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Summary Papillary thyroid microcarcinoma generally carries an excellent prognosis, and fatal cases are becoming increasingly rare. Their pathologic and molecular features, however, remain largely unknown. We describe 3 cases of papillary thyroid microcarcinoma that, despite surgical and radioiodine treatment, recurred, metastasized, and eventually caused the death of the patients. In addition to morphology, immunohistochemical (cyclin D1 and p53) and molecular analyses ( BRAF [v-raf Murine sarcoma viral oncogene homolog B1], KRAS [V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog], HRAS [v-Ha-ras Harvey rat sarcoma viral oncogene homolog], NRAS [neuroblastoma RAS viral oncogene homolog], and PIK3CA [phosphoinositide-3-kinase, catalytic, alpha polypeptide]) were performed. Interestingly, all 3 cases presented with massive lymph node metastases that showed morphological evidence of "tumor progression" (tall cell features, poorly differentiated areas, and high-grade cytologic features). Cyclin D1 was consistently immunoreactive in both primary and metastatic site, whereas p53 was negative. BRAF V600E was absent in both sites, and KRAS , HRAS , NRAS , and PIK3CA were consistently wild type. These data suggest that, in cases of metastatic papillary thyroid microcarcinoma, an accurate morphologic analysis of the metastatic deposits could contribute to a more accurate prediction of tumor behavior.

To provide an overview of ultrasound (US)-guided percutaneous ethanol injection (PEI) therapy for thyroid cystic nodules and discuss the practical and technical details.We present preliminary data of a controlled randomized study involving 281 patients (221 women and 60 men; 18 to 85 years old) with benign thyroid cystic nodules. Study inclusion criteria were local discomfort or cosmetic damage, cystic volume more than 2 mL, 50% or more fluid component, benignity as confirmed by cytologic specimen obtained by US-guided fine-needle aspiration biopsy (FNAB), and euthyroidism. Exclusion criteria were inadequate, suspicious, or positive FNAB cytology, high serum calcitonin, and contralateral laryngeal cord palsy. By random assignment, 138 patients underwent simple cyst evacuation, and 143 underwent cyst evacuation plus PEI by a skilled operator using a US-guided technique. The amount of ethanol injected was 50 to 70% of the cystic fluid extracted.Before treatment, the mean (+/-SD) nodule volume was 19.0 +/- 19.0 mL versus 20.0 +/- 13.4 mL in the PEI versus the simple evacuation group (no significant difference). After 1 year, volumes were 5.5 +/- 11.7 mL versus 16.4 +/- 13.7 mL (P0.001), with a median 85.6% versus 7.3% reduction, respectively (P0.001), of the initial volume. The median nodule volume reduction after PEI was 88.8% and 65.8% in empty body and mixed thyroid cysts, respectively. Compressive and cosmetic symptoms disappeared in 74.8% and 80.0% of patients treated with PEI versus 24.4% and 37.4% of patients treated with simple evacuation, respectively (P0.001). Side effects were minor.These data provide definitive evidence that PEI is a safe and effective treatment for thyroid cystic nodules. Unicameral thyroid cysts are the most suitable candidate nodules for PEI.

By means of semiquantitative immunocytochemistry, possible age-related changes in dopamine and cyclic AMP-regulated phosphoprotein mr 32 (DARPP-32) and glial fibrillary acidic protein (GFAP) immunoreactivities (IR) were investigated in tanycytes of the arcuate nucleus. These two markers showed opposite changes during aging. DARPP-32 IR decreased by around 70%, whereas GFAP IR increased by around 300% in 24-month-old vs. 3-month-old rats. These changes were accompanied by a progressive loss in the number of tanycytes, measured by counting of their long processes in the arcuate nucleus. No significant age-related change was observed either in GFAP IR in astrocytic populations of the mediobasal hypothalamus or in tyrosine hydroxylase IR in dopaminergic neurons of the dorsal arcuate nucleus. These observations indicate that the tanycytic population of the arcuate nucleus undergoes important modifications during aging, which include cell loss, impairment in the intracellular signalling cascade linked to DARPP-32, and hypertrophy. These changes may be related to the alterations in the neuroendocrine systems known to occur during aging.

EUS to exclude, detect and stage ampullary lesions and perform biopsy or FNA. EUS excluded suspected malignant disease in 43% of cases. Mo1477 FISH Analysis of Aspirates Increases the Sensitivity of EUS-Guided FNA for the Diagnosis of Pancreatic Adenocarcinoma Jose-Guillermo De La Mora-Levy*, Juan O. Campuzano, Judith Cruz-Velazquez, Octavio Alonso, Julio Sanchez Del Monte, Sergio R. Sobrino-Cossio, Angelica Hernandez-Guerrero Gastroenterology, National Cancer Institute, Mexico City, Mexico; Cytogenetics, National Cancer Institute, Mexico City, Mexico Background: The sensitivity of EUS-guided cytology for the diagnosis of pancreatic adenocarcinoma is between 70 & O90%; among the identified factors that predict a positive result, the presence of a cytopathologist, number and passes and posible the type of needle have been identified as helpful. Aim: To study if the addition of FISH to cytology increases the sensitivity of EUS-guided FNA. Material & Methods: Consecutive patients with a pancreatic mass, sent for EUS-guided FNA to our Unit. An Olympus GF-UCT 160 echoendoscope and 22 gauge needles (EchoTip , Cook Medical), were used. Between 1-4 passes (median: 2) were performed for preparation of slides and cell block; 1 random slide was used for FISH analysis, which was performed using a commercially available kit (Urovision ). NO cytopathologist was present during the procedure. A total of 112 patients was calculated as the number needed to demonstrate at least a 10% increase in sensitivity, assuming an average of 80% sensitivity. A positive result was considered when either cytopathology or FISH alone or both were positive. Diagnostic values were calculated for Cytology, FISH and the combination; increase in sensitivity was the main variable. Inadequate specimens were purposely not included. The gold standard was considered to be: the surgical specimen, or a combination of CA 19-9 values, appropriate clinical and imaging picture plus compatible outcome on follow-up (FU). The study was approved by the IRB of our Institution. Results: A total of 105 patients were included; 16 were excluded for various reasons and analysis was performed on 89 patients. 49 were female, with a median age of 58 years (37-84); median FU was 4 months (1-12). Diagnostic values are shown in Table 1: A 13% increase in sensitivity was found, even when the calculated number was not reached. Conclusion: The addition of FISH analysis to EUS-guided FNA increases the sensitivity and positive results in patients with pancreatic adenocarcinoma. FISH could be used routinely, specially in settings without an onsite cytopathologist and with relatively few needle passes.