Anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma may represent the ultimate dedifferentiation step of thyroid tumorigenesis and is one of the poorest cancers in human. It accounts for less than 2% of thyroid cancers and affects older patients in their sixth to eighth decade. Usual clinical presentation is a rapidly growing thyroid mass invading surrounding structures with compressive symptoms. Cervical lymph nodes enlargement and distant metastases occur frequently. Though cytological results obtained by fine needle aspiration may be suggestive of diagnosis, tissue biopsy for immunohistochemical study can be necessary to exclude lymphoma and to validate aggressive therapies. Patients developing anaplastic thyroid cancer must be referred urgently in cancer centers to plan multimodality therapeutic approach depending on their performance status. The treatment regimen combines surgery when feasible, hyperfractionated and accelerated external beam radiotherapy and doxorubicin based chemotherapy. Such treatment can provide control of locoregional disease but does not impact on overall survival in patients with distant metastases. The prognosis is dismal with a mean survival of four to nine months after diagnosis. Long survivors are patients with emerging disease presenting a resectable tumor and receiving adjuvant radiotherapy and/or chemotherapy. Therapeutic researches investigate redifferenciation strategies and targeted therapies to inhibit EGF receptors and neoplastic angiogenesis. Primary prevention of this lethal disease may consist of adequate treatment of differentiated thyroid cancers and goiters in elderly.     

Papillary thyroid carcinomas with lung metastases.

BACKGROUND: Limited information is available on the presentation, treatment outcomes, and prognostic factors of papillary thyroid carcinoma with lung metastases. METHODS: This study retrospectively analyzed the data of 2003 patients with thyroid cancer who were treated and followed up at Chang Gung Memorial Hospital from January 1979 to December 2002. In total, 1516 papillary thyroid carcinomas were enrolled. One hundred two (6.7%) papillary thyroid carcinomas with lung metastases were followed including 57 women with mean age of 41.7 +/- 17.3 years and 45 men with mean age of 49.6 +/- 17.2 years. These patients included 52 patients with papillary thyroid carcinoma who presented with lung metastases at the time of diagnosis. The 102 cases of papillary thyroid carcinomas with lung metastases included 72 cases with lung metastases only, and 30 cases with other organ involvement. RESULTS: After mean follow-up periods of 8.8 +/- 0.6 years, 28 (27.5%) of the patients with lung metastasis died, while 6 improved to clinical stage I. The 5-, 10-, 15-, and 20-year survival rates in patients with papillary thyroid carcinoma without distant metastasis and in the lung metastases groups were 99.0%, 98.5%, 98.0%, 98.0%, and 91.3%, 75.0%, 64.0%, 51.2%, respectively. Comparing the Kaplan-Meier survival curves between the patients with papillary thyroid carcinomas with lung metastases only and those with multiorgan metastases demonstrates no statistically significant difference in mortality rates. However, age, gender, postoperative thyroglobulin (Tg) level and tumor size displayed statistically significant differences between the lung metastases and no distant metastasis groups. Fifty of the 102 patients with papillary thyroid carcinomas with lung metastases developed lung metastases during follow-up. Larger amounts of remnant thyroid tissues with higher Tg levels were noted in these patients compared to those without distant metastasis. CONCLUSIONS: The prognosis of patients with papillary thyroid carcinoma with lung metastases at time of diagnosis is the same as for those whose lung metastases are discovered later. Survival analysis demonstrates no difference between lung metastases and multiorgan metastases.     

Follicular thyroid carcinomas with lung metastases: a 23-year retrospective study

Limited clinical information is specified in the presentations, results of treatment and prognostic factors of follicular thyroid carcinoma with lung metastases. In order to better characterize the information, we retrospectively analyzed the data of 2,003 thyroid cancer patients who received treatment and follow-up at the Chang Gung Memorial Hospital during the period from January 1979 to December 2002. There were 1,516 cases of papillary and 272 cases of follicular thyroid carcinomas. In the study, lung metastases of the follicular thyroid carcinomas were defined as post-operative or follow-up chest X-ray, diagnostic or therapeutic (131)I scan with positive finding of lung metastases. Serum thyroglobulin (Tg) levels under thyroxine treatment of patients with lung metastases had to be over 1.5 ng/mL. Of the follicular thyroid carcinomas, there were 70 (25.7%) with lung metastases including 50 females (mean age 54.1 +/- 12.6 years old) and 20 males (mean age 59.4 +/- 12.0 years old). Of the 70 patients, there were 53 patients (75.7%) who presented with lung metastases at the time of diagnosis. Of the 70 patients of follicular thyroid carcinoma with lung metastases, 30 patients (42.9%) died at the end of the follow-up, and only 4 patients improved to disease free status. The 5, 10, 15, and 20 year survival rates in these patients were 68.5%, 54.0%, 41.6%, 27.7%, respectively. Age, post-operative Tg level and tumor size are important prognostic factors which are demonstrated to be significantly different statistically between lung metastases group and the group of the patients without distant metastasis. Otherwise, only the tumor size and accumulative dose of (131)I therapy demonstrate a significant difference between survival and mortality groups. Seventeen of the 70 patients developed lung metastases during the follow-up period. Mean period between diagnosis and recurrence of these patients was 3.6 +/- 0.9 years. Over 75% of follicular thyroid carcinoma with lung metastases was diagnosed at the time of presentation. Forty percent (28/70 cases) of the follicular thyroid carcinoma with lung metastases had history of thyroid surgery in this study. If lung metastases are diagnosed in follicular thyroid carcinoma, it will be followed by a poor prognosis. Older patients, higher postoperative Tg, and larger tumor size in follicular thyroid carcinoma need aggressive postoperative treatment.     

Anaplastic changes associated with p53 gene mutation in differentiated thyroid carcinoma after insufficient radioactive iodine (131I) therapy.

Thirty-two patients with differentiated thyroid carcinomas with distant metastasis were examined using a radioactive iodine (131I) tracer dose prior to 131I therapy and followed up for 10 years or until death (whichever occurred first). Nineteen patients who received 131I therapy had an accumulation of 131I in the metastases (group I) and 15 of those patients were alive more than 10 years after the first 131I treatment. In contrast, all 13 patients in whom the metastases did not show accumulation of 131I died within 10 years. Of the latter group, eight patients had received 131I therapy (group II), four of whom died with anaplastic changes within 5 years of treatment. p53 gene mutation was identified by immunohistochemistry in primary thyroid carcinoma tissue from patients with anaplastic changes that were evident during total thyroidectomy. Five patients did not receive 131I therapy (group III), of whom one, who also had a p53 gene mutation in the original tumor, died with anaplastic change 10 years after thyroidectomy. Seven patients in group I had p53 gene mutations in their thyroid carcinoma tissues, but none showed anaplastic changes. Our results suggest that 131I therapy may be useful for patients with distant metastases, with or without p53 gene mutations, which show accumulation of 131I from tracer and therapeutic doses. In contrast, 131I therapy is apparently not effective in patients who do not show sufficient accumulation of 131I, but rather, may cause early anaplastic changes with a p53 gene mutation.     

Follicular thyroid carcinoma: From diagnosis to treatment

Unusual presentations with bone, lung or soft tissue metastases in initial diagnosis of follicular thyroid carcinoma have been reported occasionally. This implies how difficult it is to diagnosis this type of cancer at the pre-operative or intra-operative stage of treatment. Fine needle aspiration cytology has been shown to be an ineffective method for diagnosing vascular or capsule invasion of follicular thyroid cancer. Multiple frozen sections, usually 5 to 12 depending on the size of the tumor, can achieve a diagnostic accuracy of 98%. Clinical application of various gene expressions in thyroid follicular tumors by needle aspiration using in situ hybridization requires further investigation. Although radioactive iodide (131I) has been used as the standard treatment for follicular thyroid carcinoma with distant metastases, the effectiveness of 131I treatment for follicular thyroid carcinoma depends on the differentiation of cancer cells. The possibility of 131I for thyroid remnant ablation replacing a secondary operation for follicular thyroid carcinoma has been debated. Recent studies applied more expressions of sodium iodide symporters to attain the effect of 131I treatment and slow the proliferation of thyroid cancer cell which, in turn, slows the progression of follicular carcinoma. Consensus for the surgical procedures for the specific prognostic risks for follicular thyroid carcinoma is needed. Dedifferentiated, anti-angiogenic, or gene therapies for follicular thyroid cancer with distant metastases or anaplastic transformation comprise the principal directions in future research for this cancer.     

Factors related to the survival of papillary and follicular thyroid carcinoma patients with distant metastases.

There is limited clinical information comparing presentations and results of treatment of papillary and follicular thyroid carcinoma patients with distant metastases. We retrospectively analyzed data of 1,257 thyroid cancer patients who received their treatment and follow-up at Chang Gung Memorial Hospital. We found 992 patients with papillary carcinoma and 205 patients with follicular thyroid carcinoma. Of these, 68 patients with papillary thyroid carcinoma (6.9%) had distant metastases at the time of diagnosis or during the follow-up period. Of the follicular thyroid carcinoma patients, 69 (33.7%) had distant metastases. Of the 68 patients with papillary carcinoma, only 33 were categorized as stage IV at the time of diagnosis. Nine of the patients were categorized as clinical stage I carcinoma, 10 as stage II, and 16 as stage III. Sixteen patients (23.5%) died during the study period, all but 2 of thyroid cancer. Twelve of the 68 patients were disease-free after treatment. Of the 69 patients with follicular thyroid carcinoma, 58 were categorized as stage IV at the time of diagnosis. Six of the patients were categorized as clinical stage I carcinoma, 2 as stage II, and 3 as stage III at the time of diagnosis; all of these patients deteriorated to stage IV during the follow-up period. Of the 42 patients with follicular thyroid carcinoma involving bone, 24 presented with bone metastases during the initial diagnosis. After treatment, 25 of 69 patients with follicular carcinoma died of follicular carcinoma. Only 3 patients were disease-free after the treatment. In patients with follicular carcinoma, only tumor size was an important prognostic factor. In this study, 8 patients categorized as clinical stages I to III at the time of operation had thyroglobulin (Tg) levels less than 5 ng/mL and developed distant metastases during the follow-up period. In conclusion, at diagnosis a large group of Asian patients with metastatic well-differentiated thyroid cancer was more likely to have follicular than papillary histology, and that, as expected, metastases from follicular cancer were present earlier and more frequently, were more likely to involve bone, were more likely to be associated with mortality, and were linked to tumor size but not gender. Also unlike some other reports, treatment producing a low Tg did not always produce a good outcome. More aggressive surgical procedures may be able to improve outcomes.     

Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy

AIM: The goal of this study was to estimate the cumulative activity of (131)I to be administered to patients with distant metastases from thyroid carcinoma. METHODS: A total of 444 patients were treated from 1953-1994 for distant metastases from papillary and follicular thyroid carcinoma: 223 had lung metastases only, 115 had bone metastases only, 82 had both lung and bone metastases, and 24 had metastases at other sites. Treatment consisted of the administration of 3.7 GBq (100 mCi) (131)I after withdrawal of thyroid hormone treatment, every 3-9 months during the first 2 yr and then once a year until the disappearance of any metastatic uptake. Thyroxine treatment was given at suppressive doses between (131)I treatment courses. RESULTS: Negative imaging studies (negative total body (131)I scans and conventional radiographs) were attained in 43% of the 295 patients with (131)I uptake; more frequently in those who were younger, had well-differentiated tumors, and had a limited extent of disease. Most negative studies (96%) were obtained after the administration of 3.7-22 GBq (100-600 mCi). Almost half of negative studies were obtained more than 5 yr after the initiation of the treatment of metastases. Among patients who achieved a negative study, only 7% experienced a subsequent tumor recurrence. Overall survival at 10 yr after initiation of (131)I treatment was 92% in patients who achieved a negative study and 19% in those who did not. CONCLUSION: (131)I treatment is highly effective in younger patients with (131)I uptake and with small metastases. They should be treated until the disappearance of any uptake or until a cumulative activity of 22 GBq has been administered. In the other patients, other treatment modalities should be used when tumor progression has been documented.     

Intraocular and orbital metastasis as a rare form of clinical presentation of insular thyroid cancer

Insular carcinoma of thyroid is a rare tumor, which accounts for 4 to 6% of thyroid malignancies. Clinically and morphologically it is considered to be in an intermediate position between well-differentiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. Capsular and blood vessel invasion is seen frequently, and metastases to regional lymph nodes, lungs and bones are common. The initial presentation of distant metastasis in patients with thyroid cancer is rare. Thus metastatic thyroid carcinoma rarely involves the orbit. We report a rare case of choroidal metastasis from insular thyroid carcinoma.     

Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients.

Total (or near-total) thyroidectomy (TT) is considered by many as the most adequate treatment for papillary thyroid carcinoma (PTC). In patients who have undergone lobectomy, the necessity of performing a completion thyroidectomy (CT) is still discussed. The aim of this retrospective study was to evaluate tumor bilaterality in patients initially treated with partial thyroidectomy for PTC and who then underwent CT. We studied 182 patients treated with CT after lobectomy and/or isthmectomy for PTC diagnosed from 1969-1998. Mean age at diagnosis was 40+/-14.5 years and mean interval between partial thyroidectomy and CT was 19.8+/-56.8 months. At CT, 80 of 182 patients (44%) had one or more foci of tumor in the remaining thyroid lobe, always of the same papillary histotype, associated with ipsilateral lymph node metastases in 22 cases. In addition, 10 patients with no tumoral foci in the thyroid specimen had evidence of lymph node metastases. The rate of bilateral tumor was not different when patients were analyzed according to the classification of "low-" or "high-risk." Among several clinical features, the presence of lymph node metastases at the first surgical treatment and time interval between first treatment and CT were correlated with higher frequency of bilaterality (p = 0.033 and p = 0.044, respectively). The postsurgical 131I whole-body scan revealed the presence of persistent lymph node metastases or diffuse micronodular lung metastases in 7 and 6 patients, respectively. In conclusion, PTC was frequently bilateral in our series and this bilaterality was independent from the "low-" or "high-risk" classification. On these bases, we believe that PTC should be treated with TT when diagnosed before surgery and submitted to CT, if partial surgery was the initial intervention.     

Sequential and/or concurrent hypofractionated radiotherapy and concurrent chemotherapy in neoadjuvant treatment of advanced adenocarcinoma of the pancreas. Outcome and patterns of failure

BACKGROUND/AIMS: To investigate treatment outcome and patterns of failure of sequential chemotherapy (CHT) and/or concurrent hypofractionated radiotherapy (RT) and CHT followed by surgery in locally advanced non-metastatic pancreatic adenocarcinoma. METHODOLOGY: Seven patients with locally advanced but marginal resectable tumors (close contact but no signs of infiltration of the mesenteric vessels and/or vena portae) were treated with hypofractionated RT (5x3 Gy per week) and concurrent continuous infusion (300 mg/sqm/24 h, 7 days per week) of 5-fluorouracil (FU). Ten patients with locally advanced disease with radiologically suspected infiltration of the mesenteric vessels and/or v. portae were treated with 2 cycles of Cisplatin (75 mg/sqm) and Gemcitabine (2x1250 mg/sqm), and patients without tumor progression received the same concurrent RT/CHT as group 1. Four weeks after RT/CHT radical pancreatectomy was planned for patients with stable disease or remission. RESULTS: Toxicity was low in both groups, with no CTC grade 4 toxicity. In group 1, RT/CHT was completed in all patients. There was no radiological remission, but stable disease in 5 out of 7 patients. All 5 patients underwent resection of the primary tumor with a R0-resection in 3 patients. In group 2, 8 patients completed CHT and RT/CHT treatment as planned. There were 3 with partial remission. Operation was done in 4 patients, but only one R0 resection was achieved. The median survival time for all 17 patients is 13 months, with 1- and 2-year survival being 53% and 18%, respectively. Local progression was observed in 9, peritoneal seeding in 7 and distant metastasis (mostly liver and lung) in 8 patients. CONCLUSIONS: The neoadjuvant therapy could be administered with low toxicity. Results of this study warrant further investigation aiming at optimal tailoring in of this treatment approach in these two subgroups of patients.     

Long‐term follow‐up of patients with bone metastases from differentiated thyroid carcinoma – surgery or conventional therapy?

OBJECTIVE: Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival. PATIENTS AND DESIGN: We analysed 41 consecutive patients with bone metastases from differentiated thyroid carcinoma who had undergone thyroid surgery at Vienna University Hospital since 1966. The median follow-up time was 12 years. There were 24 females and 17 males with a mean age of 60 +/- 12 years. Primary tumour histology was follicular in 35 and papillary in six patients. Radioiodine treatment was performed in 32 with a mean administered activity of 27 +/- 24 GBq 131I. Metastases restricted to the skeleton were found in 22 whereas in 19 individuals additional extraskeletal distant metastases were seen. Twenty-seven patients had multiple bone metastases. In 21 individuals, up to five bone metastases were surgically removed with the intention of cure. RESULTS: Univariate analysis identified total thyroidectomy (P = 0.003), lymph node surgery (P = 0.001), radioiodine therapy (P = 0.036), and the absence of extraskeletal distant metastases (P = 0.017) as significant predictors of survival. Multivariate analysis failed to identify significant prognostic factors. In the subgroup of patients with distant metastases limited to the bones, univariate analysis identified, in addition to thyroid and lymph node surgery, the surgical extirpation of the bone metastases as a significant prognostic factor associated with improved survival (P = 0.025). CONCLUSIONS: These findings indicate that in patients without additional extraskeletal distant metastases, the radical surgical extirpation of bone metastases from differentiated thyroid carcinoma might be associated with improved survival.     

The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland

Background: Distant metastases at presentation are rare in well-differentiated thyroid cancer (WDTC). The objective of this study was to report outcomes for patients presenting with distant metastases managed by thyroidectomy and radioactive iodine (RAI) therapy. Methods: Fifty-two patients with distant metastases from thyroid cancer diagnosed before thyroid surgery (n=32) or on a postoperative RAI scan after thyroid surgery (n=20) were identified from a database of patients with WDTC treated between 1985 and 2005. The median age was 58 years (range 12-83 years), with a male-to-female ratio of 3:2. Forty-seven patients (90%) had total thyroidectomy and two (4%) had thyroid lobectomy, and three patients (6%) were found to be unresectable. Distant metastases were classified into pulmonary and extrapulmonary. Overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival were calculated by the Kaplan-Meier method. Factors predictive of the outcome were determined by univariate and multivariate analyses. Results: Thirty-nine patients (75%) were diagnosed with pulmonary metastases alone and 13 (25%) with extrapulmonary metastases. The sites of extrapulmonary metastases were bone in nine, mediastinum in one, pyriform sinus in one and skin in one, and one patient had synchronous lung, bone, and intracerebral metastases. After thyroid surgery, 47 patients (90%) were treated with RAI alone, and 2 patients had external beam radiation in addition to RAI. With a median follow-up after surgery of 78.5 months, the 5-year OS and DSS were 65% and 68%, respectively. Twenty-nine patients (56%) died during follow-up, of whom 24 (46%) died of thyroid cancer. Six patients (12%) developed recurrent disease in the lateral neck, and three patients (6%) developed recurrence in the thyroid bed. Over 45 years, follicular pathology and extrapulmonary metastases were predictive of lower 5-year DSS (56% vs. 100%, p<0.001; 50% vs. 70%, p=0.004; and 46% vs. 75%, p=0.013, respectively). Conclusion: Approximately half of patients with WDTC presenting with distant metastases die of disease within 5 years of initial diagnosis despite thyroid surgery and RAI. Age over 45 years, extrapulmonary metastases, and follicular pathology were significant predictors of the poor outcome.     

Distant and lymph node metastases of thyroid nodules with no pathological evidence of malignancy: a limitation of pathological examination

Among thyroid nodules arising from follicular cells, benign nodular goiter is thought not to metastasize to regional or distant organs. However, we encountered five cases that were pathologically diagnosed as benign nodular goiter but showed metastasis. The prevalence of benign nodular goiter showing metastasis was 0.17% (5 of 2978 patients). On pathology, there were no detectable signs of carcinoma or follicular adenoma lesions. Two patients showed lymph node metastasis that was pathologically confirmed as metastasis of nodular goiter. One was preoperatively and another was postoperatively detected by ultrasonography. These patients also showed distant metastases that could be ablated by radioiodine. One patient preoperatively showed lung metastasis and the remaining two showed lung and bone metastases and bone metastasis postoperatively. Pathological diagnosis of thyroid nodules has limitations, and cases diagnosed as benign nodular goiter should still undergo careful follow-up.     

Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables

From a cohort of 988 patients with differentiated thyroid carcinoma receiving primary surgical treatment between 1946 and 1970, we studied the 85 (9%) patients who had distant metastases diagnosed during life. Clinically detected metastases were found in 7% of the 859 patients with papillary cancers, 19% of the 100 patients with follicular cancers, and 34% of the 29 patients with Hürthle cell cancers. The total experience amounted to 607 patient-years of observation after the diagnosis of metastases, with a median follow-up in the 12 survivors of 23 yr (range, 13-32 yr). At the time of first diagnosis of metastases, the lungs only were involved in 53%, and bones only in 20%; 16% had multiple organ involvement. The overall mortality rates 5 and 10 yr after the diagnosis of metastases were 65% and 75%, respectively. Seventy-eight percent of all deaths were directly attributable to thyroid cancer; 82% of cancer deaths occurred within 5 yr. By univariate analysis, patient age, tumor extent, pattern of lung involvement, radioiodine uptake of the metastases, and radioiodine treatment were significant prognostic factors. By multivariate analysis, only age (as a continuous variable) at the time of first diagnosis of distant metastases (P less than 0.0001) and involvement of multiple organ sites (P = 0.0003) were independently associated with cancer mortality. The survival at 5 yr in 12 patients aged less than 40 yr with only a single organ involved was 92%. Older patients (aged greater than or equal to 40 yr) with a single metastasis (n = 59) had a lower survival (38% at 5 yr). The highest risk of cancer death (92% at 5 yr) was found in the 14 patients (any age) who at the time of first diagnosis of metastases had multiple organ involvement. The Cox regression model suggested that radioiodine therapy did not have a significant influence on survival, after adjusting for age and extent of metastatic involvement.     

Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases

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.     

Pancreatic metastasis of papillary thyroid carcinoma preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report with review of literatures

Pancreatic metastatic tumors from thyroid carcinoma are extremely rare. We report a case of an 80-year-old female with a pancreatic metastatic tumor derived from papillary thyroid carcinoma which was initially resected 158 months prior to detection of the metastatic pancreatic tumor. The patient has encountered cervical lymph-node metastasis on three occasions following the initial operation. Metastatic pancreatic lesions and cervical lymph nodes were first detected using 18-fluorodeoxyglucose positron-emission tomography/computed tomography, and she was preoperatively diagnosed using endoscopic ultrasound-guided fine-needle aspiration biopsy. A coin lesion, 10 mm in size, was detected in the left lung by chest computed tomography with no abnormal uptake in 18-fluorodeoxyglucose positron-emission tomography/computed tomography. Distal pancreatectomy and cervical lymph-node dissection were performed. Adjuvant chemotherapy with weekly paclitaxel was administered because anaplastic transformation had been detected in one of the cervical lymph nodes. The patient eventually died from multiple lung metastases 11 months after removing the metastatic pancreatic lesion. We reported a rare case of a pancreatic metastatic tumor from thyroid carcinoma, and found that 18-fluorodeoxyglucose positron-emission tomography/computed tomography and endoscopic ultrasound-guided fine-needle aspiration biopsy are useful for preoperatively diagnosing tumors.     

Anaplastic thyroid carcinoma in a 49 year-old woman with a long-standing goiter. A case report

A 49 year-old woman with anaplastic thyroid carcinoma came, for the first time, to our clinic with an enlarged supraclavicular lymph node. Ten years earlier she received a diagnosis of benign nodular goiter and has been followed up with ultrasonography, which never demonstrated any enlargement of her thyroid nodule and with fine needle aspiration biopsies (FNAB), that always proved normal. An ultrasonographic control, performed 10 months before diagnosis, showed the onset of a shell calcification all around the thyroid nodule that forbade the performance of FNAB. At initial examination in our endocrinology centre she was found to have an enlarged thyroid nodule (changing from 3.5 cm to 4.5 cm) and a supraclavicular lymph node 3 cm wide. The patient was therefore sent to the surgeon who performed a total thyroidectomy and a lymph node exenteration. The histological examination reported a thyroid anaplastic carcinoma, composed of osteoclast-like cells and large calcifications, which showed signs of local invasion and vessel infiltration; the supraclavicular lymph node proved to be a large metastasis of anaplastic thyroid cancer. Total body CT scan, bone scintigraphy and brain CT scan showed, respectively, lung, bone and brain metastasis. Postoperative chemotherapy was rapidly interrupted for acute toxicity. The patient died for lung, bone and brain metastasis, 2 months after initial examination.     

Direct esophageal metastasis from a distant primary tumor is a submucosal process: a review of six cases

Malignant esophageal stricture secondary to invasion from a tumor arising in a contiguous organ is a relatively rare finding; even more uncommon is a direct metastasis to the esophagus from a distant primary carcinoma. We present six cases, the largest current series, of esophageal strictures secondary to metastases from a separate primary cancer. We reviewed the records of 20 patients treated at Virginia Mason Medical Center between 1972 and 2000 with a diagnosis of malignant esophageal stricture secondary to an extraesophageal primary carcinoma. Patients whose stricture appeared to be secondary to esophageal invasion or compression from a contiguous tumor or lymph nodes were excluded. The remaining six patients who had metastases to the esophagus itself were reviewed with respect to the nature of the primary tumor, presentation, radiologic and endoscopic findings, and treatment. Among the 20 patients reviewed, 14 were excluded owing to either contiguous involvement from a nearby primary malignancy, regional nodal involvement, or complications of external beam radiation treatment. Six patients were considered to have direct metastasis to the esophagus from distant primary malignancies. The mean age of these patients was 72 years (range 68-74). Two of the primary lesions were lung carcinoma, while four primaries were breast cancers. The average time interval from the diagnosis of a primary tumor to esophageal involvement was 7 years in patients with breast cancer and 5 months in patients with lung cancer. Three patients were palliated with endoscopic dilation and stent placement. The other three patients have died secondary to upper gastrointestinal bleeding. Metastatic cancer to the esophagus is a rare occurrence. The process is usually submucosal and can be difficult to diagnose. The diagnosis should be considered when a patient presents with malignant dysphagia and has a background of distant carcinoma.     

Primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma of the adult: sequential intensive treatment with the F-MACHOP regimen (+/- radiotherapy) and autologous bone marrow transplantation

Few series of adult patients with primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma (ALCL) are reported in the literature; most of them have been treated with combination chemotherapy (CHT), with only an occasional patient being autotransplanted, mainly after relapsing. The remission rate ranges from 60% to 90%, but relapses are frequent (up to 60%) and precocious (mainly in the first 24 months). The aim of our study was to analyze the outcome of a series of adult patients affected by primary systemic ALCL that were treated at our institution with a sequential intensive therapeutic program including CHT, radiotherapy (RT), and autologous bone marrow transplantation (ABMT). Sixteen consecutive, unselected patients with ALCL were identified. All of them were treated with the 5-fluorouracil, methotrexate, cytosine arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) regimen; 9 of 16 (56.2%) reached a complete remission (CR). In six cases with residual mediastinal disease, involved-field RT was performed, allowing three additional patients to become free of disease. All 16 were then autotransplanted with bone marrow stem cells after conditioning with the cytosine arabinoside, etoposide, cyclophasphamide, and carmustine (BAVC) regimen. A present, 16 of 16 patients are alive and in CR. The actuarial overall survival is 100% at a median of 45.5 months, and the actuarial disease-free survival is 100% at a median of 33.5 months. These data suggest that ALCL can be successfully managed with a sequential intensive treatment (CHT +/- RT + ABMT) that prevents early relapses and projects these patients as long-term survivors.     

Clinical manifestations and diagnosis of distant metastases of differentiated thyroid carcinoma after initial therapy

We studied 58 patients with distant metastases of differentiated thyroid carcinoma diagnosed after initial therapy. Lymph node metastases were observed in 65% of the patients on initial presentation. All lymph node metastases, ninety percent of the lung metastases and only 25% of the bone metastases were asymptomatic. Radiography revealed lytic metastases in cases of bone involvement, was normal in 39.6% of the patients, and showed micrometastases in 34.5% and macrometastases in 25.8% of the patients with lung disease. Thyroglobulin (Tg) under thyroxine use was detectable in all patients without antibodies at a cut-off > 1 ng/ml, in 90% at > 5 ng/ml and in 80% at > 10 ng/ml, and after thyroxine withdrawal in 100% at a cut-off > 5 ng/ml and in 94% at > 10 ng/ml. In the case of patients with antibodies (13.8%), Tg was undetectable in half of them. Diagnostic scanning was positive in 83 and 77.6% of the patients with bone and lung metastases, respectively. After ablative therapy, the sensitivity was 100 and 93%, respectively. Eighty-five percent of patients with a negative diagnostic scan had lung metastases visible on radiographs. The determination of serum Tg is the best method in the follow-up of patients with differentiated thyroid cancer. Elevated Tg levels suggest the presence of metastases, indicating the need for ablative therapy with posttreatment scanning, which might reveal non-apparent metastases.