Marcos Tavares

Clinical prognostic factors in malignant parotid gland tumors.

OBJECTIVE: To analyze the factors in parotid malignant epithelial tumors influencing recurrences and disease-specific survival. METHODS: We retrospectively reviewed the files of 150 patients treated at our institution, from 1974 to 1998. Twenty-four patients were not treated by surgery and were excluded from this study. The remaining 126 patients were treated with surgery and 74 patients had postoperative radiotherapy. Thirty-three patients were treated with parotidectomy plus neck dissection. Neck lymph node metastasis was found in 22 patients, 5 patients had occult neck metastasis, and 4 periparotid lymph nodes metastasis. The mean age was 49 years old. According to the UICC/1997 TNM Classification, 49 patients were stage I, 27 stage II, 22 stage III, and 28 stage IV. The influence of selected factors on the 10 year disease-specific survival was analyzed using the Kaplan-Meier actuarial method and the log-rank test. RESULTS: Forty patients had mucoepidermoid carcinoma, 18 patients adenocarcinoma NOS, 18 patients acinic cell carcinoma, 15 patients adenoid cystic carcinoma, 11 patients malignant mixed tumor, 11 patients salivary duct carcinoma, and 13 patients other pathology. Twenty-five patients had recurrences: 17 had local recurrences, 4 patients had neck recurrences, and 4 were loco-regional recurrences. Five factors influenced negatively the prognosis: 1) T stage (p.00001), 2) grade (p.00001), 3) + lymph nodes (p.0007), 4) facial nerve dysfunction (p.0001), and 5) age (p.004). Patients with high-grade tumors and high-stage tumors had the worst prognosis according to the multivariate analysis. The 10-year disease-specific survival was 97% for stage I, 81% for stage II, 56% for stage III, and 20% for stage IV. CONCLUSION: The grade of the tumor and stage were the most important prognostic factor.

Risk Profiles and Penetrance Estimations in Multiple Endocrine Neoplasia Type 2A Caused by Germline RET Mutations Located in Exon 10

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. Hum Mutat 31:1–8, 2010.

Discovery of the first known benthic invasive species in the Southern Ocean: the North Atlantic spider crab Hyas araneus found in the Antarctic Peninsula

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.

Immunohistochemistry quantification by a digital computer-assisted method compared to semiquantitative analysis.

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 well-differentiated 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 computer-assisted 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.

Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma

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.

Clinical and epidemiological features of oral cancer in a medical school teaching hospital from 1994 to 2002: increasing incidence in women, predominance of advanced local disease, and low incidence of neck metastases

PURPOSE Description of clinical and epidemiological characteristics of patients who underwent surgery for oral cancer in a Medical School Teaching Hospital, and determination of differences with respect to other institutions and/or periods of time. METHOD The charts of patients undergoing surgery for oral cancer from 1994 to 2002 were reviewed. Data were collected in a spreadsheet in order to analyze clinical and epidemiological features.. 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.

Thyroid Function After Unilateral Total Lobectomy Risk Factors for Postoperative Hypothyroidism

OBJECTIVE To evaluate the incidence of postoperative hypothyroidism among patients who underwent unilateral total lobectomy and identify related factors. DESIGN Retrospective medical record analysis. SETTING Oncological center and private clinic. PATIENTS From March 1996 to July 2005, 228 euthyroid patients underwent unilateral total lobectomy for benign diseases; 168 had all the information required for inclusion in this study. MAIN OUTCOME MEASURES Serum levels of thyrotropin and antithyroidal antibodies were assessed, as well as ultrasonographic evaluation of the remaining thyroid lobe and review of all histological specimens, with emphasis on lymphocytic infiltration. Hypothyroidism was defined as thyrotropin level greater than 5.5 mU/L. RESULTS Most patients were female (88%), with a median (range) age of 45 (16-72) years. Hypothyroidism occurred in 61 cases (32.8%), during a median follow-up period of 29 months (range, 6-108 months). Statistically related factors included higher preoperative thyrotropin levels (2.1 mU/L among hypothyroid patients vs 1.2 mU/L in euthyroid patients; P < .001), smaller thyroid remnant volume (3.9 mL vs 6.0 mL, respectively; P = .003); right vs left lobectomy (P = .006), and higher thyroperoxidase antibody serum levels (P = .009). CONCLUSIONS Postoperative hypothyroidism appeared in 32.8% of the cases in this series, especially among patients with elevated preoperative thyrotropin and postoperative thyroperoxidase antibody levels, after right lobectomy and when a smaller thyroid remnant was left. After confirmation with larger prospective series, these results may support the indication for early postoperative hormone supplementation in these instances.

High Penetrance of Pheochromocytoma Associated with the Novel C634Y/Y791F Double Germline Mutation in the RET Protooncogene

CONTEXT Previous studies have shown that double RET mutations may be associated with unusual multiple endocrine neoplasia type 2 (MEN 2) phenotypes. OBJECTIVE Our objective was to report the clinical features of patients harboring a previously unreported double mutation of the RET gene and to characterize this mutation in vitro. PATIENTS Sixteen patients from four unrelated families and harboring the C634Y/Y791F double RET germline mutation were included in the study. RESULTS Large pheochromocytomas measuring 6.0-14 cm and weighing up to 640 g were identified in the four index cases. Three of the four tumors were bilateral. High penetrance of pheochromocytoma was also seen in the C634Y/Y791F-mutation-positive relatives (seven of nine, 77.7%). Of these, two cases had bilateral tumors, one presented with multifocal tumors, two cases had large tumors (>5 cm), and one case, which was diagnosed with a large (5.5 x 4.5 x 4.0 cm) pheochromocytoma, reported early onset of symptoms of the disease (14 yr old). The overall penetrance of pheochromocytoma was 84.6% (11 of 13). Development of medullary thyroid carcinoma in our patients seemed similar to that observed in patients with codon 634 mutations. Haplotype analysis demonstrated that the mutation did not arise from a common ancestor. In vitro studies showed the double C634Y/Y791F RET receptor was significantly more phosphorylated than either activated wild-type receptor or single C634Y and Y791F RET mutants. CONCLUSIONS Our data suggest that the natural history of the novel C634Y/Y791F double mutation carries a codon 634-like pattern of medullary thyroid carcinoma development, is associated with increased susceptibility to unusually large bilateral pheochromocytomas, and is likely more biologically active than each individual mutation.

Polychaete assemblage of an impacted estuary, Guanabara Bay, Rio de Janeiro, Brazil

Thirty-eight stations were sampled in Guanabara Bay, Rio de Janeiro, Brazil, to assess the spatio-temporal diversity and biomass of sublittoral polychaetes. Samples were collected during the dry (September 2000) and rainy season (May 2001) in shallow sublittoral sediments. The polychaete spatial composition showed a heterogeneous distribution throughout the bay. A negative gradient of diversity and biomass was observed towards the inner parts of the bay and sheltered areas. A wide azoic area was found inside the bay. Some high-biomass and low-diversity spots were found near a sewage-discharge point. In these areas, the polychaete biomass increased after the rainy season. A diversified polychaete community was identified around the bay mouth, with no dramatic changes of this pattern between the two sampling periods. Deposit-feeders were dominant in the entire study area. The relative importance of carnivores and omnivores increased towards the outer sector, at stations with coarse sediment fractions. Guanabara Bay can be divided into three main zones with respect to environmental conditions and polychaete diversity and biomass patterns: A) High polychaete diversity, hydrodynamically exposed areas composed of sandy, oxidized or moderately reduced sediments with normoxic conditions in the water column. B) Low diversity and high biomass of deposit and suspension-feeding polychaete species in the middle part of the bay near continental inflows, comprising stations sharing similar proportions of silt, clay and fine sands. C) Azoic area or an impoverished polychaete community in hydrodynamically low-energy areas of silt and clay with extremely reduced sediments, high total organic matter content and hypoxic conditions in the water column, located essentially from the mid-bay towards the north sector. High total organic matter content and hypoxic conditions combined with slow water renewal in the inner bay seemed to play a key role in the polychaete diversity and biomass. Sedimentation processes and organic load coming from untreated sewage into the bay may have negatively affected the survivorship of the fauna.

Angiogenesis as an indicator of metastatic potential in papillary thyroid carcinoma

UNLABELLED Angiogenesis is new blood vessel formation, a process that can lead to tumor development. Microvessel count has been correlated to metastasis in some neoplasias. PURPOSE To determine if measurement of microvessel density is useful in predicting metastasis to the cervical lymph node and prognosis in patients with papillary thyroid carcinoma. METHODS A retrospective analysis was performed in 30 patients that had undergone total thyroidectomy. They were divided in 2 groups of 15 patients--with and without metastatic disease. Immunohistochemistry was used to detect expression of CD34 in archival paraffin-embedded papillary thyroid tumors, and microvessel density was calculated based on it. Association between microvessel density and the presence of metastasis, according to histological subtype, disease recurrence, and AMES prognostic index groups was determined through statistical analysis. RESULTS The median microvessel density for the patient group without metastasis (200.0 microvessels/mm2) was apparently, but not significantly, less than that observed among metastatic disease patients (254.4 microvessels/mm2) (P=.20). When papillary carcinoma subtypes were analyzed, this difference became significant (P=02). The follicular variant exhibited a greater microvessel density than the other subtypes, independent of metastasis presence. There was an apparent, but not significant, tendency for a larger median microvessel density in the group of patients that presented recurrence (294.4 microvessels/mm2 vs 249.6 microvessels/mm2, P=.11). There was no relationship between risk level and microvessel density: in the low- and high-risk groups, the median MVD was 304.0 microvessels/mm2 and 229.6 microvessels/mm2, respectively (P=.27). CONCLUSIONS The results suggest that angiogenesis is more intense among metastatic tumors in the classic and the tall cell variants, indicating that microvessel count can be an indicator of the potential for metastasis in these subtypes of papillary thyroid carcinoma. Patients that developed recurrent disease had a tendency to exhibit higher angiogenesis; however, there was no association between microvessel density and the AMES prognostic index.