Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2–4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%–100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma.In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma and consequent incorrect recommendation for thyroid surgery.
Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609→620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.
RESULTS:A total of 374 patients having undergone 406 operations was identified. Their ages varied from 14 to 94 years (mean = 57.4 years), with 255 men (68.2%), and 295 out 366 Caucasian (80.6%). A majority had tumors of the tongue and/ or floor of mouth (55.6%), while 20.3% had lip cancer. Squamous cell carcinoma was found in 90.3%, and glandular carcinoma in 4%. T4 tumors in 39.6%, Tis or T1 lesions in 15.2% of all patients. Nearly 62% had no regional metastases, and the relative incidence in young patients (40 years or younger) reached 8.6%. CONCLUSION: In spite of the predominance of locally advanced tumors, a majority of patients had no neck metastases. The 31.8% incidence in females indicates an increasing incidence of oral cavity cancer among women when compared to previous periods at the same institution.
KEYWORDS: Head and neck neoplasms. Mouth neoplasms. Neoplasm metastasis. Population at risk. Epidemiology.Cancer of the oral cavity represents 2.6% of all malignancies affecting the Brazilian population according an estimate from the Brazilian National Cancer Institute (INCa) for 2003. Oral cancer is the eighth most common cancer in Brazil and occupies the sixth place when only men are considered. Regarding mortality, a total of 2.8% of deaths by cancer was due to malignancies in the mouth, which places oral cancer in the ninth place for mortality among all malignant tumors.
PURPOSE: To compare immunostaining quantification obtained by a digital computer-assisted method with the well-established semiquantitative analysis. METHODS: Cytoplasmic staining of galectin-3 was obtained by standard immunohistochemical reactions in 25 cases of welldifferentiated thyroid carcinoma. The expression index that associates the conventional area fraction of labeled cells with the immunostaining intensity score based on visual qualitative observation was used as the semiquantitative analysis. A digital computerassisted method is described based on the use of an image processing program (ImageLab ®). Three parameters were obtained: (1) percentage of labeled cells; (2) digital immunostaining intensity, and (3) digital expression index. The proposed method allows numerical analysis of the immunostaining intensity. RESULTS: There was a strong correlation between the immunostaining intensity obtained by the two methods (Pearson correlation coefficient, r = 0.71, P = 0.0001). The same was observed between expression indexes (Pearson correlation coefficient, r = 0.66, P = 0.0001). CONCLUSION: Results obtained with our proposed digital computer-assisted method for immunoexpression analysis were concordant with the semiquantitative analysis. In addition, digital values can also resolve disagreement among different observers about the quality of staining intensity because the digital method does not classify the results into groups, but rather provides a numerical value for each individual case; thus, it increases the diagnostic and, more importantly, the prognostic sensitivity of the immunohistochemical analysis.
The Southern Ocean around Antarctica is no longer free from invasive marine species. The North Atlantic spider crab Hyas araneus (Linnaeus, 1758) (Crustacea: Decapoda: Majidae) has been recorded for the first time from the Antarctic Peninsula. Isolated for at least 25 million years, the endemic Antarctic Southern Ocean marine fauna is now being exposed to human-mediated influx of exotic species. Invasive species and polar warming combined can foster the probability of arrival and colonization by non-indigenous species, with unpredictable consequences for the Antarctic marine biota.
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