Pathologic staging of papillary carcinoma of the thyroid with airway invasion based on the anatomic manner of extension to the trachea: a clinicopathologic study based on 22 patients who underwent thyroidectomy and airway resection

We received the clinical and pathologic features of 22 cases of papillary carcinoma of the thyroid that invaded the trachea and were treated by thyroidectomy and airway resection with or without reconstructive surgery over an interval of 16 years. We studied the fine relationships between lamina propria and lymphatics in the region between the isthmus of the thyroid and the trachea. The manner of invasion of papillary carcinoma of the thyroid was by blunt dissection along blood vessels and collagen fibers oriented perpendicularly to the tracheal lumen between cartilaginous rings. Although lymph node metastases were found in 14 patients (64%), we observed lymphangitic tumor in the tracheal mucosa in only three patients (14%). We devised a staging system for papillary carcinoma of the thyroid based on the extent of invasion of the trachea. Of the 11 patients with stage I, II, or III disease, none of six (0%) followed for 5 years died of thyroid cancer in the 5-year observation period; one patient in this group died later of thyroid cancer. Of the 11 patients with stage IV disease, five of seven (71%) followed for 5 years died of thyroid cancer in the 5-year observation period; one additional patient in this group died later of thyroid cancer.     

Structure-function studies on the inhibition of binding of alpha-thrombin to platelet GpIb alpha by the peptide D-Y-Y-P-E and the artifactual inhibitory activity of C-terminal E in this peptide

In papillary thyroid carcinoma lymphnode metastases at presentation do not seem to adversely affect survival, but do increase the risk of loco-regional tumor recurrence. The value of systematic versus selective lymphadenectomy is far less standardized, whereas the role of postoperative radioiodine in preventing either nodal recurrence or cancer death remains controversial. Clinical data of 36 N+ patients with papillary thyroid carcinoma who had undergone from 1990 to 1996 ipsilateral or bilateral neck dissection were retrospectively reviewed, to analyse the value of systematic lymphadenectomy. In our series of 50 extensive lymph node dissections (levels 2-6), the number of metastases in each specimen (mean value: 5) and the incidence of multiple level metastases (36%) were high. In 37.5% of the metastases at level 6 and in 11.1% at level 4, coexisting nodal involvement at level 2 was observed, without metastasization at intermediate levels. Multiple levels metastases and skip metastases were present in at least one third of the patients and could be excised only performing a complete dissection of the levels 2-6. Extra-capsular spread was found in 56% of the specimens. In 64.3% of these cases a functional neck dissection was performed. A modified radical or radical neck dissection was carried out in the other 35.7% of the cases. These patients received modified radical neck dissection (functional dissection with sacrifice of internal jugular vein) in 60% of the cases and radical neck dissection in the other 40%. In papillary thyroid carcinoma extensive lymphnode dissection at presentation has been stated to offer no advantage versus selective lymphadenectomy, causing increased morbidity. However, experienced surgeons report a low incidence (less than 5%) of accessory spinal nerve and cervical plexus permanent sequelae after functional neck dissection. In our opinion, patients with cervical lymph node metastases require a complete loco-regional neck dissection. Systematic lymphadenectomy, performed by lateral neck plus upper anterior mediastinal dissection, can yield a high disease-free survival. Moreover, this can limit the overall radio-iodine therapeutic dose and the risk of de-differentiation of recurrent tumor to the anaplastic type in patients with a long-term and near normal life-span.     

Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma

Records of 792 patients with differentiated thyroid carcinoma seen at the Lahey Clinic Foundation over a 40-year period were analyzed; 631 patients had a minimum followup period of 15 years. Differentiated types currently constitute nearly 90% of thyroid carcinomas. The clinical presentation has improved substantially through the years, and the results of treatment generally have improved. The per cent of patients with primarily incurable and locally unresectable disease or distant metastases has decreased from 7% before 1950 to 1% currently, and this group resulted in almost one third of the total fatalities and one half of fatalities within the first 5 years after treatment. Clear relationships were demonstrated between older age, men, extraglandular extension, blood vessel invasion, major capsular involvement, multifocal disease, and higher mortality rates. Lymph node metastases were found to exert a protective effect in all categories of disease analyzed, and this effect was directly related to the number of lymph node metastases present such that no deaths occurred in those patients who had more than 10 node metastases. Surgical treatment recommended is subtotal thyroidectomy for patients at high risk of death from disease as defined by combinations of age, sex, and extraglandular extension. Patients at low risk or with small carcinomas can be treated satisfactorily by lobectomy. Lymph node resections should be of a limited type or a modified neck dissection and should be performed only therapeutically. No improvement, as judged by mortality or recurrence rates, could be demonstrated by the use of radio therapy after surgery, and its use should be discouraged. Thyroid hormone administered for suppression of endogenous thyroid-stimulating hormone production improved mortality rates significantly in patients with papillary and mixed forms of carcinoma in all age groups but did not affect survival in patients with follicular carcinoma of the thyroid.20     

Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells

OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hürthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P < .05). A higher incidence of malignancy was found in males, but the data did not reach statistical significance (P = .0586). CONCLUSION: Most of the follicular neoplasms revealed by FNAC were benign lesions. Low echo density on ultrasonography and male sex carried a higher risk of malignancy.     

Thyroid carcinoma after high-dose external radiotherapy for Hodgkin's disease: report of three cases

Three patients (two female and one male), who had received mantle irradiation for Hodgkin's disease eight, ten, and twelve years previously, developed papillary thyroid carcinoma. The radiation doses to the necks overlying the site of thyroid cancers were 3000, 4000, and 4100 rads, respectively. It has been stated that there is no risk of developing thyroid cancer with such high doses of external irradiation but apparently this complication will be encountered in a small number of patients.     

Extracapsular invasion of lymph node metastasis is an indicator of distant metastasis and poor prognosis in patients with thyroid papillary carcinoma

BACKGROUND: In patients with thyroid papillary carcinoma, age and the presence or absence of distant metastasis are regarded as the main prognostic factors. However, the histologic characteristics of thyroid papillary carcinoma that develops distant metastasis have not yet been clarified. METHODS: The histologic findings and prognosis of 50 patients with thyroid papillary carcinoma who later developed distant metastasis (metastatic group) were compared with those of 50 patients without local recurrence or distant metastasis (control group). The age, tumor size, and gender ratio of the control group were matched with those of the metastatic group. Univariate analyses (chi-square test and/or Fisher's exact test) and multivariate analyses (logistic regression) were performed. RESULTS: Univariate analyses showed that the incidence of nonpure papillary carcinoma, absence of bone at the periphery of the tumor, invasion of the perithyroidal muscle, large lymph node deposits, and extranodal invasion were significantly higher in the metastatic group. Multivariate analyses revealed that only extranodal invasion was statistically significant (P = 0.0045) and that the odds ratio of extranodal invasion in distant metastasis was 9. Moreover, the risk of death from thyroid carcinoma was higher among the patients with extranodal invasion than those without (P <0.01). CONCLUSIONS: The presence of extranodal invasion in patients with thyroid papillary carcinoma is an indicator of distant metastasis and poorer prognosis.     

Hyperthyroidism and carcinoma of the thyroid gland

The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a few tumors are suspected preoperatively with ultrasonography or fine needle aspiration or 131 I scan. In 408 patients who underwent surgery for hyperthyroidism in our Surgery Department from January 1967 through December 1994 the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.     

A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns

BACKGROUND: The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on Cancer programs, the NCDB offers a working example of voluntary, accurate, cost-effective "outcomes management" on a both a local and national scale. In addition, it is of particular value in capturing clinical information concerning rare cancers, such as those of the thyroid. METHODS: For the accession years 1985-1995, NCDB captured demographic, patterns-of-care, stage, treatment, and outcome information for a convenience sample of 53,856 thyroid carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition) stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma. Care patterns also are discussed. RESULTS: The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC staging failed to discriminate between patients with Stage I and II disease at 5 years. Total thyroidectomy +/- lymph node sampling/dissection represented the dominant method of surgical treatment rendered to patients with papillary and follicular neoplasms. Approximately 38% of such patients receive adjuvant iodine-131 ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more extensive surgery) failed to translate into compelling differences in survival for any subgroup with papillary or follicular carcinoma, but longer follow-up is required to evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied to papillary cases. Younger age appeared to influence prognosis favorably for all thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma. NCDB data also revealed that unusual patients diagnosed with undifferentiated/anaplastic carcinoma before age of 45 years have better survival. CONCLUSIONS: The NCDB system permits analysis of care patterns and survival for large numbers of contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care, evaluating prognostic models, generating new hypotheses, and overcoming the volume-related drawbacks inherent in the study of such neoplasms. [See editorial on pages 2434-6, this issue.]     

The relevance of somatostatin receptors in thyroid neoplasia

111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).     

Changes in specific markers of haemostasis during reduction mammoplasty

We herein report a case of pure clear cell papillary thyroid carcinoma, which is the first reported case in Japan. The tumors measured 1.0 x 0.9 and 0.7 x 0.4 cm in size. An ultrasonographical examination revealed hypoechoic irregular-shaped lesions with fine internal calcifications. No lymph node metastasis was observed in any of the surgical specimens. Distant metastasis had not been observed as of 6 years after surgical treatment. The number of cases of pure clear cell papillary carcinoma reported so far are too few to clearly elucidate its characteristics; however, the ultrasonographical findings and biological behavior of this case were compatible with those of non-clear cell papillary thyroid carcinoma.     

Papillary thyroid carcinoma: justification for total thyroidectomy and management of lymph node metastases

Papillary thyroid carcinoma (PTC) is the most common epithelial thyroid tumor and comprises approximately 80% of all thyroid cancers. In this article, the authors discuss the data showing that total thyroidectomy is the treatment of choice of clinically significant PTC, and review an algorithm for the management of lymph node metastases. Although the prognosis for patients with PTC is generally good, appropriate surgical management (total thyroidectomy plus 131I and life-long TSH suppression) can further reduce recurrence and cancer death rates significantly.     

Presumption of primary sites of neck lymph node metastases on fine needle aspiration cytology

OBJECTIVES: To evaluate the accuracy of presumption of the primary sites of neck lymph node metastases based on fine needle aspiration cytology. STUDY DESIGN: Retrospective review of 133 cytologically diagnosed carcinomas with known primary sites and sufficient cellularity during a three-year period. Presumption of primary sites was carried out on randomized samples six months later. RESULTS: Some cytomorphologic characteristics are useful for presumption of primary sites, such as monolayered papillary fronds with intranuclear cytoplasmic inclusions in thyroid papillary carcinoma; large, polygonal, keratinized cells with a low nuclear/cytoplasmic ratio and anucleated squames in perioral cancers; and numerous naked nuclei, destroyed nuclei and marked lymphocytic infiltrates in nasopharyngeal cancer. The accuracy rate of presumption of primary sites was 100% (6/6) in thyroid papillary carcinoma, 83% (24/29) in perioral cancer and 77% (26/34) in nasopharyngeal cancer but low in other malignancies. CONCLUSION: Utilizing cytomorphologic characteristics, a presumption of primary sites of neck lymph node metastases could be achieved for the thyroid, perioral areas and nasopharynx.     

A neural network that predicts psychiatric length of stay

One hundred and twelve bilateral thyroidectomies for solitary thyroid nodules with suspected malignancy were performed. The incidence of malignancy in the 112 primary nodules was 42%. Twenty-nine of the 112 contralateral lobes (26%) contained malignancy, which was unsuspected in 80%. Of these 29, 20 were foci of papillary cancer < or = 5 mm and 9 were larger papillary tumors or follicular carcinoma. We analyzed these 112 patients to determine whether there was a simple method to identify those patients at risk for contralateral, unsuspected malignancy. With use of the AMES clinical staging retrospectively, 70 of the 112 patients were classified as having low-stage disease. Fifty percent (35) had cancers on the primary side and 27% (19) on the contralateral side. Of these 19 contralateral cancers, 14 were papillary cancers < or = 5 mm, 4 were papillary cancer > 5 mm and one was a 1.5 cm follicular carcinoma, a similar distribution as in the whole group of 112. When the AMES analysis then excluded those thought to be at risk for multicentricity or papillary carcinoma and examined female patients only with nonpapillary frozen sections, nonpapillary aspiration cytological results, and no history of radiation exposure, no further reduction in the proportion of contralateral cancers (7 of 26, 27%) was found. Fifty-five of the 112 patients underwent preoperative ultrasound scans. In those cases in whom the contralateral lobe had no intraoperative palpable or preoperative sonographic mass, 5 of 20 still had contralateral cancers, but all were papillary < or = 5 mm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metastatic papillary thyroid carcinoma presenting as a typical branchial cyst

Two cases of papillary thryoid carcinoma presenting as a cystic lateral neck mass are reported. This tumour characteristically presents in patients under 40-years-old and in the presence of an occult primary tumour may mimic a branchial cyst. In such cases simple aspiration of the cyst will produce a chocolate-brown serous fluid which excludes the diagnosis of a branchial cyst and is characteristic of papillary thyroid carcinoma. Cytological examination of the fluid has a high degree of sensitivity and specificity in the diagnosis of thyroid malignancy and should avoid delay in diagnosis and unnecessary surgical exploration prior to definitive treatment.     

Myelinated axon undergoes complete demyelination in the panencephalopathic--but it is merely subjected to the Wallerian degeneration in the polioencephalopathic type of transmissible spongiform encephalopathies

The aim of a cancer registry is to study the incidence of cancer in a well-determined population and to allow epidemiological research to the setting up of diagnosis and therapeutic strategies. The Belgian Thyroid Cancer Study Group (BTCSG) was founded in 1990. In the present study we report data collected from 1988 to 1995 in 397 patients with a differentiated (papillary and follicular) thyroid carcinoma living in the french-speaking area of Belgium. The sex ratio female/male is 3.5 and the median ages at the diagnosis, is similar (45 yrs, 12-82) in both sexes. Seven cases of thyroid cancer were registered in young patients less than 18 yrs old. Thyroid carcinoma were associated with multinodular goiter in more than 50% cases. Cancer was bilateral in 17%. Papillary histological type accounts for 84% in our series while its diagnosis was established in 45% at early clinical stages (TO-T1). These observations could probably be related with 1) broader indications and more aggressive options for the surgical removal of diffuse multinodular goiter, 2) more sophisticated pathologic examinations that might have led to the detection of a greater incidence of occult carcinomas, incidentally discovered. Lymph nodes metastases were present at the time of diagnosis in 20%, especially in young patients. The risk for local and/or lateral recurrence or distant metastases is significantly related to the size of the tumor, histologically verified lymph node metastases and the values of the EORTC prognostic index (> or = 50) that additionally takes into account the differentiation of the tumor. Considering our short median follow-up time of 25 months, it is currently too early to define if the controversial attitude about the extent of surgery (total thyroidectomy plus I131 or individualized surgery) can also negatively influence the risk for recurrence. In our series, eight patients died of thyroid cancer.     

Thyroid carcinoma in hyperthyroid syndromes

The relationship between hyperthyroidism and carcinoma of the thyroid is still uncertain. The incidence of thyroid carcinoma ranges from 0.3 to 16.6%. Between 1984 and 1994 the Authors observed 9 patients affected with thyroid cancer and toxic nodular goiter (4 patients) or Basedow disease (2 patients) or scintigraphic evidence of single hyperfunctioning nodule (3 patients). Six out of the 9 cases were diagnosed as papillary cancer, while three as follicular cancer. A carcinoma was diagnosed before operation in only one case, while in the other 8 patients, the diagnosis was obtained by histological examination of the specimen. Four patients underwent subtotal thyroidectomy, while five patients underwent radical lobectomy. All patients are alive and in good health; the average follow-up was 48 months.     

Prevalence and significance of lymphocyte infiltration in papillary carcinoma of the thyroid gland

OBJECTIVE: We have investigated the prevalence, signification and prognostic value of lymphocytic infiltration associated to differentiated thyroid carcinoma in our series of differentiated carcinoma of the thyroid. METHODS: We studied the presence of lymphocytic infiltration in 223 patients effected of differentiated thyroid carcinoma, 138 of them were papillary carcinoma. The diagnostic was made with optic microscopy and we studied antithyroid antibodies in these patients. In survival analysis we studied all the variables of the patients and the event used as end point was death due to thyroid carcinoma, summarized in Kaplan-Meir curve and Cox method. RESULTS: We found eight patients with differentiated thyroid carcinoma, six with papillary carcinoma, and lymphocytic thyroiditis and in three cases, antithyroid antibodies were present at low levels. We did not found any difference between the two groups and the survival rate was similar. CONCLUSIONS: These data support that in our series the prevalence of lymphocytic infiltration was low and probably without prognostic signification.     

Occult papillary carcinoma of the thyroid with pulmonary metastases

This case report describes an occult papillary adenocarcinoma of the thyroid with pulmonary metastases, discovered at autopsy. Since papillary adenocarcinoma of the thyroid usually invades adjacent structures and cervical lymph nodes in a predictable fashion, the finding of distant hematogenous spread, when the tumor is confined to the thyroid gland, is unusual, as is illustrated by a review of the literature. The patient's history included a poorly differentiated squamous cell carcinoma of the lung, which had been resected 15 years prior to death and had been followed by super-voltage radiation. The possible effects of super-voltage radiation on the pathogenesis and behavior of thyroid cancer are discussed.     

Determination of skeletal age using the Oxford Score in children with epiphyseolysis of the femur head

Differentiated thyroid carcinoma often has a favourable prognosis. However, there is no unanimity about the surgical procedure used. In this analysis we evaluated the surgical complications of 178 patients operated on for differentiated thyroid carcinoma during a 12-year period. 110 of the patients were operated in one session and 68 in two. Total thyroidectomy was performed in 106 patients and ipsilateral lobectomy together with contralateral subtotal resection in 72 patients. Tumour was bilateral or multicentric in 59 patients (33%). Hypoparathyroidism occurred in eight patients (4%), without differences between total thyroidectomies and lobectomy plus subtotal resections. Hypoparathyroidism tended to be more common after completion resection than after completion thyroidectomy (4/28 vs 1/40; P = 0.08). Accidental injury to the recurrent laryngeal nerve occurred in one patient (0.6%) during a contralateral resection. During a median follow-up of 4.5 years, tumour recurrence was detected in 22 patients (12%). In papillary carcinoma it was more common in patients who had underwent lobectomy plus contralateral resection than after total thyroidectomy (11/60 vs 3/88; P < 0.01). However, the median follow-up times were unequal. In conclusion, total thyroidectomy and even completion thyroidectomy is as safe as less radical lobectomy together with contralateral resection. Thus, total thyroidectomy should be offered to all patients with differentiated thyroid carcinoma until there is a reliable method to recommend for those patients who can be treated with less radical procedures.