Ecuador. In this country, ATC is the third most common histologic type of thyroid cancer, following papillary and follicular carcinoma. The aim of this study was to review the clinical presentation and the results of treatment of a large consecutive series of ATC patients treated at the oncological department of a general hospital in Quito, Ecuador. This is a retrospective study of 30 patients diagnosed with ATC at the Social Security Hospital, from 1982 to 1998. Symptomatic rapidly growing neck masses were generally present. All the patients had histological diagnosis of ATC. Two patients with pulmonary metastases and pleural effusion died before treatment could be instituted. Twenty-eight patients received at least one type of treatment: surgery, radiation therapy (RT), or chemotherapy (CT). The two most frequently employed therapeutic modalities were surgery followed by RT and/or CT in 14 patients and surgery alone in 9 patients. Surgery was performed in 23 patients but a complete resection was possible in only 14 patients. RT, postoperatively or alone, was given to 17 patients. Only 5 patients received doses ranging from 4,000 to 5,000 cGy and 4 patients more than 5,000 cGy. CT was administered to 17 patients. Doxorubicin alone was given to 10 patients and different combinations to the remaining patients. Local control was obtained in 8 of 14 complete resections. The prognostic value of the following parameters was studied by univariate analysis: duration of symptoms, size of the tumor, extent of glandular involvement, type of treatment, and surgical margins. A statistically longer survival was found in cases of differentiated carcinoma with areas of ATC or tumor limited to one lobe, those patients who received a complete treatment of chemotherapy, and those patients with tumors smaller than 10 cm and with duration of symptoms longer than 4 months. Longer mean survivals were seen in patients with longer duration of symptoms and smaller lesions. Five patients with focal anaplastic lesions within a differentiated thyroid carcinoma or a lesion limited to one lobe had a significant better survival (a mean of 20 months).