Surgery of differentiated cancer of the thyroid

A retrospective study on patients with differentiated thyroid carcinoma operated on at the 3rd Department of General Surgery of the University "La Sapienza" of Rome from 1970 to 1996 was performed. In 709 patients total thyroidectomy was performed as the minimal procedure acceptable, while 19 patients had subtotal thyroidectomy out of necessity. A functional ipsilateral or bilateral lymphnectomy of the neck was performed in 256 cases. This wider operation is indicated in the presence of metastatic lymph nodes and on principle in patients older than forty-five years in which at least another risk factor is present. Long term follow-up (12 years) was assured in 302 patients and the survival rate was 92% independently from the histotype (papillary or follicular). The survival rate of a group of 120 patients (80 with papillary and 40 with follicular carcinoma) was analyzed in relation to the risk factors. This group analysis demonstrated a very low mortality rate in patients with low risk index and an increased rate in patients with a high risk index.     

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.     

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.     

Pediatric thyroid cancer after the Chernobyl disaster. Pathomorphologic study of 84 cases (1991-1992) from the Republic of Belarus

BACKGROUND: During the initial period after the Chernobyl accident, large amounts of radioactive iodine were released in fallout, resulting in serious exposure to the thyroid gland in the residents of areas around the nuclear power station. Beginning in 1990, a definite increase in the incidence of thyroid cancer was noted in children of the Republic of Belarus. METHODS: Morphologic and clinical features of 84 cases of post-Chernobyl thyroid carcinoma in Belarussian children from 5 to 14 years of age are reported. The latent period for tumor development was 4-6 years, with a mean of 5.8 years. RESULTS: Papillary carcinoma was found in 83 patients and medullary carcinoma in one. Besides typical papillary carcinoma (14%), solid (34%), follicular (33%), mixed (10%), and diffuse sclerosing (9%) variants were observed. The follow-up period ranged from 8 months to 2.5 years. One patient died, local recurrence developed in 2, and cervical lymph node metastases developed in 10. To date, the incidence of local recurrence or metastatic disease after surgery was significantly higher in patients 5-8 years of age and in residents of areas nearest to the Chernobyl station. CONCLUSIONS: Post-Chernobyl pediatric thyroid carcinoma is characterized by a short latency, a higher proportion of tumors arising in young children, and an almost equal sex ratio. Microscopically, these tumors were usually aggressive, often demonstrating intraglandular tumor dissemination (92%), thyroid capsular and adjacent soft tissue invasion (89%), and cervical lymph node metastases (88%). Papillary carcinoma was diagnosed in 99% of cases, with an unusually high frequency of solid growth patterns. Morphologic changes in nonneoplastic thyroid tissue were present in 90% of the glands, and the most specific findings were vascular changes and perifollicular fibrosis.     

S-100 protein is a differentiation marker in thyroid carcinoma of follicular cell origin: an immunohistochemical study

S-100 protein, a dimer of S-100 alpha and S-100 beta subunits (S-100 alpha and S-100 beta), is widely distributed in human tissue, and several papers describing S-100 protein expression in follicular cells of the thyroid have been published. In the present study, 105 cases of thyroid carcinoma (of which 96 were papillary, four follicular, two undifferentiated, and three medullary) were analyzed immunohistochemically for the expression of S-100 protein, S-100 alpha, S-100 beta, and thyroglobulin. In papillary carcinoma, 188 lesions were studied and classified into well differentiated types (56 papillary, 45 follicular) and poorly differentiated types (41 trabecular, four solid, eight squamoid, three tall, and one insular), because the histological structure of each tumor was heterogeneous. The percentage of lesions which expressed positively for S-100 protein and S-100 alpha, respectively, according to type were: papillary, 96 and 99%; follicular, 96 and 100%; trabecular, 95 and 100%; solid, 50 and 50%; squamoid, 50 and 75%; and tall, 33 and 100%. The insular type was negative for both. For papillary carcinoma, well differentiated lesions showed stronger S-100 alpha expression than poorly differentiated lesions. S-100 alpha expression was weaker in follicular and undifferentiated carcinoma than in papillary carcinoma. Medullary carcinoma also expressed S-100 alpha. S-100 beta was positive in lesions that expressed S-100 alpha strongly. Expression of S-100 protein and S-100 alpha protein correlated with thyroglobulin synthesis in the follicular cells. It was concluded that S-100 protein, mainly S-100 alpha, exists in thyroid follicular cells, that it exists in higher quantity in most of the well differentiated lesions but in lower quantity in poorly differentiated or undifferentiated lesions, and that S-100 protein, especially S-100 alpha, is a differentiation marker in carcinoma of thyroid follicular cell origin.     

The immunohistochemical localization of S100 in the diagnosis of papillary carcinoma of the thyroid

In general, the diagnosis of papillary carcinoma of the thyroid is readily achieved based on a defined aggregate of histopathologic features. A papillary architecture is an important but not pivotal component of the diagnosis. The recognition of classic nuclear features is the essential diagnostic element. However, both the architectural and cytological hallmarks may be encountered in other conditions and produce problems in histopathologic interpretation. A papillary architecture may be encountered in hyperplastic areas of follicular neoplasms, multinodular goiter, and Graves' disease. Moreover, there may be scattered cells within several thyroid lesions that display some of the nuclear characteristics of papillary carcinoma. The distinction of these lesions from papillary carcinoma has important implications for clinical management. Thus, the availability of supportive diagnostic evidence would be helpful. In the authors' experience, the strong expression of S100 is of value in identifying papillary neoplasia and distinguishing it from examples of papillary hyperplasia. It is of supportive but not conclusive use in distinguishing follicular adenoma from the follicular variant of papillary carcinoma. The authors stress that the overwhelming factor in the distinction remains the identification of the nuclear characteristics of a papillary carcinoma. However, the authors have encountered several cases wherein the latter are either focal or absent for reasons addressed previously and have found immunohistochemistry a valuable adjunct to diagnosis. In examining papillary foci within Graves' disease, caution must be exercised; S100 expression is a phenomenon of the hyperplastic, hyperfunctional state.     

Diagnosis of occult thyroid carcinoma by thyroid ultrasonography with fine needle aspiration cytology

OBJECTIVE: To assess the role of ultrasonography and fine needle aspiration cytology (FNAC) in preoperative diagnosis of patients with occult thyroid carcinoma (OTC). STUDY DESIGN: Data on 768 thyroid carcinoma patients receiving primary treatment at Chang Gung Medical Center were retrospectively reviewed. Of these patients, 97 had OTC. To detect small thyroid nodules early and define the characteristics of clinically palpable nodules, thyroid ultrasonography with FNAC were performed on 67 histopathologically proven OTC patients. Analysis for diagnostic value was done for ultrasonography and FNAC. RESULTS: In the 67 patients receiving ultrasonography with FNAC, 23 were preoperatively diagnosed as having papillary thyroid carcinoma and 1 as having follicular carcinoma. The tumor size of these 24 preoperative FNAC-proven OTC was 0.81 +/- 0.23 cm (mean +/- SD). In the remaining patients, 10 presented pictures suspicious for malignancy, with a mean tumor size 0.63 +/- 0.24 cm, and 33 (49.3%) were diagnosed as having benign thyroid lesions in preoperative FNAC. The tumor size in these 33 lesions was 0.58 +/- 0.24 cm. Fifty-seven of the 67 OTC patients received frozen sections. Thirty-eight papillary thyroid carcinomas and four follicular carcinomas were correctly diagnosed on frozen sections. CONCLUSION: Although the rate is not high, high-resolution ultrasonography and FNAC is the best approach to preoperative diagnosis for OTC patients today.     

Immunohistochemical analysis of p27/kip1 expression in thyroid carcinoma

Cyclin-dependent kinase inhibitors, including the protein product of the p27/kip1 gene, play an important role in cell-cycle regulation. Loss of p27 expression was reported in a number of neoplasms and shown to be an independent prognostic factor in colorectal, lung, and breast carcinoma By immunohistochemical analysis, we investigated p27/kip1 expression, using a polyclonal antibody, in a series of 87 benign and malignant thyroid neoplasms. We correlated its expression with the Ki-67 labeling index and other prognostic factors. All of the thyroid neoplasms examined exhibited significantly lower p27 expression than did normal thyroid tissue (P < .001). Poorly differentiated carcinomas had the lowest p27 staining frequency of all carcinomas examined. p27 staining frequency of the papillary carcinomas was significantly lower than that of the follicular carcinomas (P < .001). This difference could not be attributed solely to the inverse correlation between the staining patterns of p27 and Ki-67, which was reported for other neoplasms, because there was no significant difference between the Ki-67 labeling indices of these two groups. The follicular variant of papillary carcinoma had a significantly higher p27 staining frequency (P = .05) than did classical papillary carcinoma. We saw no significant difference in the p27 staining frequencies between minimally and widely invasive follicular carcinomas nor between localized and nonlocalized papillary carcinoma. In summary, the p27 immunostaining pattern of thyroid neoplasms is related to neoplastic transformation and varies according to tumor phenotype. It seems, however, to have limited routine diagnostic or prognostic significance in thyroid neoplasia.     

The dynamics of thyroid diseases in the inhabitants of Kiev and Kiev Province after the accident at the Chernobyl Atomic Electric Power Station

Autoimmune affections of the thyroid gland were found to be on the increase as were Hashimoto's disease and follicular adenoma, as evidenced by a pathomorphic study in surgically removed thyroid glands of 12684 patients over 1984-1993. Rise in the frequency of malignant tumors was moderate. Increase in the incidence of papillary microcarcinoma against the background of another surgical pathology of the thyroid gland may be an unfavourable prognostic sign of further growth of morbidity of clinically manifest forms of carcinoma in Kiev and the Kiev Province.     

The extracellular matrix molecule, laminin, induces purkinje cell dendritic spine proliferation in granule cell depleted cerebellar cultures

Some thyroid neoplasms notoriously cause problems in the histologic diagnosis of their nature (follicular versus papillary for example) or their malignant potential (adenoma versus carcinoma) because of overlapping histologic features. Here, thyroid lesions are presented according to their histologic presentation (vesicular, papillary, trabecular, solid or cystic patterns, fibrosing thyroids and lymphoid infiltrate). For each entity, the most discriminant histologic features are described with emphasis on the diagnostic pitfalls and their histological clues.     

Papillary and follicular thyroid carcinoma metastatic to the skin: a case report and review of the literature

Cutaneous metastases from thyroid cancers are rare. We report the case of an otherwise asymptomatic 81-year-old woman with an enlarging scalp lesion. Her solitary skin metastasis was the presenting feature of thyroid carcinoma. Routine histopathology of the lesion was notable for an atypical clear cell neoplasm. Immunohistochemistry was positive for thyroglobulin. Subsequent resection of the thyroid gland identified separate foci (< 1 cm) for both papillary and follicular carcinoma. Although such immunohistochemical staining has been used previously, it has never been reported to provide the definitive diagnosis for a solitary cutaneous metastasis from the thyroid. Previous tumors had anatomic features in a clinical context that permitted identification by routine light microscopy. Clear cell features found in the follicular focus of carcinoma in the thyroid suggest that it is the primary. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck.     

Na+/I- symporter distribution in human thyroid tissues: an immunohistochemical study

Antipeptide antibodies raised against the carboxyl-terminal region of the human sodium/iodide (Na+/I-) symporter (hNIS) were used to investigate by immunohistochemistry the presence and distribution of the hNIS protein in normal thyroid tissues, in some pathological nonneoplastic thyroid tissues, and in different histotypes of thyroid neoplasms. In normal thyroid tissue, staining of hNIS protein was heterogeneous and limited to a minority of follicular cells that were in close contact with capillary vessels. In positive cells, immunostaining was limited to the basolateral membrane. In contrast, in Graves' disease the majority of follicular cells expressed the hNIS protein. In autoimmune thyroiditis, the number of hNIS-positive cells, was similar to that found in normal tissue. These positive cells were found essentially close to lymphocytic infiltrates. This observation supports the concept of hNIS as an autoantigen. In diffuse nodular hyperplasia, hNIS staining was heterogeneous, but the number of hNIS-positive cells exceeded that found in normal tissue. In well differentiated follicular or papillary carcinoma, the number of hNIS-positive cells was significantly lower than in normal tissue. In poorly differentiated follicular carcinoma, the number ofhNIS-positive cells was less than that found in well differentiated carcinoma, or there were no positive cells. Interestingly, in all of these thyroid tissues, the number of follicular cells exhibiting TSH receptor (TSHR) immunoreactivity was greater than the number ofhNIS-positive cells. As hNIS expression appears to be related to TSHR stimulation, the decreased number of TSHR-positive cells in cancers may contribute to the reduced capacity of neoplastic cells to concentrate iodide. In one patient with a follicular cancer with an absence of hNIS immunostaining, the total body 131I scan showed no uptake in metastatic tissue. In three cancers with positive hNIS cells, the 131I scan showed uptake in lymph node metastases. This suggests that immunodetection of hNIS could predict radioiodine uptake in thyroid cancers.     

Pediocin N5p from Pediococcus pentosaceus: adsorption on bacterial strains

Oxyphilic cell (Hürthle cell) carcinomas of the thyroid gland, variant of follicular carcinoma, are more malignant than follicular non oxyphilic cell carcinomas with a similar size and degree of invasiveness. Gross features, microscopic features of oxyphilic, clear and bicolored cells carcinomas and diagnostic techniques are related with a differential diagnosis with papillary oxyphilic cell carcinoma.     

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.     

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.]     

"High-dose" radioiodine therapy in advanced differentiated thyroid carcinoma

There is yet no consensus concerning the appropriate regimen of the application of [131I]sodium iodine (Nal) activities to patients suffering from advanced differentiated thyroid carcinoma. We report on a total of 167 applications of [131I]Nal, including 78 applications of 11.1 GBq. Response to high-activity radioiodine therapy (RIT) is correlated to the course of the disease as well as to the reaction of thyreoglobulin and acute/subacute side effects of radiation. METHODS: Following radioablation of thyroid remnants using 1.85 to 3.7 GBq[131I]Nal, 26 patients with advanced differentiated thyroid carcinoma (follicular, 11; papillary, 4;mixed-cell thyroid carcinoma, 11) were treated with repeated activities of 11.1 GBq[131I]Nal. Initial tumor staging according to UICC showed T4 in 54%, T3 in 19%, T2 in 19% and was not obtained in 8%. Differentiated thyroid carcinoma was multifocal in 23% of patients. Applied accumulated activities ranged from 14.8 to 99.9 GBq with a mean of 55.5 GBq per patient. RESULTS: Mean post-diagnostical follow-up was 73 mo, mean follow-up after diagnosis of metastatic spread was 48 mo. Follicular thyroid carcinoma remained as stable disease in 7 of 11 patients, 6 of whom showed metastatic disease after a mean of 20 mo, and only 1 complete remission was achieved using high-dose therapies, with progressive disease in the remaining patients. Overall, 73% of follicular thyroid carcinoma had progressive disease without major response to high-activity RIT. In contrast, only 20% of papillary thyroid carcinoma/mixed-cell thyroid carcinoma showed progressive disease, and complete remission was achieved in 47% of patients. Pulmonary and lymph node metastases in the majority of patients showed good response to therapy, whereas local recurrences and bone metastases showed minor reactions to RIT. After low-activity therapies 8% of patients showed WHO grade I hematotoxic reactions. After high-activity therapies, 38% of patients had WHO I, 8% WHO II and one patient had WHO III toxicity (4%). CONCLUSION: Use repetitive high-activity RIT with a maximum of 44.4 GBq applied during 1 yr and a maximum of 99.9 GBq accumulated activity resulted in a significant increase of hematotoxicity. However, during the follow-up period (mean, 4 yr), no clinical symptoms possibly related to low blood counts were seen in patients with advanced differentiated thyroid carcinoma. Initiation of high-activity RIT in reaction to metastatic tumor outspread to achieve complete remission was found to be useful in treating papillary thyroid carcinoma and mixed-cell thyroid carcinoma, but only in a minority of follicular thyroid carcinoma patients.     

Comparison of intraoperative cytology with frozen sections in the diagnosis of thyroid lesions

We retrospectively studied the usefulness of intraoperative cytology (IOC) and frozen section (FS) in the rapid diagnosis of 68 thyroid lesions. In 14 cases of papillary thyroid carcinoma, IOC correctly diagnosed 13 cases, while FS correctly diagnosed 11 cases. There was no significant difference in sensitivities, and both methods had similar specificities. In 21 cases of colloid nodule, IOC was slightly more sensitive than FS; IOC correctly diagnosed 16 cases, while FS correctly diagnosed 15 cases. However, the specificity of IOC was only 71%, but was 98% for FS. Of 17 follicular adenomas, FS diagnosed 16 as follicular neoplasms and misdiagnosed only 1 as a colloid nodule. By contrast, IOC misdiagnosed 9 follicular adenomas as colloid nodules, most of which were macrofollicular variants with abundant colloid. Of 11 follicular carcinomas, FS diagnosed all as follicular neoplasms, while IOC misdiagnosed 3 as colloid nodules. While IOC is not as accurate as FS in the diagnosis of colloid nodules and follicular neoplasms, it is highly sensitive and specific in the diagnoses of papillary carcinoma and performance of the technique is rapid and easy. In an intraoperative setting, IOC is a useful adjunct to FS in screening thyroid nodules for the presence of papillary carcinoma.     

c-Met expression of thyroid tissue with special reference to papillary carcinoma

It has become clear that papillary carcinomas of the thyroid often express the receptor for c-Met/hepatocyte growth factor (HGF) receptor, but little is known about the role of the HGF and c-Met system in the pathogenesis of thyroid carcinoma. In this study, the expression of c-Met/HGF receptor was evaluated in thyroid tissue by western blot and immunohistochemistry, and compared with the concentration of HGF. Clinicopathological characteristics were also compared. Fifteen of 20 papillary carcinomas (75%) showed c-Met bands of 145 kDa. No or only a low frequency of c-Met expression was detected in healthy thyroid tissue (0/5), thyroiditis or Basedow's disease (0/2), adenomatous goiters (0/8), follicular adenomas (1/9, 11%) and undifferentiated carcinomas (0/2). These results were confirmed by immunohistochemistry, but a relatively higher frequency of c-Met expression was detected in adenomatous goiters (25%), follicular adenoma (44%) and papillary carcinoma (100%) using formalin-fixed and paraffin-embedded materials. A strong immunoreaction for c-Met was observed in the tumor cytoplasm of papillary carcinomas among the fibrous tissues situated at the periphery of the tumor. The densitometrically measured expression of c-Met had no relation to tumor stage in papillary carcinoma, but did correlate to the concentration of HGF in papillary carcinomas. In conclusion, in thyroid lesions, c-Met was highly expressed specifically in the cytoplasm of papillary carcinomas. c-Met expression was not related to the aggressiveness of the tumor but was related to the concentration of HGF, which was probably derived from the stroma. Also, the c-Met system might play a role in the pathogenesis of papillary carcinoma of the thyroid.