Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease.

A form of Hashimoto's thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto's thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto's thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto's thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto's thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto's thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto's thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto's thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In conclusion, IgG4 Hashimoto's thyroiditis presents histopathological features quite distinct from its non-IgG4 counterpart.

IgG4-related disease of the thyroid glands.

Recent reports on Hashimoto's thyroiditis (HT) with increased numbers of IgG4-positive plasma cells suggest that this type of HT may have a close relationship to IgG4-related disease (IgG4-RD). This unique subgroup of HT is termed as IgG4 thyroiditis and reveals distinct clinical, serological, and sonographic features from the non-IgG4 thyroiditis group. On the basis of immunostaining for IgG4, HT was divided into an IgG4 thyroiditis group and a non-IgG4 thyroiditis group. Clinically, IgG4 thyroiditis was associated with younger age group, lower female-male ratio, higher levels of thyroid autoantibodies, diffuse low echogenicity, more rapid progress requiring surgical treatment and more subclinical hypothyroidism. Serum IgG4 concentrations elevated in IgG4 thyroiditis and decreased significantly after a thyroidectomy. Histopathologically, IgG4 thyroiditis showed a higher grade of stromal fibrosis, lymphoplasmacytic infiltration, and follicular cell degeneration than non-IgG4 thyroiditis. IgG4 thyroiditis may represent IgG4-RD of thyroid gland, because it shares common histopathological characteristics with IgG4-RD in other organs. The identification of IgG4-RD of the thyroid gland opens new insights not only for patient's treatment with HT but also for the development of new therapeutic approaches for this rapidly progressive destructive subtype of HT. This article mainly focuses on reviewing the unique histopathological, clinical, and serological features of IgG4 thyroiditis group of HT. The etiology and genetic changes of HT are also discussed.

Effects of fission neutrons on human thyroid tissues maintained in SCID mice.

Morphology and function (secretion of thyroid hormone) of human thyroid tissues from Graves' disease patients are well maintained in C57BL/6J-scid mice. Serum level of thyroid hormone was reduced by fission neutrons from the nuclear reactor UTR-KINKI, and changes in thyroid hormone by fission neutrons were bigger than those by low LET radiations, X-rays and (137)Cs gamma-rays, suggesting high relative biological effectiveness (RBE; 6.5) of fission neutrons. Microarray analyses revealed that about 3% of genes showed more than 4-fold change in gene expression in the unexposed thyroid tissues against surgically resected thyroid tissues from the same patient, probably due to the difficult oxygen and nutrient supply shortly after transplantation. Dose-dependent changes in gene expression against unexposed concurrent controls were observed with increasing doses of fission neutrons (0.2-0.6Gy) and (137)Cs gamma-rays (1.0-3.0Gy) and showed high RBE (4.2). Furthermore, there were some specific genes which showed more than 4-fold change in gene expression in all the thyroid tissues exposed to higher doses of radiation, especially neutrons (0.4 and 0.6Gy), but none at lower doses (0.2Gy of neutrons and 1.0 and 2.0Gy of gamma-rays). These genes related to degeneration, regeneration, apoptosis, and transcription, respond specifically and very sensitively to neutron injury in human thyroid tissues. This is the first experimental report that fission neutrons can induce some morphological and functional disorders in human tissues, showing high RBE against gamma-ray exposure. These results are useful to evaluate the risks of fission neutrons and cosmic rays to humans.

Clinical significance of extrathyroid extension to the parathyroid gland of papillary thyroid carcinoma.

Extrathyroid extension is a prominent prognostic factor of papillary thyroid carcinoma (PTC). In the UICC TNM classification, minimal extension to the sternothyroid muscle and perithyroid soft tissue is classified as T3 and further massive extension is classified as T4, the highest T grade. However, there have been few studies on the clinical significance of extension to the parathyroid gland in a large case series. In this study, we investigated the prognosis of PTC with extension to the parathyroid gland in a series of 3208 patients who underwent initial surgery between 1997 and 2004. Of these patients, 51 (1.6%) showed extension to the parathyroid gland on pathological examination. Twenty-one of these patients had massive extrathyroid extension to other adjacent organs corresponding to pT4. The remaining 30 were enrolled in this study. The disease-free survival (DFS) of these 30 patients was significantly better (p<0.0001) than that of pT4 patients and did not differ from that of patients showing minimal extrathyroid extension without extension to the parathyroid gland (p = 0.6264). Furthermore, none of these 30 patients died of carcinoma. Taken together, it is appropriate that extension to the parathyroid gland of PTC is graded as minimal extrathyroid extension (pT3), but not massive extension (pT4). Since minimal extension did not affect patient prognosis in our series, it is suggested that extension to the parathyroid gland has little clinical significance in PTC.

Prognosis of patients with papillary thyroid carcinoma having clinically apparent metastasis to the lateral compartment.

Lymph node metastasis is an important clinicopathological feature of papillary thyroid carcinoma (PTC). PTC having clinically apparent lateral node metastasis detectable on preoperative imaging studies (N1b) is known to show a dire prognosis. However, N1b cases include various levels of biological aggressiveness, depending on the size, number, laterality and invasiveness of metastatic nodes. We investigated differences in the prognoses of 621 N1b patients based on these features and compared their prognoses with those of 4297 patients without clinically apparent metastasis (N0) and 125 patients with clinically apparent central node metastasis only (N1a). Disease-free survival (DFS) and cause-specific survival (CSS) of N1b or N1a patients were significantly worse than those of N0 patients, but the prognosis of N1b patients did not differ from that of N1a patients. In the subset of N1b patients, metastatic nodes larger than 3cm, extranodal extension, or 5 or more clinically apparent metastatic nodes independently affected DFS and a combination of the former two features also showed an effect on CSS on multivariate analysis. Prognosis of N1b patients who had none of these features did not differ from that of N1a patients. It is therefore suggested that N1b patients having metastasis larger than 3cm, those showing extranodal extension, and those having 5 or more clinically apparent metastasis should regarded as high-risk, and that careful surgical treatment and postoperative follow-up are necessary.

Preoperative administration of excess iodide increases thyroid volume of patients with Graves' disease.

Preoperative excess iodide administration for patients with Graves' disease has been widely adopted by surgeons to perform surgery safely, because it decreases blood flow in the thyroid. However, surgeons often encounter the enlargement of thyroid volume after iodide administration, which makes surgery even more difficult. In this study, we retrospectively investigated the change in thyroid volume in Graves' disease that was evaluated on ultrasonography between before and after iodide administration. Eighty-nine patients who received iodide administered (KI(+) patients) and 24 in whom iodide was not administrated (KI(-) patients) before surgery for Graves' disease were enrolled in the study. The level of free T4 (FT4) significantly decreased and that of thyroid stimulating hormone (TSH) significantly increased after iodide administration. Average thyroid volume also significantly increased for KI(+) patients after iodide administration and 17% of these patients showed a 30% or more increase in thyroid volume. In KI(-) patients who were preoperatively treated only by anti-thyroid drugs, thyroid volume did not change before surgery. Preoperative TSH levels remained below measurement sensitivity in 37 of KI(+) patients, but the average thyroid volume also significantly increased after iodide administration. These findings suggest that thyroid volume in Graves' disease can increase with iodide administration not only due to TSH stimulation but also due to reasons other than TSH. Surgeons should be careful when preoperatively iodide administering to patients with Graves' disease, especially when the goiter is large.

BRAF mutation in papillary thyroid carcinoma in a Japanese population: its lack of correlation with high-risk clinicopathological features and disease-free survival of patients.

Recent studies have demonstrated that BRAF(V600E) mutation is a common event in papillary thyroid carcinoma and a majority of these lesions have shown a direct relationship between BRAF(V600E) mutation and aggressive characteristics, including a worse patient prognosis. However, there are no studies from Japan regarding this issue in a large series with adequate postoperative follow-up periods. We investigated BRAF(V600E) mutation in 631 patients with papillary carcinoma having median follow-up periods of 83 months. The prevalence of BRAF(V600E) mutation was 38.4%, and the rate was higher in carcinoma larger than 1.0 cm but did not successively increase with tumor size. Furthermore, the prevalence did not significantly increase in cases demonstrating high-risk biological features such as clinically apparent lymph node metastasis, massive extrathyroid extension, advanced age, distant metastasis at surgery, and advanced Stage. The disease-free survival of patients with BRAF(V600E) mutation did not differ from that of those without BRAF(V600E) mutation. These findings indicate that, although BRAF(V600E) mutation may play some roles in local carcinoma development, there is no evidence that BRAF(V600E) mutation significantly reflects the aggressive characteristics and poor prognosis of patients with papillary carcinoma in Japan.

Investigation of the validity of UICC stage grouping of anaplastic carcinoma of the thyroid.

OBJECTIVE: Anaplastic thyroid carcinoma arises from differentiated carcinoma and has a very aggressive character. In this study, we investigated the prognosis of patients with anaplastic carcinoma based on UICC stage. PATIENTS AND METHODS: We investigated the prognosis of 75 patients who were diagnosed as having anaplastic carcinoma at Kuma Hospital between 1983 and 2006. Of these patients, 14, 49 and 12 were classified into Stages IVA, IVB, and IVC respectively. RESULTS: Stage IVA patients showed a significantly better prognosis than Stage IVB or IVC patients (p = 0.0017). All patients with Stage IVC died of carcinoma within 1 year regardless of whether locally complete resection was performed. Prognosis of Stage IVB patients who underwent curative surgery did not differ from that of Stage IVA patients, but the prognosis of those who did not undergo surgery or only received palliative surgery was as poor as that of Stage IVC patients. CONCLUSIONS: Extensive surgical treatment is recommended for Stage IVA patients and palliative care is appropriate for Stage IVC patients. For Stage IVB patients, surgical treatment as a primary therapy is appropriate only when curative resection of the tumour is expected.

Local prognosis of patients with papillary thyroid carcinoma who were intra-operatively diagnosed as having minimal invasion of the trachea: a 17-year experience in a single institute.

BACKGROUND: Since papillary thyroid carcinoma (PTC) with tracheal invasion shows a worse prognosis, aggressive surgical treatment including airway resection has been recommended. However, little is known about local recurrence of PTC with minimal tracheal invasion after shaving or laminated resection of the tracheal cartilage. In this study, we investigated the local prognosis of patients who were intra-operatively diagnosed as having minimal tracheal invasion. METHODS: Of 6,015 patients who underwent initial surgery for PTC between 1987 and 2004, 127 (2.1%) were intra-operatively suspected of having minimal invasion to the trachea and underwent shaving or laminated resection of the tracheal cartilage. These 127 patients were enrolled in this study. RESULTS: Of 127 patients, 107 were intra-operatively regarded as having received macroscopically curative treatment (curative group), whereas minimal carcinoma remnants were suspected in the remaining 20 patients (suspicious group). To date, six patients (4.6%) (one patient in the curative group and five in the suspicious group) showed local recurrence at the tracheal edge. The local disease-free survival of patients in the curative group was better than that of those in the suspicious group (p = 0.0007), although the cause-specific survival of patients in the two groups did not differ. Cut surfaces of resected carcinoma were also pathologically examined for 119 patients and 58 (48.7%) were diagnosed as carcinoma-positive, but the cut surface status was not related to macroscopic curative treatment. Of six patients showing local recurrence, only one died of lung metastasis of carcinoma. CONCLUSION: The incidence of local recurrence of PTC with minimal tracheal invasion is low at 4.6%. Although this event might not be immediately life-threatening for patients, to improve local prognosis, local curative treatment should be pursued. In cases that are suspected of persistent carcinoma remnants, further shaving or laminated dissection should be performed, and if the carcinoma remnant cannot be eliminated, tracheal fenestration should be considered, although such high-risk tumours may be likely to recur regardless of surgical radicality.

3,5,3'-Triiodothyronine thyrotoxicosis due to increased conversion of administered levothyroxine in patients with massive metastatic follicular thyroid carcinoma.

OBJECTIVE: Some patients with massive metastatic thyroid carcinoma exhibit T(3) thyrotoxicosis. We investigated the prevalence and cause of T(3) thyrotoxicosis and the clues to the diagnosis. DESIGN: Serum free T(3) (FT(3)), free T(4) (FT(4)), and TSH were measured in patients with massive metastases from papillary, follicular, or medullary thyroid carcinomas (31, 20, and seven patients, respectively). Patients without recurrence served as controls. Thyrotoxic patients were reexamined 1 wk after withdrawal of levothyroxine. Type 1 and type 2 iodothyronine deiodinase (D1 and D2) activities were measured in three tumor tissues from thyrotoxic patients. MAIN OUTCOME: The serum FT(3) level and FT(3)/FT(4) ratio in the follicular carcinoma (FC) group were significantly higher than those in the papillary carcinoma group or patients without recurrence. Four patients (20%) in the FC group but none in the other groups demonstrated T(3) thyrotoxicosis or a FT(3)/FT(4) ratio greater than 3.5. One week after withdrawal of levothyroxine, both FT(3) and FT(4) levels decreased. Retrospective measurements of FT(3) in frozen stored sera demonstrated that FT(3) exceeded the upper normal limit when FT(4) began to decrease but remained within the normal range. Tumor tissues showed high D1 and D2 activities. CONCLUSIONS: Twenty percent of patients with massive metastatic FC exhibited T(3) thyrotoxicosis, most likely due to increased conversion of T(4) to T(3) by tumor expressing high D1 and D2 activities. Occasional measurement of serum FT(3) in addition to FT(4) and TSH is recommended in patients with massive metastatic FC, especially when serum FT(4) decreases on fixed doses of levothyroxine.

Aspiration biopsy-nucleic acid diagnosis of thyroid malignant lymphoma by vectorette PCR: experience of eight cases.

The usefulness of a new method to detect B-cell monoclonality named VR, which is a combination of the digestion with restriction enzymes and vectorette PCR, in aspiration biopsy-nucleic acid diagnosis (ABND) of thyroid malignant lymphoma was investigated. ABND was performed in 12 patients in whom malignant lymphoma was suspected. Among the patients who underwent open surgery, monoclonality was detected in the aspirates in four (50%) of eight patients with malignant lymphoma, but was not detected in one patient with Hashimoto disease. ABND using VR is a useful adjunct of aspiration biopsy cytology in the diagnosis of thyroid malignant lymphoma.

Prevalence and biological behaviour of variants of papillary thyroid carcinoma: experience at a single institute.

AIMS: There are many variants of papillary carcinoma, and some of these variants have been reported to show biological behaviours differing from that of conventional papillary carcinoma. In this study, we present our experience regarding the prevalence and prognoses of these variants of papillary carcinoma. METHODS: H&E sections from 1521 patients who underwent initial surgery for papillary carcinoma in Kuma Hospital between 1987 and 1995 were re-reviewed and classified into conventional papillary carcinoma and various histological variants. We investigated the biological behaviours of these lesions, including prognoses. RESULTS: Follicular, tall cell and oncocytic variants were observed in comparably high incidences: 6.6%, 3.9%, and 1.9%, respectively. Patients with tall cell variant showed significantly worse disease-free survival (DFS) and cause-specific survival (CSS) rates than those with conventional papillary carcinoma. The prognoses of patients with follicular variant did not differ from those of patients with conventional papillary carcinoma. Patients with oncocytic variant have not shown carcinoma recurrence. Among the rare variants, which accounted for less than 1%, columnar cell carcinoma showed a worse prognosis. CONCLUSIONS: Since patients with some variants show different clinical outcomes from those with conventional papillary carcinoma, classification of variants might be helpful to predict patient prognosis.

Differential radiation sensitivity to morphological, functional and molecular changes of human thyroid tissues and bone marrow cells maintained in SCID mice.

Morphology and function of human organs and tissues are well maintained in the improved SCID (severe combined immunodeficient) mice for a long period (approximately 3 years). To study the radiation-induced damage on human thyroid gland, human thyroid tissues transplanted to SCID mice were consecutively exposed to X-rays or 137Cs gamma-rays at high and low dose rates for approximately 2 years. Consecutive irradiation resulted in the disappearance of follicles and significant decrease of thyroid hormone secretion. Mutations in p53 and c-kit genes were induced significantly in human thyroid tissues from old head and neck cancer patients (av. 56.8 years, 4 males) and a Graves' disease patient (20 years, male) over the dose of 24 Gy (44.7+/-5.9 Gy, mean+/-S.E) and 11 Gy (20.2+/-7.8 Gy), respectively, while mutations were not detected at lower doses nor in unexposed matched controls (p < 0.01). There were significant differences in mutation frequency in the transplanted human thyroid tissues (31 years, female) between high dose rate (1.19 Gy/min; 8 in 20 tissues) and low dose rate (0.00023 Gy/min; 0 in 14 tissues) exposures (p < 0.01). Mutations were not detected in RET, K-ras and beta-catenin genes. Expression analysis by GeneChip indicated that gene expression was also well maintained in the transplanted human thyroid tissues. However, lower doses (1 or 3 Gy) of 137Cs gamma-rays can induce changes in gene expression in the transplanted human thyroid tissues. Furthermore, fatally irradiated SCID mice could survive with human bone marrow cell transplantation. When about half of mouse bone marrows were replaced by human bone marrow cells, the human bone marrow cells showed high sensitivity to gamma-irradiation; 28.0% and 0.45% survival after 0.5 and 2.0 Gy exposures, respectively.

Decrease of intrathyroidal CD161+Valpha24+Vbeta11+ NKT cells in Graves' disease.

To clarify changes in the intrathyroidal natural killer T (NKT) cell subset, which prevents autoimmunity in patients with Graves' disease (GD), we examined intrathyroidal and peripheral lymphocytes in 11 patients with GD and peripheral lymphocytes in nine healthy volunteers using three-color flow cytometry. The proportion of CD161 (+) T cell receptor Valpha24 (+) Vbeta11 (+) cells, which represent the NKT cell subset, was lower in the thyroid of patients with GD than in the peripheral blood of the same patients and in the peripheral blood of healthy subjects. These results indicate that the proportion of intrathyroidal NKT cells is decreased in patients with GD and that this decrease may contribute to incomplete regulation of autoreactive T cells in GD.

Prevalence and prognosis of familial follicular thyroid carcinoma.

Although the responsible gene has not yet been identified, patients with differentiated thyroid carcinoma, including papillary and follicular carcinomas, demonstrating a family history have been reported and patients having one or more family members with differentiated carcinoma among their first-degree relatives are designated as having familial nonmedullary thyroid carcinoma (FNMTC). In this study, we investigated the biological characteristics, including prognosis, of familial follicular carcinoma. Three hundred and nineteen patients who underwent initial surgery for follicular thyroid carcinoma between 1987 and 2004 who were enrolled in this study. Of these 319 patients, 6 patients (1.9%) in 6 families were classified as having familial follicular carcinoma based on the criteria described above. The incidence of aggressive characteristics such as male gender, age 45 years or older, poor differentiation, widely invasive carcinoma, tumor larger than 4 cm and distant metastasis at diagnosis did not differ between familial and sporadic follicular carcinomas. One patient with familial follicular carcinoma underwent re-operation because of newly detected papillary carcinoma in the remnant thyroid 160 months after the initial surgery, but none of the 6 patients with familial carcinoma showed recurrence or died of follicular carcinoma. We can therefore conclude that FMNTC of the follicular type is very rare and there is no evidence that familial follicular carcinoma is more aggressive or has a worse prognosis than sporadic follicular carcinoma. The therapeutic strategy for follicular carcinoma might depend on conventional prognostic factors such as poor differentiation and distant metastasis at diagnosis, but not on whether the carcinoma is familial or sporadic.

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.

Prognosis of patients with papillary carcinoma showing anaplastic transformation in regional lymph nodes that were curatively resected.

Anaplastic carcinoma arises from differentiated carcinoma and generally shows a dire prognosis. Anaplastic transformation may occur not only in primary tumors but also in metastatic lymph nodes. We encountered 5 cases of papillary carcinoma showing anaplastic transformation in lymph nodes that were curatively resected. Patient ages ranged from 67 to 85 years. Two of these patients showed anaplastic transformation at the initial surgery and the remaining 3 showed anaplastic transformation after repeated recurrence to the lymph nodes. After resection of anaplastic lesions of the nodes, 2 patients underwent radiation therapy, whereas the remaining 3 did not receive any adjuvant therapy. One patient died of rapid growth of lung metastasis 5 months after the resection. One patient died of carcinoma 63 months after surgery. Two patients have survived to date, 6 and 85 months after resection, respectively. The remaining one patient died of heart failure 11 months after surgery. It is therefore suggested that long-term survival can be expected for patients with differentiated carcinoma showing anaplastic transformation in the lymph node if the lesions can be curatively resected.

Apoptosis-induced decrease of intrathyroidal CD4(+)CD25(+) regulatory T cells in autoimmune thyroid diseases.

BACKGROUND: We previously showed that the proportion of CD4(+) T cells was lower and both the proportion and intensity of Fas expression on intrathyroidal CD4(+) T cells were higher in the thyroid than in the peripheral blood of patients with autoimmune thyroid disease (AITD). OBJECTIVE: To clarify whether the intrathyroidal CD4(+)CD25(+) regulatory T (Treg) cells are decreased by Fas-mediated apoptosis in patients with AITD. DESIGN: We examined intrathyroidal and peripheral lymphocytes in 20 patients with AITD (15 patients with Gravesâ disease and five patients with Hashimotoâs disease) and peripheral lymphocytes in 10 healthy volunteers by three-color flow cytometry. MAIN OUTCOME: The proportion of CD4(+)CD25(+) cells was lower in the thyroid of patients with AITD than in the peripheral blood of the same patients or the peripheral blood of the healthy subjects. The proportions of CD4(+)CD25(+)CD69() cells and Forkhead box P3 (Foxp3)(+)CD4(+)CD25(+) cells, which constitute more specific Treg subsets than CD4(+)CD25(+) cells, were also lower in the thyroid than in the peripheral blood of patients with AITD. The proportion of apoptotic cells was higher among intrathyroidal CD4(+) cells than among peripheral CD4(+) cells and higher among intrathyroidal CD4(+)CD25(+) cells than among intrathyroidal CD4(+)CD25() cells. CONCLUSION: These results indicate that intrathyroidal Treg cells are decreased in response to apoptosis in patients with AITD. This decrease in Treg cells may contribute to the incomplete regulation of autoreactive T cells in AITD.

Quantitative measurement of telomerase reverse transcriptase, thyroglobulin and thyroid transcription factor 1 mRNAs in anaplastic thyroid carcinoma tissues and cell lines.

Anaplastic thyroid carcinomas (ATC) are undifferentiated tumors that show rapid progression and dissemination. The recent increase in knowledge about cancer stem cells has attracted marked interest in ATC, since these lesions are suggested to be closely related to thyroid stem cells (TSCs). Due to the rarity of ATCs, however, the gene expression patterns that characterize these lesions have not been fully clarified. Using real-time quantitative reverse transcription-polymerase chain reaction, we measured the mRNA expression levels of three representative genes, telomerase reverse transcriptase (hTERT), thyroglobulin and thyroid transcription factor 1 (TTF-1) in twelve frozen tissue samples of ATC and six cell lines derived from ATCs. All twelve ATC specimens and six ATC cell lines showed an increased expression of hTERT mRNA but the expression levels of hTERT mRNA did not show a clear difference between ATCs and other thyroid tumors. The mean expression level of thyroglobulin mRNA in the ATCs and ATC cell lines was <10(2) times higher than that in the differentiated thyroid carcinomas. All twelve ATCs showed a loss of TTF-1 mRNA expression, but two cell lines, TCO-1 and 8505C, expressed TTF-1 mRNA. In conclusion, ATC tissues and cell lines were characterized by the expression of hTERT and a loss of thyroglobulin expression, concordant with the general recognition. However, the loss of TTF-1 expression can not characterize ATC cells, as some ATC cell lines expressed TTF-1 mRNA abundantly. This information could contribute to clarifying the nature of ATCs and could be useful in detecting TSCs, which have not yet been identified.

Long-term follow-up for patients with papillary thyroid carcinoma treated as benign nodules.

BACKGROUND: The recent prevalence of ultrasonography and fine-needle aspiration biopsy (FNAB) has facilitated the detection and diagnosis of papillary thyroid carcinoma. However, there are still cases that are preoperatively misdiagnosed and treated as benign nodules because ultrasonographic and FNAB findings do not provide sufficient evidence for a malignant diagnosis. In this study, we investigated the clinical outcomes of patients with papillary carcinoma that had not been recognized preoperatively. PATIENTS AND METHODS: We investigated the prognoses of 56 patients with papillary carcinoma who underwent thyroidectomy without node dissection under a diagnosis of benign nodules. RESULTS: None of the patients underwent further surgery such as completion total thyroidectomy and node dissection after the pathological diagnosis of papillary carcinoma was established. However, to date, only 3 patients (5.3%) showed recurrence 116, 133 and 148 months after the initial surgery, respectively. Two patients showed recurrence in the remnant thyroid and one showed recurrence in the bone. None of the patients have died of thyroid carcinoma. CONCLUSION: Papillary carcinomas misdiagnosed as benign nodules on ultrasonography and FNAB are indolent and very slow-growing. Immediate further surgery is not needed for such cases, even if they were resected as benign nodules at the initial surgery.