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1/9. Toxic multinodular goitre in a patient with generalized resistance to thyroid hormone who harbours the R429Q mutation in the thyroid hormone receptor beta gene.

    The association of resistance to thyroid hormone (RTH) due to a receptor defect with toxic multinodular goitre or with carcinoma of the thyroid has not been previously reported. Previous histopathological studies of the thyroid gland in patients with RTH have revealed changes similar to multinodular goitre, probably due to continuous stimulation by TSH. We report here a case of generalized resistance to thyroid hormone associated with a multinodular goitre, which became toxic. The patient was a 46-year-old Japanese woman who noticed a goitre although she had no symptoms of thyrotoxicosis. Initial examination revealed elevated serum thyroid hormone levels and a normal TSH level. ultrasonography disclosed a multinodular goitre with cystic lesions. Three years later, the patient complained that the goitre had become larger and that she had developed symptoms of thyrotoxicosis such as palpitation and hyperhydrosis. Progressive hyperthyroxinaemia with relatively suppressed TSH, increased radioiodine uptake and negative anti-TSH receptor antibodies led to the diagnosis of toxic multinodular goitre. Subtotal thyroidectomy was performed, and pathological examination revealed a micropapillary carcinoma within the multinodular goitre. Occurrence of thyroid carcinoma should be considered in RTH because its incidence is high in multinodular goitre. Molecular examination revealed the R429Q mutation in the thyroid hormone receptor beta gene, which is one of the mutations usually manifesting as the pituitary resistance phenotype. That thyrotoxic manifestations appeared only during toxic stage of multinodular goitre in this case suggests that the phenotype of this type of mutation can be dependent on the amount of thyroid hormone.
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2/9. A novel chromosomal translocation t(3;5)(q12;p15.3) and loss of heterozygosity on chromosome 22 in a multifocal follicular variant of papillary thyroid carcinoma presenting with skin metastases.

    Classic genetic rearrangements in papillary carcinoma of the thyroid involve the RET- or TRK proto-oncogenes. We report a novel chromosomal translocation t(3;5)(q12;p15.3), confirmed by fluorescence in situ hybridization, in a multifocal follicular variant of a papillary carcinoma of the thyroid in a 79-year-old woman, with skin metastases as a presenting symptom. Three years earlier, another cutaneous metastasis on her scalp was misdiagnosed as hidradenoma. Four tumour foci were recognized in the thyroid, two with a follicular variant of papillary carcinoma. To detect loss of heterozygosity, 14 chromosomes were investigated with 59 microsatellite markers. A clonal relationship was detected between the two foci of tumour in the thyroid gland containing follicular variant of papillary carcinoma and one of the skin lesions tested, all demonstrating loss of heterozygosity (LOH) in the same region of chromosome 22. Based on earlier reports, the low rate of LOH detected is in agreement with the diagnosis papillary carcinoma of the thyroid. Whole body scintigraphy performed after ablative therapy with radioiodine revealed multiple metastases in the lungs and skeleton. After repeated radioiodine therapy, thyroglobulin under thyroxine suppression became undetectable and post-therapeutic scintigraphy revealed important regression of metastases.
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3/9. Thyroglossal duct carcinoma in children: case presentation and review of the literature.

    carcinoma within the thyroglossal duct (TGDCa) is a very rare pediatric tumor. This report presents the case of a 15-year-old girl with TGDCa, reviews the previously published pediatric cases of this tumor, and provides diagnostic and therapeutic considerations in TGDCa in children. Twenty one cases of TGDCa have been reported, 12 of them in females. Mean age at presentation was approximately 13 years for females and approximately 12 years for males. The duration of a midcervical mass prior to the diagnosis of TGDCa varied from 3 weeks to 8 years. The size of the neck mass at presentation averaged 2 cm-4 cm. All masses were asymptomatic, and the diagnosis of TGDCa was incidental following surgery. All pediatric cases of TGDCa reported thus far were of the papillary type, except for 3 patients who presented with a mixed papillary-follicular carcinoma. Capsular invasion was detected in 10 (45%) patients. Local invasive disease was found in 5 (23%) patients, but all removed thyroid glands (12) were free of carcinoma. One patient had lung metastases. thyroidectomy with subsequent radioiodine ablation was the treatment of choice in the majority of the cases. The reported prognosis for TGDCa in children was favorable, with only one reported death.
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4/9. Importance of thyroglobulin levels for diagnosis and monitoring of follicular thyroid carcinoma in an adolescent with severe iodine deficiency.

    Optimal management of differentiated thyroid cancer in childhood is undetermined. During monitoring of thyroid carcinoma, serum thyroglobulin (hTG) levels provide valuable information. hTG levels not only increase in differentiated thyroid cancers but also in iodine deficiency because of compensation by the thyroid gland. A 14.6 year-old girl was diagnosed with nodular goiter, subclinical hypothyroidism and severe iodine deficiency. She had a very high hTG level. Despite benign fine-needle aspiration biopsy (FNAB), because the hTG level was still very high after treatment with LT4, thyroidectomy was undergone. Cytopathological examination showed minimally invasive follicular thyroid carcinoma. During follow-up, to exclude the presence of persistent/recurrent disease, the hTG level rose to an undesirably high level after withdrawal of TSH suppressive therapy, and radioiodine ablation therapy was applied. This report shows that even if there is an explanation for nodular goiter and high hTG levels, such as iodine deficiency, malignancy cannot be ruled out without thyroidectomy. FNAB is not reliable especially in iodine deficient areas. serum hTG measurement is a valuable tool for both diagnosis and follow-up of differentiated thyroid carcinoma in children.
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5/9. Composite follicular variant of papillary carcinoma and mucoepidermoid carcinoma of the thyroid. Report of a case and review of the literature.

    The follicular variant of papillary carcinoma of the thyroid gland is a commonly recognized, well-defined entity. However, primary mucoepidermoid carcinoma of the thyroid is rare, with only 21 cases reported. We describe a 29-year-old woman who presented with a mass in the right lobe of the thyroid. The tumor was classified as the follicular variant of papillary carcinoma of the thyroid with several foci of mucoepidermoid carcinoma. Both components were invading the capsule and had spread to regional lymph nodes. This is the first reported case in which both the papillary and mucoepidermoid carcinomas were present in the primary tumor and in the metastases.
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6/9. Coexistence of papillary and medullary carcinoma of the thyroid gland-mixed or collision tumour? Clinicopathological analysis of three cases.

    We present three thyroid carcinomas displaying medullary and papillary components. In two cases the papillary component was characterized by typical papillae with a fibrovascular core; in one a follicular variant of papillary carcinoma was found. The papillary component was dominant in two and the medullary in one case. One tumour showed clear-cut borders between the two components, the others displayed an intermingled pattern. Both tumour components were seen in lymph node metastases with immunostaining with antibodies to calcitonin, chromogranin a, carcinoembryonic antigen, other neuroendocrine markers and thyroglobulin. At least two of our cases are true mixed carcinomas probably arising from a common stem cell.
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7/9. Metastatic follicular carcinoma of thyroid to pericardium.

    A 62 year-old man presented with massive pericardial effusion and a thyroid nodule. One thousand ml of serosanguinous pericardial effusion was tapped and the cytology consistent with metastatic papillary carcinoma. Total thyroidectomy was done. The pathological report of the thyroid gland was follicular carcinoma, poorly differentiated with capsular and vascular invasion. The patient received a treatment of 150 mci I-131 without complications. The total body scan after I-131 treatment showed only residual thyroid tissue. There was no demonstrable abnormal uptake in other parts of the body. No significant reaccumulation of pericardial fluid occurred. The diagnosis was follicular carcinoma of the thyroid with pericardial metastasis. The patient was discharged from the hospital with an improved clinical status.
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8/9. breast cyst simulating metastases on iodine-131 imaging in thyroid carcinoma.

    False-positive radioiodine uptake has been reported in many organ systems. We describe a female patient who had mixed papillary and follicular thyroid carcinoma, and on radioiodine total-body imaging demonstrated focal, lower-right chest uptake. Special prone imaging with the right breast dependent proved that the uptake was inside the right breast. review of a recent breast ultrasound and mammograms showed this uptake to correspond to a large breast cyst. It is known that 131I breast uptake may be functional within the mammary gland. In this patient, it was due to retention within the cyst after the background activity decreased. knowledge of this phenomenon may improve the interpretation of total-body 131INa studies.
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9/9. 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.
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