Cases reported • Carcinoma, Papillary, Follicular

1/14. Encapsulated follicular variant of papillary thyroid carcinoma with bone metastases.

Although true follicular thyroid carcinoma is known to metastasize via the bloodstream and give rise to bone and lung metastases, such a pattern of spread is rare in papillary thyroid carcinoma. The follicular variant of papillary thyroid carcinoma (FVPTC) is believed to behave in a clinical manner similar to usual or classical papillary cancer and to follow a similar indolent course. There have been a few reports of "aggressive" FVPTC wherein follicular patterned tumors with nuclear features of papillary carcinoma have metastasized hematogenously; these neoplasms have been diffusely invasive or multicentric in the thyroid. We report five cases of FVPTC, which were encapsulated and simulated grossly and microscopically follicular adenomas. In two of these, the primary was discovered after clinical presentation of bone metastases. In three others, bony metastases (without other nonosseous metastases) arose 7 to 17 years after thyroid lobectomy for lesions initially diagnosed as follicular adenoma In retrospect, these three encapsulated lesions had vascular invasion. We wish to bring attention to these innocuous-appearing lesions, which, although sharing nuclear features of papillary cancer, behave clinically in an unexpectedly malignant fashion.

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2/14. 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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3/14. 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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4/14. Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases.

BACKGROUND: Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. CASE REPORTS: Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. CONCLUSION: MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.

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5/14. Cribriform-morular variant of papillary carcinoma: the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma. A case report with clinical and molecular genetic correlation.

The increased incidence of thyroid carcinomas in familial adenomatous polyposis (FAP) patients is well recognised. These thyroid neoplasms display distinctive clinicopathological features and generally show good prognostic outcome. Recently, unusual sporadic tumours that share the morphological features of FAP-associated thyroid carcinomas have also been described. In this report, we document a case of a thyroid tumour in a previously well, 46-year-old female. histology revealed a circumscribed neoplasm composed of tubular, papillary, cribriform and solid areas. The pseudostratified columnar tumour cells showed occasional nuclear grooves and rare nuclear inclusions. immunohistochemistry showed positive staining with antibodies to cytokeratin AE1/AE3, oestrogen and progesterone receptor proteins. Focal immunoreactivity was also noted with antibodies to thyroglobulin, epithelial membrane antigen, 34betaE12 and cytokeratin CK7. The absence of polyps on colonoscopy and germline mutation in the adenomatous polyposis coli (APC) gene provides evidence that this tumour represents the sporadic counterpart of FAP-associated thyroid carcinoma. The patient is well with no evidence of disease 7 months following resection of the tumour. The differential diagnoses and molecular genetics of this unusual tumour are discussed.

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6/14. 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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7/14. Macrofollicular encapsulated papillary thyroid carcinoma--a case report.

Macrofollicular encapsulated papillary thyroid carcinoma (MEPC) is a rare variant of papillary carcinoma of thyroid with a favourable clinical course. It could be mistaken for a follicular neoplasm or a hyperplastic nodule. We report cytological and histopathological features of this rare variant of papillary carcinoma in a 22 year old female with brief review of literature.

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8/14. 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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9/14. 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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10/14. Metastatic papillary thyroid carcinoma presenting as a primary renal neoplasm.

Clinically detectable thyroid cancer metastatic to the kidney is rare, with only six cases reported in the medical literature. Four of these have been follicular carcinoma, one papillary carcinoma, and one described as a thyroid adenoma. All of these had known thyroid neoplasms prior to development of their renal metastases. We report herein a seventh case of thyroid carcinoma metastatic to the kidney, unique in that the diagnosis of the kidney metastasis preceded the knowledge of the primary thyroid neoplasm. Furthermore, the follicular variant of papillary cancer, present in this case, has not been previously described in renal metastases from thyroid cancer. Treatment of the kidney metastases led to the subsequent discovery and treatment of the primary thyroid cancer. The patient underwent nephrectomy followed by total thyroidectomy, and is alive and disease-free 3 years postoperatively. Thyroid cancer metastatic to the kidney is rare clinically, but can be amenable to treatment with good long term results.

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