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Fluorescamine in cytodiagnosis of thyroid carcinomas.

Fluorescamine, which reacts with primary amino groups yielding intensely fluorescent products, was found to induce intense fluorescence in cells from medullary and papillary thyroid carcinoma. No fluorescence was detected in cells from follicular or undifferentiated carcinoma or from benign thyroid lesions, except Hürthle cell adenomas, the cells of which exhibited moderate fluorescamine-induced fluorescence. This was demonstrated on fine needle aspiration biopsy smears pretreated with formaldehyde gas. Since the fluorescamine technique is simple and rapid, it may be of value as an aid in the cytodiagnosis of thyroid neoplasms.

Biopsy, Needle↗

Lymphocytic infiltration in pediatric thyroid carcinomas.

Lymphocytic thyroiditis has been associated with an increase in the incidence of thyroid papillary carcinoma in some reports, mostly series of both adults and children. Relatively little is written about thyroiditis and follicular carcinomas. We have seen several cases of pediatric follicular thyroid carcinomas, that had an associated lymphocytic infiltrate, which led us to examine all primary malignant thyroid neoplasms in our surgical files from 1984 through 2000 to examine this relationship. We also investigated the nature of the lymphocytic infiltrate with routine immunohistochemistry. Ten patients (five male, five female, ages 4.5-21 years of age) had a thyroid carcinoma resection, six (three males and three females) with papillary carcinoma and four patients (two males and two females) with low-grade follicular carcinoma. Seven samples (one male had two cases with tumor) from patients who had a papillary carcinoma resection with tissue blocks available were identified (one patient had slides but no blocks), as were all four patients with a follicular carcinoma. The thyroid of all patients with a follicular carcinoma contained a lymphocytic infiltrate; only four of the seven papillary carcinoma samples had an associated lymphoid infiltrate. In all cases with a lymphoid infiltrate, the infiltrate was present in both lobes (both adjacent and separate from the tumor). B lymphocytes were present in the lymphoid infiltrate of three of four patients with follicular carcinomas and in 1 of 3 cases of papillary carcinomas. T cells were dispersed throughout all the tumors with lymphoid infiltrates. We conclude that pediatric follicular carcinomas have an associated lymphocytic infiltrate in the tumor and/or adjacent thyroid, more commonly than papillary carcinomas.

Adenocarcinoma, Follicular↗

Cyclin-dependent kinase inhibitor p27(Kip1) expression in thyroid cells obtained by fine-needle aspiration biopsy: a preliminary report.

Recent studies on paraffin-embedded tissue have shown that the cyclin-dependent kinase inhibitor p27(Kip1) is expressed in normal thyroid cells, whereas it is downregulated in neoplastic cells. This prospective study was undertaken to assess whether p27(Kip1) staining may also be applied to fine-needle aspiration biopsy (FNAB) samples of the thyroid. We present here our preliminary results on 100 FNABs examined for p27(Kip1) expression. p27(Kip1) expression was assessed by immunocytochemistry; the technique was optimized on smears prepared from a normal thyreocyte cell line (TL5), which conspicuously expresses p27(Kip1), and then applied to FNAB samples prospectively collected from 80 cases of nodular goiter and 20 cases of thyroid neoplasms (10 papillary carcinomas and 10 follicular neoplasms). The TL5 cell culture smears showed that methanol fixation, followed by heat-induced antigen retrieval, is the most suitable technique for p27(Kip1) staining on cytological samples. The FNAB smears similarly treated showed high p27(Kip1) expression (75%) in goiter and a significantly lower expression (35%) in neoplasms (P < 0.0001). Our preliminary results show that: 1) p27(Kip1) protein expression can be reliably assessed on cytological samples; and 2) p27(Kip1) stains nonneoplastic and neoplastic samples in a different fashion, and thus is a useful tool in thyroid cytology.

Adenocarcinoma, Follicular↗

Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue.

In order to better understand basic mechanisms of tumor development and identify potential new biomarkers, we have performed difference gel electrophoresis (DIGE) and peptide mass fingerprinting on pooled protein extracts from patients with papillary thyroid carcinoma (PTC) compared with matched normal thyroid tissue. Image analysis of DIGE gels comparing PTC and matched normal thyroid tissue protein indicated that 25% of the protein spots were differentially expressed at a 2.5-fold cutoff and 35% at two-fold. Comparison between two different pools of protein from normal thyroid tissues revealed differential protein expression of only 4% at 2.5-fold and 6% at two-fold cutoff. One hundred ninety-two protein spots were identified by MALDI-TOFMS, representing 90 distinct proteins. Excluding albumin, globins and thyroglobulin, imaging software determined 31 proteins to be differentially expressed at the two-fold (or greater) level. Individual gel comparisons (PTC vs. matched normal) from five patients established that 15/31 (48%) of these proteins exhibited statistically significant differential expression. Previously identified molecular markers in this group of proteins include cathepsin B, cytokeratin 19, and galectin-3. Novel differentially expressed proteins include S100A6, moesin, HSP70 (BiP), peroxiredoxin 2, protein phosphatase 2, selenium binding protein 1, vitamin D binding protein, and proteins involved in mitochondrial function. The use of two-dimensional gel electrophoresis (2DGE) revealed a significantly altered protein mass and/or pI in 10%-15% of proteins, suggesting alternatively spliced forms and other posttranslational modification of proteins revealed by this approach. We confirmed S100A6 as a potentially useful biomarker using immunohistochemical analysis (85% sensitivity and 69% specificity for distinguishing benign from malignant thyroid neoplasms). In summary, proteomic analysis of PTC using DIGE and mass spectrometry has confirmed several known biomarkers, uncovered novel potential biomarkers, and provided insights into global pathophysiologic changes in PTC. Many of the differences observed would not have been detected by genomic or other proteomic approaches.

Amino Acid Sequence↗

Ultrasound in head and neck surgery: thyroid, parathyroid, and cervical lymph nodes.

Ultrasound (US) of the neck is extremely sensitive in detecting thyroid, parathyroid, and cervical lymph node pathology, and is regarded as the most complete and cost-effective imaging method for evaluating the thyroid and parathyroid glands, as well as for the diagnostic evaluation of the cervical lymph node basin. US is widely used in screening high-risk individuals, evaluation of palpable and nonpalpable thyroid nodules, needle guidance for biopsy of nonpalpable and suspicious nodules, and preoperative evaluation of the extent of thyroid neoplasms, as well as in the detection of residual, recurrent, or metastatic thyroid tumors, and in observing nonsurgical cases. It has thus become an important adjunct to the practice of head and neck surgery.

Adenoma↗

Necrosis of thyroid nodules after fine needle aspiration.

In a series of 200 fine needle aspirations (FNA) of the thyroid, necrosis around the needle tract was histologically evident in 2 of 30 cases with surgical follow-up. In one case of a differentiated thyroid carcinoma, necrosis with involution of the nodule was the dominant finding. This suggests that FNA can induce necrosis and apparent clinical regression of thyroid neoplasms. We believe, however, that a positive cytologic diagnosis coupled with a clinical suspicion of neoplasm should lead to surgical intervention, despite clinical regression following FNA.

Adult↗

[Insular carcinoma of the thyroid. Apropos of a case and review of the literature].

We present a new case report of "Insular" thyroid carcinoma. The first series was published, in 1984, by Carcangiu et al. The propensity for local recurrence and early distant metastases explains the poor prognosis of this carcinoma and demands aggressive therapy at the time of diagnosis. This includes radical surgery, radiotherapy with possible chemotherapy. Clinical and pathological arguments suggest that this carcinoma could be an intermediate stage in the process of loss of differentiation of some thyroid neoplasms.

Carcinoma↗

Papillary thyroid cancer with an initial presentation of abdominal and flank pain.

PURPOSE: Well-differentiated thyroid cancer typically presents as a thyroid mass. Common sites of metastases upon presentation include cervical lymph nodes, lung, and bone. Well-differentiated thyroid cancer with clinically apparent kidney metastases is rare, with fewer than 20 cases reported in the literature. In the vast majority of these cases, the patients had known thyroid neoplasms at the time the renal metastases were identified. We report a case of papillary thyroid carcinoma that presented with abdominal pain in a 25-year-old woman with no previous history of thyroid disease. STUDY DESIGN: This study is a case report. RESULTS: The patient underwent radical nephrectomy for a right renal mass, which was diagnosed as papillary thyroid carcinoma follicular variant. During subsequent evaluation, metastatic disease was also identified in the patient's lungs. The patient was treated with total thyroidectomy and iodine 131. CONCLUSIONS: Papillary cancer, which ordinarily behaves in an indolent manner, can have unusual presentation, including disseminated metastasis on presentation. Renal metastases are extremely rare.

Abdominal Pain↗

Patterns of neoplasia in c-mos transgenic mice and their relevance to multiple endocrine neoplasia.

We have previously described a neurological phenotype for transgenic mice carrying the c-Mos proto-oncogene. Pheochromocytomas and C-cell thyroid neoplasms occur in these transgenic lines in patterns that are similar to those seen in multiple endocrine neoplasia type 2 (MEN 2). Characterization of the pathological lesions via immunohistochemistry underscores similarities between MEN 2 and these transgenic mice. When transgenic mice that do not display the MEN 2 phenotype are crossed to a different background, the progeny display the MEN 2 phenotype. Thus the interaction of the background with the transgene is such that it can suppress tumor information. This observation bears special relevance to the human syndrome in that this model system may be used to study the question of penetrance of phenotype.

Adrenal Gland Neoplasms↗

Superior mediastinal dissection in the treatment of Hürthle cell carcinoma of the thyroid.

BACKGROUND: Hürthle cell carcinoma of the thyroid frequently metastasizes to regional lymph nodes. Delayed lymph node dissection may become necessary, adding little risk to patient survivability; however, metastatic disease to the superior mediastinum that cannot be promptly detected, represents a survival threat that deserves special attention. The purpose of this study is to review our experience in managing Hürthle cell carcinoma of the thyroid and make recommendations for appropriate treatment. PATIENTS AND METHODS: A retrospective review of 371 thyroid neoplasms seen between 1987 and 1994 yielded six patients with Hürthle cell carcinoma of the thyroid gland. These include three cases treated with thyroidectomy and transcervical superior mediastinal dissection (SMD) as initial treatment and three cases treated with thyroidectomy alone. RESULTS: Of the three patients treated with SMD as part of their initial treatment, one had occult micrometastases to the superior mediastinum. All three patients remain alive and disease free at least 3 years later, whereas all three patients treated with thyroidectomy alone developed superior mediastinal metastases and died of their disease. CONCLUSION: We propose that at the time of initial surgery, a transcervical SMD may prevent spread to the superior mediastinum and therefore, improve survivability.

Adenocarcinoma↗

Molecular basis off hurthle cell papillary thyroid carcinoma.

Among thyroid neoplasms, Hurthle cell tumors (HCTs) have traditionally been a distinct diagnostic category. Hurthle cell adenomas are encapsulated follicular lesions with benign behavior. Hurthle cell carcinomas exhibit unequivocal capsular and/or vascular invasion; they are aggressive tumors with a poor prognosis. Recently, Hurthle cell papillary thyroid carcinomas (PTCs) have been identified on morphological grounds. We hypothesize that a subset of HCTs represent PTC with clinical, histological, and immunohistochemical features based on specific molecular events. ret/PTC gene rearrangements give rise to novel oncogenes that are unique to PTC. We studied a group (n = 50) of HCTs for ret/PTC gene rearrangements. Tumors were examined for papillary differentiation by light microscopic evaluation of nuclear features, by RT-PCR for ret/PTC gene rearrangements, and by immunohistochemistry for ret. Among 24 noninvasive tumors, 13 contained ribonucleic acid for ret/PTC-1, -2, or -3, and 9 of these were immunoreactive for ret. Among 19 Hurthle cell carcinomas, 15 had focal nuclear hypochromasia with grooves and/or inclusions; expressed transcripts of ret/PTC-1, -2, or-3; and exhibited ret positivity. Tumors with ret/PTC gene rearrangements tended to have lymph node metastases rather than hematogenous spread. Our results indicate that a subset of HCTs exhibit features of PTC that are attributable to specific gene rearrangements, resulting in expression of ret/PTC oncogenes. These data support subclassification of HCTs into three groups: Hurthle cell adenomas, Hurthle cell carcinomas, and Hurthle cell PTC.

Adenocarcinoma, Papillary↗

Thyroid cancer following exposure to radioactive iodine.

The thyroid gland is one of the most sensitive organs for radiation-induced oncogenesis and the magnitude of the risk from external radiation is well understood. This is not the case for internal radiation derived from the radioiodines, a matter of practical importance because of medical use and potential accidental exposure. This article reviews current knowledge derived from the follow-up of patients receiving diagnostic or therapeutic 131I and populations exposed to radioactive fallout. The latter includes the nuclear power station accident at Chernobyl and the results of atomic bomb development and testing at Hanford, the Nevada Test Site and the Marshall Islands. The most cogent information comes from Chernobyl where an epidemic of childhood thyroid cancer has followed exposure to radioiodine that was mainly 131I. Although much has been learned from this experience about the nature of radioiodine induced thyroid cancer in young children, the reconstruction of thyroid radiation doses is too preliminary to provide accurate knowledge of the risk in comparison to that from external radiation. In the Marshall Islands, much of the exposure was from short-lived radioiodines as well as external radiation, obviating the possibility to determine the risk from 131I. Exposure to 131I in the continental United States from atomic bomb testing is expected to have caused some thyroid cancers, but only in the immediate vicinity of the Nevada Test Site has any evidence of radiation-induced thyroid neoplasms been adduced. This evidence is minimally significant statistically, and not significant for thyroid cancer per se. Medical use of radioiodine has not been observed to cause thyroid cancer but very few of the patients studied were young children, the group most sensitive to thyroid radiation. Despite these limitations, this information is sufficient to make some suggestions concerning protective measures in the case of nuclear accidents and the follow up of individuals who have been exposed.

Humans↗

A clinico-pathological study of 100 patients with solitary 'cold' thyroid nodules.

One hundred consecutive patients were studied at the Auckland Hospital thyroid clinic over a two year period 1974 to 1976, who subsequently had surgical excision of a solitary cold nodule. Thyroid carcinoma was present in 17 percent, adenoma in 44 percent, colloid nodules in 25 percent and a thyroid cyst in 14 percent. Although thyroid neoplasms were significantly more frequent in patients under 40, other clinical or scan features analysed were not predictive of carcinoma or neoplasm.

Adenoma↗

Contralateral cervical and mediastinal lymph node metastasis in medullary thyroid cancer: systemic disease?

BACKGROUND: The current American Joint Committee on Cancer/International Union Against Cancer classification designates cervical and mediastinal lymph nodes as regional lymph nodes. In a unilateral thyroid neoplasm, however, involvement of the contralateral cervical lymph node compartment or the mediastinal lymph node compartment, both of which have been designated "distant" lymph nodes, may serve as a surrogate parameter of distant metastases. METHODS: This institutional series consisted of 105 consecutive patients with medullary thyroid cancer who underwent systematic dissections of both distant lymph node compartments. RESULTS: Thirty-eight patients had no distant lymph node metastasis, 36 patients had involvement of only 1, and 31 patients of both distant lymph node compartments. Significant associations (P < .001) were seen on univariate analysis between the number of involved "distant" lymph node compartments (none, one, or both) and extrathyroidal extension (3%, 33%, and 58%), the number of positive lymph nodes (means of 3, 13, and 33), and distant metastasis (8%, 36%, and 61%). In a multivariate logistic regression model, only involvement of one or both "distant" lymph node compartments (versus no distant lymph node metastasis) remained significantly related to distant metastasis in a dose-dependent fashion. CONCLUSIONS: "Distant" lymph nodes in medullary thyroid cancer should be regarded as nonregional lymph nodes because their involvement is indicative of distant metastasis.

Female↗

Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma.

AIMS: Florid vasoproliferative processes are uncommon in the thyroid gland. We report three cases of an unusual vasoproliferation involving the capsular blood vessels of thyroid carcinoma. METHODS AND RESULTS: The histological diagnoses of the three cases were made on conventional histological sections. Two cases were minimally invasive follicular carcinomas and one case was an encapsulated variant of papillary carcinoma. Some blood vessels in the tumour fibrous capsule were filled with spindly cellular proliferations forming irregular vascular clefts and papillae. Immunohistochemical studies for CD31, CD34 and muscle-specific actin confirmed that the spindly cells were mostly endothelial cells variably supported by pericytes. CONCLUSION: This peculiar intravascular endothelial hyperplasia by itself should not be mistaken for vascular invasion by tumour, but evidence of malignancy must be diligently sought by extensive sampling because the lesion has thus far been consistently associated with malignant thyroid neoplasms.

Actins↗

Radiation-induced thyroid and other head and neck tumors: occurrence of multiple tumors and analysis of risk factors.

In 2561 patients who received conventional external radiation treatment before age 15 yr for benign conditions of the head, neck, and upper thoracic area, we found an increase in the number of salivary gland tumors and benign neural tumors of the head and neck area. To determine whether patients who developed these relatively uncommon tumors were more susceptible to the long term effects of radiation, we analyzed how frequently these patients also developed benign and malignant thyroid neoplasms. Compared to the remainder of the irradiated population, the patients with salivary and neural tumors had an increased frequency of thyroid disease (19.4% vs. 11.2% for thyroid cancer and 52.4% vs. 39.9% for all thyroid nodules). Various risk factors were studied to determine whether they were related to the eventual occurrence of thyroid disease. Higher doses, being female, and lower ages at time of treatment were associated with increased risk. However, these factors did not fully explain the differences in the frequency of coexisting tumors, suggesting that additional factors, such as radiation sensitivity, may account for the increased risk.

Age Factors↗

Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications.

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas.

Adenoma↗