Diagnosis, radioiodine and radiotherapy of thyroid carcinomas

The long-term prognosis of differentiated thyroid carcinoma depends on early diagnosis and treatment of metastases and local recurrences and is modulated by several factors, age and histology being the most relevant. This article summarizes current trends in the use of radioactive iodine (131J) and gives explicit advice on its use in the treatment of these cancers. Complications of therapy are discussed in detail. We currently recommend that all patients undergoing a subtotal or total thyroidectomy are followed up by 131J thyroid scanning approximately 4 weeks after surgery. The combined use of three diagnostic modalities (measurement of serum thyroglobulin, neck ultrasonography with ultrasound-guided biopsy for detecting recurrences of carcinoma in the neck region and 131J whole-body scintigraphy) appears to give the best results in the follow up of patients with differentiated thyroid carcinoma. If any residual uptake is detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation with 1,5-3 GBq of radioactive 131J. External radiotherapy is always indicated in papillary and folliculary carcinoma in the pT4 stage of pTNM classification but not in those in pT1-3 pN0 stage. In the presence of lymph-node metastases and distant metastases, an individual treatment concept is recommended regarding all risk factors, especially the age and sex of the patient, the histology and grading of the tumor and the completeness of tumor resection. Finally, radiotherapy is usually not indicated in medullary carcinoma, whereas it is always indicated in anaplastic carcinoma.     

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.     

Neurological complications after autologous stem cell transplantation

Clinically detectable well-differentiated metastatic thyroid cancer to the kidney is rare, with only 12 cases reported in the medical literature. The authors report a case of metastatic thyroid carcinoma to the kidney in a patient with widespread dissemination. She underwent total thyroidectomy, radical left nephrectomy, radioactive ablation with I-131, radiotherapy, and thyroid suppression therapy. Well-differentiated thyroid metastatic cancer can be amenable to treatment with successful long-term results.     

Follicular adenocarcinoma of the thyroid in the maxillary sinus

No reports of metastatic thyroid carcinoma in the maxillary, ethmoid, or sphenoid sinuses can be found in the literature. A woman with severe posterior epistaxis was examined recently. She had undergone a partial lobectomy for a thyroid tumor 16 years previously. Hemorrhagic thyroid tissue was in the maxillary sinus. The results of subsequent examinations indicated thyroid deposits in the lung and spine. The patient received radioactive iodine, 100 MCi. Her lung and spine deposits lysed, and she experienced no further epistaxis. Thyroid carcinoma's ability to metastasize to a paranasal sinus is documented here. Epistaxis after a thyroidectomy for cancer now must be considered an unusual clinical manifestation of metastatic spread, unless otherwise proved. The differential diagnosis of epistaxis must now include thyroid carcinoma metastatic to the sinonasal tract.     

Modern methods of wound treatment. 1. One wound is not the same as all the others

Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and low incidence of distant metastases. Brain metastasis is extremely rare with a frequency of about 1% in reported series. In this paper we present the clinical details of one case of histologically proven brain metastasis from papillary thyroid cancer, first presented with neurological symptoms, initially treated with excisional biopsy and radiotherapy in other hospital, without clinical response. The patient was then referred to our service, where he underwent a total thyroidectomy and modified radical neck dissection, with the aim of posterior radioactive iodine treatment for the brain lesion. Unfortunately, he died of neurological complications, two months after the neck treatment. Also presented is a review of the literature of this unusual clinical presentation.     

Effect of postoperative 131I treatment on thyroglobulin measurements in the follow-up of patients with thyroid cancer

Correlation of serum thyroglobulin (Tg) levels with recurrent cancer was performed in 200 patients who had undergone a subtotal thyroidectomy for well-differentiated thyroid carcinoma. Patients were divided into three groups: (1) those not treated postoperatively with radioactive iodine, (2) those treated with low dose (30 mCi) radioactive iodine, and (3) those treated with high dose (50-250 mCi) radioactive iodine. Tg levels proved to be reliable in detecting recurrent thyroid cancer regardless of the dose of radioactive iodine given postoperatively. These results reinforce the recommendation of using the Tg assay as the primary method of following these patients postoperatively, even when there was less than a total thyroidectomy and ablation with radioactive iodine.     

Clinically significant, isolated metastatic disease to the thyroid gland

Despite being second only to the adrenal glands in terms of relative vascular perfusion, the thyroid gland is a rare site of metastatic disease; but when thyroid metastases occur, long-term survival has been reported to be dismal. To determine the incidence and management of isolated, metastatic disease to the thyroid, we reviewed our clinical experience. Between June 1986 and August 1994 ten patients underwent thyroidectomy for isolated, metastatic disease of nonthyroidal origin (mean +/- SD age 58 +/- 6 years, 30% female). The primary tumors were renal cell carcinomas (RCCs) (n = 5), esophageal adenocarcinoma (n = 1), pulmonary squamous cell carcinoma (n = 1), gastric leiomyosarcoma (n = 1), lingual squamous cell carcinoma (n = 1), and parotid gland carcinoma (n = 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 +/- 6.0 years (range 0-19.5 years). Total thyroidectomy (n = 5) or lobectomy (n = 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.     

Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine

From 1969 to 1990 there were 309 patients with differentiated thyroid carcinoma (241 papillary and 68 follicular) treated with radioactive iodine for functioning node metastases alone (n = 191) or distant metastases (n = 118) with or without node metastases. These patients represented 32.7% of 945 patients treated in our institution during the same period. Initial treatment included near-total thyroidectomy and 131I ablation of postsurgical thyroid residue, followed by L-thyroxine suppressive therapy. At the end of follow-up (mean 5.8 years), 146 patients (76.4%) in the group with nodal metastases were considered cured, as assessed by clinical and laboratory evaluation including whole body scan (WBS) and serum thyroglobulin (Tg) levels; 32 patients (16.7%) had persistent disease. Loss of 131I uptake in persistent metastatic lesions occurred in five patients (2.6%), and newly developed distant metastases occurred in eight patients (4.2%). Of the patients with distant metastases, 36.4% were cured by 131I. Distant metastases from papillary carcinomas had a higher cure rate than follicular carcinomas (p < 0.01). The metastases of four patients (5.2%) lost the property to take up radioiodine. Lung and bone metastases detectable by WBS but not by radiography were most likely to be cured by 131I. The overall survival at the end of follow-up was 95.8% in patients with only lymph node metastases and 76.0% in those with distant metastases. Tumor-related deaths were 3.6% and 23.7%, respectively. Our data indicate that 131I therapy is highly effective in the treatment of lymph node metastases from differentiated thyroid carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leukemia developing after 131I treatment for thyroid cancer in a patient with Werner's syndrome: molecular and cytogenetic studies

A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as having WS complicated with thyroid cancer seven years previously. Total thyroidectomy and radioactive iodine (131I, 100 mCi/year) therapy for seven years had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS at the age of 40 years. After six months she died from overt leukemia. We found an additional chromosome aberration of chromosome 10 in the progression of leukemia from MDS.     

Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.     

Management of the neck in thyroid cancer

The incidence of nodal metastasis in differentiated thyroid cancer ranges between 40% to 75%. Elective neck dissection is generally not advised in patients with differentiated thyroid cancer; however, if clinically apparent nodal disease is noted in the tracheoesophageal groove during surgery, central compartment clearance is advised. If clinically apparent nodal disease is present in the lateral compartment of the neck, modified neck dissection preserving the sternomastoid, accessory nerve, and jugular vein is advised. The "berry picking procedure" is generally not recommended because of the higher incidence of regional recurrence. Due consideration should be given for parathyroidal transplantation if the blood supply to the parathyroids is damaged during central compartment clearance. The incidence of lymph node metastasis is highest in young patients, however, lymph node metastasis has no bearing on long-term survival. There seems to be a higher incidence of regional recurrence in elderly individuals. If patients present with bulky nodal disease, consideration may be given for postoperative radioactive iodine dosimetry and ablation if necessary. Differentiated thyroid cancer represents a unique disease in the human body, where lymph node metastasis has no prognostic implication. Aggressive surgical clearance is advised in patients with medullary thyroid cancer in the central compartment and the jugular chain lymph nodes.     

Combination of radioiodine (131I) and probe-guided surgery for persistent or recurrent thyroid carcinoma

To improve the completeness of surgical excision of persistent or recurrent differentiated thyroid carcinoma, the following protocol was used for the treatment of 54 patients with functioning lymph node metastases: administration of 3.7 gigabecquerels (100 mCi) 131I; total body scintigraphy (TBS) on day 4; surgery on day 5, using an intraoperative probe (Gammed 2, Eurorad); and postoperative TBS with the remaining 131I activity on day 7. The 54 patients (35 women and 19 men presenting 47 papillary carcinomas, 2 well differentiated follicular carcinomas, and 5 poorly differentiated follicular carcinomas) had already undergone surgery for differentiated thyroid carcinoma: total thyroidectomy (51 patients) or lobectomy with isthmusectomy (3 patients), with lymph node dissection in 33. One to 7 131I treatments were performed before inclusion. Preoperative 131I-TBS with a high dose of 131I allowed accurate localization of previously suspected neoplastic foci and detection of yet unknown foci in 56%; it was the most sensitive tool for localizing neoplastic foci. The use of an intraoperative probe was considered decisive in 20 patients, as neoplastic foci were found inside sclerosis due to previous surgery (n = 9), at unusual sites behind vessels or in the mediastinum (n = 10), or both (n = 1). In 26 patients, it facilitated the preoperative detection of foci with 131I uptake already depicted at preoperative 131I-TBS. In all 46 patients, the completeness of excision was demonstrated by both the probe and the postoperative 131I-TBS and was confirmed during follow-up. Of note, lymph node metastases undetected by 131I-TBS or by the probe were found in 14 patients at histological examination. This clearly shows that en block dissection is the only recommended procedure. In four patients, no neoplastic foci were found and in four patients, uptake was either due to the thymus (in two) or to the salivary glands (in two).     

Papillary microcarcinoma of the thyroid. 179 cases reported since 1973

OBJECTIVES: Defined as a tumor measuring < or = 1 cm, the prognosis and treatment of occult papillary thyroid carcinoma has been the topic of some controversy. The aim of this study was to report experience with a series of 179 cases observed since 1973. PATIENTS AND METHODS: Occult papillary thyroid carcinoma was discovered in 179 patients aged 12 to 81 years (151 women and 28 men) at cervicotomy prescribed for Graves' disease (n = 9), toxic adenoma (n = 16), isolated nodule (n = 71), multinodular goiter (n = 74) or cervical node enlargement (n = 9). The surgical procedures were lobo-isthmectomy (n = 79), subtotal thyroidectomy (n = 74), or total thyroidectomy (n = 26) with node dissection in case of enlargement. Thyroxin was prescribed in all cases and annual follow-up was programmed. Five patients were lost to follow-up. RESULTS: Two cervical recurrences were observed warranting reoperation. None of the patients died from cancer-related causes. CONCLUSION: Minute papillary carcinomas of the thyroid are frequently discovered, but prognosis is generally excellent. Systematic total thyroidectomy and node dissection are not warranted. Only those lesions with an extrathyroid extension, associated node enlargement or inaugural metastasis require wide resection. These results are in agreement with a critical analysis of data reported in the literature demonstrating the exceptional nature, and in half of the cases, cure of metastatic occult papillary thyroid carcinoma.     

Benign thyroid oncocytomas. Outcome after more than 4 years

OBJECTIVES: Occasional malignant transformation after partial thyroidectomy for Hürthle cell tumours has led certain authors to propose total thyroidectomy in all cases. The aim of this retrospective study was to evaluate outcome 4 years after partial thyroidectomy in patients with Hürthle cell tumours. METHODS: Ten patients (9 females, 1 male; mean age 45 years; age range 21-65 years) underwent thyroid surgery for Hürthle cell tumours from 1980 to 1989. Lobectomy was performed in 7, subtotal thyroidectomy in 2 and tumourectomy in 1. The extemporaneous pathology examination reported 4 apparently benign vesicular lesions, 2 apparently benign oncocyte lesions, 2 fetal adenomas, 1 thyroiditis, 1 trabecular adenocarcinoma. Pathology examination of the surgical specimen reported isolated benign oncocyte tumours in 4 cases and benign oncocyte tumours with associated vesicular adenomas in 5. In 1 case it was not possible to confirm whether the oncocyte lesion was benign or malignant. All 10 patients were seen again 6 months later for consultation and thyroid hormone assays and thyroid echography in doubtful cases. RESULTS: All patients were seen for follow-up (mean 88 months; range 47-148 months). New thyroid nodules were observed in 2 but did not require surgery. No cervical lymph node enlargement was found. CONCLUSION: The diagnosis of Hürthle cell tumour was confirmed intraoperatively in 8 of the 10 cases. No malignant transformation was observed. These findings demonstrate that total thyroidectomy cannot be indicated intraoperatively and would not appear to be indicated after partial thyroidectomy.     

Medical care in 7 Chilean cities

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a recently recognized malignant neoplasm of the thyroid gland. Two additional cases of this condition which occurred in a 70-year-old woman and a 69-year-old woman are presented. The case of the 70-year-old woman (patient 1) is the first report of distant metastasis, besides lymph node metastasis, for this type of tumor. The patient initially presented with a thyroid mass, and the thyroid gland with surrounding cervical lymph nodes was removed. Because of focal keratin "pearl" formation, the tumor was misinterpreted as a metastatic squamous cell carcinoma to the thyroid. Approximately 4 years later, the patient developed a left supraclavicular mass and lung densities. A pathological fracture of the right humeral head followed, and the left supraclavicular mass recurred along with newly developed subcutaneous nodules on the chest wall and arm. Open lung and bone biopsies revealed metastatic SMECE, which was morphologically identical to that of the thyroid mass. The 69-year-old woman (patient 2) had, in 1983, undergone thyroidectomy with left radical neck dissection; this had been diagnosed as follicular carcinoma of the thyroid with lymph node involvement. After multiple isolated lymph nodes metastases, the patient developed locally extensive, recurrent tumor that showed microscopic features of SMECE. Review of the previous thyroid tumor and lymph nodes revealed the same type of histology. To our knowledge, only a single report containing eight cases of this distinctive carcinoma of the thyroid has been published. Herein we describe characteristic morphological features of two additional cases of this rare malignancy, one with distant metastasis, and we review the related literature.     

Thymic anaplastic carcinoma successfully controlled by combination chemotherapy

Thymic carcinomas are rare tumors for which the main treatments have been surgery, radiotherapy, or both. However, the role of chemotherapy is less well-defined. Here, we report a case of advanced thymic anaplastic carcinoma which was suspected to be the primary lesion, yet was successfully controlled despite brain metastases by EACUM combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, 5-FU, and methtrexate. Pathohistological findings on metastatic lesions of the right supracuravicular lymph nodes led to a diagnosis of anaplastic carcinoma. We could not give a diagnosis of thymic carcinoma because the biopsy specimen had not been taken from the thymus. There was no evidence of a primary neoplastic tumor other than thymoma. The patient was still alive 6 years and 9 months after the start of anticancer treatment and was working normally. The findings from this case should be of value to the establishment of effective combination chemotherapy regimens for advanced thymic carcinoma.     

Residual masses after chemotherapy for metastatic testicular cancer: the clinical implications of the association between retroperitoneal and pulmonary histology. Re-analysis of Histology in Testicular Cancer (ReHiT) Study Group

PURPOSE: We determined the need and sequence of retroperitoneal lymph node dissection and thoracotomy in patients with nonseminomatous testicular cancer, and with residual retroperitoneal and pulmonary masses after chemotherapy. MATERIALS AND METHODS: We studied 159 patients undergoing retroperitoneal lymph node dissection and a thoracotomy following cisplatin based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumor. Several well-known predictors for residual histology (necrosis, mature teratoma and cancer) were evaluated. RESULTS: As expected, necrosis was found more often at retroperitoneal lymph node dissection if the primary tumor was negative for teratoma, the residual mass was small or the decrease in size was great. Contrary, neither residual mass size nor the decrease in size was predictive of the histological status of the residual lung lesion. Histological findings in the retroperitoneum and lung were strongly correlated, such that necrosis at retroperitoneal lymph node dissection was associated with an 89% probability of necrosis in the lung. CONCLUSIONS: Retroperitoneal lymph node dissection should be performed before thoracotomy is considered, since the histological status at dissection is a strong predictor of that at thoracotomy.     

nm23 Protein expression in larynx cancer and the relationship with metastasis

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene and has been demonstrated to correlate inversely with metastatic potential in several tumours. To elucidate the role of nm23 in larynx carcinomas, we examined using immunohistochemistry the expression of the nm23 protein in matched sets of primary tumours and metastatic lymph nodes. nm23 Protein was expressed in all the carcinomas as well as in non-neoplastic larynx mucosa. Overexpression of nm23 protein was found in the majority of primary tumours compared with corresponding normal mucosa, while decreased expression was associated with poor differentiation and distant metastasis and/or recurrence. No significant difference in age, sex and stage was found between primary tumours with high and low nm23 protein expression. These results suggest that decreased nm23 protein expression may play a role in metastasis and/or recurrence in larynx cancer and therefore could be used as a prognostic factor.     

Expression of the Mr 67,000 laminin receptor is an adverse prognostic indicator in human thyroid cancer: an immunohistochemical study

Increased expression of the Mr 67,000 laminin receptor (LR) is a consistent event which appears as cancer cells acquire an invasive and metastatic phenotype. The Mr 67,000 LR is one of the many laminin-binding proteins able to interact with the major glycoprotein of basement membranes, laminin. The recent development of a specific monoclonal antibody directed against the Mr 67,000 LR MLuC5 has allowed us to study large retrospective groups of human cancers with the aim of correlating the Mr 67,000 LR expression to the clinical, pathological, and survival data of the patients. A significant correlation has already been established between the increased expression of Mr 67,000 LR and survival of patients with breast, colon, ovary, lung, and endometrial cancers. In this study, we investigated the possibility that the detection of Mr 67,000 LR in thyroid human cancers could also be of prognostic value. We analyzed the expression of Mr 67,000 LR with immunohistochemistry using MLuC5 antibodies in paraffin sections of 40 benign and 170 malignant thyroid human tumors. We found that Mr 67,000 LR was not usually detectable in normal thyroid tissues adjacent to the lesion. Only 3 of the 40 thyroid adenomas examined (7.5%) presented cells positive for Mr 67,000 LR. For the malignant thyroid tumors examined, we found that 22.3% of papillary thyroid carcinomas, 38% of follicular thyroid carcinomas, 40% of poorly differentiated carcinomas, 25% of medullary carcinomas, and 58.3% of anaplastic carcinomas expressed a high level of Mr 67,000 LR. Although no correlation between the Mr 67,000 LR expression and survival was found in patients with follicular thyroid carcinomas, papillary thyroid carcinomas, anaplastic carcinomas, and medullary carcinomas, there was a significant correlation in primary thyroid cancers. Our data represent the first extensive study of the Mr 67,000 LR expression in human thyroid cancers and strongly suggest that its detection could be of prognostic value in the investigation of primary thyroid cancers.     

Prognosis of visceral and osseous metastases of differentiated thyroid cancers. 24 cases

Twenty four cases of differentiated thyroid carcinoma with distant metastases are analysed. Prolonged survival periods are possible. The best prognosis in papillary forms is stressed. Metastases fixing I131 progress more slowly, as a result of treatment with radioactive iodine but apparently also by virtue of the higher degree of differentiation of such metastases. One case of apparent cure of pulmonary metastasis after treatment with radioactive iodine is described. Surgery and external radiotherapy retain a place of choice in the treatment of metastases. In our experience, chemotherapy has been disappointing.