Background: Fine-needle aspiration cytology is frequently used for differential diagnosis of neck masses of unknown origin. Inconclusive and even false-negative results are not uncommon. Aim: To evaluate the utility of thyroglobulin (Tg) measurement in fine-needle aspirates (FNA-Tg) for detecting cervical lymph node (CLNs) metastases from differentiated thyroid carcinomas. Methods: An ultrasound-guided fine-needle aspiration was done in 67 patients with 83 suspicious enlarged CLNs to obtain material for cytology and Tg measurement in the needle washout, using an immunometric chemiluminescent assay. Measurement of anti-Tg antibodies (FNA-TgAb) was also carried out in half of all the aspirates. Subjects were divided into two groups: one of 16 patients awaiting thyroidectomy and the other of 51 patients in follow-up after surgery. Results: The first group of patients had positive FNA biopsy (FNAB-Tg) in 14 out of the 18 studied CLNs with a range of 3.2-43 352 ng/ml, while FNAB-cytology indicated metastasis in only 8 out of the 14 CLNs with positive histology. A total of 65 CLNs were studied in the follow-up group. Lymphadenectomy was performed in 23 patients and 28 aspirated CLNs were removed. Histology confirmed the diagnosis of metastasis suggested by FNAB-Tg in 20 CLNs and of reactive lymphadenitis in the remaining 8 CLNs. FNAB-cytology was positive in only 11 CLNs. Sensitivity of FNAB-Tg was not affected by the studied FNAB-TgAb. Conclusions: The FNAB-Tg achieved a sensitivity of 100% in both groups. FNAB-Tg is an easy and inexpensive technique which proved to increase the diagnostic of cytology in the early diagnosis of papillary carcinoma recurrence to CLN even in the presence of serum TgAb.
Introduction. The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. Objective. Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. Methods. We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. Results. From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490–15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). Conclusions. FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules.
ObjectiveMutations in the genes coding for succinate dehydrogenase (SDHx) are the most frequent germline alterations in pheochromocytomas and paragangliomas. Evidence for the advantages associated with presymptomatic screening for SDHx mutation carriers is scarce. This study describes a nationwide cohort of these mutation carriers and aims to compare patients with clinical manifestations of the disease and those diagnosed through genetic screening. DESIGN: Cross‐sectional study.PatientsSDHx mutation carriers (n = 118) followed through the Portuguese Oncology referral centres: 41 probands and 77 nonprobands.MeasurementsAll participants were subjected to biochemical and body imaging examinations for a complete assessment of the extent and spread of disease. Clinical data obtained this way were further analysed.ResultsThe mean age of this cohort was 44.5 ± 17.4 years, and more than half carried the same founder SDHB mutation. About 50.8% of the mutation carriers developed pheochromocytomas or paragangliomas. Compared to patients diagnosed through genetic screening, those diagnosed clinically were characterized by larger tumours (P < .001), more frequent metastases (P = .024), were more frequently subjected to surgery (P = .011) and radiotherapy (P = .013), and had worse outcomes, such as macroscopic positive margins (P = .034). Persistent and/or unresectable disease and disease‐related mortality were also more frequent in symptomatic patients compared to those diagnosed through genetic screening (P = .014).ConclusionsIn this nationwide cohort study, a large proportion of mutation carriers were found to develop SDHx‐related neoplasia. Genetic testing and subsequent follow‐up resulted in the diagnosis of smaller and nonmetastatic tumours, fewer treatment procedures, fewer complications and greater number of disease‐free patients.
Context Metabolomic studies of pheochromocytoma and paraganglioma tissue showed a correlation between metabolomic profile and presence of SDHx mutations, especially a pronounced increase of succinate. Objective To compare the metabolomic profile of 24-hour urine samples of SDHx mutation carriers with tumors (affected mutation carriers), without tumors (asymptomatic mutation carriers), and patients with sporadic pheochromocytomas and paragangliomas. Methods Proton nuclear magnetic resonance spectroscopic profiling of urine samples and metabolomic analysis using pairwise comparisons were complemented by metabolite set enrichment analysis to identify meaningful patterns. Results The urine of the affected SDHx carriers showed substantially lower levels of seven metabolites than the urine of asymptomatic mutation carriers (including, succinate and N-acetylaspartate). The urine of patients with SDHx-associated tumors presented substantially higher levels of three metabolites compared with the urine of patients without mutation; the metabolite set enrichment analysis identified gluconeogenesis, pyruvate, and aspartate metabolism as the pathways that most probably explained the differences found. N-acetylaspartate was the only metabolite the urinary levels of which were significantly different between the three groups. Conclusions The metabolomic urine profile of the SDHx mutation carriers with tumors is different from that of asymptomatic carriers and from that of patients with sporadic neoplasms. Differences are likely to reflect the altered mitochondria energy production and pseudohypoxia signature of these tumors. The urinary levels of N-acetylaspartate and succinate contrast with those reported in tumor tissue, suggesting a defective washout process of oncometabolites in association with tumorigenesis. The role of N-acetylaspartate as a tumor marker for these tumors merits further investigation.
Background: Tissue inhibitor metalloproteinase 1 (TIMP1) inhibits proteins which has proteolytic activity, but in cancer it contributes for tumoral invasion and metastization. The authors investigated the expression of TIMP1 in different digestive cancer types. The aim of this study was to test TIMP1 as a serum marker since in clinical practice there is a lack of biomarkers to monitor the response to treatments or to detect early relapses.Methods: It was performed a prospective study with recent diagnosed patients with gastrointestinal cancers. Patients with esophageal, gastric, colon, rectal, hepatocarcinoma, and cholangiocarcinoma at any stage, that did not perform any type of treatment, were included. Enzyme-linked immunosorbent assays and chemiluminescence were used to quantify levels of TIMP1. The differences of the Kaplan-Meier survival curves were tested for statistical significance with the log rank test, and the 95% confidence intervals were calculated. Multivariate analysis was done using the COX proportional hazard model and a forward stepwise method. Statistical analyses were done using the IBM SPSS Statistics version 26.0. P value inferior to 0.05 was considered significant.Results: A total of 190 patients were recruited: 54.7% males, median age of 68 years old, 57.9% with colorectal cancer followed by esophagogastric disease with 22.6%. TIMP1 level were increased in 29.5%. In colon cancer, patients with higher levels of TIMP1 are associated with worse progression free survival (PFS) (P=0.007) and overall survival (OS) (P=0.036). No relationship was seen with Rat sarcoma virus (RAS), B-raf (BRAF) and Microsatellite instability status (MSI). In gastric cancer, patients with higher levels of TIMP1 are associated with worse OS (P=0.020), with no difference in PFS.Conclusions: Higher TIMP1 levels in gastric and colon cancer patients are associated with worse prognosis. Further studies are needed: higher number of patients and sequential measurements of TIMP1 during patient treatments.
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