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Thyroid tumors in children and adolescents: preoperative study.

Several studies indicate that in young patients (less than 21 years of age at the time of diagnosis), the prognosis of thyroid carcinoma (TC) is more favorable than in older patients. However, a more radical treatment approach is recommended in children and adolescents due to the higher prevalence of local lymph-node involvement in these cases. Since the extent of primary surgical treatment is closely related to the overall prognosis, preoperative diagnosis becomes essential in the management of thyroid neoplasms in young patients. In this retrospective study (1987-1998), we analyzed a surgical series of 50 children and adolescents with thyroid nodules in an attempt to establish the role of diagnostic studies in detecting malignant lesions prior to surgery. Our diagnostic protocol for evaluating thyroid nodules was based on clinical evaluation, measurement of thyroid-hormone and thyroglobulin (TG) levels, anti-TG and anti-TPO antibody titers, calcitonin, CEA, and TPA levels, sonography, scintigraphy, and fine-needle aspiration cytology (FNAC) of the thyroid nodules and any enlarged lymph nodes. Eleven of the 15 cases of histologically confirmed carcinoma were preoperatively identified as malignant lesions with the aid of FNAC. The authors conclude that the preoperative work-up of children and adolescents with thyroid nodules requires the collaboration of an experienced team of professionals, and recommend FNAC as the initial test.

Adolescent↗

Poorly differentiated insular thyroid carcinoma. A case report with identification of intact insulae with fine needle aspiration biopsy.

BACKGROUND: Subsequent to the publication of a report in 1984 entitled "Poorly Differentiated ("Insular") Carcinoma: A Reinterpretation of Langhans "wuchernde Struma," poorly differentiated insular thyroid carcinoma (PDITC) has become recognized as a distinct thyroid neoplasm. It is classified morphologically and biologically as an intermediate entity between well-differentiated (papillary and follicular) and undifferentiated (anaplastic) thyroid carcinomas. Only a few publications have addressed the findings with fine needle aspiration biopsy (FNAB). CASE: A 67-year-old female presented for evaluation of a massively enlarged thyroid gland. Fine needle aspiration biopsy of the thyroid with a 22-gauge needle showed many large, multilayered, round to oval nests of tumor cells, 0.2-0.4 mm in diameter. Rosettelike configurations of 8-15 cells, 0.025-0.050 mm in diameter, were also observed. Nests of neoplastic cells in the histologic sections were virtually identical to those in the fine needle aspiration biopsy specimens. When the patient developed metastatic cervical adenopathy one year later, a microfollicular pattern was seen on both the FNAB and histologic sections. CONCLUSION: When nests of tumor cells, 0.2-0.4 mm in diameter, are identified in a thyroid FNAB specimen, PDITC should be included in the differential diagnosis. A microfollicular pattern in a metastatic lymph node does not exclude the possibility that the primary tumor is a PDITC.

Aged↗

Unsuspected intrathyroidal parathyroid adenoma: mimic of lymphocytic thyroiditis in fine-needle aspiration specimens-a case report.

Fine-needle aspirations (FNAs) of parathyroid adenomas (PA) are infrequently encountered, but the scant literature on this topic emphasizes the difficulties in distinguishing them from thyroid neoplasms. We report on a case of an unsuspected intrathyroidal PA whose two FNA specimens mimicked almost perfectly the features of lymphocytic thyroiditis (LT). The smears from two FNAs of a "thyroid nodule" in a 22-yr-old woman were received with a clinical diagnosis of "LT." The cytological features of both specimens were similar and consisted of groups of epithelial cells in a background of numerous "naked" nuclei, interpreted as Hurthle cells and lymphocytes respectively, and leading to a cytological diagnosis of LT. Subsequent surgical excision of the "nodule" revealed a large intrathyroidal PA. The oxyphil cells and chief cells (the latter devoid of cytoplasm) present in the PA resembled Hurthle cells and lymphocytes respectively, in the FNA specimens. In conclusion, PA can give a cytological picture almost identical to that of LT in FNA material. Important clues to the diagnosis of PA in FNA specimens include the presence of prominent capillaries and the knowledge of a clinical history of hyperparathyroidism. Diagn. Cytopathol. 1999;21:276-279.

Adenoma↗

Adenoviral infection of thyroid cells: a rationale for gene therapy for metastatic thyroid carcinoma.

BACKGROUND: Patients with thyroid carcinoma experience excellent long-term survival; however, up to 16% will die of their disease. We have transformed a rat thyroid follicular cell line (FRTL-5) with a gene (TGCT) that mimics a known mutation associated with thyroid neoplasms. These cells form subcutaneous tumors that metastasize to lung in nude mice. METHODS: In anticipation of developing gene therapy against this thyroid carcinoma model, we (1) tested whether adenovirus containing the beta-galactosidase gene could infect FRTL-5 cells and neonatal rat thyroid and (2) evaluated the ability to kill FRTL-5 cells by transfecting them with a transgene in which the thyroglobulin promoter (TG) directed the expression of herpes simplex virus type I thymidine kinase (HSV1TK) and treating TG-HSV1TK-transfected cells with 5 micrograms/ml ganciclovir. RESULTS: Nearly 100% of the TG-HSV1TK but only 5% of control cells were killed by addition of ganciclovir. Histochemical staining for beta-galactosidase activity demonstrated infection of FRTL-5 cells and neonatal rat thyroid tissue by adenovirus beta-galactosidase. CONCLUSIONS: These data demonstrate the feasibility of using adenovirus as vector to infect thyroid cells in vivo and provide a rationale for development of gene therapy for treatment of thyroid cancer.

Adenoviridae↗

Hypopigmentation of a papillary carcinoma arising in a black thyroid.

We report a case of an unpigmented papillary carcinoma arising in a black thyroid induced by minocycline. Black thyroid syndrome is an unusual pigmented change seen almost exclusively in patients on minocycline, apparently resulting from an oxidative interaction between thyroid peroxidase and the drug. Twenty-six cases have previously been reported in the English literature, nine of which described an associated thyroid neoplasm. Four of these nine neoplasms were described as pale or hypopigmented. The nature of the lesion against the background of pigmentation suggests diminished function of the thyroid peroxidase in this clonal population.

Adult↗

Primary hyperparathyroidism in patients who have received radiation therapy and in patients who have not received radiation therapy.

BACKGROUND: Primary hyperparathyroidism (HPT) occurs more frequently in persons who have been exposed to low-dose therapeutic radiation. Little information is available concerning whether or not the clinical, metabolic, and pathologic manifestations, as well as outcome, differ in these patients when compared with patients with sporadic HPT. STUDY DESIGN: Records from 438 unselected patients with primary HPT, who were treated from 1982 to 1993 were retrospectively analyzed. All patients prospectively received a standard questionnaire preoperatively and postoperatively concerning clinical manifestations and a history of radiation exposure. Forty-nine patients had a history of radiation exposure (rHPT), whereas 389 did not have sporadic HPT (sHPT). RESULTS: There was no difference in gender (36 women and 13 men versus 289 women and 100 men) or age (mean of 52 +/- 12 versus 57 +/- 16 years) in patients with rHPT or sHPT. Fatigue, neuropsychiatric disorders, memory loss, nocturia, and polyurea were more common in patients with sHPT (p < 0.05), whereas pain in joints was more common in patients with rHPT (63 versus 52 percent; p < 0.001). Serum calcium levels were similar (11.1 +/- 0.8 versus 11.2 +/- 0.8 mg per dL), but serum parathyroid hormone levels were higher in rHPT (448 +/- 14 percent of upper limit of normal versus 371 +/- 12 percent upper limit of normal). The parathyroid pathology was similar in the two groups (single adenoma 74 versus 72 percent, hyperplasia 14 versus 16 percent, and double adenoma 12 versus 12 percent in rHPT versus sHPT, respectively). Thyroid pathology was more common in the rHPT group (multinodular goiter 27 versus 7 percent and papillary thyroid carcinoma 14 versus 0.3 percent). Seven (1.8 percent) of patients not receiving radiation therapy treated by us had persistent HPT, but no patients receiving or not receiving radiation therapy had recurrent HPT during the follow-up period (six years). CONCLUSIONS: Patients who have HPT after radiation treatment have more thyroid neoplasms but are otherwise quite similar to other patients with primary hyperparathyroidism.

Adolescent↗

Spindle cell metaplasia in follicular adenoma of the thyroid gland: case report and review of the literature.

Spindle cell tumors and reactive proliferations of the thyroid gland are rarely reported. In this report, we described a case of follicular adenoma with spindle cell component. The spindle cell proliferation constituted more than 90% of the 4.0 cm lesion and showed fascicular pattern with focal areas of collagenous stroma and hyalinized blood vessels. There was a transition from follicle like glandular structure to fascicular pattern. There was no mitosis and necrosis. Immunoreactivity with thyroglobulin proved that the spindle cell proliferation is of follicular origin. Also strong thyroglobulin and cytokeratin positivity of glandular areas and the gradual decrease in positivity of spindle cells showed epithelial-mesenchymal transformation/spindle cell metaplasia of the thyroid. We thought that it is important to differentiate spindle cell metaplasia in follicular lesions, especially follicular adenoma, from malignant thyroid neoplasms.

Adenoma↗

Graves' disease, follicular thyroid carcinoma and functioning pulmonary metastases.

We present a case with the unusual association of Graves' disease and functioning pulmonary metastases of follicular thyroid carcinoma. Unlike other reports of thyroid cancer and thyrotoxicosis, this patient's hyperthyroidism was related to a hyperfunctioning primary thyroid neoplasm and not merely to large amounts of functioning metastatic tumor. Thyroidectomy cured her hyperthyroidism. A lung biopsy confirmed the impression of metastatic thyroid cancer. Following therapeutic radioactive I131 pulmonary metastases completely disappeared.

Adenocarcinoma↗

Estimating sample size for epidemiologic studies: the impact of ignoring exposure measurement uncertainty.

Sample size requirements for epidemiologic studies are usually determined on the basis of the desired level of statistical power. Suppose, however, that one is planning a study in which the participants' true exposure levels are unobservable. Instead, the analysis will be based on an imprecise surrogate measure that differs from true exposure by some non-negligible amount of measurement error. Sample size estimates for tests of association between the surrogate exposure measure and the outcome of interest may be misleading if they are based solely on the anticipated characteristics of the distribution of surrogate measures in the study population. We examine the accuracy of sample size estimates for cohort studies in which a continuous surrogate exposure measure is subject to either classical or Berkson measurement error. In particular, we evaluate the consequences of not adjusting the sample size estimation procedure for tests based on imprecise exposure measurements to account for anticipated differences between the distributions of the true exposure and the surrogate measure in the study population. As expected, failure to adjust for classical measurement error can lead to underestimation of the required sample size. Disregard of Berkson measurement error, however, can result in sample size estimates that exceed the actual number of participants required for tests of association between the outcome and the surrogate exposure measure. We illustrate this Berkson error effect by estimating sample size for a hypothetical cohort study that examines an association between childhood exposure to radioiodine and the development of thyroid neoplasms.

Adolescent↗

[Thyroid tumors in the mediastinum].

The Authors studied 46 cases of thyroid neoplasm, characterized by a mediastinal involvement of different degrees, and analysed the epidemiologic, anatomo-pathological and clinical aspects thereof. Then, they, on the basis of their experience, outlined the formulation of the diagnostic ascertainments and surgical treatment.

Adult↗

Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid.

Making a histologic distinction between Hurthle cell adenomas and carcinomas sometimes may be difficult. We analyzed a series of Hurthle cell lesions to determine whether specific histologic features and expression of Ki67 and cyclin D1 could be useful in distinguishing Hurthle cell adenomas from carcinomas. Formalin-fixed, paraffin-embedded tissues from 128 Hurthle cell neoplasms, including 59 adenomas; 55 carcinomas; and 14 tumors classified as neoplasms of uncertain malignant behavior (UMB), which had equivocal capsular invasion but no vascular invasion, were analyzed for expression of Ki67 and cyclin D1 by immunostaining. The distribution of immunoreactivity for Ki67 with antibody MIB-1 was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index. None of the patients with adenomas or UMB tumors developed recurrent or metastatic disease after a mean follow-up of 7.8 and 7.9 years, respectively. Of the 55 patients with Hurthle cell carcinoma, 19 were associated with metastatic disease, 13 of whom died with disease. No patient with a Hurthle cell carcinoma without vascular invasion developed metastatic disease. The mean tumor size for Hurthle cell carcinomas (4.8 cm) was significantly larger than that of Hurthle cell adenomas (3.1 cm) or UMB tumors (3.7 cm). No patient with a Hurthle cell tumor smaller than 3.5 cm developed metastatic disease, even when vascular invasion was present. The Ki67 labeling index in Hurthle cell carcinomas (10.0 +/- 1.2) was 3-fold higher than in Hurthle cell adenomas (3.2 +/- 0.3). The Ki67 labeling index in the UMB group was 5.0 +/- 0.7. Cyclin D1 showed diffuse nuclear staining in 1 of the 59 (1.7%) Hurthle cell adenomas, in 10 of the 55 (18%) Hurthle cell carcinomas, and in none of the UMB tumors. In summary, analyses of the cell cycle proteins Ki67 and cyclin D1 in Hurthle cell thyroid neoplasms indicate that these markers may assist in distinguishing some Hurthle cell carcinomas from adenomas. Among the Hurthle cell carcinomas, large tumor size and vascular invasion are associated with clinically aggressive tumors. Our study also suggests that Hurthle cell neoplasms with only equivocal capsular invasion and no vascular invasion should behave in a benign manner.

Adenocarcinoma↗

Management of follicular and Hürthle cell neoplasms of the thyroid gland.

Management of follicular and Hürthle cell neoplasms of the thyroid gland is a common clinical problem. A diagnosis of follicular or Hürthle cell carcinoma cannot be made from a fine-needle aspiration biopsy alone because it requires histologic demonstration of capsular or vascular invasion. Thyroid lobectomy and isthmusectomy is adequate treatment of benign follicular or Hürthle cell adenoma and minimally invasive follicular carcinoma. Total thyroidectomy, radioiodine ablation, and thyrotropin-suppressive doses of thyroid hormone is advocated for the invasive subtype of follicular carcinoma and all Hürthle cell carcinomas. Monitoring of serum thyroglobulin levels postoperatively is important for detection of recurrent disease.

Adenocarcinoma↗

Nerve growth factor in medullary carcinoma of the thyroid.

In a case of medullary carcinoma of the thyroid gland assay was performed for nerve growth factor bioactivity. The tumor extract showed significant amounts of nerve growth factor bioactivity, but extracts of normal thyroid and other types of thyroid neoplasms showed no such bioactivity. Nerve growth factor may be useful as a tumor marker in the diagnosis and management of medullary carcinoma of the thyroid. It may play a role in the development of associated tumors of neural crest origin and may contribute to the development of cachexia in patients with medullary carcinoma of the thyroid.

Adult↗

Primary squamous cell carcinoma of the thyroid arising in Hashimoto's thyroiditis in an adolescent.

Squamous cell carcinoma is a rare thyroid neoplasm that has been described exclusively in adults. We report what appears to be the first example of a primary squamous cell carcinoma of the thyroid gland arising in a background of Hashimoto's thyroiditis in an adolescent female. The tumor was well demarcated, confined to the right thyroid lobe, and did not metastasize, although follow up has been limited. The squamous cell carcinoma was well to moderately differentiated, and the stroma contained an abundant inflammatory infiltrate rich in lymphocytes and eosinophils. The lack of goblet cells, extracellular mucin, and extensive stromal sclerosis excluded the diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia. Immunohistochemical staining revealed focal expression of cytokeratin 7 and diffuse labeling with cytokeratin AE1/AE3. The squamous cell carcinoma overexpressed p53 protein and showed increased proliferative activity, as evidenced by the high MIB-1 labeling index. In contrast, the tumor did not show immunoreactivity for thyroglobulin or thyroid transcription factor 1.

Adolescent↗

A review of heterotopia and associated salivary gland neoplasms of the head and neck.

Salivary tissue neoplasms may involve normal, accessory and heterotopic salivary gland tissue. A case of Warthin's tumour originating from heterotopic salivary gland tissue of the upper neck is reported. The radioactive uptake of 131I, evidenced in the neck mass in its pre-diagnostic assessment, suggested a diagnosis of cervical node involvement from a primary malignant thyroid neoplasm. A critical review of the literature on heterotopic salivary gland tissue neoplasms of the head and neck is also presented.

Adenolymphoma↗