INTRODUCTION:Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population.METHODS:The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients.RESULTS:BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC.CONCLUSION:BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our population. There is a significant correlation between BRAF mutation and lymph-node metastasis.
Abstract It is known that thyroid cancer initiation and progression occurs because of gradual accumulation of genetic and epigenetic alterations at cell level. Many mutations associated with this disease have been reported to be present in genes encoding proteins in the mitogen-activated protein kinase (MAPK) signaling pathway, specifically BRAF and RAS genes, as well as in the PI3K/Akt signaling pathway, among others. In particular, molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Previously we found BRAF and NRAS mutations are observed in a significant number of papillary and follicular thyroid carcinomas in our population, respectively. In this study, we tested the diagnostic performance of BRAF and NRAS mutation in thyroid carcinoma in fine-needle aspiration (FNA) specimens with indeterminate cytology. In total, residual material from 73 FNA samples was used (n= 16, Bethesda III; n=48, Bethesda IV and n=9 Bethesda V). BRAF codon 600 mutation and NRAS codon 61 mutations were investigated using qPCR and melting curve analysis was carried out. Diagnosis of malignancy was confirmed by histology on paired surgical specimen in 54 cases. Results In the cytologically indeterminate categories, 9.6% of specimens were BRAF V600 mutated: 1 of 16 were subcategorized as atypia of undetermined significance or follicular lesion of undetermined significance (6.3%); 2 of 48 as follicular neoplasm or suspicious for follicular neoplasm (4.1%); and 4 of 9 as suspicious for malignancy (44.4%). NRAS Q61 mutation was found in 4 patients (2 with Bethesda IV and 2 with cytology V). The BRAF V600 mutations were associated with carcinoma in 100% of cases (n = 7), whereas only 75% (n = 3) of the nodules with NRAS were associated with carcinoma. BRAF V600 and NRAS Q61 mutations had high specificity in predicting malignant carcinoma (96.8%); the sensitivity was 43.5% with a positive predictive value of 90.9% and a negative predictive value of 69.8%. In specific categories of indeterminate cytology, the pre-test risk of malignancy was 38%, 33% and 88% while the post molecular test risk of malignancy was 100%, 75% and 100% respectively. Conclusions BRAF V600 and NRAS Q61 molecular test in residual FNA samples improve diagnostic accuracy of the cytology analysis in our population and may help to better select patients for avoid inadequate or unnecessary surgeries. Presentation: No date and time listed
Paraneoplastic syndromes are a heterogeneous group of malignant diseases caused by events which involve endocrine, immune and metabolic aspects and whose symptoms vary according to the substance produced and the primary tumor. Hypercalcemia is a frequent complication in cancer patients. Prognosis of cancer patients with hypercalcemia is usually poor. A factor called parathyroid hormone related peptide, whose actions are similar to those of the parathyroid hormone, is thought to be the most common cause of malignancy associated hypercalcemia. Non-islet hypoglycemic cell tumor consists of a rare syndrome characterized by the presence of a solid tumor and severe fasting hypoglycemia determined by an insulin-independent pathway. We report a case of a 59-year-old-man with a renal tumor and a T-cell rich large B cell lymphoma who was hospitalized due to severe hypercalcemia and hypoglycemia. The laboratory examination reported hypercalcemia with inhibited PTH and hypoglycemia with inhibited insulin secretion, arriving to the conclusion of tumoral peptide production. He received denosumab and corticoid therapy. The patient died one month later despite initial improvement after medical treatment. While a single paraneoplastic manifestation may be expected in most tumors, the coexistence of two or more of them is rare, except in hepatocellular carcinomas, and it has not yet been described in renal tumors.
We report the case of a 75-year-old man who was admitted to the hospital with symptoms of severe hypoglycemia. He had a history of solitary fibrous tumor diagnosed by Pathology after its complete surgical resection eight years before. The laboratory examination reported hypoglycemia with inhibited Insulin secretion. A computed tomography of the thorax revealed a large solid heterogeneous mass in the left hemithorax. Solitary fibrous tumor is a rare neoplasm. The association of solitary fibrous tumor and paraneoplastic hypoglycemia is known as Doege-Potter syndrome and occurs in less than 5% of all solitary fibrous tumors.
We report the case of a 75-year-old man who was admitted to the hospital with symptoms of severe hypoglycemia. He had a history of solitary fibrous tumor diagnosed by Pathology after its complete surgical resection eight years before. The laboratory examination reported hypoglycemia with inhibited Insulin secretion. A computed tomography of the thorax revealed a large solid heterogeneous mass in the left hemithorax. Solitary fibrous tumor is a rare neoplasm. The association of solitary fibrous tumor and paraneoplastic hypoglycemia is known as Doege-Potter syndrome and occurs in less than 5% of all solitary fibrous tumors.
